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 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 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 .

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 community. Clinicians, 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 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

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Hong-Wei Dong MD, PhD Radha Kalluri PhD Associate Professor Assistant Professor of Research 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. Using experimental models and studying human brain, his research team has identified the cellular and molecular mechanisms in cerebral blood vessels and at the BBB that maintain normal neuronal function and structure. They have shown that BBB dysfunction and disruption of cellular cross-talk between different cell types of the neurovascular unit (i.e., endothelial cells, pericytes and astrocytes) can initiate neuronal dysfunction and injury, degeneration and loss, and accumulation of Alzheimer’s toxin Aβ and tau pathology. Findings from the Zlokovic laboratory contributed to Aβ clearance treatments in AD patients, and a new treatment for stroke with an APC analog currently in Phase 2 studies in stroke patients. His most recent interests are directed at understanding the biology of genes that influence the risk for Alzheimer’s disease using transgenic models, human iPSCs model of neurological disorders, and studying imaging and molecular biomarkers of vascular injury in the living human brain with mild cognitive impairment and AD.

8 Psychiatric Genetics The Center for Genomic Psychiatry investigates the role genes play in disorders of the mind. Dr Marcelo Coba is investigating how candidate risk factors associated to schizophrenia and other psychiatric disorders, works together in common signaling pathways, combining state-of-the-art mass spectrometry, proteomics, bioinformatics, mouse genetics and human stem cell methods. This strategy helps determine core signaling mechanisms and protein complexes, altered through development in schizophrenia, providing new molecular targets for treatment. Dr Dan Campbell discovered that a long non-coding RNA, a novel type of gene, contributes to autism risk. He seeks to understand the contributions of functional non-coding RNAs to the altered brain development of individuals with autism and schizophrenia. Dr Alex Bonnin is investigating how placental function affects fetal brain development, specifically looking at the impact of maternal infections in pregnancy and separately, the effects of maternal stress and antidepressant treatment. This research uncovers new molecular pathways for the developmental origins of mental disorders.

Considerable progress has been in made in the field of psychiatric genetics over the last year. Drs. Michele Pato, Carlos Pato and Jim Knowles participated in a large Genome- Wide Association Study of (GWAS) of schizophrenia that was published this past summer and discovered 108 genetic loci that increase the risk of the disorder, making schizophrenia one the best studied human diseases at the genetic level. Together, these three investigators are making progress on several other psychiatric disorders, such as, Obsessive Compulsive Disorder, major depression and suicide, bipolar depression, as well as developing the laboratory and software tools to enable future innovative research.

Genomics Dr Kai Wang is working on creating an automated pipeline for whole exome/genome sequencing analysis on Mendelian diseases and cancer, and for RNA-Seq analysis of single neuronal cells. His lab also investigates DNA methylation, gene expression and somatic mutations in the malignant transformation of meningiomas. Dr David Conti focuses on developing novel statistical methods to analyze next-generation sequencing data to discovery genetic variants involved in disease. This work is heavily integrated into his applied collaborations examining the genetic contribution to smoking progression and cessation, multiple sclerosis, colon and prostate cancer, asthma, lymphoma, and psychiatric disorders. Dr Gabriel Zada utilizes next-generation genomic and epigenomic profiling (i.e. DNA Methylation analysis) to study the behavior of various brain tumors. In particular, he is interested in studying the process of local tumor invasion and developing molecular classification systems for various skull base tumors, including pituitary tumors and meningiomas. He is also working to develop novel treatment strategies for skull base tumors using intranasal therapy systems.

9 Faculty Research Programs

Circuits The aim of Dr Robert Chow’s laboratory is to advance our understanding of how neuronal and hormone secretion (exocytosis) is controlled in normal and pathological states; part of the lab focuses on fundamental mechanisms (SNARE-mediated secretion), and the other on disease processes (diabetes, retinal and neuro- degeneration) or how to treat diseases (retinal degeneration). The Derek Sieburth lab combines behavioral, genetic, RNA interference, and live imaging techniques to dissect synaptic function at a systems and molecular level in the C. elegans model. Dr Li Zhang’s research is focused on understanding the structure and function of neural circuits so as to decipher the brain, which includes four aspects: 1) how neural circuits assemble and operate, 2) how circuit structure determines behavioral function, 3) how circuit functions are modulated, as well as 4) how circuit disorders lead to brain disorders. Dr Huizhong Tao’s work also explores establishment and development of functional visual circuits (please see Vision/Eye below).

Vascular Dr William Mack deploys an experimental strategy to determine the effects of air pollution on acute stroke, which is a leading cause of death and disability worldwide. He is further investigating innovative treatment platforms for rapid delivery of neuroprotective agents to otherwise inaccessible cortical territories in the setting of acute stroke. The broad interest of the Janos Peti-Peterdi lab is renal (patho)physiology, specifically the intrarenal mechanisms involved in the control of blood pressure and body fluid balance under normal and disease conditions (hypertension, diabetes). 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 (AD) and more recently amytrophic lateral sclerosis (ALS), as foundations for development of new therapies for AD and related neurodegenerative disorders as well as stroke.

Vision/Eye Photoreceptor cells are light sensitive neurons in the retina that initiate the first step in vision. One of the main objectives of Dr Jeannie Chen’s laboratory is to understand how an intracellular signaling cascade is regulated within rod and cone photoreceptor cells, and how this contributes to the specialized ability of these cells to detect dim light and bright light, respectively, and how mutations within this signaling cascade leads to blindness. Dr Greg Field is trying to understand how neurons function within circuits; current research in his lab is centered around identifying the functional connectivity between the photoreceptors (both rods and cones) and the approximately 20 distinct retinal ganglion cell types. Dr Huizhong Tao is interested in how functional visual circuits are organized to achieve specific cortical processing functions and how these circuits are established during development. She is currently examining how neural activity of various patterns leads to modulations of synaptic connections and shapes the formation of visual circuits.

10 Hearing/Ear The most common sensory abnormality in the world is age-related hearing loss. The second most common form of hearing loss is noise-induced. Dr Rick Friedman’s laboratory has demonstrated that both of these traits can be treated as common diseases and can be approached through association mapping. The primary objective of Dr Friedman’s laboratory is to study these common forms of hearing loss using a genome-wide association approach in mice. Dr Friedman’s laboratory has begun to define the genetic architecture of age-related hearing loss in mice and has identified several loci leading to susceptibility to noise-induced hearing loss. This work will provide important insights into the mechanisms underlying these common forms of hearing loss and studies in the mouse provide the power to begin to understand gene X environment interactions. The Takahiro Ohyama Lab is investigating how the cochlea, the auditory organ, develops during embryonic development. They discovered BMP signaling pathway is important for cell fate decision between sensory and non-sensory structure of mammalian cochlea. The Ohyama lab is also analyzing the mechanisms how migrating neural crest cells are incorporated into the non-sensory structure of developing cochlea, which is crucial for proper hearing functions. These projects aim to understand disease mechanisms of hearing impairment and develop translational research such as regeneration of auditory cells. Recent work from the Radha Kalluri Lab examines how biophysical differences between subpopulations of bipolar afferent neurons in the auditory and vestibular systems influence their function and their susceptibility to damage.

Understanding nervous system function and dysfunction requires the combined expertise of outstanding scientists from a variety of disciplines. It is at the Zilkha Neurogenetic Institute where great minds come together, exploring new ways to enhance our understanding of how the brain works, so we may improve the outlook for future patient care. Lab

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Alexandre

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Siemer

Ansgar

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Scientific Advancements

We share in the following pages some of the notable accomplishments by ZNI faculty over the past year.

Alexandre Bonnin The research done by the Bonnin Lab over the past year demonstrated that exposures to bacterial and viral-like immunostimulants in pregnant mice trigger different maternal and placental inflammatory responses, which induce a rapid increase of tryptophan metabolic gene expression and enzyme activity specifically in the placenta. Most importantly, this translates into rapid, differential alterations of critical neuroactive molecules, such as serotonin, in the fetal brain. These effects are likely to result in compromised serotonergic modulation of fetal brain development and have direct, long-term consequences on fetal brain circuit formation and postnatal brain function. The progress made last year, soon to be reported in a manuscript, provides strong support to the hypothesis that alteration of placental tryptophan metabolism by maternal inflammation during early gestation constitutes a new molecular pathway for the fetal programming of neurodevelopmental disorders such as autism or schizophrenia. In addition, the lab’s prenatal toxico-pharmacological exposure studies reveal unexpected, and potentially beneficial, effects of antidepressant drugs on fetal brain development, in the context of underlying maternal gestational stress. Finally, with Dr Jennifer King, LAC+USC maternal-fetal medicine fellow, the lab has started to explore a new, long-range, molecular communication pathway between the placenta and the fetal brain. Preliminary results are encouraging and may lead to future identification of new targets and biomarkers for the fetal programing of mental disorders.

12 Daniel Campbell The Campbell lab again published a high profile paper that produced widespread media . In the past two years, their work has generated media coverage from CNN, Time magazine, PBS, and Asian News International. This year, they published the first study showing a gene-environment interaction that triples the risk of autism. The lab had previously demonstrated that a genetic variant increases autism risk. Their collaborators in the USC Department of Preventive Medicine previously showed that air pollution increases the risk of autism. Putting heads and data together, they discovered that individuals with both the genetic risk factor and exposure to high levels of air pollution were at a much higher risk for autism than individuals having either the genetic factor or the air pollution exposure alone. This was the first time that anyone has shown that a combination of two known risk factors for autism can multiply to dramatically increase risk. The Campbell lab is now in the process of trying to understand the mechanisms of this gene-environment interaction. Remarkably, a major component of the mechanism appears to be a noncoding RNA, which could provide a potential treatment target for autism.

Karen Chang The Chang lab discovered the following things: 1) a protein upregulated in both Down syndrome and Alzheimer’s disease plays a surprisingly role in delaying neurodegeneration; 2) a kinase mutated in autism and upregulated in Down syndrome enhances the rate of recycling of neurotransmitters required for reliable communication between neurons. They are continuing to investigate the biological functions of both of these proteins and their contribution to neurological disorders.

Jeannie Chen Excessive light exposure is known to harm the retina and exacerbates disease progression in many retinal disorders, including age-related retinal degeneration. How light exerts its harmful effect on the retina is not well understood. The first step in one’s nighttime vision begins with photon absorption by rhodopsin, which then activates many transducin molecules. Transducin, in turn, stimulates phosphodiesterase enzyme activity to breakdown cGMP. At the plasma membrane of the rod cell, the fall in cGMP concentration causes cGMP-gated channels close, which then block the flow of ion currents into the cell. In this manner photon absorption ultimately leads to a change in current at the plasma membrane in a process called the phototransduction cascade. An over-active phototransduction cascade is known to cause retinal degeneration. During the past year, the Chen Lab showed that excessive activation of transducin, but not closure of the cGMP-gated channels, causes photoreceptor cell death by induction of the unfolded protein response. These findings provide a target for therapeutic intervention in certain retinal disorders caused by constitutive phototransduction.

13 Scientific Advancements

Robert Chow The Chow laboratory has started single-cell analysis of human spinal motor neurons of first and second trimester, correlating electrophysiology, morphology and gene transcription. This work, in the context of the NIH U01 (Chow and Knowles PIs), has paved the way for a collaboration with Dr Justin Ichida (Broad/CIRM, Keck SOM) to investigate gene changes leading to spinal motor atrophy (SMA) and amyotrophic lateral sclerosis (ALS). The Chow lab hasmade major strides in understanding how genes normally associated with neuronal development also may play a major role in determining the invasion potential of cancer. The promising work may lead to a real- time rapid screen for cancer invasion potential and a novel treatment for highly invasive cancers. In collaboration with the Langen laboratory, the Chow lab has discovered a possible new mechanism by which plasticizers may increase type 2 diabetes mellitus and Alzheimers disease risk. Plasticizers had been thought to act largely as hormone- disruptors. Our work suggests that plasticizers may play a role in damaging and/or killing pancreatic beta cells and neurons, by accelerating amyloid protein misfolding.

Marcelo Coba Many of the genes that have been implicated as risk factors for the psychiatric disorders are thought to affect the function of neuronal synapses. The Coba lab is interested to understand the molecular mechanisms linking psychiatric disease candidate genes to synaptic signaling. This year they made significant progress in the understanding of how synaptic signaling processes relates to psychiatric disease. Using Mass spectrometry, bioinformatics and mouse genetics, the lab determined the composition of different synaptic complexes, mapping more than 2,500 in-vivo, protein interactions in mouse pre-frontal cortex. They determined that these synaptic complexes were enriched in Schizophrenia candidate risk factors and that disruption of core components of these complexes, regulates the composition and association of proteins by impairment of protein-protein interactions. They also determined that a cluster of proteins related to psychiatric disease, associates in protein complexes that modulates hiPSC proliferation, and differentiation. These complexes are not functionally related to synaptic molecules and might function as an independent cluster for psychiatric disease risk.

David Conti The Conti lab has made several advances in statistical methodology for the integration of biological information in genetic association studies via the use of Bayesian stochastic search. In particular, they have developed an integrative Bayesian model uncertainty (iBMU) method, which formally incorporates multiple sources of data via a second-stage probit model on the probability that any predictor is associated with the outcome of interest. Using simulations, they demonstrate that iBMU leads to an increase in power to detect true marginal associations over more commonly used variable selection techniques, such as least absolute shrinkage and selection operator and elastic net. The increase in power and efficiency of their method becomes more substantial as the predictor-level covariates become more informative. In addition, the Conti lab has created a scalable algorithm called PEAK that improves the efficiency of MCMC by dividing a large set of variables into related groups using a rooted graph. Their algorithm takes advantage of parallel computing and existing biological databases when available.

14 Hong-Wei Dong The Dong lab made a significant progress on the NIH-funded Mouse Connectome Project (MCP, www.MouseConnectome.org), which proposes to generate the connectivity map of the entire mammalian brain and to subsequently construct its neural networks using computational technology. The MCP has produced one of the first online digital connectivity atlases, the iConnectome, which hosts ~8,200 regular users. The team has traced 600 cortical pathways and has generated the most comprehensive connectivity matrix of the mammalian . Their interactive cortical connectomic map, which features hundreds of reconstructed cortical pathways, is also available online. The data were also subjected to graph theoretical analyses, which revealed that the cortex is organized into a few relatively segregated networks. This novel work was recently published (Zingg et al., Cell 156, 1096-1111, 2014). Because of its broad scientific relevance, Cell Press and USC did a press release on the article. And it was featured on the NIH director’s blog, and was nationally recognized in the recent Interim report of the BRAIN initiative. These accomplishments were contingent upon innovative developments including pipelines for collecting, presenting, and analyzing large-scale connectivity.

Greg Field The Field lab has begun to use engineered viruses to manipulate the function of neurons in the mouse retina. These viruses allows the lab to activate or inactive with novel pharmacological agents neurons in the retina. This approach is allowing them to discover new cell types in the retina and their role in visual processing. The lab is also investigating how light and circadian rhythms impact the encoding of visual scenes by the retina. Finally, they are investigating how retinitis pigments changes retinal function and identifying promising therapies for this blinding disorder.

Rick Friedman The Friedman lab has completed a genome-wide association analysis of age- related hearing loss and noise-induced hearing loss susceptibilities in mice. They, in conjunction with collaborators from the University of Antwerp and Translational Genomics in Arizona, have recently shown the complex of age-related hearing loss in a human GWAS. They have identified at least 15 novel loci for each disease. They have demonstrated that one locus containing Nox3, an NADPH-reductase gene, is important for susceptibility to noise-induced loss and have characterized the phenotype in Nox3 mutant mice. They have identified a novel age-related hearing loss gene, Fhod3, and have demonstrated its expression in the hair cells and spiral ganglion of the mouse inner ear. They are currently embarking on cochlear organ culture expression studies and construction of a transgenic and CRISPR conditional knockout of the gene in mice. They are currently 50% finished with a GWAS for strain variation in vestibular evoked potential, a measure of gravity receptor function in mice and have a candidate gene (Dcc) at a genome-wide significant locus. They also have completed the bioinformatics analysis and are preparing a manuscript on the first RNA-seq data for the human cochlea and vestibular system. This analysis has demonstrated a host of cochlear specific genes, splice variants, and short RNAs that are specific to the inner ear. This will serve as an invaluable resource for the hearing scientific community.

15 Radha Kalluri Projects in the lab are combining in vitro patch clamp experiments, with anatomy, and computational modelling to study the biophysical basis for sensory signaling in the vestibular and auditory sensory systems. In the past year, the Kalluri lab has been working on determining if the intrinsic biophysical properties of auditory and vestibular sensory neurons contribute to functionally distinct sub-classes. They’ve recently identified groups of ion channels that may differ between functionally distinct groups of vestibular and auditory neurons. They’ve developed a computational model that tests the impact of these ion channel groups on neuronal function.

James Knowles The Knowles lab are a member of a large international consortium of researchers doing psychiatric genetics who have discovered 108 independent genetic loci responsible for the development of schizophrenia.They have completed the whole genome sequencing of ~2,000 individuals with schizophrenia, bipolar disorder and heathy controls, and were just funded to sequence another 10,000 samples. The lab continues to develop cell lines of neural progentitors from individuals with, and without, schizophrenia, and they were recently funded to examine the epigenetics of these lines. They completed and published the second Genome-Wide Association Study of (GWAS) of Obsessive Compulsive Disorder (OCD), which found evidence for the gene PTPRD. One of the best genes they found in the first OCD GWAS (BTBD3) has been developed in a mouse model of the disease. The Knowles lab was also recently funded by NIH to collect DNA and clinical information from 5,000 individuals with OCD. They have developed a novel and robust computer pipeline to determine the level of gene expression using DNA sequencing and applied it to studies of gene expression in single cells. They also have potentially identified a region of the brain with drastically different gene expression between individuals who died by suicide, as compared to those who did not suicide. Additionally, the Knowles lab received two new NIH grants. The first is to study the epigenetics of cells derived from individuals with, and without, schizophrenia (Co-PI, Peggy Farnham). The second grant is to collect an perform a GWAS study of 5,000 individuals with OCD (CO-PI, Michele Pato). Scientific Advancements Scientific 16 Photo credit: Radha Kalluri Lab Radha Kalluri credit: Photo

Ralf Langen During the past year, the Langen group continued to investigate what makes proteins misfold and take up toxic species in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and type-2 diabetes. Toward this end, they obtained novel structural information of several toxic misfolded amyloidogneic states and further developed peptide and protein-based means for inhibiting the misfolding and, thereby, preventing toxicity. The studies by the Langen group also provide insight into how environmental factors that can promote the aforementioned disesases do so by affecting protein misfolding. In collaboration with the biotechnology company PROMIDIS, the Langen group also identified a new structural state of the Huntington’s disease causing protein htt, and prevention of this structural form by post-translational modifications or small molecules is thought to be a therapeutic target. In separate studies, the Langen group identified a new mechanism, by which cells can control the shape of cellular membranes. In particular, it was found that the same protein can generate different types of curvature and that phosphorylation acts as a molecular switch that determines which membrane curvature is generated. The involvement of this switch is likely to be of relevance in several diseases, including Parkinson’s disease.

William Mack The Mack laboratory was awarded a grant to study the effects of air pollution from vehicular exhaust in the setting of acute stroke. Pilot studies demonstrated a detrimental effect of particulate matter on stroke progression. They published a paper characterizing the role of the C5 complement component in the setting of chronic cerebral hypoperfusion secondary to carotid artery stenosis. Along with our collaborators, they published several studies dissecting the genetic/ epigenetic characteristics of malignant meningiomas.

Takahiro Ohyama The Ohyama Lab is investigating how the cochlea, the auditory organ, develops during embryonic development. They discovered BMP signaling pathway is important for cell fate decision between sensory and non-sensory structure of mammalian cochlea. The Ohyama lab is also analyzing the mechanisms how migrating neural crest cells are incorporated into the non-sensory structure of developing cochlea, which is crucial for proper hearing functions. These projects aim to understand disease mechanisms of hearing impairment and develop translational research such as regeneration of auditory cells.

17 Carlos and Michele Pato In the last year, the Pato lab continued to develop the Genomic Psychiatry Cohort (GPC) and made significant progress in analyzing the genotypes of cohort participants. Additionally, in March 2014, they received a new $3.8 million grant to expand the GPC beyond Schizophrenia and Bipolar Disorder by adding an additional 5,000 participants with Obsessive-Compulsive Disorder (OCD). The GPC is a large clinical cohort of patients with schizophrenia (n=10,000), patients with bipolar disorder (n=5,000), family members (n=3,000), and control participants with no history or family history of schizophrenia or bipolar disorder (n=15,000) (Pato et al., 2013. Thus far, they have performed a variety of genotyping and whole-genome sequencing on over 12,000 GPC cases and controls. GPC participants give very broad consents (88% consent to re-contact) so that data generated can be important for a broad range of phenotypes and general population genomics. The GPC resource includes an NIMH-managed repository of genomic samples, genotype and sequence data, and detailed clinical and demographic data for investigations of mental disorders. The new grant expands the GPC by ascertaining 5,000 patients suffering from OCD and performing a genome-wide association study (GWAS) on 5,000 OCD patients and 5,000 already-ascertained and genotyped OCD-free matched controls. The Pato lab will more than double the total number of available world-wide participants for GWAS of OCD.

Janos Peti-Peterdi The Peti-Peterdi lab investigated the cellular and molecular mechanisms of glomerular kidney diseases, and identified several new potential therapeutic targets for future further development. The main focus of their studies last year was the role of podocytes, a unique pericyte-like cell type within the glomerulus, in the development of glomerulosclerosis and chronic kidney disease. They identified purinergic calcium signaling mediated by the P2Y2 receptor, as the most significant mechanism of podocyte cell-to-cell communication and propagation of podocyte injury. They showed that mouse models deficient in P2Y2 were protected from the development of proteinuria. The lab also showed, for the first time, direct visual evidence for the generation of new podocytes in the intact living mouse kidney, using a new technical innovation, serial multiphoton microscopy. They tracked the origin and fate of individually marked podocytes and resident renal mesenchymal stem cells within the living kidney using this technology. The pattern of cell migrations gave the Peti-Peterdi lab new visual clues on novel mechanisms of glomerular and renal tissue remodeling and regeneration. They are currently in the process of exploring these new mechanisms further. Lab

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18 Scientific Advancements

Ansgar Siemer The major goal of Siemer lab is to describe on a structural level how some amyloid fibrils can be toxic and responsible for neurodegenerative diseases, while others have beneficial functions as for example in long-term memory. The latter question is addressed in their research on the Orb2 functional amyloid, which is a key regulator of long-term memory in Drosophila. Besides considerable progress in defining the extend and the structure of Orb2’s amyloid core, they found that Orb2 has previously undescribed affinities to metal ions, lipids, and nucleic acids. They are following up on these finding to understand the importance of these interactions for long-term memory. Their research on the origin of toxic amyloids in neurodegenerative diseases is done in collaboration with the lab of Ralf Langen where they are working on the structure of toxic fibrils formed by the protein huntingtin important in Huntington’s Disease. With the lab’s newly installed solid-state NMR spectrometer, they could detect clear structural and dynamical differences between highly toxic amyloid fibrils and fibrils that were shown to be less toxic. In a next step, the Langen and Siemer labs will solve the structure of both the toxic and the benign huntingtin fibrils, which will give them important clues about how some amyloid fibrils can be toxic and others not.

Huizhong Tao The Tao lab made three major discoveries. First, in layer 4 of the mouse visual cortex they revealed synaptic changes induced by monocular deprivation (MD), which is a popular experimental model for studying mechanisms and treatments for amblyopia. While confirming a long-time suspicion of decreased excitatory inputs from the deprived eye, their results also generate novel insights into the expression mechanism for MD-induced cortical plasticity by demonstrating that a MD-induced general down-regulation of inhibitory inputs contributes to the increased responsiveness through the non-deprived eye. Second, by combining optogenetic techniques in specific transgenic mouse lines with intracellular voltage- clamp recordings, they found that recurrent intracortical excitatory circuits play an important role in amplifying the orientation-tuned signal relayed by the visual thalamus, while keep the overall orientation tuning preserved. This finding shed light on the organization of cortical circuits to produce sharp orientation selectivity in visual cortex. Third, they examined synaptic mechanisms underlying direction selectivity in layer 4 of the primary visual cortex. They found that direction selectivity originates from direction-tuned thalamic input, but is greatly sharpened by untuned inhibitory inputs coming from non-direction- selective fast-spiking inhibitory neurons, a major inhibitory cell type. Interestingly, the direction tuning of synaptic inputs is highly correlated with their asymmetry in spatial distribution of synaptic amplitudes. Ongoing experiments are aimed at understanding how spatial asymmetric can results in a directional bias of synaptic responses to moving stimuli.

19 Derek Sieburth The Sieburth lab is interested in how environmental cues impact behavior by influencing how neurons communicate with each other at specialized structures called synapses. They use the nematode as a model system for studying synapse structure and function because of its simple nervous system and the ability to visualize proteins in synapses in behaving animals. This year the lab discovered a new cellular signaling pathway that controls when neurons become activated during a rhythmic behavior. The lab also discovered that the neurotransmitter acetylcholine can act as a modulator of neuronal function by activating its receptor at sites far away from synapses. Finally, the lab showed that the amount of the synaptic protein neuroligin, which is implicated in autism, is controlled by a stress response pathway that functions in neurons to protect them from damage from oxidative stress.

Terrence Town The Town lab’s focus is to develop a treatment for Alzheimer’s disease by targeting the body’s immune system. Most therapies targeting the disease are thwarted by the blood-brain barrier, a natural mechanism that protects brain cells from entry of peripheral substances, and by the fact that immune responses in the brain are typically muted. However, in laboratory mice programmed to develop Alzheimer’s-like disease, the Town group has shown that certain immune cells can be coaxed into the brain from the circulation, where they attack the damaging sticky plaque buildup that is a defining feature of Alzheimer’s disease. They are continuing to pursue this line of research in hopes of developing a next-generation drug for Alzheimer’s disease. This work, which has been funded by the National Institutes of Health, the Alzheimer’s Association, and the American Federation for Aging Research, has been published in numerous high-impact journals including Science, Nature Neuroscience, Immunity, PNAS, and The Journal of Neuroscience. Of the over 100 research papers that we have published, half have been related to Alzheimer’s disease. The Town lab has revolutionized the field of Alzheimer’s disease research by generating the first rat model of the disease that manifests all of the clinico-pathological hallmarks of the human syndrome. Specifically, they made transgenic rats that over-express two mutant human transgenes that are each independently causative of familial early-onset Alzheimer’s disease: “Swedish” mutant amyloid precursor protein and deltaE9 mutant presenilin-1. Unlike their transgenic mouse cousins that develop ‘senile’ plaques but fail to manifest ‘tangles’ and frank neuronal loss, these transgenic rats-for the first time-develop the full spectrum of Alzheimer pathologies. This makes them an invaluable tool for understanding Alzheimer’s disease etiology and for testing cutting-edge therapeutics pre-clinically. Using this exciting new Alzheimer rat, they are actively pursuing collaborations with academics and with industry around the world to understand basic mechanisms of Alzheimer’s and to develop a cure for this devastating neurodegenerative disease.

Scientific Advancements

20 Tobias Ulmer Fatal age-dependent neurodegenerative diseases such as prevalent Parkinson Disease (PD) encompass the toxic misfolding of the 140-residue protein α-synuclein (αS). These diseases limit the lifespan and quality of life of an increasing and embattling portion of the human population. To guide therapeutic courses of treatment, our long-term goal is to obtain vital understanding of the structure-function and structure-dysfunction relationship of αS. To understand the root cause of αS misfolding, we performed computational studies to simulate possible starting points of misfolding. To maintain physiological function of αS upon therapeutic intervention, its random coil to helix transition upon synaptic vesicle association needs to be preserved, requiring a detailed biophysical understanding of this event. We have used a range of biophysical tools to study this random coil to helix transition. By providing comprehensive, mechanistic insight into the αS folding and misfolding pathways, it will be possible to identify novel therapeutic avenues to combat αS-based neurodegeneration while preserving physiological function.

Kai Wang The Wang lab has developed several computational tools for genome analysis, including (1) Phenolyzer, which prioritize potential disease causal genes in human genome based on observed phenotype presentations. (2) iCAGES (integrated cancer genome score), which identifies cancer driver genes and relevant drugs from whole-genome sequencing data on tumor samples. (3) Enlight, a software and web server for epigenetic annotation of variants identified from genome-wide association studies or whole-genome sequencing studies. Lab

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21 Li Zhang The Zhang lab has made tremendous efforts in methodological innovation. In particular, they established high-quality in vivo whole-cell voltage-clamp recording techniques to reveal spectrotemporal interplays between excitation and inhibition in determining auditory processing functions of individual principal neurons. Further integrating two-photon imaging guided targeted patch-recordings from inhibitory neurons, neural circuit modeling, and optogenetic manipulations of neural activity of desired cell groups, we were able to derive local excitatory and inhibitory synaptic circuits underlying specific auditory computation. They have made substantial progress in understanding the synaptic circuit basis for auditory processing, along the following research directions: a) specific and sequential laminar processing in each layer of the primary auditory cortex; b) processing of unique features of acoustic signals at several major subcortical auditory nuclei; c) postnatal development of functional synaptic circuits in the auditory cortex. For example, on cortical laminar processing, their series of studies revealed that differential excitatory/inhibitory interplays in terms of spectral, temporal and amplitopic relationships, which are inherited from variations of local circuits all recruiting a feedforward inhibitory circuit module, lead to differential laminar processing.

Berislav Zlokovic The Zlokovic lab’s progress in preclinical studies in rodent models of ischemic stroke with 3K3A- APC, a 2nd generation cytoprotective-selective APC mutant with > 90% loss of anticoagulant activity, was translated in 2014 into Phase 2 multi-center clinical trial in stroke patients. Working with the group, they have developed a new improved test to evaluate cerebrovascular integrity and blood-brain barrier damage in the living human brain during normal aging and in individuals with mild cognitive impairment and multiple sclerosis. The lab has developed a new battery of assays to access simultaneously ~30 analytes in human and rodent biofluids (CSF, plasma) including biomarkers of different cell types within the neurovascular unit (e.g., endothelial cells, pericytes, astrocytes, olgo, neurons, inflammatory response, Abeta and tau). Next, they found that perivascular pericytes control progression of Alzheimer’s neurodegenerative like process in mice including accumulation of Abeta and tau and loss of neurons using models of Alzheimer’s disease with accelerated pericyte loss. They also showed that blood-brain barrier disruption is an early event that leads to motor neuron degeneration in a mouse model of amyotrophic lateral sclerosis and that APC retards early motor neuron degeneration by preventing blood-brain barrier breakdown and eliminating neurotoxic microvascular lesions from the CNS. Two patents have been issued: one, for use of RAGE blockers to inhibit progression of Alzheimer’s pathology by blocking Abeta/RAGE interaction at the blood-brain barrier: and, second for uses of activated protein C analogs with reduced anticoagulant activity in neruological disorders and stroke.

Scientific Advancements

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Collaborations

“Science is a collaborative effort. The combined results of several people working together is often much more effective than would be that of an individual scientist working alone.”

—John Bardeen PhD, American Physicist and the only person to have won the Nobel Prize in Physics twice

23 Alexandre Bonnin Irina Burd of Johns Hopkins University; collaborating on fetal brain imaging studies following maternal exposure to stress and antidepressant drugs.

Anne Andrews of UCLA; collaborating on fast microdialysis studies to measure offspring neurochemical activity following prenatal exposure to stress and antidepressant drugs.

Gerard Karsenty of Columbia University; collaborating on a study related to the role of a bone-derived molecule in fetal brain development.

George Anderson of ; collaborating on fetal, placental and maternal measures of biogenic amines.

Robert Schwarcz of University of Maryland; collaborating on fetal, placental, and maternal measures of specific biogenic amines.

Brett Lund of USC Neurology; investigating the effect of maternal infection on fetal cytokine levels.

James Knowles of ZNI; working on single-cell transcriptome analysis of human placental cell types.

Skyla Herod of Azusa Pacific College; studying placental and fetal brain development in serotonin transporter knockout mouse model.

Daniel Campbell Wange Lu of USC Broad Institute; studying the impact of autism-related genetic variants on neuronal differentiation.

James Knowles of ZNI; studying gene expression changes caused by non-coding RNAs.

Kai Wang of ZNI; studying gene expression changes caused by non-coding RNAs.

Gerry Coetzee of USC Department of Urology; studying strategies for following up genome wide association study hits in autism.

Heather Volk of USC Department Preventive Medicine; investigating gene-environment interactions in autism.

Kevin V. Morris of Scripps Research Institute; studying the molecular mechanisms of non- coding RNAs.

Judy Van de Water of UC Davis; studying the genetic basis of altered immune sensitivities in autism

Lisa Croen of Kaiser Permanente; studying the genetic basis of altered immune sensitivities in autism. Collaborations 24 Karen Chang Tai Min of UNIST, Korea; investigating common molecular pathways altered in Down syndrome and Fragile X syndrome, two of the most common genetic causes of mental retardation.

Dion Dickman of USC Department of Neurobiology; studying the role of a novel synaptic kinase in regulating synaptic growth and function.

Jeannie Chen Amy Lee of USC Department of Biochemistry and Molecular Biology; investigating the role of endoplasmic reticulum stress in certain genetic mutations leading to blindness.

Ralf Langen of ZNI; investigating amyloid structures in eyes affected with macular degeneration and exploring therapeutic agents to dissolve these structures.

M. Carter Cornwall of Boston University; collaborating on the molecular mechanisms that regulate recovery of light sensitivity following bright light exposure.

King-Wai Yau of Johns Hopkins University School of Medicine; collaborating on the role of calcium-feedback to the olfactory sensory neurons in sensitivity adjustment during odorant adaptation.

Vsevolod Gurevich of Vanderbilt University; studying function of visual arrestins in the physiology of the photoreceptor cell.

Gordon Fain of UCLA; collaborating on mechanisms that regulate phototransduction in rod and cone photoreceptors.

Vladimir Kefalov of Washington University; investigating proteins that regulate calcium concentration in rod and cone photoreceptors.

Robert Chow Alan Yu of University of Kansas; evaluating the stoichiometry of claudin (tight junction) proteins in renal epithelial cells, using advanced microscopy techniques.

Cheng-Ming Chuong of USC Department of Pathology; studying to understand the role of calcium channels in development of chick feather bud morphology.

Justin Ichida of USC Department of Stem Cell Biology and Regenerative Medicine;studying to understand gene changes associated with the pathology of SMA and ALS.

Ralf Langen of ZNI; investigating the potentiating effect of free fatty acids in potentiating amyloid peptide cytotoxicity, in the setting of obesity in type 2 diabetes and Alzheimer’s.

Janos Peti-Peterdi of ZNI;collaborating on a project about the molecular control of renin secretion, which leverages my own expertise in synaptic protein biology and Dr. Peti- Peterdi’s expertise in renin biology.

Jeannie Chen of ZNI; Dr. Chen’s lab is using the Chow lab’s new genetically encoded ratiometric calcium indicator to study cytoplasmic calcium of photoreceptors in vivo and in vitro in mouse models of photoreceptor degeneration.

25 Robert Chow, cont’d James Knowles of ZNI; studying transcriptome variability among ostensibly identical and non-identical cells, in order to validate the newest generation of RNA-Seq platforms. They are also collaborating to identify miRNA candidates regulating the switching on of glucose-response genes in stem cells being differentiated to beta-like cells.

Mark Humayun and James Weiland of USC Department of Ophthalmology; collaborating on two projects: 1) Improving performance of the Argus II retinal prosthesis, and 2) Development of a novel photovoltaic nanoswitch for remote optical control of neuron activity.

Koping Kirk Shung of USC Viterbi School of Engineering; collaborating on a project to distinguish highly invasive breast cancer cells from less invasive cancer cells, using high-frequency ultrasound stimulation of cytoplasmic calcium elevation.

Marcelo Coba Guoping Feng of Stanley Center for Psychiatric Research, Broad Institute;collaborating on the study of SHANK3 mutations in psychiatric disorders, and their role in postsynaptic signaling.

Justin Ichida of USC Department of Regenerative Medicine and Stem Cell Research;studying hiPSC cells for the study of neurodevelopmental processes in psychiatric disease.

James Knowles of ZNI; studying the role of synaptic signaling complexes in Obsessive compulsive disorder and Schizophrenia.

Ted Abel of University of Pennsylvania; studying the role of Shank3 and AKAP signaling mechanisms associated to neurological disease.

Marco Bortolato of Kansas University; collaborating on the role of NMDAR signaling in the pathophysiological processes underlying impulsive aggression and related neurodevelopmental disorders (autism-spectrum disorder, ADHD, Tourette syndrome).

Thomas O’Dell of UCLA; collaborating on the role of TNiK and Dlgap1 signaling in synaptic plasticity, and memory.

Chao Zhang of USC; investigating the chemical genomics approaches to the study of protein kinase signaling.

Fengzhu Sun of USC Department of Computational Biology and Bioinformatics;collaborating on the analysis of protein domains and their role in synaptic signaling complexes associated to Schizophrenia.

Stephanie Dulawa of University of Chicago; studying the role of synaptic signaling complexes in Obsessve Compulsive Disorder.

26 Collaborations

David Conti Sylvia Richardson and Paul Newcombe of MRC Biostatistics Unit, Cambridge, UK;collaborating on the development of Bayesian model selection for functional integration in genetic association studies.

Graham Casey, Fred Schumacher, Steve Gruber of USC Department of Preventative Medicine; investigating the role of genetic variants in colon cancer risk using genetic association studies and functional assays.

Chris Haiman, Fred Schumacher, and Brian Henderson of USC Department of Preventative Medicine; investigating the role of genetic variants in prostate cancer.

Marc Tischkowitz of and Jonine Bernstein of Memorial Sloan Kettering Cancer Center; collaborating on WECARE Study (Women’s Environmental, Cancer, and Radiation Epidemiology) which examines genetic susceptibility and radiation exposure in breast cancer.

Fred Gilliland and Jim Gauderman of USC Department of Preventative Medicine;examining the role of genetic variation and pollution in asthma and lung function development in over 10,000 children followed for over 10 years in Los Angeles.

James Knowles and Carlos Pato of ZNI; examining genetic sequence data to identify variants involved in schizophrenia.

Wendy Cozen of USC Department of Preventative Medicine;through genetic association studies, they are investigating the role genes play in multiple myeloma and Hodgkin’s lymphoma.

Neal Benowitz of University of California San Francisco, Rachel Tyndale of University of Toronto, Caryn Lerman of University of Pennsylvania, and Gary Swan and Andrew Bergen of SRI International; as part of the Pharmocogenetics of Nicotine Addiction and Treatment, they are identifying genetic variants involved in smoking cessation and treatment response.

Duncan Thomas of USC Department of Preventative Medicine; developing new statistical approaches to the analysis of genes and environmental factors that interact via biological pathways.

Paul Marjoram, Simon Tavare, Magnus Nordborg and Sergy Nuzhdin of USC Department of Molecular and Computational Biology; as part of USC Center of Excellence in Genome Sciences, they are investigating how prior biologic knowledge can be used to influence statistical analysis.

Kiros Berhane of USC Department of Preventative Medicine; developing new statistical methods that incorporate both age and sex related changes in the dynamic relationship between weight, height and obesity as well as the complex multi-level relationships of determinants of obesity.

Lilyana Amescua of USC Department of Neurology; investigating the impact of genetics in Multiple Sclerosis using a Hispanic population sampled in Los Angeles and novel statistical methods.

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Hong-Wei Dong James Knowles and Robert Chow of ZNI, USC; initiated a multidisciplinary project to characterize cell types in the prefrontal cortex of the mouse brain.

Jean Shih of USC Department of Pharmacology; collaborating on characterizing disruption of cortico-striatal pathways in the mouse models of Autism.

X William Yang of UCLA; collaborating on characterizing connectopathies in the mouse models of Huntington’s disease.

Peyman Golshani of UCLA; collaborating on a project focusing on the optogenetic treatment of social behavior in autism.

Greg Field Alexander Sher of UC Santa Cruz; collaborating on the development of advanced, large-scale neuronal recording technologies.

Edward Callaway of the Salk Institute and Nicholas Brecha of UCLA; working to use engineered viruses to inactivate neurons in the retina to reveal their function.

E.J. Chichilnisky of Stanford University; investigating the effects of glaucoma on retinal ganglion cell physiology.

Jeannie Chen of ZNI and Noberto Grzywacz of USC; investigating the effects of retinitis pigments on retinal ganglion cell physiology.

Stephanie Dulawa of University of Chicago; studying the role of synaptic signaling complexes in Obsessve Compulsive Disorder.

Rick Friedman Jake Lusis of UCLA; collaborating on the analysis of transcriptome data and GWAS for hearing traits. Eleazar Eskin of UCLA; collaborating on the use of the Efficient Mixed Model Analysis of our GWAS data. Hooman Allayee of USC; collaborating on the analysis of GWAS for hearing and balance traits. Takahiro Ohyama of ZNI; collaborating on the development of constructs for transgenics, knockouts, and organ culture for Fhod3 experiments.

28 Radha Kalluri Carolina Abdala of USC Department of Otolaryngology; using otoacoustic emissions to non-invasively probe the status of mechanical transduction in hearing impaired humans.

Neil Segil of USC Department of Otolaryngology, Takahiro Ohyama of ZNI and Justin Ichida of USC Department of Stem Cell Biology and Regenerative Medicine;studying the molecular basis of neuronal differentiation in directly differentiated neurons.

James Knowles Carlos and Michele Pato, Oleg Evgrafov, Robert Chow, Derek Sieburth, Kai Wang, Li Zhang, Marcelo Coba, David Conti, Dan Campbell, Chris Haiman, William Mack, and Alexandre Bonnin of ZNI;collaborating on various projects.

Zemin Deng, Ting Chen, Ewa Deelman, Ann Chervenak, Peter Laird, Ben Berman, Jonathan Buckley, Graham Casey, Colin Dias, Mike Kahn, Carl Kesselman, Helena Mederios, Jerold Shinbane, Justin Ichida, Arthur Toga, Paul Thompson, Gerry Coetzee and Peggy Farnham of USC; collaborating on various projects.

Dan Stein of University of Capetown, Gerry Nestadt and Jack Samuels of Johns Hopkins University, Abby Fyer of Columbia University, Ben Greenberg and Steve Rasmussen of Brown University, James McCracken and John Piacentini of UCLA, David Pauls, Scott Rauch and Dan Geller of , Dennis Murphy and Yin Shugart of NIH, Carol Matthews of UCSF, and Stephanie Dulawa of University of Chicago;studying Obsessive compulsive disorder (OCD).

Doug Levinson of Stanford University, Myrna Weissman of Columbia University, James Potash and Bill Coryell of University of Iowa, Bill Scheftner of Rush University, Bill Lawson of Howard University, Peter Holmans of Cardiff University, Ray DePaulo of Johns Hopkins University, Doug Blackwood and Mohammad Ayub of University of Edinburgh, Jim Fallon, Fabio Macciardi and Biff Bunney of UC Irvine; working on Early-onset major depression.

Ayman Fanous of Washington DC, Veterans Administration and Doug Blackwood and Mohammad Ayub of University of Edinburgh; studying Schizophrenia.

Ed Lein and Michael Hawrylycz of Allen Institute for Brain Science , Nenad Sestan and Mark Gerstein of Yale University, Joel Kleinman, Danny Weinberg, Tom Hyde and Richard Straub of NIMH and the Lieber Brain Institute; collaborating on BrainSpan.

Ned Kalin, Pat Rosebloom, Jonathan Oler, and Drew Fox of the University of Wisconsin, Madison; working on genetic studies of anxiety in .

Ralf Langen Harvey McMahon of Laboratory of Molecular Biology in Cambridge; investigating mechanisms of membrane curvature induction by proteins.

Alasdair Steven of the NIH; using a cryo electron microscopy to look at mechanisms of membrane curvature and protein misfolding in neurodegenerative diseases.

Tobias Ulmer of ZNI; combining NMR and EPR-based approaches to determine structures of amyloidogenic proteins involved in neurodegeneration.

Collaborations

29 Ralf Langen, cont’d Martin Kast of USC Department of Molecular Microbiology & Immunology; investigating membrane-bound annexin A2 complexes as receptors for HPV entry.

Ansgar Siemer of ZNI; combining solid state and NMR and EPR-based approaches to determine structures of amyloidogenic proteins involved in neurodegeneration.

Ian Haworth of USC Department of Pharmacy; combining EPR and computational methods for determining protein structures.

Jonah Chan of UC San Francisco; studying control of membrane curvature during myelin formation and its role in multiple sclerosis.

Oliver Daumke of University of Berlin; investigating control of membrane curvature by EHD-2.

Robert Chow of ZNI; investigating membrane-mediated toxicity of amyloidogenic proteins in Alzheimer’s disease and type-2 diabetes.

Songi Han of UC Santa Barbara; using novel EPR and NMR-based methods to monitor water exposure and its application to protein misfolding and membrane interaction.

Julio Camarero of USC Department of Pharmacy; engineering cyclotides in order to make them misfolding inhibitors that could be used as drugs against Alzheimer’s disease, Parkinson’s disease and type-2 diabetes

William Mack Caleb Finch Of USC School of Gerontology and Constantinos Sioutas of USC Department of Environmental Engineering; collaborating on studies of the effects of particulate matter exposure from vehicular exhaust on the progression of stroke and cerebral hypoperfusion.

Kai Wang of ZNI; collaborating on studies characterizing genetic and epigenetic signatures of Meningiomas.

James Knowles of ZNI; working on a large study designed to evaluate cellular heterogeneity of temporal and cerebellar cells using patchclamp and RNA-Seq of single cells.

Robert Chow of ZNI; collaborating on a large study designed to evaluate cellular hetereogeneity of temporal and cerebellar cells using patchclamp and RNA-Seq of single cells.

Takahiro Ohyama Neil Segil of USC Department of Otolaryngology and Justin Ichida of USC Department of Stem Cell Biology and Regenerative Medicine;researching factors that directly transform somatic cells into auditory sensory cells.

Dean Pinchas Cohen of USC Davis School of Gerontology; testing protective effects of mitochondria-derived peptides on drug-induced hair cell damage.

Rick Friedman of ZNI; testing molecular functions of genes identified through genetic screening of mouse hearing disease model.

30 Carlos and Michele Pato Pamela Sklar of Mt. Sinai, Jordan Smoller of Harvard University, Peter Buckley of Medical College of Georgia, Dolores Malaspina of New York University, Evelyn Bromet of SUNY Stonybrook, Chris Morley of SUNY Upstate, Mark Rapaport of Emory University, Doug Lehrer of Wright State University, Diana Perkins of University of North Carolina, Fabio Macciardi of UC-Irvine, Stephen Marder of UCLA, Humberto Nicolini of Grupo de Estudios Medicos y Familiares Carracci, and Maria Helena Azevedo of University of Coimbra, Portugal; collaborating on an NIH-funded project creating a cohort of 30,000 individuals at USC for genomic studies and using next generation sequencing in multiple large scale population studies.

Steve McCarroll of Harvard University and The BROAD Institute;collaborating on extensive sequencing and genotypic projects

Michael Boehnke of University of Michigan; working on BRIDGES project on sequencing in Bipolar Disorder

Laura Bierut of Washington University; studying substance use and abuse in the Genomic Psychiatry Cohort

Oleg Egrafov of ZNI; studying olfactory neurons in psychiatric patients.

Kai Wang of ZNI; using bioinformatics and statistical genetics approaches to examine gene networks that are implicated in a variety of conditions.

James Knowles of ZNI; using next generation sequencing in multiple large scale population studies.

David Conti of USC Department of Preventive Medicine;using next generation sequencing in multiple large scale population studies.

Janos Peti-Peterdi Michael Caplan of Yale University and Jennifer Pluznick of Johns Hopkins; collaborating on the role of olfactory receptors in the kidney.

Andrew McMahon of USC; analysis of the macula densa cell molecular fingerprint.

Genevieve Nguyen of College de France, Paris; studying the role of the prorenin receptor in macula densa cells.

Dominique Eladari and Regine Cambrey of INSERM, France; working novel electrolyte transport mechanisms in the distal nephron.

Paola Romagnani of University of Florence; studying Intrarenal stem cells.

Andrew Salmon of University of Bristol; studying the role of the glomerular glycocalyx.

Thomas Benzing of University of Cologne; researching calcium imaging of podocytes in vivo.

Akira Nishiyama of Kagawa University; studying glomerular filtration of renin and prorenin.

Peter Deen of University of Nijmegen; investigating the role of GPR91 in distal nephron ion transport. Collaborations

31 Janos Peti-Peterdi, cont’d Attila Szabo and Agnes Prokai of Semmelweis;studying multiphoton imaging of the effects of calcineurin inhibitors in the kidney.

Laura Perin of Children’s Hospital Los Angeles; studying the role of amniotic fluid-derived stem cells in kidney repair.

Valter Longo of USC; studying the mechanism of liver regeneration.

Alicia McDonough of USC Department of Neurobiology and Romer Gonzalez-Villalobos of Cedars Sinai Medical Center; studying the role of the intra-renal rennin-angiotenisn system.

Rudy Ortiz of UC Merced;studying the role of mitochondrial factors in cell and tissue metabolism.

Stuart Shankland of University of Washington, Seattle;studying the mechanisms of glomerular dysfunction and repair.

Katalin Susztak of University of Pennsylvania; studying podocyte function in health and disease.

Giuseppe Remuzzi of University of Bergamo; collaborating on a clinical study of a new therapeutic approach to kidney regeneration.

Jochen Reiser of Rush University and Sanja Sever of Harvard University; studying the effects of suPAR on the glomerular filter.

Chaim Jacob of USC; studying the role of glomerular immune cells in lupus nephritis.

Derek Sieburth James Knowles of ZNI; sequencing entire genomes of the nematode C. elegans to identify mutations that cause defects in synaptic transmission.

Robert Chow of ZNI; examining how calcium regulates the release of neurotransmitters in real time from living tissue (using Total Internal Reflection Fluorescence Microscopy)

Ansgar Siemer Ralf Langen of ZNI; studying the structure and dynamic of toxic huntingtin fibril.

Kausik Si of Stowers Institute for Medical Research;studying the structure of the functional amyloid Orb2 responsible for long-term memory.

Ite A Laird-Offringa of USC; working on the characterization of aggregates formed by the HuD protein.

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Huizhong Tao Christiaan Levelt of Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences;studying how monocular deprived induces disruption of the balance between excitatory and inhibitory inputs.

Jonah Chan of University of California at San Francisco; studying how retinal activity through vision changes the maturation status of myelin wrapping on optic nerve fibers.

Josh Z. Huang of Cold Spring Harbor; researching on the functional properties of inhibitory neurons.

Gage Crump of USC Department of Cell and Neurobiology; studying a generation of inhibitory neurons specific zebrafish reporter line.

Li Zhang of ZNI; studying common inhibitory mechanisms underlying visual and auditory cortical processing.

Terrence Town Tarek Fahmy of Yale University; collaborating to design a next-generation nanoparticle drug delivery system.

Li-Huei Tsai of Harvard University; collaborating to investigate aberrant cyclin-dependent kinase activation in our novel transgenic Alzheimer rat model.

Erol Fikrig of Yale University ; interrogating neuro-immune mechanisms of West Nile encephalitis.

Richard A. Flavell of Yale University; collaborating on developing mouse models with human immune systems as a critical tool to examine stem cell graft tolerance vs. rejection.

Pasko Rakic of Yale University

Eliezer Masliah, MD of UCSD; collaborating on developing and characterizing rodent models of Alzheimer’s disease.

Caleb ‘Tuck’ Finch of USC; working together to understand different forms of neuroinflammation.

Helena Chui of USC; began discussions to validate observations that my group has made in mouse models using human Alzheimer patient samples.

Berislav Zlokovic of ZNI; working on a project together to extend his findings with the blood-brain-barrier into our novel Alzheimer transgenic rat model.

Collaborations

33 Tobias Ulmer Mark Ginsberg of UC San Diego; collaborating on the integrin receptor cell biology.Stanley Opella of UC San Diego; collaborating on the integrin receptor membrane immersion.

Kai Wang William Mack and Gabriel Zada of ZNI; working to perform integrative analysis on DNA methylation, DNA copy number change and whole-genome gene expression in several types of brain tumors.

Gary Chen of USC Department of Preventive Medicine;working to develop a copy number variation calling algorithm for whole-genome sequencing data.

James Knowles of ZNI; evaluating biological and technical noises of single-neuron RNA-Seq data and benchmarking different bioinformatics algorithms on these data.

Peter Robinson of Charité - Universitätsmedizin Berlin; developing variant annotation and prioritization software tools that incorporate phenotype information and model organism information.

Li Zhang Pin Wang of USC Department of Engineering; investigating engineering of different viral vectors.

Jonah Chan of UC San Francisco; studying myelination of cortical inhibitory neurons during development.

Huizhong Whit Tao of ZNI; investigating imaging processing in the visual cortex.

Le Ma of ZNI; studying the role of axonal guidance molecules in the formation of the spatial and functional organization of the cochlear.

Berislav V. Zlokovic of ZNI; investigating the impact of brain vascular defects on the functional cortical circuitry.

Berislav Zlokovic Arthur Toga of USC Institute of Neuroimaging and Informatics; Paul Thompson, USC Departments of Neurology, Psychiatry & Behavioral Sciences and Engineering; Scott Fraser of USC Departments of Biological Sciences and Biomedical Engineering; Helena Chui of USC Department of Neurology and USC Alzheimer’s Research Disease Center; Lon C. Schneider of USC Alzheimer’s Research Disease Center and Clinical Center and the Pharmacology program of USC NIH Alzheimer’s Disease Research Center; Terrence Town of ZNI; Hong-Wei Dong of ZNI; Roberta Brinton of USC Departments of Pharmacology & Pharmaceutical Science, Biomedical Engineering, and Neurology; and Russell Jacobs of Beckman Institute at Caltech;working on the USC Collaborative Initiative in Alzheimer’s Disease.

David M. Holtzman of Washington University in St. Louis; working on amyloid-beta metabolism and clearance in brain via LDLR receptors and role of apoE in amyloid-beta clearance.

John Griffin of Scripps Institute;working on manufacturing and testing new APC variants for stroke.

William Mack of ZNI; collaborating on hypoperfusion injury to white matter.

Collaborations

34 Berislav Zlokovic, cont’d Meng Law of USC Department of Neuroradiology and Helena Chui of USC Department of Neurology; working on MRI imaging of blood-brain barrier permeability constants in neurologically normal and MS patients and patients at risk for Alzheimer’s disease.

Collins Liu and Helena Chui of USC Department of Neurology; studying cerebrospinal fluid and plasma biomarkers of the blood-brain barrier damage in individuals at risk for Alzheimer’s disease.

Scott Fraser of USC Departments of Biological Sciences and Biomedical Engineering and Andy McMahon of USC Broad CIRM Center; working on the installation of serial two-photon tomography, cutting-edge equipment that allows for fully automated brain imaging.

Scott Fraser of USC Departments of Biological Sciences and Biomedical Engineering and Russell Jacobs of Beckman Institute at Caltech;collaborating on imaging white matter damage in small rodents due to pericyte loss using high field MRI and blood-brain barrier permeability longitudinal studies in mouse models of stroke.

Li Zhang of ZNI; collaborating on pericyte degeneration and cortical information processing.

Justin Ichida of USC Department of Stem Cell Biology and Regenerative Medicine;working on iPSC and fibroblasts from Alzheimer’s patients conversion into neurons and in vitro trials with 3K3A-APC as well as on brain organoids.

Washington University Alzheimer’s Disease Research Center; collaborating on CSF biomarkers of blood-brain barrier damage in individuals at risk for Alzheimer’s as well as individuals with mild cognitive impairment and Alzheimer’s with apoE4 allele vs. non-apoE4, as well as on postmortem brain tissue analysis and effects of apoE4 on blood-brain barrier integrity.

Nunzio Pomara and Blas Frangione of New York Medical Center; examining CSF biomarkers of blood-brain barrier injury in cognitively normal individuals at risk for Alzheimer’s.

Antonio Damasio of USC Brain Creativity Institute;studying the molecular basis of feelings.

Terrence Town of ZNI; studying pericytes in the rat model of Alzheimer’s disease.

Dean Pinchas Cohen of USC, Davis School of Gerontology; working on MSD biomarkers of vascular injury, angiogenesis, immune response and inflammation in patients at risk for Alzheimer’s disease and individuals with mild cognitive impairment and Alzheimer’s disease.

Pat Lyden of Cedars Sinai; working on Phase 2 clinical trial for stroke with 3K2A-APC.

Peter Carmeliet of Vesalius Research Center, KU Leuven; studying the role of glucose metabolism in brain endothelium during stroke.

Caleb Finch of USC; examining the blood-brain barrier permeability in 5FAD mice on different apoE genotype.

Leslie Weiner and Wendy Gilmore of USC; studying the 3K3APC treatment for multiple sclerosis.

35 Berislav Zlokovic, cont’d Jae Jung of USC; working on brain-specific TRIpartite Motif protein 9.

Michael Harrington of Huntington Hospital and USC; collaborating on imaging blood-brain barrier integrity in apoE4 individuals and CSF biomarkers.

Daniel Nation of USC;working on CSF and imaging biomarkers in individuals at high risk for hypertension.

John Morris of Wash University in St, Louis; collaborating on imaging and CSF biomarkers and apoE genotype.

Anne Fagan of Wash University in St. Louis; collaborating on CSF biomarkers and apoE genotype.

Tammie Benzinger of Wash University in St. Louis; working on maging vascular biomarkers in mild cognitive impairment. Collaborations 36 Faculty News Cohn

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37 Faculty News

The summer of 2013 brought new opportunities for partnerships in the areas of neuroimaging when Arthur Toga PhD and Paul Thompson PhD joined USC, creating the Institute for Neuroimaging and Informatics. Researchers at ZNI are establishing new collaborations with this active group, who are using mouse brain to provide accurate and reliable knowledge of the nervous system’s basic wiring diagram at the structural level. Specifically, Dr Zlokovic is working with Paul Thompson’s group on Clusterin and Alzheimer’s disease and cuprizon model of demyelination and MRI imaging. Dr Zlokovic’s group is also working with Dr Toga on vascular imaging and brain mapping.

Hong-Wei Dong MD PhD, moved his lab from UCLA to ZNI, as part of a larger recruitment of Dr Toga’s group. Dr Dong, who has a joint appointment in Neurology, has an R01 which aims to create a three- dimensional, Google Earth-like, digital Connectome atlas of the C57Black/6J mouse brain to provide accurate and reliable knowledge of the nervous system’s basic wiring diagram at the structural level. Dr Zlokovic is collaborating with Hongwei Dong on brain mapping (tractography) in new animal models of Alzheimer’s gene risk factors.

In the summer of 2013, ZNI welcomed three investigators formerly associated with the House Research Institute. Rick Friedman MD PhD, who holds a joint appointment in Otolaryngology, moved his lab to ZNI. He has an R01 which studies noise-induced hearing loss using high-resolution mapping strategies to comprehensively define loci that contribute to strain variation in phenotypes. Takahiro Ohyama PhD and Radha Kalluri PhD also relocated their laboratories from House Research Institute to ZNI. Both hold joint appointments in Otolaryngology. Dr Ohyama has an R01 that started in 2014 and Dr Kalluri has an R03 that that runs until 2016. A major goal of research in the Ohyama lab is to understand the molecular mechanisms of inner ear development at to explore the possibility of regenerating sensory cells to treat balance and hearing disorders. Dr Kalluri’s research focuses on understanding the macro-mechanical, anatomical and biophysical mechanisms that shape sensory signaling within the auditory and vestibular systems. The long-term goal of the work is to understand how targeted dysfunctions in the macro- mechanical and cellular mechanisms contribute to hearing and balance disorders.

Huizhong (Whit) Tao PhD was promoted to Associate Professor in Cell & Neurobiology. Dr Tao’s lab attempts to understand the principles underlying connectivity between neurons in the sensory cortex, which provides a structural basis for the information processing functions these nerve cells perform. Dr Tao is a past recipient of a Kirchgessner Foundation award and currently holds two grants from the National Eye Institute (NIH). A recent publication “Scaling down of balanced excitation and inhibition by active behavioral states in auditory cortex” appeared in April edition of Nature Neuroscience.

38 Derek Sieburth PhD was promoted to Associate Professor in Cell & Neurobiology. Dr. Sieburth’s research is focused on synaptic biology using C. elegans genetics. He joined ZNI following his postdoctoral appointment at Harvard, where he identified, based on RNA interference screens, over 100 new genes involved in synaptic transmission in C. elegans. He currently has an R01 grant from National Institute of Neurological Disorders and Stroke, “Stress Regulation of Snyaptic Transmission” and a satellite from the School of Gerontology (National Institute of Aging R01), “Oxygen Radical Toxicity and Protein Degeneration.”

In October 2013, Alapakkam Sampath PhD relocated his laboratory to the Jules Stein Institute at UCLA. Dr Sampath probes the connection between retinal structure/function and visual sensitivity. He received his master’s and PhD from UCLA and became ZNI faculty in 2005.

In June 2014, Le Ma PhD relocated his laboratory to Thomas Jefferson University. Dr Ma studies microtubule regulation in growth cones, linking this to CNP signaling in sensory axon development. Dr Ma received his PhD from Harvard and joined ZNI faculty in 2005.

Steve Kay PhD, DSc was named the first Distinguished Associate, Zilkha Neurogenetic Institute. According to Dr Berislav Zlokovic, Director of ZNI, a Distinguished Associate has achieved a high-level of productivity and distinction, to become a world leader in his or her field. Distinguished Associates enjoy all the benefits of membership at ZNI but also act as ambassadors for our mission and assist the Director by engaging in discussions regarding strategic planning and leadership.

Steve Kay is dean of the USC Dornsife College of Letters, Arts and Sciences and holder of the Anna H. Bing Dean’s Chair. He also holds faculty appointments in molecular and computational biology at USC Dornsife and in neurology, physiology and biophysics at the Keck School of Medicine of USC. One of the top experts on genes and circadian rhythms, Dr. Kay’s research is contributing to the development of new drugs that treat metabolic disorders such as Type 2 diabetes as well as to understanding how plants can better adapt to climate change. He is an elected member of the National Academy of Sciences and in 2014 was named by Thomson Reuters as one of “The World’s Most Influential Scientific Minds.”

We welcome Dean Kay to ZNI, where a number of faculty are interested in collaborating with him.

39 Faculty News

As the USC Alzheimer’s Disease Research Center (ADRC) approached its competitive renewal, ZNI has been working with the Dept of Neurology (Drs Helena Chui, Collins Liu) to support future directions of the ADRC, including CSF biomarker studies and imaging biomarkers of the cerebrovascular system and blood-brain barrier integrity. Should the renewal be successful, Drs Arthur Toga and Berislav Zlokovic have agreed to be part of the administrative core of the new ADRC. Dr Zlokovic would also be Associate Director of ADRC, direct one of the projects, and co-direct the Core for Neuropathology and Biomarkers. To further strengthen ties between departments across campus and USC, ZNI coordinated two major collaborative scientific events, both of which will hopefully lead to further funding:

A mini-symposium in August 2013 on current USC research related to Alzheimer ’s disease, where 10 USC PIs from multiples schools across both campuses presented their work before two key decision-makers of the Alzheimer’s Association including School of pharmacy, Dornsife, and School of Gerontology. Key participants included Drs Arthur Toga , Paul Thompson, Helena Chui, Pinchas Cohen, Scott Fraser, Robbie Brinton, and Christian Pike.

The 1st Annual Zilkha Alzheimer Symposium, “Breaking through Barriers: Neuronal, Glial and Vascular Contributions” was held on 4 April 2014, where 12 national and international leaders in the field outside USC (Peter Carmeliet MD PhD, Univ of Leuven (Belgium); Bart De Strooper MD PhD, Flanders Institute for Biotechnology (Belgium); Christian Haas PhD, Ludwig-Maximilians Univ (Munich); David M Holtzman MD, Wash U Medical School; Costantino Iadecola MD, Weill Cornell Medical College; Lennart Mucke MD, Gladstone Institutes, UCSF; Maiken Nedergaard MD DMSc, Univ Rochester Medical Center; Sangram Sisodia PhD, Univ of Chicago; Rudolph Tanzi PhD, Harvard; Tony Wyss-Coray PhD, Stanford; session chairs Maria Carrillo PhD, VP, Medical & Scientific Relations, Alzheimers Association; Roderick Corriveau PhD, Program Director, NINDS (NIH); Suzana Petanceska PhD, Program Director, NIA (NIH) and 5 USC leaders shared their unpublished work at ZNI and the Keck School of Medicine. Co-organizers for this event with Dr Zlokovic were David M Holtzman MD (Wash U) and Rudi Tanzi PhD (Harvard). The event included the participation Dr Rod Corriveau (NIH/NINDS); Dr Maria Carrillo (Alzheimer’s Association), and Gabriella Strobel (ALZFORUM). The day-long event was underwritten by a generous gift from Eva and Marc Stern. Cohn

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40 Faculty Activities Alexandre Bonnin Dr. Bonnin taught in the USC Neuroscience Graduate Program as well as Pharmacology to 1st year USC medical students. Additionally, Dr. Bonnin was an invited speaker to several national and internal symposia (including those held in France, Italy, Australia). Dr. Bonnin is also a member of the USC Institutional Biosafety Committee.

Daniel Campbell Dr. Campbell’s manuscript describing a gene-environment interaction that contributes to autism risk was covered by dozens of media outlets, including PBS News Hour, KABC-TV Los Angeles, LA Weekly, Beverly Hills Courier, and Science Daily. Dr. Campbell’s contributions to our understanding of the role of noncoding RNAs in psychiatric disorders was recognized by invitations to give lectures at the Help Group Summit, the meeting, the International Meeting For Autism Research, the UC-Irvine/Allergan Autism Update Conference, and the UCLA Extension Series: Beyond the Headlines.

Jeannie Chen Dr. Chen served on the Scientific Advisory Board of the Karl Kirchgessner Foundation.

Robert Chow Dr. Chow served as a mentor for the following programs: CIRM summer internship, CIRM Bridges internship, Bridging the Gaps: Bench to Bedside Summer Research Program, Engineering Research Center, and Engineering Health Academy. Additionally, Dr. Chow ran a workshop on patch clamp, for which 30 people across the USC campus signed up.

Hong-Wei Dong Dr. Dong was invited to give a talk for the 4th Annual Zach Hall Lecture and the 1st Annual Zilkha Symposium on Alzheimer Disease & Related Disorders at ZNI.

Radha Kalluri Dr. Kalluri was appointed as an Assistant Editor of the journal, Neurotology.

Ralf Langen Dr. Langen was a reviewer for NIH study sections.

William Mack Dr. Mack served on the Society of Neurointerventional Surgeons Board of Directors and was an Associate Scientific advisor for the journal Science Translational Medicine. Dr. Mack was appointed as an associate editor of the Journal of Neurointerventional Surgery and was appointed to the editorial board of World as the Book review section editor.

41 Carlos Pato Dr. Pato is the co-editor of Revista Brasilerira de Psiquiatri and an Associate Editor of Neuropsychiatric Genetics and American Journal Medical Genetics. He is also on the editorial board for Translational Psychiatry.

Michele Pato Dr. Pato is the co-editor of Revista Brasilerira de Psiquiatri. She is on the editorial boards of Annals of Clinical Psychiatry and Academic Psychiatry.

Janos Peti-Peterdi Dr. Peti-Peterdi served as the director of the USC Multiphoton Microsopy Core. He also established the institutional research base for a new kidney research center and applied for NIH funding for the center (P30 USC O’Brien Kidney Research Center).

Ansgar Siemer Dr. Siemer continued to serve on USC’s PIBBS (Programs in Biomedical and Biological Sciences) admission committee.

Huizhong Tao Dr. Tao served as the director Neuroscience Graduate Program core course.

Kai Wang Dr. Wang reviewed grant applications for a number of agencies, including Medical Research Council (MRC) UK, Southern California Clinical and Translational Science Institute (SC-CTSI), American Cancer Society - Institutional Research Grant (ACS-IRG), The National Science Centre Poland, NIH GCAT Study Section, and A*STAR Singapore.

Berislav Zlokovic Dr Zlokovic was named Mary Hayley & Selim Zilkha Chair in Alzheimer’s Disease Research. Dr Zlokovic presented the Society for Neuroscience Presidential Lecture: Blood Brain. He was the Co-Chair for the Alzheimer’s disease-realated dementia workshop 2013 (Vascular contributions), NINDS. Additionally, Dr Zlokovic worked closely with ADRC steering committee to reformulate the competitive application, forming new associations with a diverse group of USC faculty to strengthen the proposal, currently under review by NIH. Dr Zlokovic was selected to give the Chancellor’s Award Lecture in Louisiana State University Health Sciences Center 2014.

Dr. Zlokovic became a Fellow of the American Association for Advancement of Science. Also, in April 2014, he coordinated the 1st Annual Zilkha Symposium on Alzheimer Disease and Related Disorders “Breaking through Barriers: Neuronal, Glial and Vascular Contributions”. This day-long event featured an international group including 10 out of the 20 top neuroscientists in the world, presenting mostly unpublished data about experiments still underway, approaching AD from multiple disciplines.

Dr Zlokovic, along with the two co-organizers of the above conference, Drs David Holtzman and Rudolph Tanzi, were all three named as the most influential scientists in the world in the field of Neuroscience & Behavior by Thompson Reuters (July 2014). Faculty Activities Faculty 42 Grants and Contracts

ZNI PIs had a busy FY14. The number of grant submissions went up from 6 to 8 per month, in addition to roughly 32 progress reports each year. We had 69 sponsored proj- ects during the reporting period, many from 11 different NIH institutes. Most significantly, despite the difficult funding climate, ZNI investigators managed to increase total project costs by 8.3% over the prior year.

Total Number of Active Grants for FY14

Federal Grants 40 Federal Fellowships 1 Foundation/Private Grants 24 Non-Federal Fellowships 3 California Institute for Regenerative Medicine 1

Total 69

2014 Annually Sponsored Awards

Federal Awards $ 16,702,130 Private Foundation Awards $ 3,009,183 Industry $ 400,000

Total $ 20,111,313

43 Sponsored Projects FY13 to FY14

$25,000,000

$20,111,312 $20,000,000 $18,447,570

$15,000,000

$10,000,000

$5,000,000

$‐ FY13 FY14

Direct Costs F&A Costs Total Costs

FY13 $12,613,663 $5,833,907 $18,447,570 FY14 $13,841,591 $6,269,721 $20,111,312

44 Number of Awards by NIH Institute/Center FY14

National Institute on Deafness and Other Communication Disorders (NIDCD) 2 National Cancer Institute (NCI) 1 National Eye Institute (NEI) 4 National Human Genome Research Institute (NHGRI) 4 National Heart, Lung, Blood Institute (NHLBI) 1 National Institute on Aging (NIA) 5 National Institute of Biomedical Imaging & Bioengineering (NIBIB) 1 National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 1 NIH Bioengineering Research Partnership (BRP) 1 National Institute of Mental Health (NIMH) 15 National Institute of Neurological Disorders and Stroke (NINDS) 6

Total Federal 41

2014 ZNI Sponsored Projects by Federal Agency NCI 3% NEI NINDS NIDCD 10% 15% 5%

NHGRI 10%

NHLBI NIMH NIA 2% 37% 12% BRP 3%

NIBIB NIDDK 3% 2%

Grants and Contracts

45 Active Awards ‐ Fiscal Year 2014

ZNI Investigator Funding Agency Direct Costs F&A Costs Total Costs Project Title Children's Hospital of Los Angeles subK (National Bonnin, Alexandre Institute of Mental Health) $15,123 $9,376 $24,499 Enduring Effects of Early-Life Serotonin Signaling University of Maryland subK (National Institute of Bonnin, Alexandre Mental Health) $30,418 $19,582 $50,000 Kynurenic Acid and Cognitive Abnormalities The impact of maternal inflammation during Autism Science pregnancy on placental tryptophan metabolism, and Foundation Fellowship: the downsteam consequences on fetal brain Bonnin, Alexandre Nick Goeden $50,000 $0 $50,000 development National Institute of Campbell, Daniel Mental Health R21 $125,022 $80,343 $205,365 Non-Coding RNAs in Autism

National Institute of Biology of Non-Coding RNAs Associated with Campbell, Daniel Mental Health R01 $264,981 $150,162 $415,143 Psychiatric Disorders National Institute of Neurological Disorders Role of DYRK1A/MNB in Synaptic growth and Chang, Karen and Stroke R01 $435,312 $279,683 $714,995 function Functional Protein Interactions in Alzheimer's Chang, Karen Alzheimer's Association $272,730 $27,270 $300,000 Disease and Down Syndrome

Jerome Lejeune Systematic analysis of genes contributing to synaptic Chang, Karen Foundation $47,974 $4,796 $52,770 defects in Down syndrome Phototransduction in dark adaptation and retinal Chen, Jeannie National Eye Institute R01 $376,557 $242,565 $619,122 degeneration Arnold & Mabel Beckman Phenotyping molecular and structural heterogeneity Chen, Jeannie Initiative $100,000 $0 $100,000 of drusen towards improved AMD classification National Institute of Evaluation of Cellular Heterogeneity Using Chow, Robert Mental Health U01 $136,079 $87,090 $223,169 Patchclamp and RNA-Seq of Single Cells

National Institute of Biomedical Imaging and Bioengineering P41 Chow, Robert (BMES Satellite) $47,486 $30,402 $77,888 A Resource on Medical Ultrasound Transd

National Institutes of Health Bioengineering Experimental and Clinical Investigations of Retinal Chow, Robert Research Partnerships $126,302 $55,233 $181,535 Stimulation

USC Provost Postdoctoral Funds: Reymundo Estradiol-mediated neuronal protection against focal Chow, Robert Dominguez $23,958 $0 $23,958 ischemia involves beta-arrestin1

Zumberge Research and Evaluating Invasion Potential of Cancer Cells with Chow, Robert Innovation Fund $50,000 $0 $50,000 High-Frequency Ultrasound

National Cancer Institute Incorporating Intermediate Biomarkers of folate with Conti, David R01 $295,988 $189,556 $485,544 colorectal cancer

Strategies for Engineered Negligible Senescence (SENS) Research Whole genome sequencing of S.aleutianus: The fish Evgrafov, Oleg Foundation $3,200 $0 $3,200 with the highest longevity National Institute of Transcriptome sequencing of neuronal cell lines from Evgrafov, Oleg Mental Health R01 $419,097 $259,840 $678,937 patients with Schizophrenia

46 Active Awards ‐ Fiscal Year 2014

ZNI Investigator Funding Agency Direct Costs F&A Costs Total Costs Project Title

Karl Kirchgessner Field, Gregory Foundation $50,000 $0 $50,000 Vision Research Grant

Field, Gregory Whitehall Foundation $206,400 $18,600 $225,000 Mapping the Connectivity on the Mammalian Retina

National Institute on Deafness and other Communicative Disorders High-Resolution Mapping of Susceptibility Genes for Friedman, Rick R01 $525,618 $313,344 $838,962 NIHL Discovery of Genetic Variation influencing National Institute of Schizophrenia using next Generation DNA Knowles, James Mental Health R01 $396,000 $245,520 $641,520 sequencing

University of Wisconsin, Madison subK (National Brain Mechanisms Mediating Genetic Risk Factors for Knowles, James Institute of Mental Health) $54,483 $34,869 $89,352 Anxiety and Depression

National Institute of Knowles, James Mental Health U01 $395,238 $254,765 $650,003 The USC PsychENCODE Project National Institute of Evaluation of Cellular Heterogeneity Using Knowles, James Mental Health U01 $262,240 $164,342 $426,582 Patchclamp and RNA-Seq of Single Cells International Obsessive- Compulsive Disease Knowles, James (OCD) Foundation $43,629 $0 $43,629 Replication of Genome-Wide Association National Institute of Obsessive-Compulsive Disorder (OCD) Collaborative Knowles, James Mental Health R01 $517,920 $322,083 $840,003 Genetics Association Study National Human Genome Research Institute U01 - Robust and Portable Workflow-Based Tools for Knowles, James Satellite $71,104 $43,599 $114,703 mRNA and Genome Re-Sequencing

How structure and dynamics of monomeric CHDI Foundation huntington are modulated by post-translational Langen, Ralf (Huntington Disease) $413,803 $60,991 $474,794 modifications and polyQ length Hereditary Disease Molecular Structure of Huntington Fibrils and Langen, Ralf Foundation $50,000 $0 $50,000 Oligomers in Huntington's Disease

University of California San Francisco subK / National Multiple Initiating Myelination: A Matter of Membrane Langen, Ralf Sclerosis Society $96,767 $9,677 $106,444 Curvature Prevention of Misfolding and Membrane Batey Family Research Permeabilization in Parkinson's and Other Langen, Ralf Fund $138,312 $0 $138,312 Neurodegenerative Diseases John Douglas French Langen, Ralf Alzheimer's Foundation $42,151 $0 $42,151 Alpha-Synuclein Misfolding in Dementia

National Institute of Neurological Disorders Molecular Mechanisms of Axon Branching Synaptic Ma, Le and Stroke R01 $187,836 $117,620 $305,455 Development

American Heart Intra-arterial Magnesium Therapy in Acute Stroke: A Mack, William Association $65,679 $4,321 $70,000 Phase II Safety and Feasibility Study MRI Perfusion Permeability and Matrix Metalloproteinase-9 Levels Associated with Cerebral Brain Aneurysm Vasospasm following Aneurysmal Subarachnoid Mack, William Foundation $25,000 $0 $25,000 Hemmorhage

47 Active Awards ‐ Fiscal Year 2014

ZNI Investigator Funding Agency Direct Costs F&A Costs Total Costs Project Title

National Institute of Pato, Carlos Mental Health R01 $1,797,743 $741,011 $2,538,753 Genetic Psychiatry Cohort National Institute of Pato, Carlos Mental Health R01 $350,000 $223,708 $573,708 Genetic Psychiatry Cohort Supplement

University of Kansas subK (Tourette Syndrome Role of 5-alpha Reductase 2 and Androgens in Pato, Michele Association) $36,502 $3,650 $40,152 Tourette Syndrome

Emory University subK (National Institute of 1/2 Targeted Sequencing and Functional Evaluation Pato, Michele Mental Health) $50,000 $32,188 $82,188 of Mutations in Schizophrenia National Institute of Pato, Michele Mental Health R01 $498,474 $320,685 $819,159 Addition of OCD to the Genomic Psychiatry Cohort National Institute of Diabetes and Digestive Multiphoton Imaging of the Juxtaglomerular Peti-Peterdi, Janos and Kidney Diseases R01 $150,950 $97,772 $248,722 Apparatus American Heart Association Fellowship: Peti-Peterdi, Janos Anne Riquier-Brison $96,000 $0 $96,000 Tracking the Fate and Function of the Renin Cell Functional Characteristics of Rod Pathways in the Sampath, Alapakkam National Eye Institute R01 $78,687 $50,459 $129,146 Retina

National Institute of Neurological Disorders Sieburth, Derek and Stroke $206,872 $128,261 $335,133 Stress Regulation of Snyaptic Transmission Gerontology Satellite National Inistute on Aging Sieburth, Derek R01 $10,941 $7,025 $17,966 Oxygen Radical Toxicity and Protein Degeneration

The Function of Amyloid Proteins in Long-Term Siemer, Ansgar Whitehall Foundation $200,143 $24,857 $225,000 Memory

Zumberge Research The Structure of a Functional Amyloid in Long-Term Siemer, Ansgar Innovatiion Fund $25,000 $0 $25,000 Memory Cortical Synapic Circuitry Underlying Visual Tao, Huizhong National Eye Institute R01 $288,948 $184,926 $473,874 Processing Karl Kirchgessner Tao, Huizhong Foundation $50,000 $0 $50,000 Development of Visual Synaptic Circuitry Inhibitory Circuitry Mechanisms underlying Visual Tao, Huizhong National Eye Institute R21 $268,750 $171,750 $440,500 Cortical Development and Plasticity National Institute of Neurological Disorders and Stroke F31 Targeting Abeta phagocytosis by blocking IRAK-M Town, Terrence Fellowship: David Gate $35,832 $0 $35,832 innate immunity in Alzheimer mice National Institute on Aging An iPS Disease-in-a-Dish Model of Familial Town, Terrence R21 $26,848 $17,196 $44,044 Alzheimers

Macrophage TGF-beta-Smad 2/3 Inhibitor Therapy in Town, Terrence Alzheimer's Association $137,917 $13,791 $151,708 Transgenic Alzheimer Rats California Institute for Regenerative Medicine Role of HLA in Neural Stem Cell Rejection using Town, Terrence (CIRM) $335,073 $18,176 $353,249 Humanized Mice

48 Active Awards ‐ Fiscal Year 2014

ZNI Investigator Funding Agency Direct Costs F&A Costs Total Costs Project Title

American Federation for Re-balancing peripheral TGF-beta signaling in aged Town, Terrence Aging Research $311,423 $29,142 $340,565 Alzheimer's rats

National Institute of Neurological Disorders Peripheral TGF-beta Pathway Inhibitor Therapy in Town, Terrence and Stroke R01 $239,425 $153,408 $392,833 Alzheimer's Rats

Vanderbilt University Medical Center subK (National Human Genome Integrative Statistical Models for Pathway Analysis of Wang, Kai Research Institute) $14,182 $9,077 $23,259 GWAS Data National Human Genome Integrated variation detection annotation and analysis Wang, Kai Research Institute R01 $215,600 $138,702 $354,302 for high-throughout sequencing University of California San Diego subK (National Human Genome Accelerating Ciration of GWAS Catalog by Automatic Wang, Kai Research Institute) $5,054 $3,235 $8,289 Text Mining National Institute on Deafness and other Communicative Disorders Synaptic Circuitry Mechanisms for Auditory Cortical Zhang, Li R01 $83,397 $132,575 $215,971 Processing National Institute of Neurological Disorders Alzheimer's Abeta. Apoliproteins and Blood-Brain Zlokovic, Berislav and Stroke R01 (Javits) $412,491 $200,909 $613,400 Barrier National Institute on Aging Caloric Restriction and Alzheimers ABeta Clearance Zlokovic, Berislav Fogarty R03 $53,200 $22,414 $75,614 Pathway

Zlokovic, Berislav Cure Alzheimer's Fund $250,000 $0 $250,000 Role of PICALM in vascular clearance of amyloid- National Institute on Aging Cebrovascular Beta-Amyloidosis: A-beta CNS Zlokovic, Berislav R37 (Merit) $300,211 $192,386 $492,597 Transport Pathways

Zlokovic, Berislav Kaplan Family Foundation $25,500 $0 $25,500 Amyotrophic lateral sclerosis (ALS) Research Fund

Fidelity Biosciences Blood-Brain Barrier Pericytes: Safeguards against Zlokovic, Berislav Research Initiative (FBRI) $400,000 $0 $400,000 Amyloid-Beta Brain Degeneration National Heart, Lung, and Blood Institute (NHLBI) Zlokovic, Berislav R01 Stroke $330,297 $202,565 $532,862 Regulation of Brain Thrombosis in Stroke Models National Institute on Aging The Role of Pericytes in the Adult and the Aging Zlokovic, Berislav R01 $193,725 $124,226 $317,951 Brain

TOTAL $13,841,591 $6,269,721 $20,111,313

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50 4th Annual Zach Hall Lecture

One of ZNI’s signature events, the 4th Annual Zach Hall Lecture took place on November 19, 2013 in the Herklotz Seminar Room at ZNI. The lecture, which is named in honor of ZNI’s inaugural director Zach W. Hall PhD, is a day-long affair, featuring scientific reports, seminars, poster session as well as opportunities for graduate students and postdoctoral fellows to mix and mingle with established scientists and senior faculty and in formal and informal ways.

The afternoon began with a presentation by Hong-Wei Dong MD, PhD, Associate Professor in the Department of Neurology and ZNI faculty. His talk was entitled “Assembling the Global Cortico-Cortical Network in the Mouse Brain.” Dr Dong preceded the keynote lecture delivered by Marcus E. Raichle MD of the Washington University in St. Louis. Dr. Raichle is Professor of Radiology, Neurology, Anatomy, and Neurobiology. He is also a member of the National Academy of Sciences, the Institute of Medicine and the American Academy of the Arts & Sciences. Dr. Raichle, renowned in the field of for more than 40 years, gave a talk entitled “The Restless Brain.”

The seminars were followed by a scientific poster session featuring over 40 displays across multiple disciplines from over 25 ZNI laboratories. The range of work speaks to the depth and breadth of the types of research conducted at ZNI. The poster session always affords time for spontaneous yet valuable discussions among the students and researchers at ZNI as well as visiting members of the scientific community across the Southland.

The annual Zach Hall lecture shines an important spotlight on the latest research being done at ZNI and across the globe. Cohn

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Photo L to R: Dr. Berislav Zlokovic, Dr. Hong-Wei Dong, Dr. Zach Hall, and Dr. Marcus Raichle

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Photo Top L to R: Hong-Wei Dong, Bart De Strooper, Helena Chiu, Tony Wyss-Coray, Art Toga, Sangram Sisodia, Terrence Town, Lennart Mucke, Christian Haass, Paul Thompson, Costantino Iadecola. Bottom, L to R: Scott Fraser, Rudy Tanzi, Maiken Nedergaard, Berislav Zlokovic, Maria Carrillo, Roderick Corriveau, David Holtzman

1st Annual Zilkha Symposium on Alzheimer Disease & Related Disorders

More than a dozen researchers and policymakers from across the globe gathered at the Zilkha Neurogenetic Institute (ZNI) on 4 April 2014, to participate in the 1st Annual Zilkha Symposium on Alzheimer Disease & Related Disorders entitled “Breaking through the Barriers: Neuronal, Glial and Vascular Contributions.” The international conference was organized by ZNI Director Berislav V. Zlokovic, who holds the Mary Hayley & Selim Zilkha Chair in Alzheimer’s Disease Research at the Keck School of Medicine of USC, along with Rudolph Tanzi, Joseph P. & Rose F. Kennedy Professor of Neurology at Harvard University and David M. Holtzman, Andrew B. & Gretchen P. Jones Professor and Chair of Neurology at Washington University in St. Louis. The all-day symposium featured presentations of mostly unpublished work, experiments still underway that are approaching Alzheimer Disease (AD) from multiple directions. Investigators shared data about the varied roles of different influences on AD: genetic, vascular, inflammation, astrocytes, neurons and ending with new and innovative methods for mapping changes in the brain, using advanced imaging technology employed by Arthur Toga, Paul Thompson and Hong-Wei Dong at the Keck School of Medicine of USC.

52 L to R: Dr. Tony Wyss- Coray, Dr. Rudy Tanzi, and Dr. Helena Chui in between talks at the 1st Annual Zilkha Symposium on Alzheimer Cohn Disease & Related Disorders Steve

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USC Executive Vice Provost Michael Quick offered introductory remarks for the symposium, followed by ZNI friend and benefactor, Selim Zilkha, who provided a reminder to all attendees of the importance of continued scientific collaboration to “arrest and reverse this terrible disease”. Following Mr Zilkha’s remarks, Maria Carrillo, Vice President of Medical & Scientific Relations at the Alzheimer’s Association, announced that Mr Zilkha and Mary Hayley would be honored in July with the 2014 Jerome H. Stone Philanthropy Award for Alzheimer’s Research, an international award honoring the world’s leading philanthropists and their transformational impact on the global Alzheimer’s research field. The award was presented in July, at the Alzheimer’s Association International Conference in Copenhagen, Denmark. Maria Carrillo chaired several sessions at the Zilkha Symposium, along with Roderick Corriveau, Program Director of Extramural Research Programs at the National Institute for Neurological Disorders & Stroke, NIH and Helena Chui, McCarron Professor & Chair of Neurology and Director of the Alzheimer’s Disease Research Center at USC.

Gabrielle Strobel, Executive Editor of the alzforum.org website—a web-based scientific community dedicated to furthering the research and understanding of Alzheimer Disease and related neurodegenerative disorders—attended the Zilkha Symposium and summarized the cutting-edge developments presented at the event in a comprehensive four-part series published on the site: Part I, the relationship between hypertension and Alzheimer Disease and dementia; Part II, the importance of studying the blood brain barrier (BBB) in Alzheimer research; Part III, the controversial method of research via parabiosis (blood-sharing experiments); and Part IV, the indirect way in which sleep and gene regulation affects neurodegeneration. To view the entire series go to http://www.alzforum.org > News > Conference Coverage.

A short video about the conference is available at http://tinyurl.com/AAIC2014ZNI.

Dr. Christian Haass gives his talk to an engaged audience. Cohn

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Special Lectures

53 Academic Activities

Every year, ZNI offers a multitude of academic activities that range from our regular seminar series to more interactive student-led Journal Clubs. We pride ourselves in inviting some of the best minds in the field to come and share their expertise and latest findings through our seminar series. Additionally, we encourage in-house collaboration and cooperation through more intimate affairs like the Neurodegeneration Journal Club, led by Brian Leung, a graduate student in Dr. Terrence Town’s Lab. Some of the offerings from FY14 are below.

ZNI Seminar Series

July 2013 “Co-evolution of Breast to Brain Metastasis and Neural Progenitor Cells” Josh Neman PhD, Beckman Research Institute, CalTech / City of Hope Cancer Center

August 2013 “The Trials and Tribulations of the Spiny Mouse: A Non-Model Species for Perinatal Research” Hayley Dickinson PhD, Monash University

September 2013 “SERT Gene Variants: A Complex Case for Involvement in Mood Disorders and Their Treatment” Anne Andrews PhD, UCLA

“Developmental Patterning of the Inner Ear” Takahiro Ohyama PhD, ZNI

October 2013 “The Organization of Sensory Signals in the Inner Ear” Radha Kalluri PhD, ZNI

“The Molecular Basis of Long Lasting Memory” Kausik Si PhD, Stowers Institute/ University of Kansas

“EPAC Signaling Links miR-129 Expression in Regulation of Learning and Social Behaviors” Youming Lu MD, PhD, Louisiana State Univ/ Huazhong Univ of Sciences and Technology

December 2013 “Membrane Protein Trafficking in Photoreceptors” Wolfgang Baehr PhD, University of Utah

54 January 2014 “Mitochondrial Peptides and their Roles in Alzheimer’s and Other Diseases of Aging” Dean Pinchas Cohen MD, USC, Davis School of Gerontology

“Brain-State Dependent Membrane Potential Dynamics in Visual Cortex” Peyman Golshani MD, PhD, UCLA

February 2014 “Personal Genomes & Clan Genomics” James Lupski MD, PhD, Baylor College

“Visible Brain-wide Networks at Single-Neuron Resolution with Micro-Optical Sectioning Tomography” Qingming Luo PhD, Britton Chance Center/ Huazhong University of Sciences & Technology

March 2014 “Age-Related and Noise-Induced Hearing Loss: Complex Traits” Rick Friedman MD, PhD, ZNI

“Behind the Scenes at Nature: Insights into Science Publishing” Magdalena Skipper PhD, Nature

“Synaptic and Circuitry Mechanisms of Psychiatric Disorders” Guoping Feng PhD, MIT

“Retinal Output Channels: Distinct Networks for Synching the Clock and Stabilizing the Visual World” David Berson PhD, Brown University

April 2014 “Capillary Dysfunction in Alzheimer’s Disease and Stroke” Leif Ostergaard MD, PhD, Aarhus University

“Mechanics of Bacterial Cell Membranes” Christoph Haselwandter PhD, USC

May 2014 “The Machinery of Neuronal Exocytosis – Molecular Mechanisms and Disease Implications” Jingshi Shen PhD, University of Colorado at Boulder

“Cortical Circuits for Vision” Massimo Scanziani PhD, UC San Diego

June 2014 “In Vivo Optogenetic Manipulation of Cells within the Neurovascular Unit Leads to Local Changes in Neural Activity” Tyler Brown PhD, Brown University

“Network Coding of Fear and Extinction in Mouse Frontal Cortex” Joshua Trachtenberg PhD, UCLA

55 Neurodegeneration Journal Club

January 2014

“Amyloid-β signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer’s disease” M.E. Seward et al, Cell 2013

“Neuroprotection through Excitability and mTOR Required in ALS Motoneurons to Delay Disease and Extend Survival” S. Saxena et al, Neuron 2013

February 2014

“Identification of novel modifiers of Ab toxicity by transcriptomic analysis in the fruitfly” G. Favrin et al, Scientific Reports 2013

March 2014

“Regional Neuronal Network Failure and Cognition in Late-Onset Sporadic Alzheimer Disease” S.F. Carter et al, American Journal of Neuroradiology 2014

NRSA Grant Training

In conjunction with the USC Program in Neuroscience, ZNI hosted workshops for graduate students who might be interested in submitting proposals under the National Institute of Health (NIH)’s Ruth L Kirchstein National Research Service Awards (NRSA). The NRSA program is a family of grants provided by the NIH for training researchers in the behavioral sciences and health sciences. They are a highly selective and very prestigious source of funding for doctoral and postdoctoral trainees and notably difficult to obtain. Only applications with very good impact scores are funded, based on budget cutoffs determined by each individual NIH institute.

The two-day workshops, held once each semester, are team-taught at ZNI by M Carter Cornwall MD PhD, Professor of Physiology & Biophysics at the University of Utah; and ZNI faculty members Alapakkam Sampath PhD, Associate Professor of Physiology & Biophysics and Jeannie Chen PhD, Professor of Cell & Neurobiology. The workshops cover tips and tricks, sample successful applications, writing critiques but also have students submit their draft applications for an in-depth and critical review. Individuals who avail themselves to this opportunity dramatically increase their success rate when submitting final NRSA grant applications.

Academic Activities

56 Los Angeles Brain Bee 2014

After ZNI hosted this event with UCLA and Los Angeles City College (LACC) the year prior at USC, the 2014 LA Brain Bee was held at the Brain Research Institute at UCLA.

Organized by Drs Chris Evans (UCLA) and Amy Sweetman (LACC) with significant contributions by the Interaxon groups at UCLA and USC, the day was a great success. Over 80 high school students from scores of LA area high schools competed for the top prizes.

The event was enhanced by the assistance of undergraduate and graduate volunteers from USC and UCLA. With their help, in addition to the written and oral competitions, students participated in a scavenger hunt looking through dozens of poster displays for key facts about neuroscience, research, and career information. A guest lecture “Everyday Neuroscience: Migration and the American Dream” was given by Dr Peter Whybrown, Professor & Executive Chair of the Department of Psychiatry at UCLA. The day closed with three rounds of a “Jeopardy” style competition resulting in the winners participating in a trophy ceremony.

“It was great to see the many different avenues I can take in terms of my educational future. I’m definitely going to be a neuro-something!”

–Shyam Chandrasekar 1st place winner of LA Brain Bee

When all the results were tallied, the winner was Shyam Chandrasekar a junior from Tustin District High School. Shyam went on to place 12th in the National Brain Bee held later in 2014 in Baltimore, Maryland.

ZNI is pleased to be a part of this terrific event that engages with the community to provide scientific awareness and education for bright young minds across Southern California. We look forward to the 2015 event, tentatively scheduled to be held at University of California, Irvine.

57 Residents of an assisted care facility in east Los Angeles sing along with LA Opera.

Music to Remember

A joint program offered by LA Opera, the Alzheimer’s Association, California Southland Chapter, the Zilkha Neurogenetic Institute (ZNI) and Alzheimer Disease Research Center (ADRC) at the Keck School of Medicine of USC

Whether it is a couple’s favorite melody (“our song”), an aria from a famous opera, a lullaby, a hymn or a holiday carol, music evokes . Music stirs the soul, but also involves the brain, in ways neuroscientists are still exploring: Listening to music involves the auditory pathways, auditory cortex and sensory association cortex. Registering emotion likely involves the amygdala. Memory is accessed via the hippocampus. The connections among these regions help guide and process a complicated set of actions within the brain.

This past year, the Zilkha Neurogenetic Institute formed a unique partnership with the Alzheimer’s Association, California Southland Chapter and LA Opera, to bring music—and perhaps memories—to people who need it most, those experiencing various stages of dementia. A pilot project brought young singers from LA Opera to perform for residents (and workers) in long-term care and assisted living facilities throughout Los Angeles.

This pilot program was made possible by research funds from the ZNI, as well as the generosity of Alzheimer’s Association, California Southland Chapter and LA Opera. As an added benefit, the performers went caroling on the Health Science Campus, surprising workers and visitors at the Keck School of Medicine of USC. We received such positive feedback from the community that we will continue this program again in 2014.

Young singers from LA Opera serenade workers outside the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC.

58 ZNI Graduate Students

The robust graduate student population at ZNI comes from a variety of USC programs and departments: Neuroscience, Preventive Medicine, Biostatistics and Physiology & Biophysics, and PIBBS (Programs in Biomedical and Biological Sciences) , which includes degrees in Cancer Biology & Genomics; Development, Stem Cells & Regenerative Medicine; Medical Biology; and Molecular Structure & Signaling). Each graduate student works with a ZNI faculty mentor for up to 5 years. Below is a current list of students at ZNI and their projects.

Nick Goeden (Alexandre Bonnin): Placental Tryptophan Metabolic Dysfunction: A Potential Pathway for the Developmental Programming of Mental Disorders

Juan Velasquez (Alexandre Bonnin): “Effects of Maternal Depression and Antidepressant Treatments on Fetal Neurodevelopment

Jessica DeWitt (Daniel Campbell): Neurobiological Impact of Non-Coding RNAs with Genome-wide Significant Association with Autism

Brent Wilkinson (Daniel Campbell): Neurobiological Impact of Rare Loss-of-function Mutations Associated with Autism

Jillian Shaw (Karen Chang): A Role for Nebula/DSCR1 in Ameliorating Axonal Transport Defects Associated with Alzheimer’s Disease

Joo Yeun Lee (Karen Chang): A Novel DnaJ Domain Protein Regulates Synaptic Development and Maintains Stem Cell Niche in Drosophilia

Syed Qadri (Karen Chang): Regulation of Synaptic Vesicle Endocytosis by the Minibrain Kinase

Kasey Rose (Jeannie Chen): Live Cell Imaging of Retinal Photoreceptors

Jung Hwa Cho: (Robert Chow): Calcium Sensitivity of Large-dense Core Vesicle Exocytosis in Complexin 2 Knock-out Mouse Chromaffin Cells

Jason Lou (Robert Chow): Improving Performance of Argus II Retinal Prosthesis

Steven Walston (Robert Chow): Improving Performance of Argus II Retinal Prosthesis

Victoria Wolseley (Robert Chow): Photovoltaic Nanoswitches for Remote Optical Control of Neurons

Lan Yue (Robert Chow): Photovoltaic Nanoswitches for Remote Optical Control of Neurons

Madison Zitting(Robert Chow): Calcium Sensitivity of Large-dense Core Vesicle Exocytosis in Complexin 2 Knock-out Mouse Chromaffin Cells

Muye Zhou (Hong-Wei Dong): Mouse Connectome Project

59 Sneha Ravi (Greg Field): Mapping the Complete Neural Output of the Mouse Retina

Xiaoyang Yao (Greg Field): Light Adaptation Across Parallel Pathways in the Mouse Retina

Tingrui Wang (Rick Friedman): Fhod3 Transgenic and Knockout Mouse Model Construction

Anthony Myint (Rick Friedman): GWAS for Vestibular Variation in Mice

Christopher Ventura (Radha Kalluri): The role of Hyperpolarization-activated Inward Currents in Shaping Neuronal Function in the Vestibular Nerve

Emily Chen (James Knowles): Investigating Major Depressive Disorder by Next-Generation Sequencing and Differential Gene Expression in Brains of Suicide Completers

JaeMun Hugo Kim (James Knowles): Single Cell RNA Sequencing

Edder Lopez (James Knowles): Differentiation of Neural Progenitors in 2D and 3D Cultures

Chris Armoskus (James Knowles/Kai Wang): Statistical Analysis of Genetic Variation Predisposing to Schizophrenia

Mark Ambroso (Ralf Langen): Curvature Driven Myelination by Myelin Basic Protein

Alan Okada (Ralf Langen): Understanding and Preventing Misfolding in Neurodegeneration and Diabetes

Natalie Kegulian (Ralf Langen): Identifying Toxic Conformations in Huntingtin

Trisha Staab (Derek Sieburth): Regulation of Neuronal Function by the Conserved SKN-1/Nrf Stress Response Pathway in

Han Wang (Derek Sieburth): Regulation of Rhythmic Behaviors in Neuropeptide Signaling

Ninad Agashe (Ansgar Siemer): Oligomer Formation of the Functional Amyloid Orb2A

Silvia Cervantes (Ansgar Siemer): Structural Characterization of Orb2A by EPR

Sandy Falk (Ansgar Siemer): Interaction of Orb2 Isoforms A and B”

Maria Conrad (Ansgar Siemer): Oligomer Formation and Membrane Interaction of Orb2A

Brian Zingg (Huizhong Tao): Using Optogenetics to Dissect a Circuit for Innate Defense Behavior

Xiaolin Chou (Huizhong Tao : Development of the Thalacortical Receptive Fields in Mice

Leena Ibrahim Marosh (Huizhong Tao): Cross Model Modulation in the Primary Visual Cortex

Lingyun Li (Huizhong Tao): A Feedforward Inhibitory Circuit Mediates Lateral Refinement of Auditory Cortical Processing

Brian Leung (Terrence Town): TREM2/DAP12 Cerebral Innate Immune Signaling in Vertebrates and Invertebrates and A Disease in a Dish Model: An iPS Model for Familial Alzheimer’s Disease

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David Gate (Terrence Town): Targeting Abeta Phagocytosis by Blocking IRAK-M Innate Immunity in Alzheimer Mice

Thomas Schmidt (Tobias Ulmer): Dual Effects of Transmembrane Proline Residues on Integrin Activity

ChengLiang Dong (Kai Wang): Comparison of Functional Prediction Methods for Non Synonymous SNPs in Exome Sequencing Studies of Human Disease

Yunfei Guo (Kai Wang): “Enlight: A Web-based Tool to Integrate GWAS Results with Biological Annotations & SeqMule: An Automated Pipeline for Whole Genome/Exome Analysis on Mendelian Diseases”

Hui Yang (Kai Wang): Phenotype-based Detection of Causal SNPs and CNVs from Next-generation Sequencing Data

Chao Ling (Kai Wang): Genome-Scale Profiling of DNA Methylation in Sporadic Pituitary Macroadenomas

Haiying Jia (Kai Wang): Technical Evaluation of Long-range PCR in Next-generation Sequencing

Young Joo Kim (Li Zhang): Molecular Mechanisms for the Development of Auditory Cochlear Innervation Pattern

Yatang Li (Li Zhang): Synaptic Mechanisms Underlying Contrast-Dependent Sharpening of Orientation Selectivity in Mouse Visual Cortex

Lukas Mesik (Li Zhang): Functional Characterization of Inhibitory Interneurons During Development

Xiaorui Ray Xiong (Li Zhang): Differential Gain Control and Synaptic Scaling Underlies Binaural Computation

Mu Zhou (Li Zhang): Generation of Intensity Selectivity in the Central Auditory Pathway

Pan Kong (Berislav Zlokovic): Glut1 and Picalm

Anita Ramanathan (Berislav Zlokovic): The Role of Pericytes in Cerebral and Vascular Metabolism

Melanie Sweeney (Berislav Zlokovic): APOE ε4 Allele Modulates Risk for CSF Biomarkers of Neurovascular Injury in Alzheimer’s Disease

Divna Lazic (Berislav Zlokovic): Understanding the role of Mfsd2a transporter in blood-brain barrier dysfunction in Alzheimer’s disease

ZNI Graduate Students

61 ZNI Postdoctoral Trainees

Industrious members of any laboratory, postdoctoral trainees continue their training and education by conducting their own experiment under the guidance of an established faculty member. Working on multiple projects provides key support for the faculty member while establishing the postdoctoral research scientist’s interests. Listed below are ZNI’s postdoctoral trainees and the titles of their research projects.

Jennifer King (Alexandre Bonnin): Investigation of a New Cellular Communication Mechanism Between the Placenta and the Fetal Brain

Yen Chan (Alexandre Bonnin): Maternal Infection Effects on Fetal Brain Development

Tian Wang (Jeannie Chen): Phototransreduction in Dark Adaptation and Retinal Degeneration

Reymundo Dominguez (Robert Chow): Single-cell Analysis

Nan Lee (Robert Chow): Invasion Potential of Cancer Cells

Ming-Yi Sonya Lin (Robert Chow): Single-Cell Analysis” and “Photovoltaic Nanoswitches for Remote Optical Control of Neurons”

Andrew Weitz (Robert Chow): Imaging Platform for Determining Tumor Invasiveness

Jing Li (Marcelo Coba): Synaptic Signaling Networks

Zhu Chen (David Conti): Using Quantile Regression for Pathway Analysis in Genome- wide Studies

Lilit Chemenyan (David Conti): “Bayesian Model Selection for Functional Integration in Genetic Association Studies”

Nicholas Foster (Hong-Wei Dong): Mouse Brain Connectome Mapping of Cortical and Striatal Long-distance Axon Projection Deficits in Huntington’s Disease Mouse Models

Michael Bienkowski (Hong-Wei Dong): The Mouse Connectome Project

Juemei Wang (Rick Friedman): GWAS for Noise-induced Hearing Loss in Mice

Pezhman Salehi Dermanaki (Rick Friedman): Novel genes Involved in Age-related and Noise-induced Hearing Loss in Mice

Joel Lavinsky (Rick Friedman): Nox3 and Noise-induced Hearing Loss and a GWAS for Vestibular Variation in Mice

Qingzhong Li (Rick Friedman): Fhod3, A Novel Candidate for Age-related Hearing Loss in Mice

62 Jose Mario Isas (Ralf Langen): Structural Studies of Huntingtin Misfolding

Toru Miwa (Takahiro Ohyama): Molecular Analysis of Developmental Mechanisms of Developing Mouse Inner Ear

Charlotte Buckley (Janos Peti-Peterdi): Interactions between the Renin Cell and the Macula Densa

Anne Riquier-Brison (Janos Peti-Peterdi): The Role of the GPR91/Succinate Pathway in Renovascular Hypertension

Kengo Kidokoro (Janos Peti-Peterdi): Tracking Podocyte Fate in Nephrotic Syndrome

James Burford (Janos Peti-Peterdi): The Role of Podocyte Calcium in Glomerular Diseases

Federica Barutta (Janos Peti-Peterdi): Tunneling Nanotubules in the Glomerulus

Rachel Service (Ansgar Siemer): Structural Characterization of Functional and Disease-related Amyloid

Kevin Doty (Terrence Town): Using Genome Wide Approaches to Identify and Modulate Beneficial Neuroinflammation in Alzheimer’s Disease

Tara Weitz (Terrence Town): TGF-beta Inhibitor Therapy in a Transgenic Rat Model of Alzheimer’s Disease

Marie-Victoire Guillot-Sestier (Terrence Town): Implication of the Anti-Inflammatory Cytokine Interleukin-10 in Inntate Immune Response to Amyloidogenesis in Alzheimer’s Disease

Rodrigo Lopez Leal (Terrence Town): An iPS Disease-in-a-Dish Model of Familial Alzheimer’s and Generation of a Conditional Rat Model for Genetic Ablation of Neural Stem Cell

JiHong Kim (Kai Wang): Comparative Analysis of Multiple RNA-Seq Quantification Tools & Development of Fully Automated RNA-Seq Analysis Pipelines

Kassandra Kisler Elliott (Berislav Zlokovic): Pericyte Regulation of Neurovascular Coupling and Local Brain Oxygen Supply

Axel Montagne (Berislav Zlokovic): Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging to Evaluate Blood-Brain Barrier Integrity in Alzheimer’s Disease and Related Disorders

Amy Nelson (Berislav Zlokovic): The Role of Pericytes in Hippocampal Function

Yaoming Wang (Berislav Zlokovic): Regulation of Brain Thrombosis in Stroke Models

Gil Carvalho (Berislav Zlokovic): Cellular Basis of Feelings and Sentience

63 One of the most common ways for scientists to formally share their research is to publish an article in a scientific journal focused on a particular area of study. A typical scholarly, scientific journal article is peer-reviewed, discusses the authors’ original research, offers thoughtful analy- sis of the results, and cites relevant papers from other authors that relate to the research. Scien- tists (and editors of these publications) rely on their colleagues, the reviewers, to ensure a critical review of the science is conducted, with all aspects of the approach and techniques described, so that conclusions reached are empirically sound. This process, which takes place as discoveries are made, takes many months of back-and-forth responses between authors and editors and in rare cases, can exceed a year’s time.

A journal’s impact factor is a measure of the frequency with which the average article in a journal has been cited in a particular year. The impact factor is calculated by dividing the number of citations in the current year to articles published in the two previous years by the total number of articles published in the two previous years. While the expectation is that all peer-reviewed publications move science forward, in some areas of study coverage is not as widespread and thus the impact factor of a journal in a highly specialized field will not necessarily have the same impact factor as the broader journals like Science and Nature. How many papers an institution has in high-impact journals is just one of several measures of productivity.

Last year, ZNI faculty published 148 papers, and 17.5% of these were in high impact journals, which represents a 3.5% increase over the prior year. Congratulations to all the ZNI scientists who had their work published in FY14.

FY14 Faculty Publications

64 Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang YY, Lee H, Srinivas P, Gao XB, Suyama S, Langer T, Mann JJ, Horvath TL, Bonnin A, Karsenty G. Maternal and offspring pools of osteocalcin influence brain development and functions. Cell. 2013 Sep 26;155(1):228-41. doi: 10.1016/j.cell.2013.08.042.

Goeden N and Bonnin A. (2013) Ex vivo perfusion of the mouse placenta for maternal-fetal interaction studies during pregnancy; in: The guide for investigation of mouse pregnancy (Croy, Yamada, DeMayo and Adamson, Eds.), Academic Press / Elsevier, pp 661-671.

Volk HE, Kerin T, Lurmann F, Hertz-Picciotto I, McConnell R, Campbell DB. Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene. Epidemiology. 2014 Jan;25(1):44-7.

Abrahams BS, Arking DE, Campbell DB, Mefford HC, Morrow EM, Weiss LA, Menashe I, Wadkins T, Banerjee-Basu S, Packer A. SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs). Mol Autism. 2013 Oct 3;4(1):36. doi: 10.1186/2040-2392-4-36.

Wilkinson, B. and Campbell, D.B. Contribution of long noncoding RNAs (lncRNAs) to autism spectrum disorder risk. International Review of Neurobiology. 113: 35-59. 2013.

DeWitt, J. and Campbell, D.B. Targeting noncoding RNA for treatment of autism spectrum disorders. In: Frontiers in Autism Research, Diagnosis and Treatment. (Editor: Hu) 2014. Cohn

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65 Chen, CK Bregere C, Paluch J, Lu JF, Dickman DK, Chang KT. Activity-dependent facilitation of Synaptojanin and synaptic vesicle recycling by the Minibrain kinase.. Nat Commun. 2014 Jun 30;5:4246

Shaw JL, Chang KT. Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling. PLoS Genet. 2013;9(9):e1003792. doi: 10.1371/journal.pgen.1003792. Epub 2013 Sep 26.

Chang KT, Ro H, Wang W, Min KT. Meeting at the crossroads: common mechanisms in Fragile X and Down syndrome. Trends Neurosci. 2013 Dec;36(12):685-94. doi: 10.1016/j.tins.2013.08.007. Epub 2013 Sep 25. Review.

Niescier RF, Chang KT, Min KT. Miro, MCU, and calcium: bridging our understanding of mitochondrial movement in axons. Front Cell Neurosci. 2013 Sep 10;7:148. doi: 10.3389/fncel.2013.00148. Review.

Chen J. The physiological roles of arrestin-1 in rod photoreceptor cells. Handb Exp Pharmacol. 2014;219:85-99. doi: 10.1007/978-3-642-41199-1_4.

Song X, Seo J, Baameur F, Vishnivetskiy SA, Chen Q, Kook S, Kim M, Brooks EK, Altenbach C, Hong Y, Hanson SM, Palazzo MC, Chen J, Hubbell WL, Gurevich EV, Gurevich VV. Rapid degeneration of rod photoreceptors expressing self-association-deficient arrestin-1 mutant. Cell Signal. 2013 Dec;25(12):2613-24. doi: 10.1016/j.cellsig.2013.08.022. Epub 2013 Sep 3.

Weitz AC, Behrend MR, Ahuja AK, Christopher P, Wei J, Wuyyuru V, Patel U, Greenberg RJ, Humayun MS, Chow RH, Weiland JD. Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses. J Neural Eng. 2014 Feb;11(1):016007.

Bortolato M, Godar SC, Tambaro S, Li FG, Devoto P, Coba MP, Chen K, Shih JC. Early postnatal inhibition of serotonin synthesis results in long-term reductions of perseverative behaviors, but not aggression, in MAO A-deficient mice. Neuropharmacology. 2013 Dec;75:223-32. doi: 10.1016/j.neuropharm.2013.07.003. Epub 2013 Jul 16.

Y. Feng, D. O. Stram, S. K. Rhie, R. C. Millikan, C. B. Ambrosone, E. M. John, L. Bernstein, W. Zheng, A. F. Olshan, J. J. Hu, R. G. Ziegler, S. Nyante, E. V. Bandera, S. A. Ingles, M. F. Press, S. L. Deming, J. L. Rodriguez-Gil, J. R. Palmer, O. I. Olopade, D. Huo, C. A. Adebamowo, T. Ogundiran, G. K. Chen, A. Stram, K. Park, K. A. Rand, S. J. Chanock, L. Le Marchand, L. N. Kolonel, D. V. Conti, D. Easton, B. E. Henderson, and C. A. Haiman, “A comprehensive examination of breast cancer risk loci in African American women.,” Hum Mol Gen, p. ddu252, May 2014.

T. H. T. Cheng, M. Gorman, L. Martin, E. Barclay, G. Casey, P. A. Newcomb, D. V. Conti, F. Schumacher, S. Gallinger, N. M. Lindor, J. Hopper, M. Jenkins, D. J. Hunter, P. Kraft, K. B. Jacobs, D. G. Cox, M. Yeager, S. E. Hankinson, S. Wacholder, Z. Wang, R. Welch, A. Hutchinson, J. Wang, K. Yu, N. Chatterjee, N. Orr, W. C. Willett, G. A. Colditz, R. G. Ziegler, C. D. Berg, S. S. Buys, C. A. McCarty, H. S. Feigelson, E. E. Calle, M. J. Thun, R. B. Hayes, M. Tucker, D. S. Gerhard, J. F. Fraumeni, R. N. Hoover, G. Thomas, S. J. Chanock, J. Ciampa, J. Gonzalez-Bosquet, S. Berndt, L. Amundadottir, W. R. Diver, D. Albanes, J. Virtamo, S. Weinstein, F. R. Schumacher, G. Cancel-Tassin, O. Cussenot, A. Valeri, G. L. Andriole, E. D. Crawford, C. A. Haiman, B. Henderson, L. Kolonel, L. L. Marchand, A. Siddiq, E. Riboli, T. J. Key, R. Kaaks, W. Isaacs, S. Isaacs, K. E. Wiley, H. Gronberg, F. Wiklund, P. Stattin, J. Xu, S. L. Zheng, J. Sun, L. J. Vatten, K. Hveem, M. Kumle, M. Tucker, D. S. Gerhard, M. P. Purdue, M. Johansson, D. Zelenika, J. R. Toro, G. Scelo, L. E. Moore, E. Prokhortchouk, X. Wu, L. A. Kiemeney, V. Gaborieau, W.-H. Chow, D. Zaridze, V. Matveev, J. Lubinski, J. Trubicka, N. Szeszenia-Dabrowska, J. Lissowska, P. Rudnai, E. Fabianova, A. Bucur, V. Bencko, L. Foretova, V. Janout, P. Boffetta, J. S. Colt, F. G. Davis, K. L. Schwartz, R. E. Banks, P. J. Selby, P. Harnden, A. W. Hsing, R. L. Grubb III, H. Boeing, P. Vineis, F. Clavel-Chapelon, D. Palli, R. Tumino, V. Krogh, S. Panico, E. J. Duell, J. R. Quirós, M.-J. Sanchez, C. Navarro, E. Ardanaz, M. Dorronsoro, K.-T. Khaw, N. E. Allen, H. B. Bueno-de-Mesquita, P. H. M. Peeters, D. Trichopoulos, J. Linseisen, B. Ljungberg, K. Overvad, A. Tjonneland, I. Romieu, A. Mukeria, O. Shangina, V. L. Stevens, S. M. Gapstur, P. D. Pharoah, D. F. Easton, S. J. Weinstein, L. Vatten, I. Njølstad, G. S. Tell, C. Stoltenberg, R. Kumar, K. Koppova, S. Benhamou, E. Oosterwijk, S. H. Vermeulen, K. K. H. Aben, S. L. van der Marel, Y. Ye, C. G. Wood, X. Pu, A. M. Mazur, E. S. Boulygina, N. N. Chekanov, M. Foglio, D. Lechner, I. Gut, S. Heath, H. Blanche, K. G. Skryabin, J. D. McKay, N. Rothman, M. Lathrop, P. Brennan, B. Saunders, H. Thomas, S. Clark, and I. Tomlinson, “Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP,” Eur J Hum Genet, May 2014.

66 FY14 Faculty Publications

J. D. Figueroa, S. S. Han, M. Garcia-Closas, D. Baris, E. J. Jacobs, M. Kogevinas, M. Schwenn, N. Malats, A. Johnson, M. P. Purdue, N. Caporaso, M. T. Landi, L. Prokunina-Olsson, Z. Wang, A. Hutchinson, L. Burdette, W. Wheeler, P. Vineis, A. Siddiq, V. K. Cortessis, C. Kooperberg, O. Cussenot, S. Benhamou, J. Prescott, S. Porru, H. B. Bueno-de-Mesquita, D. Trichopoulos, B. Ljungberg, F. Clavel-Chapelon, E. Weiderpass, V. Krogh, M. Dorronsoro, R. Travis, A. Tjonneland, P. Brenan, J. Chang-Claude, E. Riboli, D. Conti, M. Gago-Dominguez, M. C. Stern, M. C. Pike, D. Van Den Berg, J.-M. Yuan, C. Hohensee, R. Rodabough, G. Cancel-Tassin, M. Roupret, E. Comperat, C. Chen, I. De Vivo, E. Giovannucci, D. J. Hunter, P. Kraft, S. Lindstrom, A. Carta, S. Pavanello, C. Arici, G. Mastrangelo, M. R. Karagas, A. Schned, K. R. Armenti, G. M. M. Hosain, C. A. Haiman, J. F. Fraumeni, S. J. Chanock, N. Chatterjee, N. Rothman, and D. T. Silverman, “Genome-wide interaction study of smoking and bladder cancer risk.,” Carcinogenesis, p. bgu064, May 2014.

A. M. Leventhal, W. Lee, A. W. Bergen, G. E. Swan, R. F. Tyndale, C. Lerman, and D. V. Conti, “Nicotine dependence as a moderator of genetic influences on smoking cessation treatment outcome.,” Drug Alcohol Depend, vol. 138, pp. 109–117, May 2014.

Cheng, J. M. Kocarnik, L. Dumitrescu, N. M. Lindor, Chang-Claude J, C. L. Avery, C. P. Caberto, S. A. Love, M. L. Slattery, A. T. Chan, J. A. Baron, L. A. Hindorff, S. L. Park, F. R. Schumacher, M. Hoffmeister, P. Kraft, A. M. Butler, D. J. Duggan, L. Hou, C. S. Carlson, K. R. Monroe, Y. Lin, C. L. Carty, S. Mann, J. Ma, E. L. Giovannucci, C. S. Fuchs, P. A. Newcomb, M. A. Jenkins, J. L. Hopper, R. W. Haile, D. V. Conti, P. T. Campbell, J. D. Potter, B. J. Caan, R. E. Schoen, R. B. Hayes, S. J. Chanock, S. I. Berndt, S. Kury, S. Bezieau, J. L. Ambite, G. Kumaraguruparan, D. M. Richardson, R. J. Goodloe, H. H. Dilks, P. Baker, B. W. Zanke, M. Lemire, S. Gallinger, L. Hsu, S. Jiao, T. A. Harrison, D. Seminara, C. A. Haiman, C. Kooperberg, L. R. Wilkens, C. M. Hutter, E. White, D. C. Crawford, G. Heiss, T. J. Hudson, H. Brenner, W. S. Bush, G. Casey, L. Le Marchand, and U. Peters, “Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.,” Gut, vol. 63, no. 5, pp. 800–807, May 2014.

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(2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature genetics 45, 984-994, PMID:23933821.

Hartz, S.M., Pato, C.N., Medeiros, H., Cavazos-Rehg, P., Sobell, J.L., Knowles, J.A., Bierut, L.J., Pato, M.T., for the Genomic Psychiatry Cohort, C., Abbott, C., Azevedo, M.H., Belliveau, R., Bevilacqua, E., Bromet, E.J., Buckley, P.F., Dewan, M.J., Escamilla, M.A., Fanous, A.H., Fochtmann, L.J., Kinkead, R., Kotov, R., Lehrer, D.S., Macciardi, F., Malaspina, D., Marder, S.R., McCarroll, S.A., Moran, J., Morley, C.P., Nicolini, H., Perkins, D.O., Potkin, S.G., Purcell, S.M., Rakofsky, J.J., Rapaport, M.H., Scolnick, E.M., Sklar, B., Sklar, P., Smoller, J.W., Sullivan, P.F., and Vivar, A. (2014). Comorbidity of Severe Psychotic Disorders With Measures of Substance Use. JAMA psychiatry, PMID:24382686.

Guffanti, G., Torri, F., Rasmussen, J., Clark, A.P., Lakatos, A., Turner, J.A., Fallon, J.H., Saykin, A.J., Weiner, M., Initiative, A.t.A.s.D.N., Vawter, M.P., Knowles, J.A., Potkin, S.G., and Macciardi, F. (2013). Increased CNV-region deletions in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) subjects in the ADNI sample. Genomics 102, 112-122, PMID:23583670.

71 Davis, L.K., Yu, D., Keenan, C.L., Gamazon, E.R., Konkashbaev, A.I., Derks, E.M., Neale, B.M., Yang, J., Lee, S.H., Evans, P., Barr, C.L., Bellodi, L., Benarroch, F., Berrio, G.B., Bienvenu, O.J., Bloch, M.H., Blom, R.M., Bruun, R.D., Budman, C.L., Camarena, B., Campbell, D., Cappi, C., Cardona Silgado, J.C., Cath, D.C., Cavallini, M.C., Chavira, D.A., Chouinard, S., Conti, D.V., Cook, E.H., Coric, V., Cullen, B.A., Deforce, D., Delorme, R., Dion, Y., Edlund, C.K., Egberts, K., Falkai, P., Fernandez, T.V., Gallagher, P.J., Garrido, H., Geller, D., Girard, S.L., Grabe, H.J., Grados, M.A., Greenberg, B.D., Gross-Tsur, V., Haddad, S., Heiman, G.A., Hemmings, S.M., Hounie, A.G., Illmann, C., Jankovic, J., Jenike, M.A., Kennedy, J.L., King, R.A., Kremeyer, B., Kurlan, R., Lanzagorta, N., Leboyer, M., Leckman, J.F., Lennertz, L., Liu, C., Lochner, C., Lowe, T.L., Macciardi, F., McCracken, J.T., McGrath, L.M., Mesa Restrepo, S.C., Moessner, R., Morgan, J., Muller, H., Murphy, D.L., Naarden, A.L., Ochoa, W.C., Ophoff, R.A., Osiecki, L., Pakstis, A.J., Pato, M.T., Pato, C.N., Piacentini, J., Pittenger, C., Pollak, Y., Rauch, S.L., Renner, T.J., Reus, V.I., Richter, M.A., Riddle, M.A., Robertson, M.M., Romero, R., Rosario, M.C., Rosenberg, D., Rouleau, G.A., Ruhrmann, S., Ruiz-Linares, A., Sampaio, A.S., Samuels, J., Sandor, P., Sheppard, B., Singer, H.S., Smit, J.H., Stein, D.J., Strengman, E., Tischfield, J.A., Valencia Duarte, A.V., Vallada, H., Van Nieuwerburgh, F., Veenstra-Vanderweele, J., Walitza, S., Wang, Y., Wendland, J.R., Westenberg, H.G., Shugart, Y.Y., Miguel, E.C., McMahon, W., Wagner, M., Nicolini, H., Posthuma, D., Hanna, G.L., Heutink, P., Denys, D., Arnold, P.D., Oostra, B.A., Nestadt, G., Freimer, N.B., Pauls, D.L., Wray, N.R., Stewart, S.E., Mathews, C.A., Knowles, J.A., Cox, N.J., and Scharf, J.M. (2013). Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS genetics 9, e1003864, PMID:24204291.

Hodges, L.M., Fyer, A.J., Weissman, M.M., Logue, M.W., Haghighi, F., Evgrafov, O., Rotondo, A., Knowles, J.A., and Hamilton, S.P. (2014). Evidence for Linkage and Association of GABRB3 and GABRA5 to Panic Disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, PMID:24755890.

Mattheisen, M., Samuels, J.F., Wang, Y., Greenberg, B.D., Fyer, A.J., McCracken, J.T., Geller, D.A., Murphy, D.L., Knowles, J.A., Grados, M.A., Riddle, M.A., Rasmussen, S.A., McLaughlin, N.C., Nurmi, E.L., Askland, K.D., Qin, H.D., Cullen, B.A., Piacentini, J., Pauls, D.L., Bienvenu, O.J., Stewart, S.E., Liang, K.Y., Goes, F.S., Maher, B., Pulver, A.E., Shugart, Y.Y., Valle, D., Lange, C., and Nestadt, G. (2014). Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Molecular psychiatry, PMID:24821223.

McGrath, L.M., Yu, D., Marshall, C., Davis, L.K., Thiruvahindrapuram, B., Li, B., Cappi, C., Gerber, G., Wolf, A., Schroeder, F.A., Osiecki, L., O’Dushlaine, C., Kirby, A., Illmann, C., Haddad, S., Gallagher, P., Fagerness, J.A., Barr, C.L., Bellodi, L., Benarroch, F., Bienvenu, O.J., Black, D.W., Bloch, M.H., Bruun, R.D., Budman, C.L., Camarena, B., Cath, D.C., Cavallini, M.C., Chouinard, S., Coric, V., Cullen, B., Delorme, R., Denys, D., Derks, E.M., Dion, Y., Rosario, M.C., Eapen, V., Evans, P., Falkai, P., Fernandez, T.V., Garrido, H., Geller, D., Grabe, H.J., Grados, M.A., Greenberg, B.D., Gross-Tsur, V., Grunblatt, E., Heiman, G.A., Hemmings, S.M., Herrera, L.D., Hounie, A.G., Jankovic, J., Kennedy, J.L., King, R.A., Kurlan, R., Lanzagorta, N., Leboyer, M., Leckman, J.F., Lennertz, L., Lochner, C., Lowe, T.L., Lyon, G.J., Macciardi, F., Maier, W., McCracken, J.T., McMahon, W., Murphy, D.L., Naarden, A.L., Neale, B.M., Nurmi, E., Pakstis, A.J., Pato, M.T., Pato, C.N., Piacentini, J., Pittenger, C., Pollak, Y., Reus, V.I., Richter, M.A., Riddle, M., Robertson, M.M., Rosenberg, D., Rouleau, G.A., Ruhrmann, S., Sampaio, A.S., Samuels, J., Sandor, P., Sheppard, B., Singer, H.S., Smit, J.H., Stein, D.J., Tischfield, J.A., Vallada, H., Veenstra-VanderWeele, J., Walitza, S., Wang, Y., Wendland, J.R., Shugart, Y.Y., Miguel, E.C., Nicolini, H., Oostra, B.A., Moessner, R., Wagner, M., Ruiz-Linares, A., Heutink, P., Nestadt, G., Freimer, N., Petryshen, T., Posthuma, D., Jenike, M.A., Cox, N.J., Hanna, G.L., Brentani, H., Scherer, S.W., Arnold, P.D., Stewart, S.E., Mathews, C.A., Knowles J.A., Cook, E.H., Pauls, D.L., Wang, K., and Scharf, J.M. (2014). Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study. Journal of the American Academy of Child and Adolescent Psychiatry 53, 910-919, PMID:25062598.

Miller, J.A., Ding, S.L., Sunkin, S.M., Smith, K.A., Ng, L., Szafer, A., Ebbert, A., Riley, Z.L., Royall, J.J., Aiona, K., Arnold, J.M., Bennet, C., Bertagnolli, D., Brouner, K., Butler, S., Caldejon, S., Carey, A., Cuhaciyan, C., Dalley, R.A., Dee, N., Dolbeare, T.A., Facer, B.A., Feng, D., Fliss, T.P., Gee, G., Goldy, J., Gourley, L., Gregor, B.W., Gu, G., Howard, R.E., Jochim, J.M., Kuan, C.L., Lau, C., Lee, C.K., Lee, F., Lemon, T.A., Lesnar, P., McMurray, B., Mastan, N., Mosqueda, N., Naluai-Cecchini, T., Ngo, N.K., Nyhus, J., Oldre, A., Olson, E., Parente, J., Parker, P.D., Parry, S.E., Stevens, A., Pletikos, M., Reding, M., Roll, K., Sandman, D., Sarreal, M., Shapouri, S., Shapovalova, N.V., Shen, E.H., Sjoquist, N., Slaughterbeck, C.R., Smith, M., Sodt, A.J., Williams, D., Zollei, L., Fischl, B., Gerstein, M.B., Geschwind, D.H., Glass, I.A., Hawrylycz, M.J., Hevner, R.F., Huang, H., Jones, A.R., Knowles, J.A., Levitt, P., Phillips, J.W., Sestan, N., Wohnoutka, P., Dang, C., Bernard, A., Hohmann, J.G., and Lein, E.S. (2014). Transcriptional landscape of the prenatal human brain. Nature 508, 199-206, PMID:24695229. 72 Cohn

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Samuels, J., Shugart, Y.Y., Wang, Y., Grados, M.A., Bienvenu, O.J., Pinto, A., Rauch, S.L., Greenberg, B.D., Knowles, J.A., Fyer, A.J., Piacentini, J., Pauls, D.L., Cullen, B., Rasmussen, S.A., Stewart, S.E., Geller, D.A., Maher, B.S., Goes, F.S., Murphy, D.L., McCracken, J.T., Riddle, M.A., and Nestadt, G. (2014). Clinical correlates and genetic linkage of social and communication difficulties in families with obsessive-compulsive disorder: Results from the OCD Collaborative Genetics Study. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 165, 326-336, PMID:24798771.

Schizophrenia Working Group of the Psychiatric Genomics, C. (2014). Biological insights from 108 schizophrenia- associated genetic loci. Nature 511, 421-427, PMID:25056061.

Staab, T.A., Evgrafov, O., Knowles, J.A., and Sieburth, D. (2014). Regulation of Synaptic nlg-1/Neuroligin Abundance by the skn-1/Nrf Stress Response Pathway Protects against Oxidative Stress. PLoS genetics 10, e1004100, PMID:24453991.

Lai Y, Kim S, Varkey J, Lou X, Song JK, Diao J, Langen R, Shin YK Nonaggregated α-Synuclein Influences SNARE-Dependent Vesicle Docking via Membrane Binding.. Biochemistry. 2014 Jun 24;53(24):3889-96. doi: 10.1021/bi5002536. Epub 2014 Jun 13.

Ambroso MR, Hegde BG, Langen R. Endophilin A1 induces different membrane shapes using a conformational switch that is regulated by phosphorylation. Proc Natl Acad Sci U S A. 2014 May 13;111(19):6982-7. doi: 10.1073/ pnas.1402233111. Epub 2014 Apr 28.

Shah C, Hegde BG, Morén B, Behrmann E, Mielke T, Moenke G, Spahn CM, Lundmark R, Daumke O, Langen R. Structural insights into membrane interaction and caveolar targeting of dynamin-like EHD2. Structure. 2014 Mar 4;22(3):409-20. doi: 10.1016/j.str.2013.12.015. Epub 2014 Feb 6.

Cheng CY, Varkey J, Ambroso MR, Langen R, Han S. Hydration dynamics as an intrinsic ruler for refining protein structure at lipid membrane interfaces. Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):16838-43. doi: 10.1073/pnas.1307678110. Epub 2013 Sep 30.

Wen T, He S, Attenello F, Cen SY, Kim-Tenser M, Adamczyk P, Amar AP, Sanossian N, Mack WJ. The impact of patient age and comorbidities on the occurrence of “never events” in cerebrovascular surgery: an analysis of the Nationwide Inpatient Sample. J Neurosurg. 2014 Jun 27:1-7. [Epub ahead of print]

FY14 Faculty Publications

73 Chang JJ, Mack WJ, Saver JL, Sanossian N Magnesium: potential roles in neurovascular disease.. Front Neurol. 2014 Apr 15;5:52. doi: 10.3389/fneur.2014.00052. eCollection 2014. Review.

Tenser MS, Mack WJ. Plaque Morphology and Embolic Protection Strategies in Carotid Artery Stenting. World Neurosurg. 2014 Feb 16. pii: S1878-8750(14)00153-3. doi: 10.1016/j. wneu.2014.02.023. [Epub ahead of print] No abstract available.

Lucas J, Mack WJ. Effects of ionizing radiation on cerebral vasculature. World Neurosurg. 2014 Mar-Apr;81(3-4):490-1. doi: 10.1016/j.wneu.2014.01.006. Epub 2014 Jan 18.

Fargen KM, Blackburn S, Deshaies EM, Carpenter JS, Jabbour P, Mack WJ, Rai AT, Siddiqui AH, Turner RD, Mocco J. Final results of the multicenter, prospective Axium MicroFX for Endovascular Repair of IntraCranial Aneurysm Study (AMERICA). J Neurointerv Surg. 2014 Jan 6. doi: 10.1136/neurintsurg-2013-011049. [Epub ahead of print]

Liu Q, He S, Groysman L, Shaked D, Russin J, Cen S, Mack WJ. White matter injury due to experimental chronic cerebral hypoperfusion is associated with C5 deposition. PLoS One. 2013 Dec 30;8(12):e84802. doi: 10.1371/journal.pone.0084802. eCollection 2013.

Pease M, Ling C, Mack WJ, Wang K, Zada G.The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature. PLoS One. 2013 Dec 18;8(12):e82619. doi: 10.1371/journal.pone.0082619. eCollection 2013.

He S, Pham MH, Pease M, Zada G, Giannotta SL, Wang K, Mack WJ. A review of epigenetic and gene expression alterations associated with intracranial meningiomas. Neurosurg Focus. 2013 Dec;35(6):E5. doi: 10.3171/2013.10.FOCUS13360. Review.

Chang X, Shi L, Gao F, Russin J, Zeng L, He S, Chen TC, Giannotta SL, Weisenberger DJ, Zada G, Wang K, Mack WJ. Genomic and transcriptome analysis revealing an oncogenic functional module in meningiomas. Neurosurg Focus. 2013 Dec;35(6):E3. doi: 10.3171/2013.10. FOCUS13326.

Zada G, Yashar P, Robison A, Winer J, Khalessi A, Mack WJ, Giannotta SL. A proposed grading system for standardizing tumor consistency of intracranial meningiomas. Neurosurg Focus. 2013 Dec;35(6):E1. doi: 10.3171/2013.8.FOCUS13274.

Chandra RV, Meyers PM, Hirsch JA, Abruzzo T, Eskey CJ, Hussain MS, Lee SK, Narayanan S, Bulsara KR, Gandhi CD, Do HM, Prestigiacomo CJ, Albuquerque FC, Frei D, Kelly ME, Mack WJ, Pride GL, Jayaraman MVVertebral augmentation: report of the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery.. Society of NeuroInterventional Surgery. J Neurointerv Surg. 2014 Jan;6(1):7-15. doi: 10.1136/neurintsurg-2013-011012. Epub 2013 Nov 6. No abstract available.

I Schuberg S, Song S, Saver JL, Mack WJ, Cen SY, Sanossian N.mpact of emergency medical services stroke routing protocols on Primary Stroke Center certification in California. Stroke. 2013 Dec;44(12):3584-6. doi: 10.1161/STROKEAHA.113.000940. Epub 2013 Oct 8.

Gao F, Lin E, Feng Y, Mack WJ, Shen Y, Wang K. Characterizing immunoglobulin repertoire from whole blood by a personal genome sequencer. PLoS One. 2013 Sep 13;8(9):e75294. doi: 10.1371/journal.pone.0075294. eCollection 2013.

Mehta V, Mack WJ. Balloon Test Occlusion in the Setting of Vessel Sacrifice: Procedural Refinements and Adjunct Assessment Measures.. World Neurosurg. 2013 Sep 11. pii: S1878- 8750(13)01067-X. doi: 10.1016/j.wneu.2013.08.036. [Epub ahead of print]

Fargen KM, Blackburn S, Carpenter JS, Jabbour P, Mack WJ, Rai AT, Siddiqui AH, Turner RD, Mocco J. Early results of the Axium MicroFX for Endovascular Repair of IntraCranial Aneurysm (AMERICA) study: a multicenter prospective observational registry. J Neurointerv Surg. 2013 Sep 11. doi: 10.1136/neurintsurg-2013-010887. [Epub ahead of print] FY14 Faculty Publications FY14 Faculty 74 He S, Russin JJ, Adamczyk P, Giannotta SL, Amar AP, Mack WJ. A Persistent Primitive Hypoglossal Artery Arising from the External Carotid Artery Associated with Subarachnoid Hemorrhage. World Neurosurg. 2013 Jul 9. pii: S1878-8750(13)00761-4. doi: 10.1016/j. wneu.2013.06.015. [Epub ahead of print] Review.

Edlund RK, Ohyama T, Kantarci H, Riley BB, Groves AK. (2014). Foxi transcription factors promote pharyngeal arch development by regulating formation of FGF signaling centers. Dev. Biol. 390: 1-13. PMCID: 24650709

McGrath LM, Yu D, Marshall C, Davis LK, Thiruvahindrapuram B, Li B, Cappi C, Gerber G, Wolf A, Schroeder FA, Osiecki L, O’Dushlaine C, Kirby A, Illmann C, Haddad S, Gallagher P, Fagerness JA, Barr CL, Bellodi L, Benarroch F, Bienvenu OJ, Black DW, Bloch MH, Bruun RD, Budman CL, Camarena B, Cath DC, Cavallini MC, Chouinard S, Coric V, Cullen B, Delorme R, Denys D, Derks EM, Dion Y, Rosário MC, Eapen V, Evans P, Falkai P, Fernandez TV, Garrido H, Geller D, Grabe HJ, Grados MA, Greenberg BD, Gross-Tsur V, Grünblatt E, Heiman GA, Hemmings SM, Herrera LD, Hounie AG, Jankovic J, Kennedy JL, King RA, Kurlan R, Lanzagorta N, Leboyer M, Leckman JF, Lennertz L, Lochner C, Lowe TL, Lyon GJ, Macciardi F, Maier W, McCracken JT, McMahon W, Murphy DL, Naarden AL, Neale BM, Nurmi E, Pakstis AJ, Pato MT, Pato CN, Piacentini J, Pittenger C, Pollak Y, Reus VI, Richter MA, Riddle M, Robertson MM, Rosenberg D, Rouleau GA, Ruhrmann S, Sampaio AS, Samuels J, Sandor P, Sheppard B, Singer HS, Smit JH, Stein DJ, Tischfield JA, Vallada H, Veenstra-VanderWeele J, Walitza S, Wang Y, Wendland JR, Shugart YY, Miguel EC, Nicolini H, Oostra BA, Moessner R, Wagner M, Ruiz-Linares A, Heutink P, Nestadt G, Freimer N, Petryshen T, Posthuma D, Jenike MA, Cox NJ, Hanna GL, Brentani H, Scherer SW, Arnold PD, Stewart SE, Mathews CA, Knowles JA, Cook EH, Pauls DL, Wang K, Scharf JM. Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross- disorder study. J Am Acad Child Adolesc Psychiatry. 2014 Aug;53(8):910-9. doi: 10.1016/j. jaac.2014.04.022. Epub 2014 Jun 24.

T Guffanti G, Gaudi S, Fallon JH, Sobell J, Potkin SG, Pato C, Macciardi F. ransposable elements and psychiatric disorders. Am J Med Genet B Neuropsychiatr Genet. 2014 Apr;165B(3):201-16. doi: 10.1002/ajmg.b.32225. Epub 2014 Feb 28.

Davis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, Derks EM, Neale BM, Yang J, Lee SH, Evans P, Barr CL, Bellodi L, Benarroch F, Berrio GB, Bienvenu OJ, Bloch MH, Blom RM, Bruun RD, Budman CL, Camarena B, Campbell D, Cappi C, Cardona Silgado JC, Cath DC, Cavallini MC, Chavira DA, Chouinard S, Conti DV, Cook EH, Coric V, Cullen BA, Deforce D, Delorme R, Dion Y, Edlund CK, Egberts K, Falkai P, Fernandez TV, Gallagher PJ, Garrido H, Geller D, Girard SL, Grabe HJ, Grados MA, Greenberg BD, Gross-Tsur V, Haddad S, Heiman GA, Hemmings SM, Hounie AG, Illmann C, Jankovic J, Jenike MA, Kennedy JL, King RA, Kremeyer B, Kurlan R, Lanzagorta N, Leboyer M, Leckman JF, Lennertz L, Liu C, Lochner C, Lowe TL, Macciardi F, McCracken JT, McGrath LM, Mesa Restrepo SC, Moessner R, Morgan J, Muller H, Murphy DL, Naarden AL, Ochoa WC, Ophoff RA, Osiecki L, Pakstis AJ, Pato MT, Pato CN, Piacentini J, Pittenger C, Pollak Y, Rauch SL, Renner TJ, Reus VI, Richter MA, Riddle MA, Robertson MM, Romero R, Rosàrio MC, Rosenberg D, Rouleau GA, Ruhrmann S, Ruiz-Linares A, Sampaio AS, Samuels J, Sandor P, Sheppard B, Singer HS, Smit JH, Stein DJ, Strengman E, Tischfield JA, Valencia Duarte AV, Vallada H, Van Nieuwerburgh F, Veenstra-Vanderweele J, Walitza S, Wang Y, Wendland JR, Westenberg HG, Shugart YY, Miguel EC, McMahon W, Wagner M, Nicolini H, Posthuma D, Hanna GL, Heutink P, Denys D, Arnold PD, Oostra BA, Nestadt G, Freimer NB, Pauls DL, Wray NR, Stewart SE, Mathews CA, Knowles JA, Cox NJ, Scharf JM. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genet. 2013 Oct;9(10):e1003864. doi: 10.1371/journal.pgen.1003864. Epub 2013 Oct 24.

Rees E, Walters JT, Chambert KD, O’Dushlaine C, Szatkiewicz J, Richards AL, Georgieva L, Mahoney-Davies G, Legge SE, Moran JL, Genovese G, Levinson D, Morris DW, Cormican P, Kendler KS, O’Neill FA, Riley B, Gill M, Corvin A; Wellcome Trust Case Control Consortium, Sklar P, Hultman C, Pato C, Pato M, Sullivan PF, Gejman PV, McCarroll SA, O’Donovan MC, Owen MJ, Kirov G. CNV analysis in a large schizophrenia sample implicates deletions at 16p12.1 and SLC1A1 and duplications at 1p36.33 and CGNL1. Hum Mol Genet. 2014 Mar 15;23(6):1669-76. doi: 10.1093/hmg/ddt540. Epub 2013 Oct 26. 75 FY14 Faculty Publications

de Candia TR, Lee SH, Yang J, Browning BL, Gejman PV, Levinson DF, Mowry BJ, Hewitt JK, Goddard ME, O’Donovan MC, Purcell SM, Posthuma D; International Schizophrenia Consortium; Molecular Genetics of Schizophrenia Collaboration, Visscher PM, Wray NR, Keller MC. Additive genetic variation in schizophrenia risk is shared by populations of African and European descent. Am J Hum Genet. 2013 Sep 5;93(3):463-70. doi: 10.1016/j.ajhg.2013.07.007. Epub 2013 Aug 15.

A Zhao Z, Webb BT, Jia P, Bigdeli TB, Maher BS, van den Oord E, Bergen SE, Amdur RL, O’Neill FA, Walsh D, Thiselton DL, Chen X, Pato CN; International Schizophrenia Consortium, Riley BP, Kendler KS, Fanous AH. ssociation study of 167 candidate genes for schizophrenia selected by a multi-domain evidence-based prioritization algorithm and neurodevelopmental hypothesis. PLoS One. 2013 Jul 29;8(7):e67776. doi: 10.1371/journal.pone.0067776. Print 2013.

Gomes JB, Van Noppen B, Pato M, Braga DT, Meyer E, Bortoncello CF, Cordioli AV. Patient and family factors associated with family accommodation in obsessive-compulsive disorder. Psychiatry Clin Neurosci. 2014 Aug;68(8):621-30. doi: 10.1111/pcn.12172. Epub 2014 Apr 13.

Peti-Peterdi ,J Burford JL, Hackl MJ. Can kidney regeneration be visualized? Nephron Exp Nephrol. 2014;126(2):86. doi: 10.1159/000360673. Epub 2014 May 19.

Burford JL, Villanueva K, Lam L, Riquier-Brison A, Hackl MJ, Pippin J, Shankland SJ, Peti-Peterdi .J Intravital imaging of podocyte calcium in glomerular injury and disease. J Clin Invest. 2014 May 1;124(5):2050-8. doi: 10.1172/JCI71702. Epub 2014 Apr 8.

A Da Sacco S, Lemley KV, Sedrakyan S, Zanusso I, Petrosyan A, Peti-Peterdi ,J Burford J, De Filippo RE, Perin L. novel source of cultured podocytes. PLoS One. 2013 Dec 12;8(12):e81812. doi: 10.1371/journal.pone.0081812. eCollection 2013.

Hackl MJ, Burford JL, Villanueva K, Lam L, Suszták K, Schermer B, Benzing T, Peti-Peterdi .J Tracking the fate of glomerular epithelial cells in vivo using serial multiphoton imaging in new mouse models with fluorescent lineage tags. Nat Med. 2013 Dec;19(12):1661-6. doi: 10.1038/nm.3405. Epub 2013 Nov 24.

Svenningsen P, Burford JL, Peti-Peterdi .J ATP releasing connexin 30 hemichannels mediate flow-induced calcium signaling in the collecting duct. Front Physiol. 2013 Oct 16;4:292. doi: 10.3389/fphys.2013.00292. eCollection 2013.

Miyashita T, Burford JL, Hong YK, Gevorgyan H, Lam L, Mori N, Peti-Peterdi .J Localization and proliferation of lymphatic vessels in the tympanic membrane in normal state and regeneration. Biochem Biophys Res Commun. 2013 Oct 25;440(3):371-3. doi: 10.1016/j.bbrc.2013.09.054. Epub 2013 Sep 19.

Gueutin V, Vallet M, Jayat M, Peti-Peterdi ,J Cornière N, Leviel F, Sohet F, Wagner CA, Eladari D, Chambrey R. Renal β-intercalated cells maintain body fluid and electrolyte balance. J Clin Invest. 2013 Oct 1;123(10):4219-31. doi: 10.1172/ JCI63492. Epub 2013 Sep 24.

Kishore BK, Zhang Y, Gevorgyan H, Kohan DE, Schiedel AC, Müller CE, Peti-Peterdi .J Cellular localization of adenine receptors in the rat kidney and their functional significance in the inner medullary collecting duct. Am J Physiol Renal Physiol. 2013 Nov 1;305(9):F1298-305. doi: 10.1152/ajprenal.00254.2013. Epub 2013 Aug 28.

76 Shen H, Giordano F, Wu Y, Chan J, Zhu C, Milosevic I, Wu X, Yao K, Chen B, Baumgart T, Sieburth D, De Camilli P. Coupling between endocytosis and sphingosine kinase 1 recruitment. Nat Cell Biol. 2014 Jul;16(7):652-62. doi: 10.1038/ncb2987. Epub 2014 Jun 15.

Wang H, Sieburth D. PKA controls calcium influx into motor neurons during a rhythmic behavior. PLoS Genet. 2013;9(9):e1003831. doi: 10.1371/journal.pgen.1003831. Epub 2013 Sep 26.

Chan JP, Staab TA, Wang H, Mazzasette C, Butte Z, Sieburth D. Extrasynaptic muscarinic acetylcholine receptors on neuronal cell bodies regulate presynaptic function in Caenorhabditis elegans. J Neurosci. 2013 Aug 28;33(35):14146-59. doi: 10.1523/JNEUROSCI.1359-13.2013.

Siemer AB (2014) Antifreeze Proteins by Solid-state NMR: Methods and Applications. eMagRes, 3, 153–160

Siemer AB (2013) Magic Angle Spinning Solid-State NMR on Proteins. Encyclopedia of Biophysics

Zhou M, Liang F, Xiong XR, Li L, Li H, Xiao Z, Tao HW, Zhang LI. Scaling down of balanced excitation and inhibition by active behavioral states in auditory cortex. Nat Neurosci. 2014 Jun;17(6):841-50. doi: 10.1038/nn.3701. Epub 2014 Apr 20.

Li YT, Liu BH, Chou XL, Zhang LI, Tao HW. Strengthening of Direction Selectivity by Broadly Tuned and Spatiotemporally Slightly Offset Inhibition in Mouse Visual Cortex. Cereb Cortex. 2014 Mar 20. [Epub ahead of print]

Li LY, Xiong XR, Ibrahim LA, Yuan W, Tao HW, Zhang LI Differential Receptive Field Properties of Parvalbumin and Somatostatin Inhibitory Neurons in Mouse Auditory Cortex.. Cereb Cortex. 2014 Jan 14. [Epub ahead of print]

Xiong XR, Liang F, Li H, Mesik L, Zhang KK, Polley DB, Tao HW, Xiao Z, Zhang LI. Interaural level difference-dependent gain control and synaptic scaling underlying binaural computation. Neuron. 2013 Aug 21;79(4):738-53. doi: 10.1016/j. neuron.2013.06.012. Cohn

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77 Li LY, Li YT, Zhou M, Tao HW, Zhang LI. Intracortical multiplication of thalamocortical signals in mouse auditory cortex. Nat Neurosci. 2013 Sep;16(9):1179-81. doi: 10.1038/nn.3493. Epub 2013 Aug 11.

Li YT, Ibrahim LA, Liu BH, Zhang LI, Tao HW. Linear transformation of thalamocortical input by intracortical excitation. Nat Neurosci. 2013 Sep;16(9):1324-30. doi: 10.1038/nn.3494. Epub 2013 Aug 11.

Wang SZ, Ibrahim LA, Kim YJ, Gibson DA, Leung HC, Yuan W, Zhang KK, Tao HW, Ma L, Zhang LI. Slit/Robo signaling mediates spatial positioning of spiral ganglion neurons during development of cochlear innervation. J Neurosci. 2013 Jul 24;33(30):12242-54. doi: 10.1523/JNEUROSCI.5736-12.2013.

Ma WP, Li YT, Tao HW. Downregulation of cortical inhibition mediates ocular dominance plasticity during the critical period.. J Neurosci. 2013 Jul 3;33(27):11276-80. doi: 10.1523/JNEUROSCI.5598-12.2013.

Gate D, Danielpour M, Rodriguez Jr. J, Kim G-B, Levy R, Bannykh S, Breunig JJ, Kaech S, Flavell RA, and Town T. T Cell TGF-β Signaling Abrogation Restricts Medulloblastoma Progression (2014). PNAS, in press.

Weitz TM, Gate D, Rezai-Zadeh K, Town T. MyD88 is dispensable for cerebral amyloidosis and neuroinflammation in APP/PS1 transgenic mice (2014). American Journal of Pathology, in press.

Lokappa SB, Suk JE, Balasubramanian A, Samanta S, Situ AJ, Ulmer TS. Sequence and membrane determinants of the random coil-helix transition of α-synuclein. J Mol Biol. 2014 May 15;426(10):2130-44. doi: 10.1016/j.jmb.2014.02.024. Epub 2014 Mar 6.

Samanta S, Situ AJ, Ulmer TS. Structural characterization of the regulatory domain of brain carnitine palmitoyltransferase 1. Biopolymers. 2014 Apr;101(4):398-405. doi: 10.1002/bip.22396.

Mazumder P, Suk JE, Ulmer TS. Insight into α-synuclein plasticity and misfolding from differential micelle binding. J Phys Chem B. 2013 Oct 3;117(39):11448-59. doi: 10.1021/jp402589x. Epub 2013 Sep 12.

Jia H, Guo Y, Zhao W, Wang K. Long-range PCR in next-generation sequencing: comparison of six enzymes and evaluation on the MiSeq sequencer. Scientific Reports, 4:5737, 2014 (PMID: 25034901)

McGrath LM, Yu D, Marshall C, Davis LK, Thiruvahindrapuram B, Wang K, Scharf JM. Copy number variation in obsessive- compulsive disorder and Tourette syndrome: A cross-disorder analysis study. Journal of the American Academy of Child and Adolescent Psychiatry, 53:910-919, 2014 (PMID: 25062598)

Wei WH, Guo Y, Kindt A, Merriman TR, Semple CA, Wang K, Haley CS. Abundant local interactions in the 4p16.1 region suggest functional mechanisms underlying SLC2A9 associations with human serum uric acid. Human Molecular Genetics, pii:ddu227, 2014 (PMID: 24821702)

Jager M, Wang K, Bauer S, Smedley D, Krawitz P, Robinson PN. Jannovar: A Java Library for Exome Annotation. Human Mutation, 35:548-555, 2014 (PMID: 24677618)

St. Pourcain B, Skuse DH, Mandy WP, Wang K, Hakonarson H, Timpson NJ, Evans DM, Kemp JP, Ring SM, McArdle WL, Golding J, Davey Smith G. Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence. Molecular Autism, 5:18, 2014 (PMID: 24564958)

78 Ling C, Pease M, Shi L, Punj V, Shiroishi MS, Commins D, Weisenberger DJ, Wang K, Zada G. A Pilot Genome- Scale Profiling of DNA Methylation in Sporadic Pituitary Macroadenomas: Association with Tumor Invasion and Histopathological Subtype. PLoS ONE, 9: e96178, 2014 (PMID: 24781529)

Wang L, Swierczek SI, Hickman K, Walker K, Wang K, Drummond J, Doddapaneni H, Muzny DM, Gibbs RA, Wheeler DA, Prchal JT. The relationship of JAK2V617F and acquired UPD at chromosome 9p in polycythemia vera. Leukemia, 28: 938- 941, 2014 (PMID: 24463469)

Robinson P, Köhler S, Oellrich A, Sanger Mouse Genetics Project, Wang K, Mungall C, Lewis SE, Washington N, Bauer S, Seelow DS, Krawitz P, Gilissen C, Haendel M, Smedley D. Improved exome prioritization of disease genes through cross species phenotype comparison. Genome Research, 24:340-348, 2014 (PMID: 24162188)

Chen G, Chang X, Curtis C, Wang K. Precise inference of copy number alterations in tumor samples from SNP arrays. Bioinformatics, 29:2964-2970, 2013 (PMID: 24021380)

St. Pourcain B, Whitehouse AJ, Ang WQ, Warrington NM, Glessner JT, Wang K, Timpson NJ, Evans DM, Kemp JP, Ring SM, McArdle WL, Golding J, Hakonarson H, Pennell CE, Smith GD. Common variation contributes to the genetic architecture of social communication traits. Molecular Autism, 4:34, 2013 (PMID: 24047820)

Gao F, Ling C, Shi L, Commins D, Zada G, Mack W, Wang K. Inversion-mediated gene fusion involving NAB2-STAT6 in an unusual malignant meningioma. British Journal of Cancer, 109:1051-1055, 2013 (PMID: 23860521)

Shi M, Inn K-S, Yang A, Zhao Z, Liang Q, Versteeg GA, Amini-Bavil-Olyee S, Wong L-Y, Cho H, Zlokovic BV, Park S-H, García-Sastre A, Jung J. (2014) Negative regulation of NF- αB activity by brain-specific TRIpartite Motif protein 9 Nature Communications 5: 4820 (DOI: 10.1038/ncomms5820)

Winkler EA, Sagare AP, Zlokovic BV (2014) The pericyte: a forgotten cell type with important implications for Alzheimer’s disease? Brain Pathol 24, 371-386.

Montine TJ, Koroshetz W, Babcock D, Dickson D, Galpern W, Glymour MM, Greenberg S, Hutton M, Knopman D, Kuzmichev A, Manly J, Marder K, Miller B, Phelps C, Seeley W, Sieber B-A, Silverberg N, Sutherland M, Torborg C, Waddy S, Zlokovic BV, Corriveau RA for the ADRD 2014 Conference Committee (2014). Recommendations of the Alzheimer’s Disease-Related Dementias Conference Neurology 83(9): 851-60.

Zhao Z, Zlokovic BV. Blood-brain barrier: a dual life of MFSD2A? Neuron. 2014 May 21;82(4):728-30. doi: 10.1016/j. neuron.2014.05.012.

Winkler EA, Sengillo JD, Sagare AP, Zhao Z, Ma Q, Zuniga E, Wang Y, Zhong Z, Sullivan JS, Griffin JH, Cleveland DW, Zlokovic BV. Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice. Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):E1035-42. doi: 10.1073/pnas.1401595111. Epub 2014 Mar 3.

Sagare AP, Bell RD, Zhao Z, Ma Q, Winkler EA, Ramanathan A, Zlokovic BV (2013) Pericyte loss influences Alzheimer-like neurodegeneration in mice Nature Communications 4: 2932 (DOI: 10/1038/ncomms3932)

Halliday MR, Pomara N, Sagare AP, Mack WJ, Frangione B, Zlokovic BV (2013) Elevated cyclophilin A levels and matrix metalloproteinase-9 activity in cerebrospinal fluid of cognitively normal apolipoprotein E4 carriers correlate with blood- brain barrier breakdown JAMA Neurol 70 (9), 1198-1200.

FY14 Faculty Publications

79 Sagare A, Bell R, Srivastava A, Sengillo J, Singh I, Nishida Y, Chow N, Zlokovic, BV (2013) A lipoprotein receptor cluster IV mutant preferentially binds amyloid-b and regulates its clearance from the mouse brain J Biol Chem 288, 15154-15166.

Wang Y, Zhao Z, Chow N, Rajput PS, Griffin JH, Lyden PD, Zlokovic BV. Activated protein C analog protects from ischemic stroke and extends the therapeutic window of tissue-type plasminogen activator in aged female mice and hypertensive rats. Stroke. 2013 Dec;44(12):3529-36. doi: 10.1161/STROKEAHA.113.003350. Epub 2013 Oct 24.

Halliday MR, Pomara N, Sagare AP, Mack WJ, Frangione B, Zlokovic BV. Relationship between cyclophilin a levels and matrix metalloproteinase 9 activity in cerebrospinal fluid of cognitively normal apolipoprotein e4 carriers and blood- brain barrier breakdown. JAMA Neurol. 2013 Sep 1;70(9):1198-200. doi: 10.1001/jamaneurol.2013.3841.

Lyden P, Levy H, Weymer S, Pryor K, Kramer W, Griffin JH, Zlokovic BV (2013) Phase 1, safety, tolerability and pharmacokinetics of 3K3A-APC in healthy adult volunteers. Current Pharm Design 19, no. 42 (2013): 7479–7485.

Mosnier LO, Fernández JA, Davis TP, Zlokovic BV, Griffin JH (2013) Influence of the 3K3A-activated protein C variant on the in vitro fibrinolytic activity of tPA Thrombosis Hemostasis (11(11):2059-62. doi: 10.1111/jth.12400. PMID:24034518

FY14 Faculty Publications

80 ZNI Administration

Nearly 300 people work at the Zilkha Neurogenetic Institute (ZNI)—faculty, postdoctoral fellows, staff, students and visitors—all of whom receive support from a team of talented individuals who have the collective goal of reducing the administrative burden as much as possible so the science may thrive.

The senior administrative officer for ZNI is David Warren who oversees all day‐ to‐day activities at the ZNI, managing multiple budgets and providing financial reporting, supervising the areas of payroll/personnel, grants management, purchasing, facilities, construction and equipment acquisition. David actively participates in faculty recruitment, public relations, fund development and superintends ZNI’s programmatic events for all faculty, staff, students and visitors. David works closely with Dr Zlokovic to establish strategies designed to serve the mission of the institute, as well as set and enforce processes to ensure effective and efficient operations. This past year, among other projects, David worked closely with Keck Research Advancement and Keck Public Relations and Marketing to revamp and redesign the ZNI website, which is expected to re-launch in early 2015.

David is greatly assisted by a strong team of people who deploy their skills and expertise to provide world-class support for our world-class researchers. Barbara Lockley, Office Manager and Home Department Coordinator, manages all aspects of payroll and HR. USC rolled out a new integrated payroll system, the first in over 30 years, and Barbara spent much of 2014 becoming an expert in Workday. Barbara also works closely with Marlen Turcios who monitors graduate student set- ups, submits visas and prepares faculty dossiers. Marlen split much of her time in 2014 helping establish and track subcontracts as well as prepare and approve effort reporting across sponsored projects for internal and external certification. Rusty King is the Facilities Manager for our 125,000 sq ft building, supervising all services, construction, remodels and moves while also ensuring smooth and safe installation and operation of a variety of specialized equipment, from microscopes and lasers to NMRs. Rusty works closely with colleagues in many central departments and oversees the glassware and autoclave core for the Institute as well.

81 Gabriela Torres manages all pre- and post-award grants management, providing individual support for each PI: analyzing guidelines from multiple sources, preparing budgets, submitting grants and administering nearly 100 sponsored projects at any time, from proposal to close-out. Leslie Ortiz was promoted in 2014 to Budget/Business Analyst. Leslie employs eMarket and Kuali among other systems to prepare or approve purchasing orders; she analyzes policies to manage the travel and reimbursements for personnel across 30 laboratories. Leslie engages a network of USC departments to ensure PIs are able to access often unique supplies from a variety of vendors. Briana Armour recently joined ZNI as a Project Specialist for Dr Zlokovic, assisting with his calendar, meetings as well as coordinating complex programs.

A special thanks to Julie Carl, Project Specialist who coordinates ZNI Seminars, Symposia and special events. Julie collects and assembles the content for ZNI publications, including programs, posters, email blasts, website, promotional items, our newsletters and this annual report, frequently partnering with Keck PR on layout and design.

FY14 Operating Budget

Forward Income From FY13 Expenses Balance

Program Funds (Endowment) $2,417,995 $1,126,514* $3,113,951 $430,559

Departmental Funds (KSOM-Provided) Administrative $506,851 N/A $511,469 $(4,618) Facilities $150,000 N/A $156,388 $(6,388)

Deans Development Funds $1,350,402 N/A $1,339,396 $11,006

Philanthropy Unrestricted Gifts $674,450 $188,364 $665,048 $197,766

*includes $976,041 for solid-state NMR encumbered in FY12, expensed in FY14

ZNI Administration

82 Cohn

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Photo Mr Selim Zilkha welcomes Dr Zach Hall at the 4th Annual Zach Hall Lecture at ZNI while USC University Professor Jean Shih looks on.

83 ZNI Development

Hazel Breen serves as Executive Director of Development at the Keck School of Medicine, under the Keck Medicine Initiative for neurosciences. The Zilkha Neurogenetic Institute is an integral part of a broader USC neuroscience initiative that is exploring new ways to examine nervous system function in order to better understand the underlying causes of neurological and psychiatric disorders. At this world-class center for research excellence, USC faculty, fellows and graduate students are reaching across boundaries to embrace methods and techniques from other fields of study to discover innovative cures and treatment for neurogenetic diseases such as Alzheimer’s, Parkinson’s, Multiple Sclerosis and many other devastating illnesses.

Under the Keck Medicine Initiative, the Zilkha Neurogenetic Institute fundraising priorities include: • Seed funding to allow ZNI investigators to pursue innovative research, leading to further external sponsored project support • Graduate and postdoctoral fellowships to assist in the recruitment of clinical and research leaders of the highest distinction who share our vision of excellence and innovation • Core research facilities with state-of-the art equipment and laboratories

Gifts and grants help us meet our nation’s growing demand to improve the quality of life for individuals and society by promoting health, preventing and curing disease and advancing medical research. By applying emerging technologies and forging new partnerships and collaborations, ZNI investigators will continue to lead Keck Medicine of USC into the forefront of medical research and treatment. We hope you will join us in contributing to the future of transformative medicine and patient care.

Please contact Hazel Breen at [email protected] or at (323) 442-2684 if you would like more information regarding select research funding and capital naming opportunities.

84

Zilkha Neurogenetic Institute 1501 San Pablo Street Los Angeles, CA 90033 Phone: (323) 442-2144 Fax: (323) 442-2145 Email: [email protected] www.usc.edu/zni

© 2014 Keck Medicine of USC