URMC-099 Combats Surgery-Induced Delirium, Cognitive Dysfunction in Preclinical Model of Orthopedic Surgery
Wednesday, November 6, 2019
Living microglia, genetically marked to glow green, in the cerebral cortex with magenta colored blood vessels from a mouse treated with URMC-099.
A new study published in the Journal of Neuroinflammation found that prophylactic treatment with URMC-099 – a “broad spectrum” mixed-lineage kinase 3 inhibitor – prevents neuroinflammation-associated cognitive impairment in a mouse model of orthopedic surgery-induced perioperative neurocognitive disorders (PND).
PND, a new term that encompasses postoperative delirium, delayed neurocognitive recovery, and postoperative neurocognitive disorder, is the most common complication after routine surgical procedures, particularly in the elderly. Following surgery, such as hip replacement or fracture repair, up to 50 percent of patients experience cognitive disturbances like anxiety, irritability, hallucinations, or panic attacks, which can lead to more serious complications down the line. Currently, there are no FDA-approved therapies to treat it.
Developed in the laboratory of Harris A. “Handy” Gelbard, M.D., Ph.D., director of the Center for Neurotherapeutics Discovery at the University of Rochester Medical Center, URMC-099 inhibits damaging innate immune responses that lead to inflammation in the brain and accompanying cognitive problems. Using animal models of diseases like HIV-1-associated neurocognitive disorders, Alzheimer’s disease and multiple sclerosis, Gelbard has shown that the compound blocks enzymes called kinases (such as mixed lineage kinase type 3, or MLK3) that respond to inflammatory stressors inside and outside cells.
Gelbard and Niccolò Terrando, Ph.D., director of the Neuroinflammation and Cognitive Outcomes laboratory in the Department of Anesthesiology at Duke University Medical Center, used an orthopedic surgery mouse model that recapitulates features of clinical procedures such as a fracture repair or hip replacement, which are often associated with PND in frail subjects. In a pilot experiment, they treated one group of these mice with URMC-099 before and after surgery, and another group prior to surgery only. Gelbard and Terrando’s teams, including first author Patrick Miller-Rhodes, a senior pre-doctoral student in the Neuroscience Graduate Program working in the Gelbard lab at URMC, measured the following:
- How the surgery affected the central nervous system and the immune cells (microglia) that reside there was evaluated using stereology and microscopy.
- Surgery-induced memory impairment was assessed using the “What-Where-When” and Memory Load Object Discrimination tasks.
- The acute peripheral immune response to surgery was assessed by cytokine/chemokine profiling and flow cytometry.
- Long-term fracture healing was assessed in fracture callouses using micro-computerized tomography and histomorphometry analyses.
- For additional details see the “Materials and Methods” section of the study
The team found that the surgery disrupted the blood brain barrier and activated microglia (a first line immune responder present in the inflamed brain), which led to impaired object place and identity discrimination when the mice were subject to the “What-Where-When” and Memory Load Object Discrimination tasks. Both URMC-099 dosing methods prevented the surgery-induced microgliosis (increase in the number of activated microglia) and cognitive impairment without affecting fracture healing.
“A major concern regarding the use of anti-inflammatory drugs for PND is whether they will affect fracture healing. We found that our preventive, time-limited treatment with URMC-099 didn’t influence bone healing or long-term bone repair,” said Gelbard and Terrando, professor of Neurology, Neuroscience, Microbiology and Immunology, and Pediatrics at URMC and associate professor of Anesthesiology at Duke University Medical Center, respectively. “These findings of improvement in cognition and normal fracture healing provide compelling evidence for the advancement of URMC-099 as a therapeutic option for PND.”
“Right now we have nothing to treat this condition,” said Mark A. Oldham, M.D., assistant professor in the department of Psychiatry at URMC who treats patients with PND. “We work hard to provide good medical care, including helping people sleep at night and making sure they are walking, eating and drinking, but it isn’t clear that these efforts have any meaningful long-term impact.”
According to Oldham, recent studies that track patients following an episode of PND show that many of them don’t resolve completely, and that they have a new cognitive baseline after delirium.
“It is increasingly an accepted fact that after delirium, people have suffered some kind of neurological insult, which leaves them cognitively or functionally worse off than before the incident,” he noted.
Next steps for the research include identifying definitive mechanisms for pain modulation, immune cell trafficking and neuro-immune characterization in PND. Gelbard and Terrando are tackling some of these questions with funds from the National Institutes of Health (RO1 AG057525). The current study was also funded by multiple grants from the NIH (P01MH64570, RO1 MH104147, RO1 AG057525 and F31 MH113504). The University of Rochester has four issued U.S. patents and multiple issued patents in foreign countries covering URMC-099.
Medical Student Gordon Wong presents at the annual URMC Medical School poster session
Monday, October 21, 2019
Dr. Georas (left) and Gordon Wong
Medical Student Gordon Wong presented a poster at the annual URMC Medical School poster session, describing his summer research project. Gordon studied how protein kinase D regulates airway inflammation and epithelial barrier integrity in mouse models of airway inflammation and viral infections. He made some very exciting discoveries, working with graduate student Janelle Veazey, specifically elucidating how protein kinase D controls the recruitment of neutrophils to the lungs.
Leigh Wexler Graduates!
Friday, September 6, 2019
Dr. Leigh Wexler and Dr. Portman (From Left)
Congratulations to Dr. Leigh Wexler, who successfully defended their thesis this week, earning a Ph.D. in Genetics from the GDSC program. Leigh’s thesis research in the Portman Lab focused on the regulation of neuronal circuit function and behavior in the nematode C. elegans. It’s been known for many years that males of this species tend to leave a food source to find mates, but that depriving males of food causes them to reprioritize feeding behavior over exploration. One important component of this behavioral flexibility is regulated chemosensory function. Well-fed males detect food poorly, partly due to low expression of a food-associated chemoreceptor called ODR-10, but food-deprived males upregulate ODR-10, increasing food attraction and decreasing food-leaving behavior. In contrast, hermaphrodites (the female equivalent in C. elegans) are strongly attracted to food and exhibit high levels of ODR-10 expression even when well-fed.
Leigh’s research probed the mechanism by which ODR-10 expression is influenced by feeding status in males. They found that signals through two conserved pathways, involving the TGFβ-family ligand DAF-7 and the insulin-like (IIS) receptor DAF-2, are important for keeping ODR-10 expression low in well-fed males. Further, Leigh found that males in which the IIS pathway is constitutively active fail to upregulate ODR-10 when starved. Interestingly, the DAF-7 signal appears to act upstream of IIS, indicating that a cascade of neuroendocrine interactions is necessary for repressing ODR-10. And DAF-7 does not act as a sensor of the starved male’s physiological state, but rather conveys information about the presence of food in the environment.
Together, Leigh’s research demonstrates that C. elegans males assess their external state, rather than their metabolism, when deciding whether to take the risk of leaving food to find a mate, and that this occurs through a multistep neuroendocrine feedback loop. Leigh’s work also provides important insights into how internal and external states are integrated by the nervous system to influence gene expression, neuronal circuit function, and behavior. This work will appear in an upcoming issue of Current Biology. We wish Leigh all the best as she set out to Boston, to start her post-doctoral career in the laboratory of Max Heiman at Harvard.
Janelle Veazey Receives Outstanding Student Mentor Award
Wednesday, September 4, 2019
Immunology Graduate Student Janelle Veazey received the Outstanding Student Mentor Award at the School of Medicine and Dentistry Convocation Ceremony on Wednesday, September 4th, Janelle was selected by the faculty of the Graduate Program in Microbiology & Immunology, in recognition of her outstanding commitment and dedication to mentoring undergraduate or graduate students. Congratulations Janelle!
Deb Fowell Authors Study on Immune Cell Navigation Systems
Tuesday, August 13, 2019
When immune cells get recruited to infections, tumors, or other sites of inflammation they exit the blood stream and begin searching for the damage. But how they effectively traverse the body’s tissue and home in on their targets is unclear. A new study led by Deborah Fowell, Ph.D. suggests that T cells have distinct navigation systems that help them pinpoint their targets.
Fowell’s research team, based in the David H. Smith Center for Vaccine Biology and Immunology in the Department of Microbiology and Immunology made the discovery by visualizing the immune system in real time using intravital multiphoton microscopy. The technology allows you to look directly into the skin and observe the dynamic behavior of immune cells ‘live.’ Their findings were published earlier this month in the journal Immunity.
“We thought that locating the infection foci was a passive event for immune cells; that they used the tissue as a scaffold to weave their way through this complex matrix to get to their target,” said Fowell, Dean’s professor in the Department of Microbiology and Immunology. “We discovered that they are pre-programmed to respond to certain cues within the tissue microenvironment that help them find their targets more efficiently.”
The team hopes that discovering these specialized programs for migration in tissues will provide new therapeutic targets that enable manipulation of the immune response in a disease-specific or tissue-specific fashion, rather than globally suppressing the immune system. Possibilities include boosting protective immunity in diseases where the immune system is inefficient, such as chronic infections and tumors, and limiting immunity in diseases that are exacerbated by the immune system, like autoimmunity and heart disease.
Hen Prizant, Ph.D., a postdoctoral fellow in Fowell’s lab and Alison Gaylo-Moynihan, M.D., Ph.D., a former student in the lab are co-first authors. Graduate students Ninoshka R.J. Fernandes, Hannah Bell, Dillon C. Schrock, Tara Capece, Brandon Walling, and Christopher Anderson contributed to the study. Faculty members David Topham, Minsoo Kim, Alan Smrcka and James Miller are also authors.
Fowell credits the new finding to the power of NIH Program Project Grants (P01), which allow faculty, trainees and students to explore uncharted scientific territory and branch out among different disciplines. For example, the team reached across Elmwood Avenue to have conversations with astrophysicists and engineers on River Campus about how objects move through and are found in space. The P01 that funded the research was awarded to Fowell (PI) and Kim, Topham and Miller in 2014.
Supriya Mohile Headlines MSTP 19th Annual Retreat
Monday, August 12, 2019
The Medical Scientist Training Program’s 19th Annual Retreat was held on August 9, 2019, at the Rochester Yacht Club. The retreat is an opportunity for the student body to gather to discuss science and welcome the incoming class. This year, the MSTP welcomed six new students: Maya Anand (Columbia University), Thomas Delgado (University of Florida), Svetlana Markova (Kharkiv National Medical University), Michael Meadow (UCLA), Gavin Piester (University of Rochester), and Victor Zhang (University of Rochester).
2019 Incoming Students
This year’s Keynote address was given by Dr. Supriya Mohile, Professor of Medicine and Surgery at the University of Rochester, and was titled “Improving Care Delivery and Outcomes for Older Patients with Cancer and their Caregivers.” Dr. Mohile highlighted the need for geriatric assessments in oncology to properly address concerns such as tolerability and toxicity of cancer treatments. She described the large clinical studies that are ongoing which demonstrate the feasibility of implementing geriatric assessments in oncology and stressed the need for all clinicians who treat elderly patients to use tools available to them to address concerns that are unique to this population.
The morning science session concluded with short talks by several current MSTP students. Second year medical student Emily Isenstein discussed her work on proprioceptive and visual integration in children with autism, Fara Tolibzoda Zakusilo (G2) discussed the role for the extracellular matrix in Alzheimer’s disease, Jesse Wang (G3) spoke about the development of a digital medical scribe, Booyeon Han (G4) described her work to understand the tumor-draining lymph node in pancreas cancer, and Aimee Morris (M4) spoke about resting state functional connectivity in focal dystonia.
Following lunch, Kerry O’Banion, MSTP director, gave an update on curricular changes occurring in the medical school, which was followed by a presentation by students who attended the National MD/PhD Conference at Copper Mountain in July. New students were elected to the MSTP student council to end the afternoon. We look forward to another exciting year for the MSTP!
SMD's Aleta Anthony Named Director of Equity, Inclusion & Research Education Support
Friday, August 9, 2019
The Office for Graduate Education and Postdoctoral Affairs (GEPA) at the School of Medicine and Dentistry has announced the appointment of Aleta Anthony to the role of Director of Equity, Inclusion and Research Education Support.
The directorship is a newly-created position aligning with the University of Rochester and the Medical Center’s broader mission to support equity and inclusion through strategic efforts, organizational programming, and inclusion initiatives. As director, Aleta will provide leadership and direction to GEPA to foster an environment where all members of the GEPA community are supported and acknowledged for diverse backgrounds and experiences.
In a commitment to promoting equity and inclusion for students and postdocs, Richard Libby, Ph.D., who is senior associate dean for GEPA, worked with the University of Rochester Medical Center’s Office for Inclusion and Culture to create Anthony’s new role.
Anthony joined the School of Medicine and Dentistry in 2017 as the director of graduate enrollment for Ph.D., master’s, and certificate programs. In addition to her new role leading GEPA’s equity and inclusion efforts, she will continue her work building and enhancing recruitment strategy for the school’s biomedical sciences and health sciences graduate programs.
Single Brain Region is Key to Assessing the Impact of Repetitive Head Hits, Concussions
Wednesday, August 7, 2019
While a brain injury can be difficult to locate, new research identifies a single region of the brain that can be used to examine the impact of a concussion or repeated hits to the head.
The finding, published today in Science Advances, also supports the emerging idea that traumatic brain injury is not limited to people who sustain a concussion; it can result from repetitive head hits that are clinically silent–those that do not produce the visible signs or symptoms of a concussion. These subconcussive hits have been increasingly recognized as a potential threat to long-term brain health and as a possible cause of chronic traumatic encephalopathy (CTE).
Jeffrey Bazarian, M.D., M.P.H., professor of Emergency Medicine, Neurology, Neurosurgery and Public Health Sciences at the University of Rochester Medical Center and a co-author of the study says that the location of a brain injury varies widely from person to person. This is a major obstacle for physicians trying to diagnose brain injury using imaging techniques.
“This study is important because we found that no matter where the head gets hit, the force is translated into a single region of the brain known as the midbrain,” noted Bazarian, who treats concussion patients and conducts research related to traumatic brain injury. “Midbrain imaging might be a way in the future to diagnose injury from a single concussive head hit, as well as from repetitive sub-concussive head hits.”
University of Rochester fourth-year medical student Adnan Hirad, Ph.D., the first author of the research added, “Our findings do not dispute the fact that head-injury effects are distributed throughout the brain, but the midbrain may serve as a ‘canary in a coal mine’ in terms of identifying damage. From this study we know that the midbrain region, which is linked to brain functions often affected by a concussion, is the place to look to identify the impact of clinically defined concussions with visible symptoms and silent brain injuries that can’t be observed simply by looking at or behaviorally testing a player, on or off the field.”Read More: Single Brain Region is Key to Assessing the Impact of Repetitive Head Hits, Concussions
Thursday, July 11, 2019
After successfully defending his thesis, MJ has completed the PhD portion of his MD/PhD studies. MJ’s studies investigated the genetic basis of bone-matrix quality, an underappreciated property of bone that contributes significantly to bone strength and is of great clinical importance for understanding of bone pathology such as osteoporosis. MJ used both a classical population genetics approach as well as a systems genetics approach, and found that bone matrix characteristics such as morphology and matrix composition are indeed inheritable properties. In addition, using an estrogen-deficient model of post-menopausal bone loss, he was able to identify gene networks that may play an important role in osteoporosis. His results suggest that bone matrix quality is influenced by genetics and participates in maintaining tissue-level mechanical properties. Furthermore, identifying putative regulatory genes is clinically significant as they are presumptive targets for developing novel therapeutics. During his thesis work, MJ was the recipient of a CTSI Pilot Trainee Grant and scored a fundable F31 predoctoral fellowship from NIAMS. With his GDSC doctorate in hand MJ will return to medical school to obtain his M.D. Best of luck in your future ventures, MJ!!
Scott Friedland Defends Thesis
Thursday, July 11, 2019
This week M.D./Ph.D. student Scott Friedland defended his doctoral thesis. Arriving at the GDSC in 2014, Scott pursued his Ph.D. under the mentorship of Dr. Aram Hezel. As a student Scott was granted travel awards to a national physician scientist conference and selective course at Cold Spring Harbor Labs. His thesis, titled Arid1a, a subunit of the SWI/SNF chromatin remodeling complex, is a barrier to KrasG12D-driven tumorigenesis, studied the role of SWI/SNF, a chromatin remodeling complex, in pancreatic function and disease, which has implications for the fields of cancer and developmental biology. These findings may, in time, impact the treatment of diseases such as pancreatitis and pancreatic cancer. Scott will be reinitiating his medical education alongside the class of 2021 here at the University of Rochester School of Medicine, and is interested in pursuing a career as an oncologist and cancer researcher. Congratulations Dr. Scott Carl Friedland!
Study Points to Stabilization of TRAF3 Protein to Fight Age-Related Bone Loss
Wednesday, June 26, 2019
A new study led by Brendan Boyce, M.B.Ch.B.., professor of Pathology & Laboratory Medicine and the Center for Musculoskeletal Research and Zhenqiang Yao, MD., Ph.D., assistant professor of Pathology & Laboratory Medicine suggests that age-related osteoporosis could be prevented or treated through pharmacologic stabilization of the protein, TNF receptor-associated factor 3 (TRAF3).
The collaborative study was published in Nature Communications after five years of work by Boyce and fellow URMC researchers who note the need to better understand the mechanisms through which osteoporosis occurs in order to develop new drugs that can be given to help prevent or reverse the disease.
The study notes that the process by which young, healthy peoples’ bones are naturally rebuilt, deteriorates as people age or go through menopause. Increased inflammation, or inflammaging, leads to an increase in bone-degrading osteoclast cells and a reduction in bone-forming osteoblasts, resulting in osteoporosis.
Existing treatments that prevent bone destruction offer long term solutions, but many patients are reluctant to take them because they fear side effects of the drugs, while bone forming drugs can be administered only for short periods to help patients suffering from chronic osteoporosis.
The paper shows that the protein, TGF-beta, which is released in increasing amounts from bone during aging, causes breakdown of TRAF3 in osteoblast precursor mesenchymal progenitor cells. This leads to a reduction in the number of osteoblasts and less bone repair and indirectly to increased numbers of osteoclasts and more bone destruction.
By stabilizing TRAF3 levels in bone cells through new drugs, the authors provide a novel mechanism for how treatments may offer a more long-term solution for patients. This is especially crucial as more people live longer and are exposed to a greater risk of fractures and early death.
Lemonade Stand Supports Efforts to Cure Childhood Cancer
Friday, June 21, 2019
For the 10th year in a row, Danielle Benoit, associate professor of biomedical engineering, and mentees from her lab will hold their fundraiser in support of Alex’s Lemonade Stand Foundation and its efforts to cure childhood cancer. You can donate online or drop by the lab’s lemonade stand from 10 a.m. to 1 p.m. Saturday, June 22, at the Rochester Public Market, 280 Union Street North or from 9 a.m. to 1 p.m. Sunday, June 23, at the Brighton Farmers Market,1150 Winton Road South.
Liwei Wang, Ph.D. Graduate of the Cellular and Molecular Pharmacology and Physiology PhD Program won the Fenn Award for best thesis
Thursday, June 20, 2019
Liwei Wang, Ph.D. Graduate of the Cellular and Molecular Pharmacology and Physiology PhD Program won the Fenn Award for best thesis, the award was presented at the 2019 Commencement Dinner by Richard Libby, Senior Associate Dean for Graduate Education and Postdoctoral Affairs following an introduction from Dr. Wang's faculty mentor, Dr. David Yule.
The award was for Dr. Wang's thesis, entitled "Region-specific Proteolysis Differentially Regulates Inositol 1,4,5-trisphosphate Receptor Activity " Dr. Wang is currently a Postdoctoral Fellow in the laboratory of Prof. Stefan Feske at NYU, Langone Medical School. His current research involves investigating the role of ion channels in immunological tolerance and immunity.
About the Award
Dr. Wallace Fenn was a Professor of Physiology at the University of Rochester School of Medicine and Dentistry from 1924 to 1961. He served as the Chairperson of the Department of Physiology from 1924 to 1959 and thereafter until his death in 1971, he was appointed by the University to the position of Distinguished University Professor of Physiology. As well, Dr. Fenn served as the Associate Dean of Graduate Studies from 1957 to 1959.
To read more regarding this award, please visit the department of Biochemistry and Biophysics website.
A Graphic Design Revolution For Scientific Conference Posters
Tuesday, June 18, 2019
“Other templates didn't necessarily ask you to think about what you were putting on them because they allowed it all,” says Derek Crowe, a PhD student in biomedical genetics in Hucky Land's lab with a former career in visual communication and design, “In order to use Mike's layout though, my hand is forced.”
With the new template, scientists need to think about their core message, but some people have a difficult time figuring out how to do that, or how to use visuals to present their message. Without proper science communication training, even a better poster template doesn’t work.
Crowe has taken matters into his own hands. Not only does he teach a course on visual communication for scientists at the University of Rochester, but he also shared his poster design tips online. In a nod to Morrison’s “better poster”, Crowe’s is a “butter poster”. He provides step by step instructions on how to organize the poster, and how to think about the content in a visual way.
“Like the graphic novel did for literature, visual languages have the power to add more dimensions to scientific storytelling,” says Crowe, “I’m excited to see what happens as the greater science community begins to take advantage of well-established visual storytelling tools.”Read More: A Graphic Design Revolution For Scientific Conference Posters
Romeo Blanc Receives Multiple Awards From the International Society for Stem Cell Research (ISSCR)
Thursday, June 13, 2019
Romeo Blanc postdoctoral fellow in the Chakkalakal Lab was the recent recipient of the Podium presentation, Travel award, and Merit Awards from the International Society for Stem Cell Research (ISSCR) for the upcoming annual meeting in Los Angeles CA, June 26 – June 30, 2019.
The first award, called Travel Award, came from the ISSCR itself and covers registration and/or cash award. The second award, called Abstract Merit Award is made to highlight some outstanding selected abstract which is chosen by ISSCR as well.
CMPP Students Host Guest Speaker Dr. Ehsan Sarafraz-Yazdi
Tuesday, June 11, 2019
To fortify the involvement of graduate students in academic affairs, the Department of Pharmacology and Physiology (CMPP) hosted student nominated guest speaker: Dr. Ehsan Sarafraz-Yazdi, Ph.D., M.P.H., Founder and CEO of NomoCan Pharmaceuticals, LLC. Dr. Yazdi was nominated by PhD candidate Edward Ayoub and chosen by CMPP graduate students to spend a day at URMC. During his visit, Dr. Yazdi connected with faculty and students, and presented a seminar highlighting a new microfluidic system to study anti-cancer drug responses ex-vivo. Dr. Yazdi also shared his vision and inspiration to start his own pharmaceutical company at a URBEST Career Story hosted by Dr. Tracey Baas. CMPP will continue to host a student-nominated guest speaker annually.
Left to right: Lily Cisco, Dr. Ehsan Yazdi, Edward Ayoub, Kai Ting Huang, Alexander Milliken, Matthew Rook
Upcoming Thesis Defenses
Friday, June 7, 2019
Rebeckah Burke, chemistry, “Colloidal Semiconductor Nanocrystals for Photocatalytic Proton Reduction.” 10 a.m. June 11, 2019. 108 Goergen Hall. Advisor: Todd Krauss.
Philipp Birklbauer, mathematics, “Theoretical and Computational Explorations in Vector Spaces Over Finite Fields.” 2:30 p.m. June 12, 2019. Hylan 1106A. Advisor: Alex Iosevich.
Molly McCann, epidemiology, “Degree of Bystander-Patient Relationship and Prehospital and Emergency Department Care for Opioid Overdose.” 10 a.m. June 14, 2019. Helen Wood Hall | 1W 502. Advisor: Todd Jusko.
Jie Luo, biology, “The Role of Androgen Receptor in Different Prostate Cancer Therapies.” 12:30 p.m. June 14, 2019. Room 2-6424 Medical Center. Advisor: Chawnshang Chang.
GDSC Student, Tom O’Connor Earns First Place in 2019 Sharing Your Science in A Social World Contest.
Monday, June 3, 2019
Finishing his first year of GDSC studies on a high-note, Tom O’Connor (member of the Chakkalakal & Dirksen Labs) together with his teammate Griffin Schroeder, have won first place in the 2019 ‘Sharing Your Science in A Social World’ contest. Sponsored by URBEST, this contest encourages students to communicate their research to a broad audience using videography. For their entry, imbedded above, Tom and Griffin emphasized the work being done in the Noble Lab, where Tom worked during his first rotation. The video, URBEST 2019: Translational Science, highlights how the Noble Lab sets itself apart by re-purposing FDA approved drugs for different clinical applications, expediting the bench-to-clinic transition.
Congratulations Tom and Griffin!
Imaging That Twinkle in Your Eye: Assessing Vascular Health by Imaging Blood Cells in the Retina
Tuesday, May 14, 2019
Jesse B. Schallek, Ph.D., assistant professor in the Department of Ophthalmology, describes a new, noninvasive approach to assess vascular health in the journal eLife. Schallek’s lab, part of the Flaum Eye Institute, developed a method to visualize how single blood cells flow through vessels of the eye using adaptive optics imaging.
The transparency of the eye provides a natural window to the retina, an extension of the brain. Vascular physiology is best studied noninvasively inside the living body, but seeing the details of how microscopic blood cells interact within the vasculature has not been possible with current tools such as fMRI. Schallek’s team developed high-resolution adaptive optics combined with fast camera capture to visualize single-cell blood flow dynamics in the living mouse eye.
“We’re able to image single blood cells and measure their speed. Remarkably, this can be achieved in vessels of all sizes, from the smallest capillaries to the largest retinal vessels,” said Schallek. “This approach may eventually provide a view of patient vascular health without the need for blood draws or dyes.
Krystel Huxlin, Ph.D., Associate Chair for research in the Department of Ophthalmology adds, “This method has the potential to enable early diagnosis of cardiovascular disease and diabetic neuropathy, and will also be of interest to investigators studying blood flow in the context of stroke and neurodegenerative diseases like Alzheimer’s.
The study was conducted in large part by Optics graduate students Aby Joseph and Andres Guevara-Torres. “My research interest involves using my physics/optics background to provide insights into biological questions,” said lead-author Joseph. “This paper, at the intersection of physical sciences and neuroscience, provides a novel and noninvasive imaging approach that may advance our understanding of blood flow dynamics in brain and retinal vessels smaller than the width of a human hair.
Schallek’s team, part of the Advanced Retinal Imaging Alliance (ARIA), is now deploying the method in healthy human eyes to establish metrics that will enable researchers to better elucidate the events that initiate and propagate disease. A pre-clinical investigation, funded by the Dana Foundation, is beginning to use this powerful approach to compare what happens in normal and diabetic retinas of human subjects. Schallek holds secondary appointments in the Department of Neuroscience and the Center for Visual Science. The research was funded by the National Eye Institute at the National Institutes of Health and by a Career Development Award from Research to Prevent Blindness.
UR CTSI Student Continues on the Road to Success
Monday, May 13, 2019
Kristen Bush Marshall received her Ph.D. in Translational Biomedical Science in January 2019 and is currently serving as a postdoctoral associate in the Rochester Center for Health Informatics under the mentorship of Martin Zand, M.D., Ph.D. She has just been matched with her top-ranked choice: a field assignment in Denver for a two-year Epidemic Intelligence Service Fellowship. This position with the local health department and the state pf Colorado Department of Public Health and Environment responds to local and state-wide outbreaks allowing Bush Marshall to use her knowledge of healthcare-associated infections.
May 10th: 8th Annual Lecture on Biomedical and Health Science Ethics
Friday, May 3, 2019
The 8th Annual Lecture on Biomedical and Health Science Ethics will be given by Daniel E. Acuna, assistant professor in the School of Information Studies at Syracuse University.
Attendance at the lecture, from 2-3 p.m. Friday, May 10 in the Class of ’62 Auditorium (G-9425), is mandatory for Medical Center graduate students and postdoctoral appointees.
Acuna’s lecture is entitled: “How to Catch a Scientific Figure Falsifier: Analysis and statistical reporting of potential figure element reuse and splicing across millions of images.” This special lecture is part of ongoing instruction in responsible conduct of research (RCR) required of grad students and postdocs by the National Institutes of Health.
As part of ongoing efforts to satisfy this requirement, the University of Rochester sponsors periodic RCR lectures and workshops. In addition to completing the Ethics and Professional Integrity in Research Course (IND501/506), all graduate students and postdoctoral appointees are expected to participate in these lectures and workshops.
Refreshments will be available in Flaum Atrium following the lecture.
Upcoming PhD dissertation defenses
Friday, May 3, 2019
Valeriia Sherina, statistics, “Statistical Methods for qPCR Data Near the Limit of Detection.” 11 a.m. May 10, 2019. Helen Wood Hall | 1W-509. Advisor: Matthew McCall.
Nicolas Riquelme Carrasco, economics, “Essays on Mechanism Design and Multiple Privately Informed Principals.” 10 a.m. May 10, 2019. Harkness 113. Advisor: Paulo Barelli.
Emily Wu, microbiology & immunology, “Uncovering the Role of TNF-alpha in the Genesis of Inflammatory Interstitial Lung Disease in the TNF-Transgenic Mouse Model of Rheumatoid Arthritis.” 1 p.m. May 17, 2019. Ryan Case Method Room 1-9576 (Medical Center). Advisor: Edward Schwarz.
BMB Graduates Receive College Prizes
Thursday, May 2, 2019
2019 College Prize Recipients
- Katherine Woo: Ayman Amin-Salem Memorial Prize
- Fayth Kim: the Janet Howell Clark Prize
- Nicholas Lim: Irene Bush Steinbock Award
- Kavya Bana: Helen S. Jones Memorial Fund
Next-Gen Women in Science: Dalia Ghoneim
Thursday, May 2, 2019
GDSC student Dalia Ghoneim from the Matthews lab was awarded the prestigious Perricone MD Born Seekers fellowship. The $20,000 award recognizes the inspiring achievements of young women in science, and is the culmination of the Scientista Foundation’s video competition, in which young women tell their personal journey in STEM. Dalia was able to tell her remarkable story in the award-winning video clip with the help of two talented fellow GDSC-students: cameraman, sound expert and producer Adam Cornwell, and speech-editor Matt Ingalls. As a single mother of four, Dalia is now approaching the successful completion of her PhD in Genetics. She was invited to give her speech and accept her award at the Scientista Symposium 2019 in Boston, MA. The Scientista Foundation’s vision is to support the next generation of female scientists – and we can’t wait to see what Dalia will do next! Congratulations!!
Congratulations to Sijiu Wang for receiving Mathematica summer fellowship!
Wednesday, May 1, 2019
This is a highly competitive program, which only accepts 1-3 fellows in healthcare unit nationally each year. The past awardees were all from top universities, including Harvard, U of Penn, and U of Chicago! With the support of this fellowship, Sijiu will be working on her own independent dissertation work and gaining additional experience from Mathematica researchers. Great work, Sijiu!
AnnaLynn Williams Receives Vincent du Vigneaud Award
Tuesday, April 30, 2019
AnnaLynn Williams, recent PhD epidemiology graduate, has been selected to receive this year’s Vincent du Vigneaud Award which will be presented at the PhD Commencement Dinner on May 17th. This award "is presented annually to a graduating student whose thesis work is judged to be unique in potential for stimulating and extending research in the field.?" (See attached for more information about Dr. du Vigneaud and the award.) The selection committee has deemed her work as the best example of what this award represents. Please join me in congratulating AnnaLynn!
Jayme Olson earns (CTSI) Trainee Award
Tuesday, April 30, 2019
Jayme a GDSC-graduate student in the Palis Lab was recently awarded a Clinical and Translational Science Institute (CTSI) Trainee Award. This one-year fellowship will fund cutting edge work on the in vitro generation of human red blood cells. Cultured human red blood cells (RBCs) have the potential to serve as a supplemental source of blood for transfusion therapy, and as a tool for clinical and research diagnostic. However, a major barrier in generating sufficient numbers of cultured RBCs cells is the limited ex vivo self-renewal capacity of adult-derived erythroblasts. Work in the Palis Lab has identified Bmi-1, a member of the polycomb repressive complex 1 (PRC1), as a critical regulator of erythroid self-renewal. Bmi-1 also plays a role in normal erythroid precursor maturation. Jayme will test the hypothesis that Bmi-1 regulates erythroid self-renewal and terminal maturation using different PRC1 members. Ultimately, these proposed studies will pave the way for the generation of sufficient numbers of cultured RBCs for blood typing and transfusion therapy, as well as the establishment of in vitro models for the study of erythroid intrinsic diseases.
31st Genetics Day at the University of Rochester
Monday, April 29, 2019
The University of Rochester hosted its 31st Annual Genetics Day Symposium with a poster session displaying genetics research from more than fifty post-doctoral fellows, graduate and undergraduate students. The meeting started with a strong lineup of faculty presentations, highlighting ongoing Genetics Research and as well as new faculty recruits. Speakers included Dr. Amanda Larracuente, Dr. Doug Anderson, Dr. Peng Yao, Dr. Xin Zhiguo Li and Dr. Paul Boutz. Keynote speaker Dr. Phillip Zamore, from the University of Massachusetts, delivered the 17th Annual Fred Sherman Lecture. This year’s poster prizes were awarded to:
- Leigh Wexler: A male-specific neuroendocrine feedback loop couples food signals for feeding behavior in C. Elegans
- Matthew Tanner: Identifying sequence determinants of altered RNA splicing in myotonic dystrophy.
- Dr. Jacquelyn Lillis: Single-cell transcriptome analysis of embryonic erythro-myeloid progenitor cells reveals lineage heterogeneity.
- Jayme L. Olsen: Bmi-1 regulates human erythroblast ex vivo self-renewal.
- Anissa Elahi: Transglutaminase 2 as a therapeutic target to facilitate recovery after spinal cord injury.
- Zhengfen (Jeff) Liu: DNA damage-specific regulation of cell cycle checkpoint by γ-h2ax.
We congratulate each poster winner and look forward to the 32nd Genetics Day next year!
A link to additional Genetics Day 2019 photos can be found here.
'Longevity Gene' That Helps Repair DNA And Extend Life Span Could One Day Prevent Age-Related Diseases In Humans
Tuesday, April 23, 2019
Scientists studying longevity believe a gene could explain why some animals live longer.
In 18 species of rodents with varying life spans, researchers looked at sirtuin 6 (SIRT6), a gene that plays a role in bodily processes such as aging, cellular stress resistance and DNA repair.
Over time, DNA inevitably suffers what are known as double-strand breaks (DSBs) that can cause genes to mutate, triggering aging and diseases like cancer.
Dirk Bohmann, a professor of biomedical genetics at the University of Rochester Medical Center, explained in a statement, “[DSBs] are always going to be there, even if you’re super healthy. One of the main causes of DSBs is oxidative damage and, since we need oxygen to breathe, the breaks are inevitable.”
While animals with relatively short life spans don’t have so many DSBs, Bohmann explained, “if you want to live for 50 years or so, there’s more of a need to put a system into place to fix these breaks. The SIRT6 protein seems to be the dominant determinant of lifespan. We show that at the cell level, the DNA repair works better, and at the organism level, there is an extended lifespan.”
To answer whether SIRT6 works harder in species that live longer, the team studied 18 rodents, from mice expected to live around three years to beavers and mole rats with life expectancies of up to 32 years. Animals with stronger SIRT6 proteins were found to live longer.
This was also apparent when they compared the molecular differences in the SIRT6 proteins of mice and beavers. And by dosing human cells and fruit flies with the SIRT6 from a mouse and a beaver, as expected, the scientists found the beaver protein was more potent than the mouse protein.Read More: 'Longevity Gene' That Helps Repair DNA And Extend Life Span Could One Day Prevent Age-Related Diseases In Humans
2019 Three Minute Thesis Winners
Monday, April 22, 2019
2019 Three Minute Thesis Winners, Emily Hangen, Greg Madejski and Brandon Berry
On April 4th, 2019 The University of Rochester held the 4th Annual Three Minute Thesis competition finals. Eight Finalists were selected and spoke for 3 minutes on their chosen research topic.
- Emily Warner, Neuroscience Graduate Student
"Memories can change the way we smell"
- Brandon Berry, Pharmacology and Physiology Graduate Student
"Light Activated Mitochondria"
- Emily Hangen, Arts, Sciences and Engineering
"Expectations: Helpful or Harmful?"
- Rainier Barrett, Chemical Engineering Graduate Student
"Computer-Aided Drug Discovery: Machine Learning and Computational Chemistry"
- Nancy Cardona, Obstetrics and Gynocology Postdoctoral Fellow
"Determinants of urinary biomarkers of pesticide exposure among pregnant women in Costa Rica"
- Greg Madejski, Biomedical Engineering Postdoctoral Associate
"Microplastics: In your food and water"
- Elizabeth Anson, Human Development Graduate Student
"Youth Violence: Everything I needed to know, I learned in preschool"?
- Kolja Keller, Philosophy Graduate Student
After careful deliberation by both the judging panel and the audience, the winners of the 2019 Three Minute Thesis competition were:
Judge’s Winner: Emily Hangen
Judge’s Runner-Up: Greg Madejski
People’s Choice: Brandon Berry
Congratulations to Emily, Greg and Brandon! Video and Photos of the event can be found on the Three Minute Thesis Website
31st Annual Genetics Day Symposium
Monday, April 22, 2019
The Departments of Biomedical Genetics and Biology, with the support of the University Committee for Interdisciplinary Studies, host the 31st annual Genetics Day Symposium on Thursday, April 25, from 9:30 a.m. to 4 p.m. in the Class of ’62 Auditorium and Flaum Atrium. This year’s Fred Sherman Lecturer will be Phillip Zamore, a Howard Hughes Medical Institute investigator and professor of biomedical sciences at the University of Massachusetts Medical School, giving a talk titled “piRNAs and the Struggle to Reproduce.”Read More: 31st Annual Genetics Day Symposium
Handy Gelbard Honored for Pediatric HIV/AIDS Research
Wednesday, April 17, 2019
Handy Gelbard, M.D., Ph.D., professor and director of the Center for Neurotherapeutics Discovery at URMC, is the 2019-2020 recipient of the Herman and Gertrude Silver Award, which honors individuals who have made significant contributions in the field of pediatric HIV and AIDS. The award is given by the Children’s Hospital of Philadelphia (CHOP) and the Department of Pediatrics of the Perelman School of Medicine at the University of Pennsylvania. Past award winners include a Nobel laureate and HIV investigators from leading academic institutions, the National Institutes of Health (including the current directors of the Office of AIDS Research and the National Institute of Allergy and Infectious Diseases), and the Centers for Disease Control and Prevention.
For the past 10 years Gelbard’s lab has been developing a compound called URMC-099, which dampens inflammation and has shown promise in reversing the neurological problems associated with HIV. Children with HIV who are taking combination antiretroviral therapies are extremely vulnerable to inflammation; the developing nervous system is of particular concern, as inflammation in the brain can lead to major cognitive problems.
The possibility of a new class of therapies that reduces the burden of neuroinflammation and supports normal synaptic architecture (the basis for learning and memory) offers considerable hope for children that are saddled with the unwanted burden of HIV, despite effective control of the virus.
Gelbard believes the path forward for URMC-099 as an adjunct agent for children living with HIV and neurologic disease will likely involve combination therapy with next generation antiretroviral agents. This is a priority in resource-limited settings such as Africa, and Gelbard is working with David Bearden, M.D., assistant professor in the division of Child Neurology at URMC to help advance uses for URMC-099 in pediatric patients there. Bearden’s work is supported by a National Institute of Neurological Disorders and Stroke grant to Gretchen Birbeck, M.D., M.P.H., professor of Neurology and Michael Potchen, M.D., professor of Imaging Sciences. The work is also supported by the University of Rochester Center for AIDS Research.
Gelbard will receive the Silver Award in November during a two-day symposium at CHOP. He will present pediatric grand rounds describing his progress in inventing the class of compounds spearheaded by URMC-099 and its role in treating pediatric and adult HIV infection and its complications. He’ll also give a seminar on current and future developments related to URMC-099 to attendees from multiple medical and scientific institutions in Philadelphia.
TBS Student is Finalist in "Shark Tank"-Style Competition
Monday, April 15, 2019
Congratulations to Jesse Wang, a student in the UR CTSI Translational Biomedical Science Ph.D. program, who was one of four finalists in the ACP Innovation Challenge 2019. Wang presented his "digital scribe" technology at this “Shark Tank”-style competition hosted by the American College of Physicians, on Saturday, April 13. His digital scribe technology can capture statistical speech analysis and natural language conversation between a physician and patient and automatically update eRecord. The system would capture and document the appropriate information during a patient interview, alleviating physicians' workload.
URMC Trainee Travel Awards 2019
Monday, April 15, 2019
This award assists students and trainees at the University of Rochester School of Medicine and Dentistry to attend important national or international meetings at which they will present their research and make professional connections. Two awards of up to $1000 will be given this funding cycle: one for clinical research and one for basic sciences research.
This award is best suited to advanced students for whom conference attendance can be expected to have the largest career impact. The most competitive applications will be from presenting authors (either poster or platform presentations) who are in the mid to late stages of their educational experience. Apply by Friday, May 3, 6:00 pm.
Read the full RFA.
A prescription for physician frustration
Thursday, April 11, 2019
Jesse Wang remembers exactly when his crusade began.
The doctor he had seen since childhood turned a computer screen towards him during an office visit, in obvious frustration.
He couldn’t get the program started to make the required entries in Wang’s electronic medical record.
“This is absurd,” his doctor said. “I just want to be able to talk to you like I used to.”
Wang, who is pursing both a medical degree and a PhD in translational biomedical science at the University of Rochester, understands the frustration. Especially when he reads studies showing it’s not unusual for physicians to be online maintaining patient e-records from 5 in the morning until 9 at night.
“It’s not what I signed up for; it’s not what any doctor signed up for,” Wang says.
Thanks to Rochester’s Medical Scientist Training Program, which allows him to combine his interest in medicine with his passion for coding, Wang is well positioned to do something about the problem.
He’ll explain how, as one of four finalists in the ACP Innovation Challenge — a “Shark Tank”-style competition hosted by the American College of Physicians on April 13 in Philadelphia.
During an eight-minute pitch in front of a panel of judges — and an audience of 100 or more physicians — Wang will describe the virtual assistant he is creating. The device will use speech recognition and natural language processing to take over the job of maintaining patient e-records, freeing up physicians to concentrate on their patients.
“It would be like Amazon Alexa,” Wang says. “There would be a little speaker in the room that would be recording while your doctor talks to you and, based on that conversation, the device would know what to enter into the e-record.”
“I think the key that will make this work is that doctors are already encouraged to use what’s called a patient-centric communication style.”
For example, physicians are encouraged at the end of a visit to sum up a patient’s concerns and their plan to address them. Physicians would use a phrase like “to make sure I understand.” The virtual assistant would recognize the phrase as a cue to transcribe everything from that point to the next cue, such as when the physician says, “Do I have that right?”
The device would be less expensive than hiring a transcriptionist, Wang says, and less obtrusive for patients who find it hard enough to divulge personal health information when there’s just a physician in the room.
He already has a prototype for transcribing the summary portion of a patient’s visit.
‘Seamlessly see what the problem is — and fix it’
Wang, who is from Westford, Massachusetts, came to Rochester after majoring in physiology and neurobiology at the University of Connecticut.
He is now in his fourth year of Rochester’s Medical Scientist Training (MD/PhD) Program, which currently enrolls 66 students. The program incorporates the MD and PhD degrees into a cohesive curriculum that endows the select group of students with the clinical and basic science skills needed to understand disease and to translate that understanding into new therapies.
Students spend the first two years on their medical degrees, then complete their PhDs in four years before returning for the last two years of medical school.
Wang is pursuing his PhD in translational biomedical science under the direction of Henry Kautz, professor and former chair of computer science and founding director of the Goergen Institute of Data Science.
Wang is now thinking about forming his own company after he graduates. He would use his medical and computing background to pursue his virtual e-record assistant and other medical-related projects full time.
“Physicians go to programmers for help with a lot of things besides e-records. It might be for applications for telemedicine,” Wang says. “But it can be hard for them to convey what they need to a programmer who doesn’t have a medical background.
“I’ll have that background. I’ll be able to very seamlessly see what the problem is — and fix it.”
Danielle Benoit ‘Embodies the Spirit’ of Teaching and Mentorship
Thursday, April 11, 2019
Danielle Benoit, an associate professor of biomedical engineering who has provided research experiences for more than 80 undergraduates in her lab, is the second recipient of the College Award for Undergraduate Teaching and Research Mentorship. (University of Rochester photo / J. Adam Fenster)
Danielle Benoit says it’s “an outstanding opportunity for everybody involved” when undergraduates do research in her lab.
Former students Tim Felong ’14, Amanda Chen ’14, and Janet Sorrells ’17 will all vouch for that.
“I wouldn’t be in medical school right now if it weren’t for Danielle’s mentorship,” says Felong, now at the University at Buffalo’s Jacobs School of Medicine and Biomedical Sciences.
Chen, a graduate research fellow in biological engineering at MIT, says, “Danielle’s lab was one of the biggest reasons why I chose to pursue a graduate degree. She gave me the opportunity to work on an independent project, publish a first-author paper, present at conferences, and more.”
And, “the more time I spend in academia the more amazed I am with how Dr. Benoit managed to keep up with so many things,” says Sorrells, now a graduate research fellow in bioengineering at the University of Illinois at Urbana-Champaign. “I’m very thankful for everything I learned from her.”
Benoit, an associate professor of biomedical engineering, is this year’s recipient of the College Award for Undergraduate Teaching and Research Mentorship at the University of Rochester.
The award, first presented last year, is funded by chemistry alumnus Frederick Lewis ’68 (PhD) and his wife, Susan Rice Lewis. It salutes tenured faculty members in Arts, Sciences & Engineering who teach large, introductory classes as well as advanced seminars and independent study projects, and who mentor research experiences, especially those that involve laboratory training in the sciences and engineering. (Read more about this new award recognizing faculty for their mentorship. )
The award will be presented to Benoit at the Undergraduate Research Exposition on April 19 at the Welles-Brown Room of Rush Rhees Library.
Benoit “embodies the spirit of this award through her dedication to undergraduate learning through classroom teaching, research experiences, and mentoring,” says Diane Dalecki, chair of the Department of Biomedical Engineering. “The research training and mentoring that undergraduates receive from Professor Benoit primes them for continued success as graduate students and throughout their professional careers.”
For example, several of the undergraduate students from her lab, including Chen and Sorrells, have received prestigious National Science Foundation graduate research fellowships to support their graduate studies.
Teaching at ‘multiple levels’
Benoit, who joined the University of Rochester in 2010, develops therapeutic biomaterials for tissue regeneration and targeted drug delivery. For example, she and her collaborators developed a device that selectively delivers drugs to sites of bone resorption to heal fractures and treat osteoporosis. She has also pioneered the development of hydrogel-based engineered extracellular matrices for bone and salivary gland tissue regeneration.
She has been lead, corresponding, or co-author of more than 70 papers in top journals; has received numerous grants, including an NSF CAREER award; has garnered nine approved or pending patents; and was recently elected a fellow of the American Institute of Medical and Biological Engineering.
She has provided research experiences for more than 80 undergraduates in her lab.
“For me, part and parcel of being a faculty member here is to teach on multiple levels, not just in the classroom but also in the lab, where I can teach undergraduate and graduate students alike the best, cutting-edge research practices,” Benoit says.
Students say the benefits of working in the Benoit Lab extend beyond the research skills they learn.
“Danielle has always been my go-to mentor for all sorts of advice – moral, social, intellectual – and was a powerful advocate for me if I ever found myself in a challenging situation,” Chen says.
Felong says he especially appreciated the “culture” of the lab, which was more like a “family environment. She takes the time to really get to know her students—their interests and hobbies. She hosts biannual parties, where you get to interact with her energy-packed, fun family. I think this openness and mutual appreciation for life inside and outside of work is really motivating for many people my age. I know it was for me.“
Seeing the potential in students
In addition to mentoring students in her lab, Benoit teaches courses including Advanced Biomaterials, Controlled Release Systems, Research Methods, and, starting this spring, Cell and Tissue Engineering, which is the capstone course for biomedical engineering majors with concentrations in that subfield.
She also developed and taught for eight years a biomaterials course, required of all biomedical engineering majors, that typically enrolls about 70 students. She designed the laboratory components of the course so they would dovetail with a biomedical computation and statistics course students take at the same time.
“Students complete laboratories in biomaterials one week, and then analyze data they collected by applying statistical approaches from the other course the following week,” Dalecki says. “This is an excellent pedagogical approach for students to understand how concepts they’re learning in different classes combine to enhance their skills as an engineer.”
Sorrells served as a teaching assistant for the biomaterials course under Benoit. She says Benoit brought the same level of “engagement” to the course that she brings to her lab. “She collected student feedback often and took it very seriously, trying different things to see how to best educate students and equip them with skills like scientific writing and knowledge of biomaterials.”
Benoit also supervises a senior design team each year, meeting with teams at least weekly, guiding them in their design and engineering, and mentoring them on teamwork and project management.
Perhaps the ultimate measure of a good teacher is the ability to inspire, motivate, and serve as a role model.
“Danielle suggested that I apply for the Research Initiative Award for Undergraduates, which is much like a grant application,” Felong says. “I never would have thought that I had a shot at winning that grant, but I applied and ended up getting it.” Benoit, as well as Andrew Shubin ’16 (PHD), ’18M (MD), the graduate student with whom Benoit paired Felong in her lab “saw potential in me that I didn’t see in myself.”
Chen says she “often reflects on mentorship behaviors that I hope to build into my own management style – now as I work with undergraduate trainees (at MIT), but also in my future career. And I find myself often thinking back to my experiences in Danielle’s lab.”
Research Roundup: Stephen Dewhurst Explores the Latest Bench-to-Bedside Projects
Monday, April 8, 2019
Transitions and Trials
Stephen Dewhurst, Ph.D., Vice Dean for Research
Almost 10 years ago, Brad Berk had the idea that the Medical Center should position itself to take a lead in the new field of cell-based therapies by constructing a manufacturing facility that could produce those cells under the highly regulated conditions that are required by the FDA. Brad’s vision was that, by doing this, we would enable UR to deliver first-in-human therapies to patients.
Fast forward, and the facility we built – the Upstate Stem Cell cGMP Facility (USCGF) – is working in coordination with Torque Therapeutics (Cambridge, MA) to produce modified T cells that are being infused into cancer patients as part of a clinical trial that started earlier this month.
As with most research partnerships, our relationship with Torque is fundamentally a relationship between people, and an expression of trust in the team led by USCGF Director Luisa Caetano-Davies. It’s worth noting that only two years ago, Luisa was a postdoctoral fellow in Chris Proschel’s lab. Her subsequent success and growth are the combined result of a lot of hard work, intelligence and – in no small measure – opportunities created by our URBEST program.
The Torque trial is a huge step for the USCGF because it represents the first time that a cell-based product produced by our facility has been administered to human subjects. But it’s also an important step for our Medical Center, when viewed in the broader context of our evolving approach to clinical trials.
Pat Ames is heading up a new Office of Clinical Research, working with Martin Zand, Steven Wormsley and many others to lead the implementation of a clinical trial management system to improve our clinical trials infrastructure. This system will streamline and automate many cumbersome clinical research processes and reduce administrative burden on our research teams, helping us conduct more clinical trials and offer more treatments to our patients and community members.
At the same time, Paul Barr in the Wilmot Cancer Institute (WCI) was just awarded a major new grant to support WCI involvement in National Cancer Institute (NCI) cooperative group clinical trials. This award establishes URMC as one of 30 lead academic sites within the NCI consortium, a designation rarely given to an institution that (currently) does not have an NCI-designated cancer center.
Perhaps most exciting of all, Mark Noble and Nimish Mohile recently received a highly encouraging score for a proposal that would (if funded, as we hope it will be!) launch a first-in-human trial of a new cancer treatment that is the result of fundamental research conducted in the Noble laboratory. Based on a new tumor-specific vulnerability, and discovery of existing drugs with the unexpected property of attacking this vulnerability, the new therapy eliminates cancer stem cells in glioblastoma (one of the most deadly human cancers).
This is exactly the kind of bench-to-bedside science that Brad envisaged ten years ago. We’ve made lots of progress, and there’s more to come. It’s an exciting time to be involved in research at the Medical Center.
Announcing Regulatory Science Student Competition Winners
Tuesday, April 2, 2019
Twelve teams competed this year in the sixth annual America’s Got Regulatory Science Talent student competition. Teams proposed a wide range of novel solutions to address the nine scientific priority areas outlined in the Food and Drug Administration’s (FDA) Strategic Plan for Advancing Regulatory Science. From a farm-to-table produce-tracking app to a public alert system for product recalls and disease outbreaks, this year’s competition was full of innovation. Learn more about the top three winners on the UR CTSI Stories blog.
John Lueck Publishes Study on New RNA Technology in Nature Communications
Thursday, March 28, 2019
Michael Golinkoff (left), one of the founders of Emily’s Entourage; Phil Thomas (middle), cystic fibrosis researcher at UT Southwestern, John Lueck (right), assistant professor of Pharmacology and Physiology at URMC.
There are all sorts of “typos” in our DNA that can lead to disease. One kind of typo – a premature termination codon or PTC – is responsible for 10 to 15 percent all genetic diseases, including cystic fibrosis and Duchenne muscular dystrophy. PTCs lead to the production of short and often deleterious proteins.
A recent paper by John Lueck, Ph.D., assistant professor of Pharmacology and Physiology and Neurology, shows how high-throughput screening may be used to fix these typos and lessen disease severity. Published in Nature Communications, the study found that modifying tRNA (a type of RNA molecule that helps convert messenger RNA or mRNA into protein) can help the cell make a full length protein, even with a PTC in the middle of the gene. With this new technology to modify tRNA, the authors were able to use gene therapy to suppress faulty versions of a gene in skeletal muscle, and instead force the cells to produce a full-length protein.
At the moment, most investigational therapies for inherited diseases are focused on small molecules, which to this point have not been successful. “For many of these diseases, including cystic fibrosis and Duchenne muscular dystrophy, there are no therapies and patients rely on palliative care,” explains Lueck. “Our engineered tRNA platform puts another iron in the fire for development therapeutics and we’re hopeful that the technology can be translated into a viable treatment for patients in the near future.”
While these studies are still in the early stages, Lueck was recently awarded a unique pilot grant from Vertex Pharmaceuticals to continue this work. This work was funded by Emily’s Entourage and the Cystic Fibrosis Foundation and accomplished with the collaboration of researchers at the Cystic Fibrosis Foundations Therapeutics Lab, the Wistar Institute, University of Iowa, and Integrated DNA Technologies, Inc.
HSR PhD students will present research at 2019 ARM
Wednesday, March 27, 2019
Eight students from the Health Services Research and Policy PhD Program will be presenting their research at the 2019 Annual Research Meeting (ARM) in Washington, D.C.
“AcademyHealth’s Annual Research Meeting shares important findings and showcases the latest evidence to move research into action and improve health and health care”. Participants were selected on a competitive basis.
- Medicare’s Voluntary Lower Extremity Joint Replacement Bundled Payment is Associated with Exacerbated Racial Disparities in Hospital Readmissions
- Understanding the Role of Paternal Economic Support in Early Childhood Development Among Families with Unmarried Mothers
- Shared Decision-Making and Cancer Patients’ Experience with Physician Communication
- Did Medicaid Expansion Matter in States with Generous Medicaid?
- The Impact of the Affordable Care Act Medicaid Expansions on Mortality
- Analyzing Opioid-Related Hospitalization Data: The Role of Increases in the Number of Recordable Diagnosis Fields
- Continuity of Care and Health Care Cost among Community-dwelling Older Veterans Living with Dementia
- A Social Network Analysis of Nursing Home Medical Staff Organization
- Does the Dementia Care “National-Partnership” Improve Outcomes for Nursing Home Residents with Dementia?
- Rural Nursing Homes Were Associated with Lower Risk Adjusted Rates of Emergency Department Visit but Higher Mortality
- Application of Machine Learning Ensemble Models to Predict Hospitalizations and Emergency Department Visits of Long-Stay Nursing Home Residents
Di Yan, Sijiu Wang, Helena Temkin-Greener, Shubing Cai
Upcoming PhD dissertation defenses
Wednesday, March 27, 2019
Ninoshka Fernandes, biomedical engineering, “CD4+ Effector T cell interactions with the Extracellular Matrix at Sites of Inflammation.” 2:15 p.m. March 29, 2019, 3-6408 K-307 Auditorium (Medical Center). Advisors: Deborah Fowell and Edward Brown.
Abigail Freyer, chemistry, “Investigation of Doped Nanocrystals Utilizing Electrostatic Force Microscopy.” Noon, April 1, 2019. 209 Computer Studies Building. Advisor: Todd Krauss.
Tianran Hu, computer science, “Decoding Human Lives from Social Media Data.” Noon, April 3, 2019. Dewey 2110E. Advisor: Jiebo Luo.
Allison Li, pathology, “Assessing the Role of Myelodysplastic Syndrome (MDS)-Induced Bone Marrow Microenvironment Remodeling in MDS Progression.” 1 p.m., April 3, 2019. 1-7619 Lower Adolph (Medical Center). Advisor: Laura Calvi.
Mohammad Kazemi, electrical engineering, “Scalable Spin Torque Driven Devices and Circuits for High Performance Memory and Computing.” 2:30 p.m. April 8, 2019. Computer Studies Building 703. Advisor: Mark Bocko.
Thomas Nevins, physics, “Fronts and Filaments: Methods for Tracking and Predicting the Dynamical Effects of Advection on Excitable Reactions.” 11 a.m., April 12, 2019. Bausch and Lomb 106. Advisor: Douglas Kelley.
Study Aims to Predict, Prevent Acute Kidney Injury
Tuesday, March 26, 2019
Acute kidney injury — a sudden decline in kidney function — occurs frequently among hospitalized patients with serious, long-lasting effects and even increased risk of death. It’s often preventable, but we currently lack the ability to reliably predict when it will happen and to whom. That is why researchers at the Clinical and Translational Science Institute (UR CTSI) analyzed data from over 34,000 patients to develop a risk score for acute kidney injury that could help doctors intervene and prevent it.
Part of the reason we can’t predict when a patient will develop acute kidney injury is that while some risk factors are known, we often don’t use them in a coordinated way. For example, machine learning papers often focus on factors that increase risk of acute kidney injury, such as diabetes and medications, but not those that lower that risk. On top of that, most previous studies have looked at single hospitalizations for all patients, many of whom have not been previously hospitalized. By not looking at patients’ past data, those studies missed the opportunity to discover health factors or patterns that reliably precede acute kidney injury.
Samuel Weisenthal, an MD-PhD student, and Martin Zand, co-director of UR CTSI, took a different tack, focusing on re-hospitalized patients. The pair and their colleagues analyzed electronic health record data from patients’ prior hospitalizations to identify factors that predict acute kidney injury. From those factors, they used machine learning to developed a risk score that could be calculated for patients at the time of re-hospitalization.
“Developing an accurate risk index for acute kidney injury in re-hospitalized patients could have a major impact on hospital care, particularly if it could allow preventive intervention or better tailored treatments from the time of hospital admission,” says Zand, who is also the senior associate dean for clinical research at URMC.
For example, acute kidney injury caused by radiocontrast dye or chemotherapy can be prevented by administering fluids or altering a patient’s treatment plan. When these factors are adjusted accordingly, patients fare better and the cost and length of stay can be decreased.
And while such predictive systems require extensive validation before clinical deployment, this work is a step toward creating acute kidney injury predictions, specifically for re-hospitalized patients.
“This study will hopefully help move us in the direction of an automated, locally trained tool that leverages sometimes hidden, longitudinal electronic health record data to estimate acute kidney injury risk without manually ordering tests or collecting and entering data,” says Zand.
Read the full study in PLOS One.
Cell Biology of Disease Alumnus appears on Fox Rochester
Monday, March 25, 2019
Cell Biology of Disease Alumnus and current Postdoctoral Fellow Zach Murphy appeared on Fox Rochester to discuss how red blood cells are produced in the body and how they affect infant development. See the video on the Fox Rochester Website
Genetics Day will feature lecture by UMass researcher
Monday, March 25, 2019
Phillip D. Zamore, Howard Hughes Medical Institute investigator and professor of biomedical sciences at the University of Massachusetts, will lecture on piRNAs and the Struggle to Reproduce at the 31st Annual Genetics Day, to be held 9 a.m. to 3:15 p.m. April 25 in the Class of ’62 Auditorium and Flaum Atrium.
Register for a poster presentation by 5 p.m. Monday, April 15. Cash prizes will be awarded for graduate student and postdoc posters.
Rebecca Lena Awarded Founders Affiliate Summer Fellowship from the American Heart Association (AHA)
Monday, March 25, 2019
Congratulations to Rebecca Lena for receiving the Founders Affiliate Summer Fellowship from the American Heart Association (AHA). The title of her proposal is “Comparative analysis of 9-TB, Doxycycline, and Minocycline in a mouse model of post-cardiac arrest syndrome (PCAS).”
This work is one of several projects underway in the Neurovascular Protection Group, whose goal is to develop new therapies for acute stroke and cardiac arrest.
The American Heart Association supports highly promising, undergraduate students for full-time research fellowships over a minimum of ten weeks during the summer. The goal of this program is to encourage students to pursue careers in cardiovascular and stroke research.
NYS Lawmakers vote to raise the smoking age from 18 to 21 - Rahman Lab interviewed
Wednesday, March 6, 2019
Lawmakers in the New York state Assembly have voted to raise the smoking age from 18 to 21.
The legislation, which passed the Democrat-led chamber on Wednesday, prohibits the sale of tobacco, as well as electronic cigarettes, to anyone under 21.
"I always thought that we were going to be the generation to stop smoking and then all of these new products came out and we are at step one," said Monica Jackson, a research assistant at the University of Rochester.
She said she doesn't smoke, but some of her friends do.
"I think just educating people and putting it in their heads this is not good for us," she added.
Jackson is part of a team of researchers at the university, including Dr. Irfan Rahman. Dr. Rahman has been helping conduct a study on the impacts of smoking and vaping for more than 10 years. Some of his work has also been published.
"This is really bad for high schoolers and middle schoolers when their lungs are developing, and if they vape it's interfering with lung development," he explained.
When asked about raising the age to buy tobacco and e-cigarettes, Dr. Rahman said it won't do much.
"The problem will never be solved by increasing the age. Overall it will not address the issue of toxicity and diseases," he said.
Throughout the years, Dr. Rahman says he's studied the evolution of different products to consume tobacco and nicotine.
When it comes to research on Juul products, he said, "we found metals such as copper, we published a paper, we found lung injuries, inflammation and stress in the lungs."
The elevated smoking age is already the law in seven states, and several cities around the country, including New York City.
Some people think passing such a law is going too far.
"The idea for them to choose when they finish high school when they become adults it's more applicable, so i think 19 would be more of an applicable age," said James McGuinness a Rochester resident.
Brandon Barr is the manager of Exscape Smoke Shop and Vapor Lounge. He said the age of 21 at least is giving you more life experience, and more of a chance to educate yourself about the thing you want to do.
He said if the law is passed, it likely won't impact his business directly.
"I think convenience stores and things like that probably will because they have more of a high customer volume," he added.
Barr said the topic of education should be at the center of this debate. He said he works to educate all of his customers about what they are buying.
"Some of these very high level nicotine juices if you were to put them in certain kinds of vapes it can put so much nicotine into you - you could get sick," he said.
The measure is backed by Governor Andrew Cuomo, and has broad support in the Democrat-controlled state Senate, where it has yet to be scheduled for a vote.
Cuomo released a statement after the Assembly passed the bill.
"The lifelong health effects and human misery caused by tobacco use cannot be understated and New York needs to do everything in its power to keep tobacco products out of the hands of our young people. That's why I made raising the age of tobacco sales to 21 one of the first proposals of my Justice Agenda and I applaud the Assembly and particularly Assembly Member Rosenthal for taking action on this very important issue today. I urge the Senate to follow suit and help make this a stronger and healthier New York for all."
Julie Hart of the American Cancer Society Cancer Action Network called the measure "common sense" and said it will reduce the number of young people who become addicted.Read More: NYS Lawmakers vote to raise the smoking age from 18 to 21 - Rahman Lab interviewed
Reshaping our understanding of how the brain recovers from injury
Tuesday, March 5, 2019
New Medical Center research in the journal Proceedings of the Royal Society B sheds light on how the damage in the brain caused by a stroke can lead to permanent vision impairment. The findings could provide researchers with a blueprint to better identify which areas of vision are recoverable, facilitating more effective interventions to encourage vision recovery.
“The integration of a number of cortical regions of the brain is necessary in order for visual information to be translated into a coherent visual representation of the world,” says Bogachan Sahin, an assistant professor of neurology and co-author of the study. “And while the stroke may have disrupted the transmission of information from the visual center of the brain to higher order areas, these findings suggest that when the primary visual processing center of the brain remains intact and active, clinical approaches that harness the brain’s plasticity could lead to vision recovery.”
The research has formed the basis of a new clinical trial for stroke patients with vision loss that is now under way at URMC and lead by Sahin. The study involves a class of drugs called selective serotonin reuptake inhibitors, the most common of which is the antidepressant Prozac. The inhibitors are known to enhance neuroplasticity – the brain’s ability to rewire itself and form new connections to restore function after damage. The hypothesis is that the drug will help restore vision by fostering the development of new connections between areas of the brain necessary for interpreting signals from the healthy eye cells.
A stroke in the primary visual cortex can result in blind areas in the field of vision. While some patients spontaneously recover vision over time, for most the loss is permanent. A long-known consequence of damage to neurons in this area of the brain is the progressive atrophy of cells in the eyes, called retinal ganglion cells. When this occurs, it becomes more likely that the person will not recover vision at that location.
The new research involved 15 patients treated at Strong Memorial and Rochester General Hospitals for a stroke that affected the primary visual processing area of the brain. The participants took vision tests, underwent scans in an MRI to identify areas of brain activity, and were administered a test that evaluated the integrity of cells in their retina.
The team found that the survival of the retinal ganglion cells depended upon whether or not the primary visual area of the brain to which they are connected remained active. Eye cells that were connected to areas of visual cortex that were no longer active would atrophy and degenerate, leading to permanent visual impairment.
However, the researchers observed that some cells in the eye remained healthy, even though the patient could not see in the corresponding field of vision. This finding suggests that these eye cells remain connected to unscathed neurons in the visual cortex and that visual information was making its way from the eyes to the visual cortex, even though this information was not being interpreted by the brain in a manner that allowed sight.Read More: Reshaping our understanding of how the brain recovers from injury
Grant Marks Two Decades of NIH Support for Muscular Dystrophy Research
Tuesday, February 26, 2019
Deposits of toxic RNA (red) are seen here inside muscle cell nuclei (blue) from an individual with myotonic dystrophy
The University of Rochester Medical Center (URMC) has received $8 million from the National Institutes of Health (NIH) to support pioneering research on muscular dystrophy. The grant, which is a renewal of URMC’s Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, will fund ongoing work to investigate the genetic mechanisms and progression of this complex multi-system disease, research that has led scientists to the threshold of potential new therapies for myotonic dystrophy.
“The mission of the URMC Wellstone Center is to promote research that leads to effective treatments for muscular dystrophy,” said Charles Thornton, M.D., a professor in the URMC Department of Neurology and director of the URMC Wellstone Center. “This new funding will enable us to continue a research program that has been forged from a true partnership between bench scientists, clinical researchers, and patients and their families.”
URMC is home to one of six NIH-designated Wellstone Centers in the nation. URMC was selected in the first cycle of funding when the program was launched 16 years ago and is the only Wellstone Center that has been continuously funded since the program’s inception. With the current award, URMC has received a total of $29.8 million in NIH funding to study the disease since 2003.
The URMC Wellstone Center focuses on myotonic dystrophy, a disease that can be lethal in infants and adults and is characterized by progressive disability. Researchers at URMC have been studying myotonic dystrophy for more than 30 years and their work has transformed our understanding of the biological mechanisms of the disease. The new funding will support a long-standing collaboration between researchers at the University of Rochester and RNA scientists at the University of Florida.
Approximately 40,000 Americans have myotonic dystrophy, which is one of the most common forms of muscular dystrophy. People with the disease have muscle weakness and prolonged muscle tensing (myotonia), which makes it difficult to relax muscles after use. Eventually many patients have difficulty walking, swallowing, and breathing.Read More: Grant Marks Two Decades of NIH Support for Muscular Dystrophy Research
Xi Lin Wins Award
Tuesday, February 19, 2019
Xi Lin, MS, 2019 ORS/RJOS Young Female Investigator Travel Grant awarded by the Orthopaedic Research Society, Women's Leadership Forum, and the Ruth Jackson Orthopaedic Society.
Xi is a Student of Lianping Xing, PhD, Pathology. Her research interest is OA pathogenesis: how macrophages contribute to localized inflammation through their effect on the lymphatic system.
Mason Doolittle Awarded ASBMR Travel Grant
Friday, February 15, 2019
Madison Doolittle, M.S., Current Ph.D. Trainee in the Cell Biology of Disease program at the School of Medicine and Dentistry was awarded an ASBMR Travel Grant to attend the Herbert Fleisch Workshop in Brussels Belgium March 2019. Madison is a student of Cheryl Ackert-Bicknell, PhD, CMSR., his research focus is on Identification and Characterization of Novel Genetic Determinants of Osteoporosis and Bone Mineral Density (BMD)
Matt Ingalls wins Prestigious Poster Prize at Gordon Conference
Friday, February 15, 2019
Matt Ingalls With Poster
Matt Ingalls with other award winners
GDSC student Matt Ingalls won an award for his poster presentation at the 2019 Gordon Research Conference for Salivary Glands and Exocrine Biology in Galveston, Texas (February 2nd – 8th). The GRC brought together leading researchers in the field of salivary gland biology from around the world. Matt’s poster, titled “Lineage Tracing Following Radiation Treatment Unveils Intrinsic Regeneration Potential in Adult Salivary Glands”, highlights differences in radiation response between the submandibular and parotid salivary glands. Utilizing lineage tracing models his work demonstrates the intrinsic regeneration potential of the adult salivary gland. The NIH-supported research was conducted in the laboratory of Dr. Catherine Ovitt and was co-authored by E. Maruyama and P. Weng. -- Congratulations Matt!
Kristen Bush Marshall Successfully Defends Her Thesis
Monday, February 11, 2019
Kristen Bush Marshall successfully defended and submitted her thesis for the PhD in Translational Biomedical Science, with a focus in Infection and Immunity: From Molecules to Populations
Dr. Bush Marshall's research focus was The use of electronic health records (EHR), predictive analytics, and network science to understand infection mobility and improve patient outcomes. Her research was conducted in the labs of Dr. Martin Zand & Dr. Gourab Ghoshal
She will be starting a postdoctoral position with her mentor, Dr. Martin Zand on 2/16, and will be heading down to the CDC for the EIS Fellowship starting in the summer
PREP Scholar Seble Negatu Receives Award
Monday, February 11, 2019
Seble Negatu – PREP Scholar in the laboratory of Dr. Deborah Fowell
Seble Negatu was one of 9 recipients of the American Association of Immunologists (AAI)-sponsored immunology presentation awards at the ABRCMS meeting in November 2018 in Indianapolis, IN. https://www.abstractsonline.com/pp8/#!/5759/presentation/882
At the meeting, AAI members and meeting chairs, Robert Binder and Cherie Butts, also presented Seble with a 2019 AAI Young Scholars Travel Award, to attend the 2019 AAI Annual Meeting this May in San Diego.
GDSC student Adrian Molina-Vargas co-founds ADSE chapter to tackle underrepresentation in STEM
Friday, February 1, 2019
February 1, 2019
In the front row from the left, Keon Garrett, Ellen Matson, Raven Osborn, and Antonio Tinoco Valencia; and in the back row from the left, Marian Ackun-Farmmer, Heta Gandhi, Adrian Molina Vargas, Shukree Abdul-Rashed, and Liz Daniele are among the founding members of the new Rochester chapter of the Alliance for Diversity in Science and Engineering. (University of Rochester photo / J. Adam Fenster)
Raven Osborn thought long and hard about continuing a PhD at the University of Rochester. Other minority students she knew at the Medical Center had also felt the isolation, the constant “being on edge” and “code-switching”—shifting the way they express themselves—that comes with being an underrepresented minority in a STEM field.
“Can I do this for another five and half years?” she wondered.
Antonio Tinoco, a DREAMer who was born in Mexico and raised in Los Angeles, is a fourth year PhD student in the department of chemistry on the River Campus. He can remember only one or two occasions when a visiting faculty member of underrepresented minority background was invited to give a seminar in his department.
“My goal is to go into academia to be a professor, do research, and teach. But there are so few examples to follow,” he says. “I don’t even know of anyone who, as a DACA recipient or DREAMer, is a professor in chemistry. So, I could easily tell myself nobody has done it; it’s impossible; maybe I should look for something else.”
Instead, Tinoco, Osborn, and five other graduate students have banded together to form the University of Rochester chapter of the Alliance for Diversity in Science and Engineering (ADSE). The mission of the national ADSE, which was founded in 2014, is to increase the participation of underrepresented groups in academia, industry, and government through graduate student organizations that reach out to students and scientists of all ages and backgrounds.
Other ADSE chapters are at the University of California campuses at Berkeley and Davis, the University of Central Florida, the University of Colorado, Columbia University, Drexel University, Georgia Institute of Technology, University Maryland, New York University, Northeastern University, and Texas A&M.
Tinoco, the president and founding member of the new chapter, says its immediate goals are twofold:
- Establish a diversity lecture series to bring underrepresented faculty from other universities to Rochester. “It would be an opportunity for underrepresented minority students here to say ‘Wow, there’s someone out there like me who is making it, so maybe there’s hope for me.’” Underrepresented minority postdoctoral fellows would also be invited, especially ones who might be interested in eventually teaching here, Tinoco says.
- Provide a space where underrepresented graduate students in STEM fields from across the University can meet, network, and hold workshops and panels to openly discuss the issues they face. “If we can openly discuss these things, we won’t feel as isolated,” Tinoco says.
The chapter has been certified by the University and will receive funding through the University’s David T. Kearns Center for Leadership and Diversity. ADSE’s goals fall well within the Kearns Center’s mission to expand the educational pipeline through the doctoral degree for low-income, first-generation college, and underrepresented minority students, says Liz Daniele, the center’s assistant director for graduate diversity.
Inviting underrepresented faculty from other campuses to give a science-based talk, but also give a diversity-themed talk about their academic journey “is a great model,” she says. “And that’s why Kearns is happy to support several semesters of lectures.”
“I think this is exactly the type of thing that the University needs right now,” says Ellen Matson, assistant professor of chemistry, who will be the chapter’s faculty advisor. She, too, is excited about the proposed diversity lecture series—as a way to inspire and motivate students to finish their programs and pursue STEM careers, and also “showcase our research programs and facilities to diverse early-career scientists and post-doctoral research fellows interested in pursuing independent academic research careers.”
“Overall, I think that the University of Rochester community, particularly at the graduate level, will really benefit from having a chapter of the Alliance for Diversity in Engineering and Science on campus,” Matson says.
Osborn, who is serving as the chapter’s treasurer, does not regret her decision to stay at Rochester to pursue a PhD in translational biomedical science. “I’ve been very lucky to work with faculty members like Tim Dye, Steve Dewhurst, and Juilee Thakar,” she says.
Osborn received a medical center community outreach award as a leader in the Rochester Young Scientists Club’s program, which encourages pupils at inner-city elementary schools to start thinking like scientists. She is excited to be serving on the search committee for a new vice president for equity and inclusion at the University.
She is hopeful that ADSE will bring together underrepresented graduate students, now separated by Elmwood Avenue “divide” between the River Campus and the Medical Center and the separate “silos” of their STEM disciplines.
And she agrees with Matson that the University will benefit from having a chapter of ADSE.
“This is an amazing institution, and we have so many resources here. If we can make this a place where people who have different backgrounds feel comfortable, where their different perspectives are welcomed, it can only better the institution as a whole.”Read More: GDSC student Adrian Molina-Vargas co-founds ADSE chapter to tackle underrepresentation in STEM
Former Biochemistry Student Jerry Madukwe, Ph.D. travels to West Africa to Speak With Students
Wednesday, January 30, 2019
Jerry Madukwe, Ph.D., who received his Ph.D. in Biochemistry (2018), and is currently a postdoctoral fellow at Yale University, recently completed a 2-week science-outreach trip to West Africa. Jerry was invited by the West Africa Center for Cell Biology of Infectious Pathogens at the University of Ghana, and the Department of Life sciences at the University of Ilorin in central Nigeria to talk about the work he did as a PhD student and about graduate school in the United States. Jerry, who hails from Nigeria, and got his BS from Lee University in Tennessee, also used the opportunity to visit his former elementary school where he talked to fifth grade pupils about science (see photos), and to demonstrate DNA extraction from bananas. The kids were very excited by his visit, and Jerry found the experience very fulfilling.
Study suggests how high blood pressure might contribute to Alzheimer’s
Monday, January 28, 2019
The brain’s system for removing waste is driven primarily by the pulsations of adjoining arteries, University of Rochester neuroscientists and mechanical engineers report in a new study. They also show that changes in the pulsations caused by high blood pressure slow the removal of waste, reducing its efficiency.
This might explain the association between high blood pressure and Alzheimer’ disease, the researchers say. Alzheimer’s, the most common cause of dementia among older adults, is characterized by abnormal clumps and tangled bundles of fibers in the brain.
The study, reported in Nature Communications, builds upon groundbreaking discoveries about the brain’s waste removal system by Maiken Nedergaard, co-director of the University’s Center for Translational Neuromedicine. Nedergaard and her colleagues were the first to describe how cerebrospinal fluid is pumped into brain tissue and flushes away waste. Subsequent research by her team has shown that this glymphatic waste removal system is more active while we sleep and can be damaged by stroke and trauma.
This latest research shows “in much greater depth and much greater precision than before” how the glymphatic system functions in the perivascular spaces that surround arteries in the outer brain membrane, says Douglas Kelley, an assistant professor of mechanical engineering and an expert in fluid dynamics. His lab is collaborating with Nedergaard’s team as part of a $3.2 million National Institute on Aging grant.
For this study, Humberto Mestre, a PhD student in Nedergaard’s lab, injected minute particles in the cerebrospinal fluid of mice, and then used two-photon microscopy to create videos showing the particles as they moved through the perivascular spaces.Read More: Study suggests how high blood pressure might contribute to Alzheimer’s
Dr. Kuan Hong Wang comes to the University of Rochester
Monday, January 21, 2019
We are pleased to welcome Dr. Wang to the University of Rochester Medical Center, the Department of Neuroscience and the Del Monte Institute for Neuroscience from the NIH.
Dr. Wang comes to us as the former chief of the Unit on Neural Circuits and Adaptive Behaviors at the National Institute of Mental Health. Dr. Wang received his B.A. in Biochemical Sciences from Harvard College and his Ph.D. from the University of California at San Francisco, where he studied the molecular regulators of sensory axon growth and branching during development with Marc Tessier-Lavigne. Dr. Wang obtained postdoctoral training with Susumu Tonegawa at the Massachusetts Institute of Technology, where he examined the ways in which cortical neurons respond to an animal’s experience by directly visualizing the molecular activity of a given set of neurons over several days in the live animal. With this approach, he revealed a physiological function of neural activity regulated gene Arc in sharpening stimulus-specific responses in visual cortex.
Research Roundup: Dealing with Failure and an Unfunded Grant Application
Wednesday, January 9, 2019
Stephen Dewhurst, Ph.D., Vice Dean for Research
It’s something we rarely talk about: how it feels when a grant application isn’t funded. And yet, it’s by far the most common outcome for any such submission – an unavoidable consequence of paylines that are in the low teens or single digits.
The months between the submission of a grant and its review pass surprisingly quickly. And then time slows to a crawl. The self-doubt and self-criticism become more insistent. And hope flickers – such a fragile thing, in the end.
Recently, after submitting a grant application, I found myself logging onto the NIH website every day after the review panel had met, to see if the scores had been posted. Eventually, they appeared.
This particular grant isn’t going to be funded.
It’s a horrible feeling. A private hurt that’s immeasurably hard to share with colleagues, family and friends. That’s because the narrative is one of failure.
But, I’ve chosen to write about it anyway – because we’ve all been here. Because shame thrives in secrecy and loses its power when we talk about it (something I learned from Brené Brown).
What has helped is input from friends. One wrote: “Thank you for sharing this. I’m glad you did. As Directors etc., we don’t share enough of the worries, the worthiness/unworthiness and the vulnerabilities that things like grants.... bring to the work and to our sense of ourselves as ‘good’ researchers, colleagues, leaders and people.”
She went on to say: “I wish I had great advice. I have nothing. Except that you are a good person, a good mentor.... and whatever happens, you will still be those things. If you receive the grant, you know what your work will be; if you don’t, you will have new and different work to do.”
It’s also true that a life in science requires resilience -- the ability to pick oneself up after a fall and to learn and improve from failure. No one ever said that it would be easy.
In a few weeks, the summary statement will be released and I’ll start thinking (with my colleagues) about ways to address the reviewers’ concerns. Until then, I’ll keep a space in my heart for these words of Samuel Beckett: “I can’t go on. I’ll go on.”
TBS Student Explores Drug Repurposing to Treat Infectious Disease
Tuesday, January 8, 2019
Infectious diseases still pose a big health risk in resource-limited areas of the world. A fourth-year student in the UR CTSI's Translational Biomedical Sciences Graduate Program, Marhiah Montoya, is exploring the possibility of repurposing pre-existing estrogen receptor drugs, like tamoxifen, to fight these infections. Read Montoya's mini-review in mBio.
TBS Student Dissertation Defense
Monday, January 7, 2019
UR CTSI Translational Biomedical Science graduate student, Kristen Bush Marshall, will defend her dissertation, titled, “Inpatient mobility to predict hospital-onset Clostridium difficile: a network approach,” on Friday, January 18. She will discuss her use of electronic health records and network analysis of hospital-onset clostridium difficile, a life-threatening infection triggered by taking antibiotics. Martin Zand, M.D., Ph.D., has been her advisor and mentor for the past three years.
Bush Marshall is committed to becoming an epidemiologist, with a clear focus on infection prevention and understanding the fundamental mechanisms of disease transmission in communities and healthcare facilities.
Date: Friday, January 18
Time: 12:00 pm
Location: Helen Wood Hall Auditorium 1W-304
UR-RCMI Scholarly Exchange Request for Applications
Monday, January 7, 2019
Faculty, staff, and students at the University of Rochester can apply now for funding to support research collaboration activities with their counterparts from any institution in the Research Centers in Minority Institutions (RCMI) program.
The UR-RCMI Scholarly Exchange Program awards up to five projects a maximum of $3,000 each to help colleagues from different cultures, disciplines, and academic appointments build partnerships and produce abstracts, publications, or grant applications together and to foster the next generation of researchers from underrepresented populations.
Learn more and access the application from the UR CTSI Stories blog.
If you have questions, please contact Ivelisse Rivera, M.D., UR-RCMI Exchange Coordinator.
Applications are due Friday, January 25.