Annual Report 2020

ANNUAL Report FY 2020 USC Zilkha Neurogenetic Institute Department of Physiology & Neuroscience Clicking on a section in the Table of Contents will take you to that section. Table of Clicking on any page number will return you to the Table of Contents Contents 02 Letter from the Director 03 History and Mission 04 Faculty Biography 39 Awards & Recognition 42 Graduate Students 44 Postdoctoral Fellows 46 Visiting Scholars 47 Administration 48 Research and Advancements 62 Scholastic Activities 80 Publications 90 Cores and Research Centers Courtesy of Berislav Zlokovic Lab 96 Grants and Funding 104 Events 105 Zach Hall Lecture 106 2020 Los Angeles Brain Bee 107 Irene McCulloch Distinguished Lecture in Neuroscience 108 Zilkha Seminar Series 111 LA Opera Music to Remember Collage of images taken by the Zlokovic Lab 112 Operating Budget 113 Development Cover photo courtesy of: Huizhong Tao 3 Letter from History and the Director Mission Dear Friends, It takes a true visionary to anticipate years ahead of time, the There is no getting around it: we have been through some tough times best approaches toward addressing the growing problem of this year and we will undoubtedly continue to face new challenges over neurodegenerative diseases in our population, years before it would the next several months or perhaps longer. Yet even as we lament for become a worldwide major health and economical problem. Two decades our pre-pandemic routines, we move on with a strengthened resolve ago, having experienced the devastation of Alzheimer Disease (AD) in his to continue our important work. Trial-and-error is what science is all own family, entrepreneur Selim Zilkha turned his attention from about. building and overseeing successful multinational corporations and other renewable energy enterprises, to provide to the Keck School of Medicine of Research is experimentation, trying new tools to address age-old questions. Applying USC resources to establish an Institute in his name, a biomedical research home lessons learned in the past to map out novel ways to explore ideas in the future. Solid for studies of the aging brain, specifically Alzheimer’s and related diseases research involves following a conviction through difficult times while remaining . Combined with an endowment by the WM Keck Foundation, the Zilkha nimble enough to redirect attention when new challenges—or opportunities—arise. Neurogenetic Institute came online in 2003. I must say I have been most In the years since, a community of scientists has grown, with investigators who look into “Fresh activity is the only means of impressed with our researchers fundamental neural networks associated with vision and hearing working side-by-side with this past year. Before protein structure scientists who are trying to understand the effects of protein folding and overcoming adversity.” COVID-19, the trajectory misfolding in the brain. One research group is examining how placental function affects of accomplishments in grant fetal brain development while another looks into which genes are involved in memory loss funding, publications and associated with Alzheimer’s disease. Another principal investigator (PI)’s group studies —Johann Wolfgang von Goethe scientific advancements was genetic risk factors and molecular mechanisms underlying schizophrenia and other psychiatric already increasing in the disorders, and applies this knowledge to Alzheimer’s, and in an adjacent lab, a physician- department and the Institute. scientist pursues next-generation genomic and epigenomic profiling to study the behavior of various brain tumors. Faculty are looking at Alzheimer Disease itself from many different Then, when forced out of their laboratories by an emerging virus, our Principal Investigators (PIs) found angles, including the effects of major genetic risk factors on the vascular system of the brain a way to recapture momentum through new activities. Within a few weeks, as work shifted to home sites, and their effects on cognitive decline and dementia. regular Zoom meetings were established, new tasks distributed and teams reconfigured, data continued to be analyzed, manuscripts drafted, and a new work-from-home environment began to thrive. Collaborations between groups are expanding our knowledge, even as the next generation of scientists are being trained by these same researchers. How does ischemic stroke influence one’s chances of developing Alzheimer’s? How leaky While nothing replaces what can be done at the bench, in this new configuration, productivity was maintained and blood vessels break the blood brain barrier in the hippocampus, brain center for memory and other cognitive function, remarkably, in some cases, increased. Indeed, 129 publications went to press by our faculty this year. It is this resolve causing cognitive impairment? What is the role of prions, amyloid-beta and TAU? How do we use these results to develop that propelled the department of Physiology & Neuroscience in 2020 to be named #1 in the nation for NIH funding by new therapies for Alzheimer’s and related diseases? What can we be pursuing now to come up with new treatments and the Blue Ridge Medical Institute. And thankfully, we are gradually returning to our laboratories, even if in split shifts to prevention of dementia for the future? accommodate best safety practices. Using animal models as well as running experiments in Drosophila and C elegans, and deploying high-performance The accomplishments that are in the pages that follow come from 78 graduate students just starting their studies, 45 computer models incorporating high-resolution imagery, principal investigators are using cutting-edge approaches to postdocs continuing their training and all levels of faculty, who keep their eye on the prize even amid unexpected answer these questions and more, applying gold standard research processes and sharing the results with their colleagues. distractions. Thank you for taking the time to read their stories, to discover their passion. We can all use a bit of inspiration The Zilkha Institute is home to two different nuclear magnetic resonance (NMR) imaging systems, as well as a 7T right now and these researchers definitely provide it. magnetic resonance imaging (MRI) system combined with positron emission tomography (PET) to examine structures at the cellular level. Core instrumentation available to researchers includes a transmission electron microscope (tEM), Stay safe and all the best, several confocal and multiphoton microscopes, as well as a sophisticated biomarker core. The Zilkha Neurogenetic Institute and faculty within the department of Physiology & Neuroscience are devoted to the mission as stated by Mr Zilkha and Mary Hayley, to “arrest and reverse” Alzheimer’s and neurodegenerative disease. We Betza welcome your participation. 2 3 Brian Applegate PhD Frank Attenello MD MS Visiting Professor, Areas of Research Areas of Research Assistant Professor, Imaging Inner Ear Mechanics Genomics Brain Tumors Otolaryngology Diagnostic Imaging Middle Ear Mechanics Neurological Surgery Vibrometry Vascular Dr. Applegate received his B.S. in chemistry from Wright State University and his M.S. and Ph.D. in Frank Attenello is an Assistant Professor of Neurosurgery specializing in treatment of primary and chemistry from The Ohio State University. After completing a postdoctoral fellowship in the Department metastatic brain tumors in his surgical practice and laboratory. Research in the laboratory focuses on of Chemistry at the University of North Carolina at Chapel Hill, working on water cluster growth in mechanisms of cortical response to cellular stress and injury in the brain, and mechanisms of glioblastoma superfluid helium, he joined the Biophotonics group at Duke University directed by Prof. Joe Izatt. growth and chemotherapy resistance. Special emphasis is placed upon the role of long noncoding RNAs While at Duke, he won a National Institutes of Health postdoctoral fellowship award. Upon completing and pericytes in cell stress. Our laboratory utilizes functional CRISPR-based screens, primary patient- his fellowship he joined the Department of Biomedical Engineering at Texas A&M University where he derived tumor models and transgenic models for study. worked for over a decade. In early 2019 he moved his lab to the University of Southern California to the department of Otolaryngology–Head&Neck Surgery. Research in his lab has been supported by grants Dr. Attenello received combined BS/MS degrees in Molecular Biochemistry and Biophysics from Yale from the National Institutes of Health, the Department of Defense, and the National Science Foundation, University. He then received his medical degree from Johns Hopkins University School of Medicine, including an NSF CAREER award. where he received the institutional Harvey Cushing Neurosurgery Award and the Ronald L. Bittner national Neuro-oncology research award. His work on glioblastoma and neural stem cells at Johns Over the last decade we have been working on technologies for functional imaging of the ear. The Hopkins was supported by a fellowship from the Howard Hughes Medical Institute. He then completed resulting devices are capable of measuring vibrations of the middle and inner ear with picometer neurosurgical residency at the University of Southern California, with a postdoctoral fellowship in tumor (~4x10-11 inches) scale sensitivity and micron scale spatial resolution. Multiple devices have been genetics at the University of California, San Francisco. developed to image

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