Zilkha Neurogenetic Institute 2013-2014 annual report Table of Contents 2 Director’s Letter 3 History and Mission 4 ZNI Faculty 8 Faculty Research Programs 12 Scientific Advancements 23 Collaborations 37 Faculty News 41 Faculty Activities 43 Grants and Contracts 50 Special Lectures 51 4th Annual Zach Hall Lecture 52 1st Annual Zilkha Symposium on Alzheimer’s Disease & Related Disorders 54 Academic Activities 56 Neurodegeneration Journal Club/NRSA Grant Training 57 Los Angeles Brain Bee 58 Music to Remember - LA Opera/Alzheimer’s Association 59 ZNI Graduate Students 62 ZNI Postdoctoral Trainees 64 FY14 Faculty Publications 81 ZNI Administration 83 ZNI Development 1 Dear Friends, The World Health Organization estimates that devastating brain disorders and diseases affect more than one billion people worldwide. Last year, President Obama launched the BRAIN Initiative as a large-scale effort to equip researchers with fundamental insights necessary for treating a wide variety of brain disorders like Alzheimer’s, schizophrenia, autism, epilepsy, and traumatic brain injury. Research on the brain is surging. The United States and the European Union have launched new programs to better understand the brain. Scientists are mapping parts of mouse, fly and human brains at different levels of magnification. Technology for recording and imaging brain activity has been improving at a revolutionary pace. Yet the growing body of data—maps, atlases and so-called connectomes that show linkages between cells and regions of the brain— represents a paradox of progress, with the advances also highlighting great gaps in understanding. Specifically, interpreting these brain-wiring maps, and ultimately establishing the approach that physicians and scientists will use to treat neurological diseases, requires a clear understanding of brain circuitry, information that can only be obtained through basic research like the fine work being performed at ZNI. Scientists at ZNI are working harder than ever and achieving strong recognition for doing so. I am proud to say that of the 148 of papers published last year by our investigators, 17.5% were in high-impact journals, up 3.5% from last year. Similarly, despite the difficult funding climate, total grant dollars brought in by director’s letter director’s ZNI researchers is up 8.3% over last year. We also show in the following pages that ZNI investigators continue significant collaborations across USC, the region and around the world. This is great science. As ZNI investigators deploy novel approaches to examine and understand the underlying structure of and relationships between the various components that comprise the nervous system, we are driving translational research more and more toward transformative medicine. Please join us on this exciting road of discovery. All the best, “The human brain is the most complicated biological structure in the known universe. We’ve only just scratched the surface in understanding how it works or, unfortunately, doesn’t quite work when disorders and disease occur.” —Francis S. Collins MD PhD, Director, National Institutes of Health (NIH) 2 History and Mission With the support of the WM Keck Foundation and a generous gift from Mr Selim Zilkha, the Zilkha Neurogenetic Institute (ZNI) broke ground in more than one way just over 12 years ago. Some questioned why a new institute devoted to nurturing the best basic scientists would be located on a medical campus. But as entrepreneurs like Mr Zilkha know all too well, cutting-edge endeavors frequently receive considerable scrutiny and he and the Keck School of Medicine of USC persevered. Now with more than 30 laboratories populated by hundreds of researchers, ZNI is fast becoming the hub of the USC neuroscience community. Clinicians, physician scientists along with researchers and trainees at all levels—from undergraduate to graduate to postdoctoral—are forging collaborations across departments, disciplines and schools. And we are beginning to see other universities follow this model, aligning traditional wet lab research space directly amid their clinical operations. With the feedback between physicians and scientists, the work at ZNI is aimed to identify those at risk, promote preventive measures, develop innovative therapies and ultimately discover and translate cures from bench to bedside, for a spectrum of devastating brain disorders from Alzheimer’s disease to schizophrenia. However, despite the major advances that science is making in understanding how the human brain works, some neurodegenerative disorders and psychiatric conditions are on the rise and becoming more frequent, outpacing diagnostic and treatment approaches. Only if scientists like those working at ZNI continue to devote their efforts toward their areas of research, if they have access to significant funding, and if robust collaborations on Alzheimer’s and other brain diseases endure, only then will our efforts eventually lead to preventive approaches that could reduce memory loss and other serious symptoms that occur as a result of brain diseases. Alzheimer’s is the sixth-leading cause of death in the country and the only cause of death among the top 10 in the United States that cannot be prevented, cured or even slowed. 3 ZNI Faculty Alexandre Bonnin PhD Robert H. Chow MD, PhD Assistant Professor Associate Professor Cell & Neurobiology Physiology & Biophysics Daniel B. Campbell PhD Marcelo Coba PhD Assistant Professor Assistant Professor Psychiatry & the Behavorial Sciences Psychiatry & the Behavioral Sciences Karen Chang PhD David V. Conti PhD Assistant Professor Professor Cell & Neurobiology Preventive Medicine Jeannie Chen PhD Zemin Deng PhD Professor Assistant Professor of Research Cell & Neurobiology Psychiatry & the Behavioral Sciences 4 Hong-Wei Dong MD, PhD Radha Kalluri PhD Associate Professor Assistant Professor of Research Neurology Otolaryngology Oleg Evgrafov PhD James A. Knowles MD, PhD Associate Professor of Research Professor Psychiatry & the Behavioral Sciences Psychiatry & the Behavioral Sciences Greg Field PhD Ralf Langen PhD Assistant Professor Professor Cell & Neurobiology Biochemistry & Molecular Biology Rick A. Friedman MD, PhD Le Ma PhD Professor Assistant Professor of Research Otolaryngology Cell & Neurobiology 5 William Mack MD Janos Peti-Peterdi MD, PhD Assistant Professor Professor Neurological Surgery Physiology & Biophysics Takahiro Ohyama PhD Alapakkam Sampath PhD Assistant Professor of Research Associate Professor Otolaryngology Physiology & Biophysics Carlos Pato MD, PhD Derek Sieburth PhD Professor & Chair Associate Professor Psychiatry & the Behavioral Sciences Cell & Neurobiology Michele Pato MD Ansgar Siemer PhD Professor Assistant Professor Psychiatry & the Behavioral Sciences Biochemistry & Molecular Biology 6 Huizhong W. Tao PhD Gabriel Zada MD Associate Professor Assistant Professor Cell & Neurobiology Neurological Surgery Terrence Town PhD Li Zhang PhD Professor Associate Professor Physiology & Biophysics Physiology & Biophysics Kai Wang PhD Berislav V. Zlokovic MD, PhD Assistant Professor Director, Zilkha Neurogenetic Institute Psychiatry & the Behavioral Sciences Professor & Chair Physiology & Biophysics Tobias S. Ulmer PhD Associate Professor Biochemistry & Molecular Biology ZNI Faculty 7 Faculty Research Programs Scientists at the Zilkha Neurogenetic Institute reach across boundaries to embrace methods and techniques from many fields of study. They work to identify new approaches for examining nervous system function, so we may all better understand the underlying causes of neurological and psychiatric disorders. Areas of research overlap considerably (e.g., vision and circuits), and every Principal Investigator (PI) has multiple projects ongoing at any one time. Here is an overview of the current topics of study with related examples: Alzheimer and Related Diseases The Protein Structure group (Drs Ralf Langen, Ansgar Siemer and Tobias Ulmer) investigate the structure of proteins involved in debilitating diseases such as Alzheimer’s disease (AD) but also Parkinson’s and Huntington’s disease. Because many disorders of the nervous system are thought to arise from alterations in the structure of cellular proteins, these studies aim to help us understand the molecular basis of neural pathology, with a look toward devising new treatments for the cure and prevention of these diseases. Dr Karen Chang’s lab is trying to determine the role nebula/DSCR1 plays in ameliorating axonal transport defects and memory loss associated with Alzheimer’s disease; relatedly her group is trying to identify the genotype to phenotype correlations in Down syndrome. Dr Jeannie Chen is studying how Annexin A5 modifies disease progression in a mouse model for Alzheimer’s disease. Dr Hong-Wei Dong’s lab is studying the organizational principle of the brain wiring and how these circuits are disrupted in mouse models of Huntington’s and Alzheimer’s diseases. Dr Terrence Town and his team are developing new animal models of Alzheimer’s disease and related disorders to study the role of the immune system in dementia and other devastating disorders of the mind. Dr Berislav Zlokovic’s laboratory has a long standing interest in understanding the role of cerebral blood vessels and blood-brain barrier (BBB) in pathogenesis of neurodegenerative disorders such as Alzheimer’s disease and more recently amytrophic lateral sclerosis, as foundations for development of new therapies for AD and related neurodegenerative disorders as well as stroke.