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 Commmencement 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+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 Pharmaceutials, 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.