News

The green stain highlights
myelin, a substance essential
for a healthy nervous system
that's destroyed in children
with Krabbe disease. The study
treatment was able to rescue
myelin in mice.

University of Rochester Medical Center researchers believe they have identified a potential new means of treating some of the most severe genetic diseases of childhood, according to a study in PLOS Biology.

The diseases, called lysosomal storage disorders (LSDs), are caused by disruptions in the functioning of the stomach of the cell, known as the lysosome. LSDs include Krabbe disease, Gaucher disease , metachromatic leukodystrophy and about 40 related conditions. In their most aggressive forms, they cause death of affected children within a few years after birth.

The URMC team, led by Mark Noble, Ph.D., discovered for the first time how specific toxic waste products that accumulate in LSDs cause multiple dysfunctions in affected cells. They also found that several drugs already approved for other uses have the unexpected ability of overcoming the cellular toxic build-up, providing new opportunities for treatment.

A University of Rochester study has found that older adults with excellent memories have more efficient connections between specific areas of the brain — findings that could hold promise for the prevention of dementia and cognitive decline.

Although researchers have historically viewed memory deterioration as an inevitable part of the aging process, a small group of older adults — called “supernormals” — are able to maintain their memory capacities much better than their peers. Feng (Vankee) Lin, PhD, an assistant professor in the University of Rochester School of Nursing, is spearheading a new approach to the study of Alzheimer’s disease by exploring what can be learned from these individuals.

In a study on the topic published in Cortex, an international journal devoted to the study of cognition and the relationship between the nervous system and mental processes, Lin and her team explored differences in brain function among three groups of older adults: supernormals, who were defined as having higher than average memory scores for their age, older adults diagnosed with amnestic mild cognitive impairment who are at high risk for developing Alzheimer’s disease, and a healthy control group. The study is the first to compare the brain function of supernormals to those who are at risk for developing Alzheimer’s.

Nina Schor, M.D., Ph.D., William H. Eilinger Chair of Pediatrics at the University of Rochester Medical Center (URMC), will step down as chair in June 2017. Schor served 11 years as pediatrician-in-chief at UR Medicine’s Golisano Children’s Hospital, and under her leadership, the Department of Pediatrics fulfilled a decades-long dream of building a standalone children’s hospital in Rochester; the new facility opened its doors to patients in July 2015. "I don’t want to downplay the significance of the new hospital, but it’s really what we do inside of it and because of it that’s so important,” said Schor. “I look at the academic physicians and physician scientists who came to Rochester with just a dream and a fire in their belly and how they’ve now brought those dreams to fruition — that’s what I’m most proud of.”

The Department of Pediatrics grew from 110 faculty members to over 170 during Schor’s tenure, creating new divisions in palliative care, sleep medicine, allergy, and hospitalist medicine. Research centers focused on premature infants, translational molecular programs, and red blood cell development also developed under Schor’s leadership.

“Not only was the new hospital built under Nina’s leadership, but she truly championed the project, ensuring that every detail was designed with patients and families in mind,” said Mark Taubman, M.D., URMC CEO and Dean of the School of Medicine and Dentistry. “She has been the face of the children’s hospital and inspired trust in our families, physicians, and donors at a time when we very much needed the community’s support.”

A new study challenges the hypothesis that nerve cells in the brains of individuals with Autism Spectrum Disorders do not reliably and consistently respond to external stimuli. “Our findings show there is no measurable variation in how individuals with autism respond to repeated visual and tactile stimuli,” says senior author John Foxe, the Kilian J. and Caroline F. Schmitt Professor in Neuroscience.

Matt Cavanaugh, a fifth year Neuroscience Graduate Program student in Dr. Krystel Huxlin’s lab was awarded an NIH Individual Pre-doctoral Fellowship from the National Eye Institute for his project entitled: Properties of training-induced visual recovery in cortical blindness (2016-2019).

Congratulations Matt!

Nina Schor, M.D., Ph.D., William H. Eilinger Chair of Pediatrics and the pediatrician-in-chief at UR Medicine’s Golisano Children’s Hospital, has been named a Fellow of the American Association for the Advancement of Science (AAAS), the world’s largest general scientific society.

AAAS, which will publish the announcement on Nov. 25 in its journal Science, selects Fellows based on their scientifically and socially distinguished efforts to advance science or its applications. Schor has spent much of her career investigating neuroblastoma — which is among the most common childhood cancers — and was recognized for “her distinguished contributions to developmental neuroscience and neuropharmacology, particularly using molecular neuroscientific discoveries to design innovative therapies for tumors of the developing nervous system.”

Researchers at the University of Rochester Medical Center believe they have identified a new means of enhancing the body's ability to repair its own cells, which they hope will lead to better diagnosis and treatment of traumatic nerve injuries, like those sustained in car accidents, sports injuries, or in combat. In a study published today, the team showed that a drug previously approved for other purposes can 'wake up' damaged peripheral nerves and speed repair and functional recovery after injury.

The study appearing in EMBO Molecular Medicine, demonstrates for the first time that 4-aminopyridine (4AP), a drug currently used to treat patients with the chronic nerve disease, multiple sclerosis, has the unexpected property of promoting recovery from acute nerve damage. Although this drug has been studied for over 30 years for its ability to treat chronic diseases, this is the first demonstration of 4AP's benefit in treating acute nerve injury and the first time those benefits were shown to persist after treatment was stopped.

Study authors, Dr. John Elfar, associate professor of Orthopaedics, and Mark Noble, Ph.D., Martha M. Freeman, M.D., Professor in Biomedical Genetics, and their laboratory team, found that daily treatment with 4AP promotes repair of myelin, the insulating material that normally surrounds nerve fibers, in mice. When this insulation is damaged, as occurs in traumatic peripheral nerve injury, nerve cell function is impaired. These researchers found that 4AP treatment accelerates repair of myelin damage and improvement in nerve function.

Armond Collins, a second year medical student, presents the study he conducted with us this summer under the auspices of a Babigian Fellowship. Armond studied changes in myelination in amygdala and cortex of adult rats that had been exposed to 3 day bout of a repeated variable stressor during adolescence. His works follows up studies by Michele Saul, PhD that indicate that adolescent stress results in decreased oligodendrocyte precursors in the amygdala in the week following the stress.

Maiken Nedergaard, M.D., D.M.Sc.

More than $4.5 million in new grants to the lab of University of Rochester Medical Center scientist Maiken Nedergaard, M.D., D.M.Sc., underscore the important role the brain's waste disposal system may play in a range of neurological disorders. The new awards will advance understanding of how small vessel disease and traumatic brain injury can give rise to cognitive and behavioral problems.

Nedergaard and her colleagues first unveiled the brain's unique method of removing waste -- dubbed the glymphatic system -- in a paper in Science Translational Medicine in 2012. The research revealed that the brain possesses a circulation network that piggybacks on blood vessels and uses cerebral spinal fluid to flush away waste products from brain tissue. Since that time, the team has gone on to show that the glymphatic system works primarily while we sleep, could be a key player in diseases like Alzheimer's, and is disrupted after traumatic brain injury.

Rebecca Rausch, a fifth year neuroscience graduate student in Dr. Richard Libby's lab was awarded an NIH Individual Pre-doctoral Fellowship from the National Eye Institute for her project entitled: The Role of Notch and BMP Signaling in Anterior Segment Dysgenesis (2016-2019).

Congratulations Becca!

Aggressive forms of neuroblastoma contain a specific protein in their cells’ nuclei that is not found in the nuclei of more benign forms of the cancer, and the discovery, made through research from the University of Rochester Medical Center (URMC), could lead to new forms of targeted therapy.

EYA1, a protein that contributes to ear development, is present in the cytoplasm of many neuroblastoma tumors, but this protein migrates to the nucleus in the cells of more aggressive forms of the disease. The research, recently published in two medical research journals, allows for the development of targeted drugs that will work to prevent the neuroblastoma from reaching this more aggressive stage; researchers at URMC and elsewhere have already begun testing some of these potential treatments in a laboratory setting.

“Neuroblastoma is one of the most common and deadly forms of childhood cancer, and this discovery allows us to identify drugs that prevent the change in EYA1 structure and potentially minimize the danger to a child who has this disease,” said Nina Schor, M.D., Ph.D., professor of Pediatrics and Neuroscience and the William H. Eilinger Chair of Pediatrics at URMC.

Congratulations to the following people for winning teaching and student achievement awards at this year's SMD Opening Convocation.

Faculty Teaching, Mentoring & Diversity Awards

• Deborah Cory-Slechta, PhD
• John Olschowka, PhD

Medical & Graduate Student Achievement Awards

• Alexandra McHale - Irving L. Spar Fellowship Award
• Gavin Jenkins - Merritt and Marjorie Cleveland Fellowship
• Neal Shah - J. Newell Stannard Graduate Student Scholarship Award
• Grayson Sipe - Outstanding Student Mentor Award

Make sure to congratulate each of them when you see them.

Join Pat White on Saturday, September 10 from 2-4pm at the Pittsford Barnes and Noble as she is featured at the UR Science Cafe discussion

Over the typical course of Rett syndrome, initial language and communication abilities deteriorate dramatically between the ages of 1 and 4 years, and a majority of these children go on to lose all oral communication abilities. It becomes extremely difficult for clinicians and caretakers to accurately assess the level of preserved auditory functioning in these children, an issue of obvious clinical import. Non-invasive electrophysiological techniques allow for the interrogation of auditory cortical processing without the need for overt behavioral responses. In particular, the mismatch negativity (MMN) component of the auditory evoked potential (AEP) provides an excellent and robust dependent measure of change detection and auditory sensory memory. Here, we asked whether females with Rett syndrome would produce the MMN to occasional changes in pitch in a regularly occurring stream of auditory tones.

The paper "Prefrontal Neurons Represent Motion Signals from Across the Visual Field but for Memory-Guided Comparisons Depend on Neurons Providing these Signals" will be published in J. Neuroscience shortly.

Visual decisions often involve comparisons of sequential visual motion that can appear at any location in the visual field. We show that during such comparisons, the lateral prefrontal cortex (LPFC) contains accurate representation of visual motion from across the visual field, supplied by motion processing neurons. However, at the time of comparison, LPFC neurons can only use this information to compute the differences between the stimuli, if stimuli appear at the same retinal location, implicating neurons with localized receptive fields in the comparison process. These findings show that sensory comparisons rely on the interactions between LPFC and sensory neurons that not only supply sensory signals but also actively participate in the comparison of these signals at the time of the decision.

Make sure to read the article when it comes out.

Researchers have identified an inner ear deficiency in children with Autism that may impact their ability to recognize speech. The findings, which were published in the journal Autism Research, could ultimately be used as a way to identify children at risk for the disorder at an early age.

“This study identifies a simple, safe, and non-invasive method to screen young children for hearing deficits that are associated with Autism,” said Anne Luebke, Ph.D., an associate professor in the University of Rochester Medical Center Departments of Biomedical Engineering and Neuroscience and a co-author of the study. “This technique may provide clinicians a new window into the disorder and enable us to intervene earlier and help achieve optimal outcomes.”

“Auditory impairment has long been associated with developmental delay and other problems, such as language deficits,” said Loisa Bennetto, Ph.D., an associate professor in the University of Rochester Department of Clinical and Social Sciences in Psychology and a co-author of the study. “While there is no association between hearing problems and autism, difficulty in processing speech may contribute to some of the core symptoms of the disease. Early detection could help identify risk for ASD and enable clinicians to intervene earlier. Additionally, these findings can inform the development of approaches to correct auditory impairment with hearing aids or other devices that can improve the range of sounds the ear can process.”

Congratulations to Ashley Bui, a rising senior in Brain and Cognitive Sciences, on her presentation July 22, 2016. Her talk Projections from the Temporal Cortex to the Basal Nucleus of the Amygdala in the Macaque highlighted data from her summer project in our lab. The amygdala is required for computing which of the complex sensory stimuli that an individual encounters are emotionally meaningful, so that appropriate action can be taken. Ashley’s preliminary data shows that specific portions of the temporal cortex, which are critical for processing complex visual and auditory information, communicate with different regions of the amygdala. The results suggest that cortical areas that process complex visual information on 'what' and 'where' an object is (or is moving) are communicating with specific amygdala subregions. Thus, while determining the emotional importance of ‘what or who’ is important, biologic movements also likely influence amygdala activity and coding. We are happy that she will continue this work through the Fall semester.

Second year NGP student, Monique Mendes, had a unique opportunity to play alongside the Rochester Philharmonic Orchestra in their Side-by-Side Reading Session – a program that pairs amateur and professional musicians in a joint rehearsal and performance at Kodak Hall on July 21st.
Congratulations Monique!

Ryan Dawes successfully defended his thesis, "β-Adrenergic Receptor Signaling Constrains Breast Cancer Progression and Modulates Tumor-Associated Exosome Content And Function" on July 18, 2016.

Congratulations Dr. Dawes!

Rebecca Lowery has successfully defended her thesis, "The Role of Microglia and Fractalkine Signaling in Experience-dependent Synaptic Plasticity". Congratulate her when you see her.

Congratulations Dr. Lowery!

Elissa Wong, a fifth year toxicology graduate student in Ania Majewska’s lab, received the Margaret and William F. Neuman Scholarship Award in Environmental Medicine for exemplary scholarship and citizenship. Dr. William Neuman was the chair of the Department of Radiation Biology and Biophysics for many years and helped to create the Toxicology Training Program and the Environmental Health Science Center. Dr. Margaret Neuman received her PhD in Biochemistry from the University of Rochester. Later, working here, she researched the effects of uranium on bone biochemistry, and was an expert on the regulation of bone minerals.

The criteria for receiving this are as follows: 1) scholarship, 2) scientific excellence, 3) productivity, and 4) exceptional citizenship to the field of toxicology.

Congratulations Elissa!

A collaborative project involving Associate Professor Amy Kiernan of the Flaum Eye Institute has been chosen as one of the 2016-17 University Research Awards. One of just eight applications chosen by senior research leadership, the proposal entitled, "Understanding cell turnover and injury recovery in the corneal endothelium" will be funded $75.000 annually.

A new study shows that repeated radiation therapy used to target tumors in the brain may not be as safe to healthy brain cells as previously assumed. The findings, which appear in the International Journal of Radiation Oncology, Biology, Physics, show that the treatment also kills important support cells in the brain and may cause as much, if not more damage, than single dose radiation therapy.

“This study suggests that conventional repeated radiation treatments offer no significant benefit to brain tumor patients,” said Kerry O’Banion, M.D., Ph.D., a professor in the University of Rochester Medical Center (URMC) Department of Neuroscience and lead author of the study. “It also shows that certain cell populations in the brain are vulnerable to radiation and this may help explain why so many brain cancer patients experience cognitive problems after treatment.”

A new study out today in the journal Translational Psychiatry sheds further light on the idea that schizophrenia is a sensory disorder and that individuals with the condition are impaired in their ability to process stimuli from the outside world. The findings may also point to a new way to identify the disease at an early stage and before symptoms become acute.

Because one of the hallmarks of the disease is auditory hallucinations, such as hearing voices, researchers have long suspected a link between auditory processing and schizophrenia. The new study provides evidence that the filtering of incoming visual information, and also of simple touch inputs, is also severely compromised in individuals with the condition.

“When we think about schizophrenia, the first things that come to mind are the paranoia, the delusions, the disorganized thinking,” said John Foxe, Ph.D., the chair of the University of Rochester Medical Center Department of Neuroscience and senior author of the study. “But there is increasing evidence that there is something fundamentally wrong with the way these patients hear, the way they feel things through their sense of touch, and in the way in which they see the environment.”

Join us in congratulating Laurel for being selected as one of 4 Professors of the year from a extraordinary field of 63 candidates.

Laurel Carney, professor of biomedical engineering, won in the Engineering field. Her research focuses on the complex network of auditory nerve fibers that transmit the inner ear’s electrical signals to the brain with the goal of better hearing aids.

Carney earned her M.S. and Ph.D degrees in electrical engineering at the University of Wisconsin-Madison. She was an associate professor of biomedical engineering at Boston University and professor of biomedical engineering at Syracuse University before joining the Rochester faulty in 2007. She serves as professor in three departments – biomedical engineering, neurobiology and anatomy, and electrical and computer engineering.

Elissa Wong, a 4th year Toxicology Graduate Program student in Dr. Ania Majewska's lab received a perfect 10 review score and was awarded an NIH (NRSA) Individual Pre-doctoral Fellowship from the NIAAA. The title of her project is: Synaptic plasticity and microglial-synapse interactions after developmental alcohol exposure (2016-2018).
Congrats Elissa!

Grayson Sipe, recent doctoral graduate from the Majewska lab, received the Robert Doty prize for the 2016 outstanding dissertation in neuroscience. The Doty prize is named in the honor of longtime faculty member Robert Doty, who made great contributions to neuroscience research at the University of Rochester and nationally. It is awarded on the basis of the impact and importance of research, novelty of experimental design, independence and creativity of the student and research implications and relevance for neuroscience. Grayson’s thesis entitled “The Role of P2Y12 in non-pathological microglial functions during synaptic plasticity”, which he successfully defended on February 19th, 2016, embodied all these characteristics. Grayson has now moved to his postdoctoral position with Dr. Mriganka Sur at MIT. Dr. Peter Shrager presented Grayson the prize at the annual neuroscience retreat on Friday, April 29th.

Congratulations Grayson!!!

A study out today in the journal Science sheds new light on the biological mechanisms that control the sleep-wake cycle. Specifically, it shows that a simple shift in the balance of chemicals found in the fluid that bathes and surrounds brain cells can alter the state of consciousness of animals.

The study, which focuses on a collection of ions that reside in the cerebral spinal fluid (CSF), found that not only do these changes play a key role in stimulating or dampening the activity of nerve cells, but they also appear to alter cell volume causing brain cells to shrink while we sleep, a process that facilitates the removal of waste.

"Understanding what drives arousal is essential to deciphering consciousness and the lack thereof during sleep," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Center for Translational Neuromedicine and lead author of the study. "We found that the transition from wakefulness to sleep is accompanied by a marked and sustained change in the concentration of key extracellular ions and the volume of the extracellular space."

The current scientific consensus is that the brain is "woken up" by a set of neurotransmitters -- which include compounds such as acetylcholine, hypocretin, histamine, serotonin, noradrenaline, and dopamine -- that originate from structures deep within the brain and the brain stem. This cocktail of chemical messengers serve to activate -- or arouse -- a set of neurons in the cerebral cortex and other parts of the brain responsible for memory, thinking, and learning, placing the brain in a state of wakefulness.

Aleta Stevens, an NGP student in Dr. Amy Kiernan's lab, secured a 3-year NIH Individual Pre-doctoral Fellowship, F31 entitled, "Elucidating the role of SOX2 in inner ear development."

Excellent work Aleta!

Neuroscience Graduate Program students, Aleta Steevens (Dr. Amy Kiernan lab) and Heather Natola (Dr. Chris Pröschel lab) were awarded the 2016 Edward Peck Curtis Award for Excellence for Graduate Student Teaching.

Only a handful of these are awarded each year, and all this year's nominees were extremely well-qualified.

Congratulations to both!!!

Congratulations Dr. Cloninger on successfully defending your thesis!!

Electron microscope image of animal cells (colored blue) cultured on an array of carbon nanotubes

Researchers have developed a new and highly efficient method for gene transfer. The technique, which involves culturing and transfecting cells with genetic material on an array of carbon nanotubes, appears to overcome the limitations of other gene editing technologies.

The device, which is described in a study published today in the journal Small, is the product of a collaboration between researchers at the University of Rochester Medical Center (URMC) and the Rochester Institute of Technology (RIT).

“This platform holds the potential to make the gene transfer process more robust and decrease toxic effects, while increasing amount and diversity of genetic cargo we can deliver into cells,” said Ian Dickerson, Ph.D., an associate professor in the Department of Neuroscience at the URMC and co-author of the paper.

New research shows that our brains may be hardwired to become sensitive to stressful environments at an early age and, if overstimulated, this may contribute to anxiety disorders and even psychotic syndromes later in life.

The study, which appears in the journal Brain Structure and Function, focuses on two structures deep in the brain. The central nucleus of the amygdala (Ce) is thought to be involved in responses to immediate threats and stimulus, such as becoming startled or freezing in reaction to a loud noise. The bed nucleus of the stria terminalis (BST) is thought to be involved in regulating a person’s state of vigilance, such as determining whether or not an environment or a situation poses a potential threat. Animal and human studies show that when the BST is activated by a threatening situation, we tend to slow down, become quieter, and stress hormones spike.

While Ce and BST reside in different parts of the brain, the two areas are hardwired to each other by axonal tracts – basically, bundles of long distance axon fibers that enable the separate regions to communicate with each other. However, until now it has not been clear when these connections form or the way in which they interact with each other.

In the study published today, a team of researchers led by Julie Fudge, M.D., with the Department of Neuroscience observed that these connections are made at a very early stage of development in non-human primates. They also found that the direction of the connection is essentially a one way street. The Ce – or immediate fear signaling center – conveys information to the BST, the structure that mediates general threat sensing or anxiety states. This arrangement suggests that repeated activation of the Ce by immediately fearful or traumatic events may shape long-term anxiety states in the BST.

Microglia (green) with purple representing the P2Y12 receptor which the study shows is a critical regulator in the process of pruning connections between nerve cells.

A new study out today in the journal Nature Communications shows that cells normally associated with protecting the brain from infection and injury also play an important role in rewiring the connections between nerve cells. While this discovery sheds new light on the mechanics of neuroplasticity, it could also help explain diseases like autism spectrum disorders, schizophrenia, and dementia, which may arise when this process breaks down and connections between brain cells are not formed or removed correctly.

“We have long considered the reorganization of the brain’s network of connections as solely the domain of neurons,” said Ania Majewska, Ph.D., an associate professor in the Department of Neuroscience at the University of Rochester Medical Center (URMC) and senior author of the study. “These findings show that a precisely choreographed interaction between multiple cells types is necessary to carry out the formation and destruction of connections that allow proper signaling in the brain.”

The study is another example of a dramatic shift in scientists’ understanding of the role that the immune system, specifically cells called microglia, plays in maintaining brain function. Microglia have been long understood to be the sentinels of the central nervous system, patrolling the brain and spinal cord and springing into action to stamp out infections or gobble up dead cell tissue. However, scientists are now beginning to appreciate that, in addition to serving as the brain’s first line of defense, these cells also have a nurturing side, particularly as it relates to the connections between neurons.

Make sure you congratulate Grayson Sipe on defending his thesis.
Way to go Grayson!

A study out today provides new insight into how the brains of drug addicts may be wired differently. The findings, which appear in the journal Psychopharmacology, show that while drug users have very strong motivation to seek out "rewards," they exhibit an impaired ability to adjust their behavior and are less fulfilled once they have achieved what they desire. Addressing this disconnect between the craving for a drug and the ability to regulate behavior may be one of the keys to breaking the cycle of addiction.

"The vast majority of people, when faced with something they want, will assess how achievable the goal is and adjust their actions and expectations in order to maximize their potential to achieve it," said John Foxe, PhD, the chair of the Department of Neuroscience at the University of Rochester Medical Center and senior author of the study. "However, it appears that the integrity of this system of assessment and self-regulation is impaired in substance abusers and this may contribute to the risk-taking behaviors and poor decision-making commonly associated with this population."

Dirk Bohmann, Ph.D., an accomplished molecular biologist and scientific leader at the University of Rochester School of Medicine and Dentistry, has been appointed Senior Associate Dean for Basic Research pending approval of the University’s Board of Trustees.

Bohmann’s term is effective Jan. 1, 2016, and he’s begun making plans to improve the links between the Medical Center’s vast research community and its leadership, and to strategically integrate the science and education missions.

“I really consider this to be a service function for the scientific community,” said Bohmann, who holds the Donald M. Foster MD Professorship in Biomedical Genetics. “I hope to receive input from my colleagues and I look forward to interacting with them to come up with ways to improve our existing strengths and foster new ideas.”

New research shows that the cells responsible for protecting the brain from infection and inflammation are also responsible for repairing the system of defenses that separates the brain from the rest of the body. These findings have significant clinical implications because certain cardiovascular drugs could possibly impede the brain’s ability to repair itself after a stroke or other injury.

“This study shows that the resident immune cells of the central nervous system play a critical and previously unappreciated role in maintaining the integrity of the blood-brain barrier,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study. “When this barrier is breached it must be rapidly repaired in order to maintain the health of the brain and aid in recovery after an injury – a process that could be impaired by drugs that are intended to prevent this damage in the first place.”