NeURoscience | Vol 6 | 2020

NEUROSCIENCE University of Rochester | Ernest J. Del Monte Institute for Neuroscience Vol. 6 - 2020

Past, Present, and Future Converge in Neuroscience Education PG 3

F R O M T H E D I R EC TO R ’ S D E S K

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John J. Foxe, Ph.D. Kilian J. and Caroline F. Schmitt Chair in Neuroscience Director, The Ernest J. Del Monte Institute for Neuroscience Professor & Chair, Department of Neuroscience

On the cover John Olschowka, Ph.D., Ania Majewska, Ph.D., David Kornack, Ph.D.

Photo by John Schlia Editor

Kelsie Smith Hayduk Contributor

Mark Michaud Design by

Brittany Colton & Kathy Mannix 2

t has been a season of adapting.

Like labs across the nation, we have undertaken the complex efforts to rampdown research and work from home, and then to ramp back up again and safely return to the lab. Change is never easy, but being a part of a team that has embraced the challenges presented by the global COVID-19 pandemic is a source of pride, a feeling that has only strengthened in recent months. Yet despite all this change, students graduated on time, research was published, and grants were awarded.

On that last point, the Del Monte Institute for Neuroscience received monumental news this month. URMC has been designated an Intellectual and Developmental Disabilities Research Center (IDDRC) by the National Institute of Child Health and Human Development (NICHD). This designation puts URMC among an elite group of institutions advancing IDD research and will enable us to build upon our rich history of scientific innovation in this field and help transform how we provide care to families and patients with these conditions. We will share more about this effort in a future edition of NeURoscience.

In a few weeks, we will welcome the largest-ever incoming class to the Neuroscience Graduate Program. Given that milestone, we thought it appropriate to look back at the long-standing history of neuroscience education at the University of Rochester. Originally known as Anatomy, our department was one of the first five basic science disciplines that could be studied at URMC. Our cover story looks back at this history, explores the present, and reflects on what the future may hold. It provides insight into how the Del Monte Institute is providing the next generation of scientists with a hands-on learning environment alongside some of the field’s brightest minds.

You will meet some of the faculty behind the current success of the program as well as graduate students who share the benefits of collaborating across a number of disciplines, working in labs, and having opportunities to publish in elite journals. You will also hear from incoming students who are eager to advance their careers and take the next step in their scientific journey.

Our newest faculty member Julian Meeks, Ph.D., has already proven to be a valuable member of our team. Moving from Texas to Rochester in the midst of the COVID-19 pandemic, Meeks got his lab up and running and went right to work.

Inspired to take neuroscience classes during his undergraduate work following his grandfather’s Parkinson’s diagnosis, his research now focuses on how olfactory cues, including pheromones, guide animal social and reproductive behaviors. We're excited he is joining the important work being undertaken at URMC. You can also read more about the groundbreaking research that the institute continues to generate – from the work of Paul Geha, M.D., that could provide a way to measure the risk of chronic pain, to the culmination of more than a decade of research from the lab of Steve Goldman, Ph.D., that’s now paving the way for clinical trials on a possible treatment for multiple sclerosis.

I hope this issue finds you and your loved ones safe and well.

In Science,

John J. Foxe, Ph.D.

NEWS BRIEFS

URMC Designated an Intellectual and Developmental Disabilities Research Center URMC has been named a national leader in intellectual and developmental disabilities research. The National Institute of Child Health and Human Development has designated URMC as an Intellectual and Developmental Disabilities Research Center (IDDRC) joining 13 other institutions across the country with this designation.

The new center, which will be led by John Foxe, Ph.D., and Jonathan Mink, M.D., Ph.D., places URMC among an elite group of institutions advancing IDD research and care – only a handful of other intuitions hold this designation along with the Leadership Education in Neurodevelopmental Disabilities and University Center for Excellence in Developmental Disabilities programs.

The $6 million five-year grant will support five research clusters: . Rare and orphaned diseases of neurodevelopment . Neuro-inflammatory mechanisms in pathological brain development . Parental stress and early life exposure as determinants of brain development . Multisensory and sensorimotor integration . Autism spectrum disorder These research clusters are comprised of 105 investigators with 197 current or pending research projects.

Photo by Matt Wittmeyer

Animal Study Shows Human Brain Cells Repair Damage in Multiple Sclerosis A new study shows that when specific human brain cells are transplanted into animal models of multiple sclerosis and other white matter diseases, the cells repair damage and restore function. The study, published in the journal Cell Reports, provides one of the final pieces of scientific evidence necessary to advance this treatment strategy to clinical trials.

The study, led by Steve Goldman, M.D., Ph.D., co-director of the Center for Translational Neuromedicine, showed that when human glia progenitor cells are transplanted into adult mouse models of progressive multiple sclerosis, the cells migrated to where needed in the brain, created new oligodendrocytes, and replaced lost myelin. The study also showed that this process of remyelination restored motor function in the mice. The researchers believe this approach could also be applied to other neurological disorders, such as pediatric leukodystrophies – childhood hereditary diseases in which myelin fails to develop – and certain types of stroke affecting the white matter in adults.

This research is in the process of being developed by a University of Rochester start-up company, Oscine Therapeutics. The company’s experimental transplant therapy for multiple sclerosis and other glial diseases, such as Huntington’s disease, is currently under early FDA review for clinical trials.

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NEWS BRIEFS

Largest Long-Term Study of Adolescent Brain Development to Continue at URMC The University of Rochester Medical Center (URMC) will continue play a leading role in the largest long-term study of brain development and child health. The National Institutes of Health has renewed its support to the Adolescent Brain Cognitive Development (ABCD) study at URMC, allocating $7.5 million to the study for the next seven years.

“We are immensely proud of the part that the University of Rochester plays in the ABCD study,” said John Foxe, Ph.D., director of the Del Monte Institute for Neuroscience. “That children here in Rochester are part of a major national study, and are contributing to our knowledge of brain development is really fantastic and gives the Rochester community a voice in how national health policy is developed over the coming decade.”

Through 2026, URMC will continue to collect data on the 340 local participants. The Medical Center joined the study in 2017 and is one of 21 sites across the country. In all, the study is following 11,750 children through early adulthood looking at how biological development, behaviors, and experiences impact brain maturation and other aspects of their lives, including academic achievement, social development, and overall health.

The data from the study – broken down into the subcategories of sex, racial/ethnic group, and socioeconomic status – has, to date, yielded 32 research papers. These analyses have led to a better understanding of the association between certain traits and experiences in adolescence (e.g., sleep, body mass index, family conflict, screen time) and brain physiology and other outcomes, such as cognitive ability and mental illness (e.g., depression and suicide).

The ABCD Study, like many other research projects, is adapting to the restrictions necessary to address COVID-19. Scientists will conduct virtual assessments as long as needed so that valuable data will not be lost, and participant health and safety will be ensured.

Tufikameni Brima, Ph.D., with the Cognitive Neurophysiology Lab, works with a volunteer in the ABCD study. / University of Rochester Medical Center Photo

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Past, Present, and Future Converge in Neuroscience Education The campus of the University of Rochester Medical Center is quieter than normal as social distancing continues – but the research and renowned education programs that have been a staple at the institution for 95 years are moving forward.

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he cultivating of future neuroscientists is engrained in the tradition here. Today, the Del Monte Institute for Neuroscience serves as an umbrella for the cross disciplinary work being done at the University, while students get access to first-hand learning and are given a place to attempt to answer their own scientific questions. Dating back to 1925, the Department of Neuroscience – originally named Anatomy – was one of the five original basic science disciplines that could be studied at the Medical Center. It is a proud legacy for those who teach in the Department, and these professors are now just weeks away from welcoming the largest class ever accepted into the Neuroscience Graduate Program (NGP).

“I think this reflects the many initiatives that have been put in place in the last few years to enhance training experience – the addition of new required and elective coursework, writing skills enhancement, mentor training – along with the really excellent research that has been done by our students and their success when they leave us to pursue their careers,” said Program Director of the Neuroscience Graduate Program Ania Majewska, Ph.D. Among the incoming students is Evan Newbold, a graduate of Lafayette College with a degree in neuroscience and minor in aging studies. “The research at the UR is very closely aligned with my interests,” Newbold said. “There is a great opportunity to conduct work that can have a meaningful impact in the biomedical fields and, ultimately, address some portion of the unmet medical needs impacting our society.”

Victoria Popov will be Newbold’s classmate this fall. URMC’s culture and collaboration is much of what lead her to the university. “What interested me is the continued university-wide growth in neuroscience, commitment and support for diverse groups, including those who are D/deaf or hard of hearing, and the vast amount of opportunities there are to be involved in.”

Collaboration is invaluable for current students. “There are not many places where you can attend clinical rounds and your lab's journal club in the same day,” says 5th year Ph.D. candidate Humberto Mestre, M.D. Mestre has co-authored research papers published in prominent journals, such as Science. He was first author on a paper that showed the glymphatic system – normally associated with the beneficial task of waste removal – goes awry during a stroke and floods the brain, triggering edema and drowning brain cells. This work was conducted under the guidance of Maiken Nedergaard, M.D., D.M.Sc., and his experience in her lab has been an invaluable component of his education. In addition to working on groundbreaking projects, Mestre has been given the freedom to investigate his own questions, with guidance ready when needed. “These experiences have allowed me to learn how to navigate multidisciplinary collaborations and to see first-hand how powerful these collaborations can be in addressing fundamental biological questions.”

An opportunity to see research from a basic science and translational perspective has been a highlight of 4th year Ph.D. student Kathleen Miller-Rhodes' experience. Working in the lab of Marc Halterman, M.D., Ph.D., Miller-Rhodes’ research focuses on the interaction between the lung and brain following a stroke. “We are interested in understanding this 3

dynamic interplay because clinical data suggests that lung injury can exacerbate neurological injury, and vice versa,” Miller-Rhodes said. “What is great about this project is that even though I’m a neuroscientist, I have had the chance to also learn about lung structure and physiology.”

Providing an interdisciplinary experience for students is intentional. According to Majewska, the program is designed to create an environment that welcomes other perspectives while studying the broad field of neuroscience.

At the helm of this work is John Foxe, Ph.D., director of the Del Monte Institute for Neuroscience since 2015, and chair of the Department of Neuroscience. “From the onset, we have been focused on research and finding ways to better understand and find effective treatments for neurological disorders. It’s an exciting time in modern neuroscience and to cultivate new scientists at a world-renowned institution will only bolster the work being done, and forge a path to new discoveries.”

John Olschowka, Ph.D., came to URMC as a professor of Neuroscience in 1983. “In my 37-years here, John Foxe has heralded, by far, the largest growth and development in neuroscience at the university,” Olschowka said. “I think the quality of the faculty and the program that we put together here are key components to our success. And our graduate program has evolved a lot, especially in the last 20 years or so.” In that time, Olschowka and M. Kerry O’Banion, M.D., Ph.D., vice-chair of Neuroscience, combined their labs. With research focused on central nervous system neuroinflammation, the O’Banion-Olschowka labs use grant work to train students, but also look to students for new questions. “We tend to use the new directions they come up with as pilot data for our next grant. It is really their creativity that helps propel where we are going as a lab.”

That type of training trickles down to the undergraduate neuroscience program at the University of Rochester, which benefits from its proximity to the Medical Center. “Students are learning about neuroscience by actually doing it,” David Kornack, Ph.D., associate professor of Neuroscience, said. The brightest undergraduate students are cultivated by hands-on learning. Labs at URMC and the Del Monte Institute provide students with the unique opportunity to participate in research without a diploma. “They get to learn about the culture of neuroscience; they get to learn about the social aspects of being a scientist working in a lab with graduate students, technicians, postdocs, and professors. They have a tremendous opportunity.”

Students – both at the graduate and undergraduate level – benefit from the opportunity to be a part of a field that is accelerating our understanding of the human brain, at an institution with a rich history, and in an environment that nurtures lasting cross-disciplinary relationships. “My endeavors in research, professional development, and networking with a wide variety of researchers have been cultivated at URMC,” said Katherine Andersh, a 4th year student in the NGP. With research focused on the role of neuroinflammation in neurodegenerative diseases, specifically glaucoma, Andersh hopes in her final years of study she will be able to “identify potential targets that could be inhibited or activated to promote neuroprotection and prevent vision loss in glaucoma.”

“I am fortunate to be a part of research groups and around individuals Monique Mendes, 5th year NGP student, at her May that are as excited about science as I am,” 5th year NGP student Monique 2018 graduation with a Master's in Neuroscience.

Mendes said. “The conversations are lively and challenging. I appreciate the diversity in opinions and approach to a scientific question.”

“I think it’s critical to bring new people into science,” Majewska said.

“Science is really made up of new ideas of individuals who bring new perspectives. We’re positioned to do that because we really care about the students we bring in.”

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George W. Corner, M.D., teaches an anatomy class at URMC during the 192526 school year. Corner was a professor and the first chair of Anatomy, the precursor of the Department of Neuroscience.

INCOMING NGP STUDENTS Victoria Popov, M.S. – RIT Biomedical Sciences, B.S. and Professional Studies, M.S.

Anthony Bryan Crum, M.S. – Brigham Young University Neuroscience

Paige Nicklas – Edinboro University of Pennsylvania Psychology

Yanya Ding – University of Wisconsin-Madison – Neurobiology and Psychology

John Gonzalez Amoretti – Universidad Ana G. Mendez - Chemistry

Michael (Mike) Giannetto – RIT – Biotechnology and Molecular Bioscience

Abigail Sawicki – Messiah College - Biology, Biomedical Concentration

Bingyu Sun, M.S. – Columbia University in the City of New York - Biostatistics

Amy Bucklaew – Canisius College - Biology and Animal Behavior, Ecology, and Conservation

Dennisha King – Agnes Scott College – Neuroscience and Public Health

Rachel Seldowitz – James Madison University - Biology, Neuroscience concentration

Maleelo (Lelo) Shamambo – Rhodes College - Neuroscience

Evan Newbold – Lafayette College – Neuroscience, B.S. 5

STUDENTS’ PERSPECTIVE The future of Neuroscience will be determined by the resolve of those in the field. This is part of the catalyst behind the success of the Neuroscience Graduate Program. “I think it is critical to teach and train the next generation of scientists. Science is really made up of new ideas and individuals who bring new perspectives. The minute it stagnates then there is no progress,” said Ania Majewska, Ph.D., program director of the Neuroscience Graduate Program.

Th e Futu re of N e u roscie n ce: I n Th e ir Own Wo rds

Kathleen Miller-Rhodes 4th year Neuroscience Ph.D. student

“What I love about Neuroscience is that it is so interdisciplinary. Many neuroscientists are also immunologists and physiologists – their discipline lies not only within the brain, but also in understanding other peripheral systems. I believe that to truly improve outcomes for patients, neuroscience research needs to evaluate how the periphery can influence the brain (and vice versa). In learning how the brain interacts with the rest of the body, we can develop therapeutics that globally improve outcomes."

Humberto Mestre, M.D. 5th year Neuroscience Ph.D. student

“There is a recent effort in trying to understand what each cell in the brain is doing. This is uncovering an incredible amount of heterogeneity and diversity in terms of the variety of different cells in the brain and speculating about their individual function. I am excited to see how neuroscience will begin to construct a more complete view of how the microscopic components scale up to the macroscopic correlates, with the goal of ultimately generating a multiscale view of how the brain works and how it interacts with other organ systems.”

Evan Newbold Incoming student, Neuroscience, B.S., Lafayette College

“I think neuroscience and the brain are scarcely understood relative to other body or organ systems, and while that means there is so much to learn it also means that there is so much improvement to be made in our understanding. There are so many smart people dedicating their lives to solving problems in neuroscience and I’m so excited to see all the discoveries that will be made and the solutions that are produced.”

Victoria Popov Incoming student; Biomedical Sciences, B.S. and Professional Studies, M.S., RIT

“I am most excited to observe the impact recent wide range technological breakthroughs will have. Particularly in computational work to translating between neural mechanism and cognitive function. For instance, UR is at the forefront of our future through the Cognitive Neurophysiology Laboratory’s use of Mobile Brain/Body Imaging (MoBI). I aspire to utilize MoBI to develop a rehabilitative system that will improve cognitive functioning in individuals with schizophrenia-spectrum disorders who are hearing, D/deaf, or hard-of-hearing.”

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F A C U LT Y P R O F I L E

also become quite involved in the technology of whole brain microscopy. This is a way to visualize the anatomy of small-animal brains using techniques such as light sheet microscopy and clear tissue imaging.

How did you become interested in your field of study?

Like a lot of people who go into biomedical sciences, there's often a personal motivation for getting interested in studying something difficult. As a person who had a grandfather diagnosed with Parkinson's disease, I became interested in taking classes in neuroscience as an undergraduate; my undergraduate major was biomedical engineering. Over time, I became more and more curious about neurophysiology, and studying chemosensory systems from the physiological and theoretical perspectives are both fascinating. I am also motivated by a desire to learn more about how internal, emotional states can be influenced by the sensory systems and what we experience in the world.

Q&A with Julian Meeks, Ph.D. Julian Meeks, Ph.D., joined the Del Monte Institute for Neuroscience in May 2020 as an associate professor in Neuroscience. Julian earned his B.S. in Biomedical Engineering from Saint Louis University, and his Ph.D. in Neuroscience from Washington University in 2006. His research focuses on how olfactory cues – conveyed through the sense of smell – including pheromones, guide animal social and reproductive behaviors.

Tell us a little bit about your research.

The lab is really founded to study the sense of smell, and even more broadly, the chemosensory systems.

Chemosensory means sensing chemicals, and that can mean odors that we're familiar with, such as the smell of a flower, a strawberry, or red wine. But it can also mean sensing things like carbon dioxide, or a steroid found in sweat. Chemical sensing is done by neurons and other cells that interact with the nervous system. We study chemosensation starting in the periphery (for example, the nasal epithelium), where chemicals are sensed, and then follow the signals as they travel through the brain. The brain interprets and organizes information from the blends of chemicals so that the animal can use the information to guide its behavior. We’ve

Is there anyone at UR that you're particularly looking forward to collaborating with?

The two that I am most eager to work with are Krishnan Padmanabhan, Ph.D., who also shares interest in the olfactory systems, and Kuan Hong Wang, Ph.D., who studies experience dependent plasticity (learning) in the nervous system. I think there's going to be a great opportunity to start expanding our research from a very basic science-oriented program to one that includes more research into other aspects of chemosensation in mammals and in humans. For example, we're eager to start studying how anosmia (the loss of sense of smell), which happens as a result of traumatic brain injuries (and COVID-19), contributes to difficult comorbidities, such as anhedonia, the lack of a drive to seek pleasure, and depression.

What are your first impressions of Rochester?

It's pretty amazing that we were able to experience a record low and a record high temperature in the same month that we got here! The town itself – we're really going to love. It's great to see that people really make use of all of the openness – all of the public parks and spaces. Even with the lockdown, we can all go out and enjoy nature. And I really like the creative culture, which we hope to explore once it is safe to do so. It's also very clear to tell that this is a music town. I'm not a musician, but I'm sort of music nerd. The music culture here is just deeper and more sophisticated than I'm used to, but I'm really looking forward to being around that.

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NEWS BRIEFS

Researchers Find Way to Measure Chronic Pain Risk

Paul Geha, M.D.

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The size of a small area of the brain – mostly known for its role in decision-making – is giving scientists insight into risk for chronic pain.

Paul Geha, M.D., assistant professor in the URMC departments of Neuroscience, Neurology, and Psychiatry, and fellow researchers used an MRI to look at the limbic system of the brain and found the size of the nucleus accumbens, a component of the system, confers risk for developing chronic pain and altered nucleus accumbens activity is a signature of the state of chronic pain.

Predicting and measuring pain has always been a challenge for health care providers and patients. Geha believes this research, which was published in the journal PNAS, could be a vital step to changing that. With more and larger studies he foresees these findings playing a significant role in helping providers determine if a person is at greater risk to develop chronic pain. Knowing this could change the course of treatment, follow-up care, and pain management.

Golisano Pediatric Behavioral Health and Wellness Building Opens

The new $12 million, 36,000-square-foot Golisano Pediatric Behavioral Health and Wellness building will provide outpatient and partial hospitalization services for patients with depression, anxiety, psychosis, substance abuse, posttraumatic stress disorder, and other behavioral and emotional conditions.

Del Monte Institute for Neuroscience Executive Committee John Foxe, Ph.D.

B. Paige Lawrence, Ph.D.

Director, The Ernest J. Del Monte Institute for Neuroscience Kilian J. and Caroline F. Schmitt Chair in Neuroscience Professor and Chair, Department of Neuroscience

Wright Family Research Professorship - Dean’s Office M&D Professor and Chair, Department of Environmental Medicine

Bradford Berk, M.D., Ph.D.

John Romano Professorship in Psychiatry Professor and Chair, Department of Psychiatry

Director, The University of Rochester Neurorestoration Institute Professor of Medicine, Cardiology

Robert Dirksen, Ph.D.

Hochang (Ben) Lee, M.D.

Shawn Newlands, M.D., Ph.D., M.B.A. Professor and Chair, Department of Otolaryngology

Lewis Pratt Ross Professorship of Pharmacology and Physiology Professor and Chair, Department of Pharmacology and Physiology

Webster Pilcher, M.D., Ph.D.

Diane Dalecki, Ph.D.

Ernest & Thelma Del Monte Distinguished Professor in Neuromedicine Professor and Chair, Department of Neurosurgery

Distinguished Professor of Biomedical Engineering Chair, Department of Biomedical Engineering

Jennifer Harvey, M.D.

Duje Tadin, Ph.D. Professor, Department of Brain & Cognitive Sciences

Professor and Chair, Department of Imaging Sciences

Robert Holloway, M.D., M.P.H. Edward A. and Alma Vollertsen Rykenboer Chair in Neurophysiology Professor and Chair, Department of Neurology

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Neuroscience Graduate Program faculty meeting in April 2020, weeks after the University of Rochester implemented virtual learning.

Thank you to both faculty and students for adjusting so quickly to the new reality and finishing the 2019/2020 school year strong.

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