Annual Report 2017
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Zilkha Neurogenetic Institute ANNUAL REPORT 2016 - 2017 The period covered in this report is July 2016 through June 2017. All photos are by Chris Shinn unless otherwise noted. Special thanks to Emily Chu for her work preparing this report. 2 CONTENTS 4 Director’s Letter 5 History and Mission 7 ZNI Faculty 10 Faculty News 14 Faculty Research Programs 22 Scientific Advancements 33 Academic and Community Activities 37 Collaborations 48 FY 15 Faculty Publications 66 Teaching 69 ZNI Postdoctoral Trainees 72 ZNI Graduate Students 76 Zach Hall Travel Award Winners 77 NRSA Grant Training 78 Grants and Contracts ZNI Events 90 ZNI Seminar Series Special Lectures 93 7th Annual Zach Hall Lecture 94 Mary Hayley and Selim Zilkha Chair in Alzheimer’s Disease Research 95 4th Annual Zilkha Symposium on Alzheimer’s Disease & Related Disorders ZNI Collaborative Events 96 Joint ADRD ZNI Pilot Program 97 Los Angeles/Irvine Brain Bee 98 Music to Remember 99 ZNI Administration 100 ZNI Development 3 Director’s Letter As I complete my 5th year as Director of the Zilkha Neurogenetic Institute (ZNI), I find myself reflecting on the many significant advances this outstanding group of researchers has made, while I also consider all the exciting developments the new era may hold. Most similar institutes have been around decades longer than ZNI, which is just over 12 years old, yet our accomplishments–detailed in this report–rival or best some of the leading research neuroscience institutes in the world. For example, we continue to secure grants from a wide breadth of sponsors and in FY17 we increased our external funding to $24.3M in total costs. ZNI Investigators further promote advancements in science by publishing in high-impact journals. The newly formed department of Physiology & Neuroscience–where the majority of ZNI faculty hold primary appointments–has been rising in the rankings, from 51 in 2012 to 20 in 2016; and as more awards are received, we expect in short order to be ranked among the top five in the nation. And ZNI has welcomed scores of leaders in their respective fields to share their findings via our international symposia and regular seminar series. During the last five years, working together, we have transformed the Institute into a well-integrated USC powerhouse of discovery and translational neuroscience research by forming new centers and cores, and strengthening and expanding other programs. Discoveries from ZNI have contributed to the development of clinical trials in Alzheimer’s patients (Phase 2 and 3 studies) based on clearance of Alzheimer’s toxin amyloid-beta from the brain and/or blockade of its re-entry into the brain, with a goal to arrest and/or reverse cognitive decline, and for stroke based on activated protein C treatment (currently in phase 2 studies in stroke patients) to protect the brain from damage caused by a loss of blood flow to the brain during stroke attack. We have also identified genes associated with the risk for schizophrenia, and discovered molecular pathways in cerebral blood vessels linked to some key genes influencing the pathophysiology of Alzheimer’s disease pointing to new therapeutic targets. These are just a few of the advancements being made at ZNI. When I accepted the position of director in 2012, I stated that my clear goal is to make ZNI one of the top neurosciences institutions in the country and the world. We have been working persistently to achieve this goal with the critical help of all ZNI faculty and ZNI administrative support, and close collaboration and support from the Keck School of Medicine and USC administration and the community at large. To help drive the ZNI closer to the top endowed neuroscience institutes in the US, over the next few years we will be looking to increase our development activities by securing more funds for endowed chairs and the ZNI endowment. As we look to the future, I invite you to join us on our journey through this world of discovery. All the best, Berislav V. Zlokovic, MD, PhD 4 DIRECtor'S Letter History and Mission The Zilkha Neurogenetic Institute built in 2003. Dementias and Alzheimer’s disease are the fifth leading cause of death, with more than 5 million Americans living with Alzheimer’s Disease in 2017; by 2050, this number could rise to 16 million. The direct costs to American society of caring for those with Alzheimer’s and other dementias will total an estimated $259 billion; by 2050, these costs could rise to $1.1 trillion. The Zilkha Neurogenetic Institute (ZNI) has a broad focus and mission on examining pathogenesis and treatment of neurological and psychiatric disorders. For example, Investigators study Alzheimer and Related Diseases in multiple labs at ZNI. The Protein Structure group investigates the structure of proteins involved in Alzheimer’s, Parkinson’s and Huntington’s disease. Other investigators are studying brain circuits involved in vision and hearing, the role of the immune system in dementia, the role of cerebral blood vessels and blood-brain barrier in brain degeneration, genes that influence the risk for schizophrenia, depression and autism, and the biology of genes carrying the risk for Alzheimer’s and Down syndrome. These studies aim to help investigators understand the molecular and cellular basis of neurological and psychiatric disorders, looking toward devising new treatments for the cure and prevention. ZNI Investigators are also developing new molecular biomarkers and new imaging techniques in the living human brain for early diagnosis of Alzheimer’s and other neurological disorders associated with cognitive impairment. HIStorY AND MISSION 5 Established in 2003 by a generous gift from Selim Zilkha and Mary Hayley and further support from the WM Keck Foundation, the Zilkha Neurogenetic Institute serves as the nexus for a larger USC Neuroscience Initiative, encompassing scientists throughout the University. An organized research unit of the Keck School of Medicine at the University of Southern California, the ZNI is housed in a five-story, 125,000 sq ft building on the Health Sciences Campus, a state-of-the-art facility that allows basic scientists and physician-researchers to concentrate and collaborate. Faculty, postdocs, staff and students from a large and diverse array of USC departments, institutes, divisions and centers participate in collaborative interactions between researchers working at ZNI, including the Alzheimer’s Disease Research Center, the Broad Center for Regenerative Medicine and Stem Cell Research, Stevens Institute for Neuroimaging and Informatics, Departments of Neurology, Neurosurgery, Psychiatry & the Behavior Sciences, Integrated Anatomical Sciences, Biochemistry & Molecular Medicine, Otolaryngology, Molecular Microbiology & Immunology and the division of Bioinformatics (department of Preventive Medicine), as well as the Dornsife College, Andrus School of Gerontology and Viterbi School of Engineering. The hallmark of our vision is to create a highly participatory and creative scientific culture where investigators from a myriad of disciplines abandon their research silos and unite to conduct science research that matters to those affected by these diseases. Clinicians, physician-scientists along with researchers and trainees at all levels are dedicated to understanding the complexities of brain diseases and disorders, developing innovative therapies and ultimately discovering and translating cures from bench to bedside. At ZNI, we try to break through the typical barriers that separate the public from the scientific process, inviting the community to become catalysts in the discovery process by helping fund promising new research initiatives. 6 HIStorY AND MISSION ZNI Faculty Frank Attenello, MD, MS Alexandre Bonnin, PhD Daniel Campbell, PhD Assistant Professor Assistant Professor Assistant Professor Neurological Surgery Cell & Neurobiology Psychiatry & the Behavioral Sciences Karen Chang, PhD Jeannie Chen, PhD Robert H. Chow, MD, PhD Assistant Professor Professor Professor Cell & Neurobiology Cell & Neurobiology Physiology & Biophysics Marcelo Coba, PhD David V. Conti, MD, PhD Hong-Wei Dong, MD, PhD Assistant Professor Professor Associate Professor Psychiatry & the Preventitive Medicine Neurology Behavioral Sciences ZNI FACultY 7 Oleg Evgrafov, PhD Rick A. Friedman, MD, PhD Russell E. Jacobs, PhD Associate Professor of Research Professor Professor of Research Psychiatry & the Otolaryngology Physiology & Biophysics Behavioral Sciences Radha Kalluri, PhD James A. Knowles, MD, PhD Ralf Langen, PhD Assistant Professor of Research Professor Professor Otolaryngology Psychiatry & the Biochemistry & Behavioral Sciences Molecular Biology Brian Lee, MD, PhD William Mack, MD Axel Montagne, PhD Assistant Professor Assistant Professor Assistant Professor of Research Neurological Surgery Neurological Surgery Physiology & Biophysics Takahiro Ohyama, PhD Mariangela Nikolakopoulou, PhD Janos Peti-Peterdi, MD, PhD Assistant Professor of Research Assistant Professor of Research Professor Otolaryngology Physiology & Biophysics Physiology & Biophysics 8 ZNI FACultY Ahbay Sagare, PhD Derek Sieburth, PhD Ansgar Siemer, PhD Assistant Professor of Associate Professor Assistant Professor Research Cell & Neurobiology Biochemistry & Physiology & Biophysics Molecular Biology Huizhong W. Tao, PhD Terrence Town, PhD Tobias S. Ulmer, PhD Associate Professor Professor Associate Professor Cell & Neurobiology Physiology & Biophysics Biochemistry & Molecular Biology Jobin Varkey, PhD Kai Wang, PhD Gabriel Zada, MD Assistant