TMARC Director/Principal Investigator
Igor Grant, M.D. (Mary Gilman Marston Distinguished Professor and Chair of Psychiatry) has an extensive track record in research on both HIV and drugs including methamphetamine (METH), alcohol, and polysubstance use. He has directed multidisciplinary and multi-site projects for many years. Dr. Grant also has fostered the careers of young scientists, having been dissertation Chair for more than 30 graduate students and senior mentor to numerous junior faculty, many of whom now have independent peer review supported research careers.
Dr. Grant will be assisted by three Co-Directors representing the disciplines of Neurobiology, Neurology, and Infectious Disease, as well as by a mid-level faculty Center Manager and a junior faculty Associate Center Manager.
Cristian L. Achim, M.D., Ph.D. (Professor of Psychiatry and Pathology; TMARC Co-Director/Director, Neuroscience and Animal Models (NAM) Core) is a neuroscientist who contributed to the early observations on the nature of brain injury in HIV disease. More recently, his work has focused on the role of chaperone proteins (immunophilins) in HIV neuropathogenesis, while his clinical research involves an international study on neurologic effects of clade F infection in Romanian adolescents.
Ronald J. Ellis, M.D., Ph.D. (Professor of Neurosciences; TMARC Co-Director/Co-Investigator, Behavioral Assessment and Neuromedical (BAM) Core) is a neurologist, trained in neuropsychology, who has performed extensive research on viral compartmentalization in the central nervous system (CNS), as well as the utility of cerebrospinal fluid (CSF) as a window into neurologic events in living persons. His clinical work and research are focused on the neurological manifestations of HIV infection and their pathogenesis and treatment, particularly dementia, neurocognitive disorders, and sensory polyneuropathy. Dr. Ellis has held leadership positions within numerous NIH-funded clinical trials networks, including the AIDS Clinical Trials Group (ACTG). He is frequently consulted by the National Institutes of Health (NIH) to serve on advisory boards, grant review committees, and other expert bodies.
Scott L. Letendre, M.D. (Professor of Medicine; TMARC Co-Director/Co-Director, BAM Core) has worked closely with Dr. Grant for more than a decade on many San Diego-based and multisite projects, including as Core Director of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) initiative Laboratory and Biomarkers Core. An infectious disease physician, he has contributed to our understanding of inflammatory biomarkers in the CSF, demonstrated a relationship between such biomarkers and METH use, identified important links with other pathogens that infect people living with HIV, and has contributed to modeling the distribution of antiretroviral drugs into the CNS. Dr. Letendre will assist Dr. Grant in infectious disease-related and laboratory aspects of TMARC.
Mariana Cherner, Ph.D. (Associate Professor of Psychiatry; TMARC Center Manager) is a neuropsychologist with expertise in neurobehavioral functioning at the intersection of HIV and substance. She has received several NIDA-funded grants aimed at investigating the host genetics of brain dysfunction among individuals with HIV and METH dependence.
Erin E. Morgan, Ph.D. (Assistant Professor, Psychiatry; TMARC Associate Center Manager) received graduate and postdoctoral training in clinical neuropsychology. In addition to having been awarded pilot and developmental projects to investigate the cognitive and everyday functioning sequelae of HIV infection and METH dependence, she is also the Director of TMARC Project 3 (see description below).
Senior Personnel from the Cores Include:
Behavioral Assessment and Medical (BAM) Core
Robert K. Heaton, Ph.D. (Distinguished Professor of Psychiatry; Co-Director, BAM Core/Chief, Neuropsychiatric Unit) is an internationally esteemed neuropsychologist who has contributed to the development of widely used neuropsychological methods and approaches to test interpretation, including development of norms. Dr. Heaton has extensive research experience in neurocognitive complications of HIV and comorbid conditions and was greatly influential in crafting the current nomenclature for HIV-associated neurocognitive disorders. Dr. Heaton also directs the HIV Neurobehavioral Research Center (HNRC). Scott L. Letendre, Ph.D. (Co-Director, BAM Core/Chief, Neuromedical and Laboratory Unit) and Ronald J. Ellis, M.D., Ph.D. (see descriptions above). Sanjay R. Mehta, M.D. (Assistant Professor of Medicine) has a broad expertise in basic, translational, and clinical research, with a focus on viral evolution, host genetics, and molecular epidemiology. J. Hampton Atkinson, M.D. (Professor of Psychiatry) performed some of the earliest work on psychopathology in HIV, and more recently, METH effects on adherence to antiretrovirals (ARVs). Thomas D. Marcotte, Ph.D. (Associate Professor of Psychiatry) has extensive experience in the neuropsychology of HIV and substance use. He has served as the Center Manager of the HIV Neurobehavioral Research Center (HNRC) for over 15 years and was a Co-I on previous NIDA-funded Program Projects. With respect to the impact of neurocognitive impairment, he has led numerous studies examining driving performance in HIV+ individuals, as well as other neurologic conditions, including the effects of substance use and aging. Erin E. Morgan, Ph.D. (see description above).
Neuroimaging (NI) Core
Gregory G. Brown, Ph.D. (Professor of Psychiatry; Director, Neuroimaging Core) has been doing magnetic resonance imaging (MRI) studies of neuropsychiatric disorders since the late 1980's. His imaging research has involved the use of MR spectroscopy (MRS), blood-oxygen-level dependent (BOLD) imaging and arterial spin labeling (ASL) to investigate the brain substrate of disordered neurobehavioral function in disorders ranging from schizophrenia to stroke. Thomas T. Liu, Ph.D. (Professor of Radiology and Bioengineering) is the Director of the UCSD Center for Functional MRI (CFMRI). His areas of research include the design and analysis of experiments for functional MRI (fMRI) and the development of novel imaging methods to measure cerebral blood flow (CBF) and volume. Miriam Scadeng, Ph.D. (Associate Professor of Radiology) has experience in performing structural and functional MRI on several different animal models, including mice. Christine Fennema-Notestine, Ph.D. (Associate Professor of Psychiatry and Radiology) conducts research that emphasizes development and validation of MRI methods and the clinical application of these methods to the HIV infected and METH using populations. Her work aims to provide a more sensitive characterization of underlying neuropathogenesis and to better understand the relationship between neuroimaging biomarkers and cognitive, psychiatric, and neuromedical profiles. Sarah L. Archibald, M.A. (Specialist, Psychiatry and Center for Human Development) is a neuroanatomist with expertise in neuroimaging methods. She works on research that applies imaging techniques to study the neurocognitive effects of HIV disease and METH abuse in humans and animals. In addition she is involved in studies of neurodevelopment in children. Craig E.L. Stark, Ph.D. (Professor of Neurobiology & Behavior at the University of California, Irvine) focuses on the brain mechanisms involved in learning and memory, primarily with the use of MRI to evaluate the structural and functional properties of the medial temporal lobe. He has experience in investigating individuals with unique memory properties, from individuals with amnesia to those with mild cognitive impairment to those with healthy aging. His lab has developed high-resolution MRI techniques, such as coregistration of subcortical structures across participants in structural and fMRI imaging, including the striatal areas under investigation.
Neuroscience and Animal Models (NAM) Core
Cristian L. Achim, M.D., Ph.D. (Director, NAM Core; see description above). Marcus Kaul, Ph.D. (Chief, NAM Core—Animal Models Unit) has more than 15 years of experience in supervising the breeding of rodents; in addition to his NAM Core duties, Dr. Kaul is also Director of Project 5 (see description below). Virawudh Soontornniyomkij, M.D. (Assistant Research Scientist, Department of Psychiatry) is a neuropathologist who has contributed to the understanding of HIV neuropathogenesis. His current research focuses on the role of METH and anti-HIV therapy in the development of cerebral small vessel disease and HIV-associated neurocognitive disorders. Dr. Soontornniyomkij will assist Dr. Achim in human and animal pathology work in the NAM Core.
Pilot and Developmental (PAD) Core
Mariana Cherner, Ph.D. (Director, PAD Core; see description above). Stuart A. Lipton, M.D., Ph.D. (Professor of Neurosciences, UCSD) is internationally recognized for his contributions to the development of models of HIV neuropathogenesis, including excitotoxicity, oxidative stress, and inflammation.
Administrative Coordinating Core (ACC)
Igor Grant, M.D. (Head of ACC/Chief, Executive Unit), Mariana Cherner, Ph.D. (Center Manager), and Erin E. Morgan, Ph.D. (Associate Center Manager)—see descriptions above. Ian S. Abramson, Ph.D. (Professor of Mathematics; Chief, Data Management and Information Systems (DMIS) Unit/Co-Investigator, Statistics Unit) has expertise in the use of advanced repeated measures techniques and their implementation with flexible algorithms. Dr. Abramson has also collaborated with multi-disciplinary researchers on the development of appropriate and novel techniques to model highly complex multivariate data over time. Florin Vaida, Ph.D. (Associate Professor of Biostatistics; Chief, Statistics Unit) has extensive experience in analyzing data from HIV studies with expertise in analysis of longitudinal data, mixed effects models and smoothing, and statistical approaches in the presence of missing data, including informative dropout. J. Hampton Atkinson, M.D. (Chief, Participant Unit; see description above).
As mentioned above, for Project Leaders, we have focused on young faculty with innovative ideas, and have tried to pair them with more senior investigators. These faculty include:
Project 1: Cross-Species Risk Behaviors & Age
Arpi Minassian, Ph.D. (Associate Professor of Psychiatry; Director, Project 1) studies cognition in severe mental illnesses such as bipolar disorder and schizophrenia, as well as medical illnesses such as HIV and Hepatitis C and substance dependence conditions. She has developed expertise in psychophysiological paradigms, particularly those that can be translated to both humans and animals. This cross-species approach to studying brain dysfunction is aimed at advancing our understanding of both the biology and the treatment of serious illnesses. She is a Co-Investigator of a federally-funded grant studying cognition and inhibition across the spectrum of Bipolar Disorder and another grant on the relationships between cognitive deficits and endocannabinoids in this disease. She has also been the recipient of a NARSAD Young Investigator Award. Dr. Minassian will be assisted in her project by: William Perry, Ph.D. (Professor of Psychiatry), who has extensive neuropsychological expertise, and has been one of the pioneers in the use of the human open field paradigm; and Jared W. Young, Ph.D. (Associate Professor of Psychiatry), who has expertise in developing and utilizing cross-species tests of cognitive functioning for the development of cognitive therapeutics, will design and aid in the conductance of the TMARC animal experiments. Additionally, Mark A. Geyer, Ph.D. (Professor of Psychiatry), who is an internationally-regarded neuroscientist with an extensive track record of expertise in the use of models to probe processes and circuitries that are thought to underlie psychopathological states, will act as a Consultant on P1.
Project 2: Neural Substrates of Decision-Making
Amanda B. Grethe, Ph.D. (Assistant Professor of Psychiatry; Director, Project 2) is interested in the role of the basal ganglia in reward and expectancy, and how these behaviors are altered in substance dependence and eating disorders. She was the PI of a recently completed NIDA-funded K-award related to the neuroimaging of reward feedback and expectancy in healthy volunteers and in individuals diagnosed with stimulant dependence. She will be assisted by: Susan F. Tapert, Ph.D. (Professor of Psychiatry), who has extensive experience in the application of fMRI and diffusion tensor imaging (DTI) to examine substance dependence in adolescents and young adults; and Assawin Gongvatana, Ph.D. (Assistant Research Scientist, Psychiatry) who has experience in fMRI and DTI as it pertains to HIV infection and alcoholism.
Project 3: Social Cognition, Risk, & Age
Erin E. Morgan, Ph.D. (Assistant Professor, Psychiatry; Director, Project 3) is interested in the use of cognitive models to address research questions in clinical populations, such as HIV and METH dependence, to elucidate the neurocognitive and neurobehavioral mechanisms of real-world outcomes. In particular, her research focuses on the extent to which HIV transmission risk behavior can be explained by deficits in the skills and abilities that underlie social interaction, known as social cognition. Dr. Morgan's Senior Advisor on Project 3 will be Igor Grant, M.D., who is the PI and Director of TMARC (see description above). Carla Sharp, Ph.D. (Professor of Psychology at the University of Houston), a Consultant on P3, has considerable expertise in social cognition, reward processing and emotional processing, and as such can provide valuable feedback regarding the scientific aims and objectives of P3, as well as our overarching theoretical model of social cognition and corresponding methods of assessment.
Project 4: Cognitive Deficits in Mouse Models
Svetlana Semenova, Ph.D. (Assistant Professor of Psychiatry; Director, Project 4) is interested in investigating the risk factors and neurobiological mechanisms that contribute to the development of dependence to various drugs of abuse. The risk factors of interest include individual differences in sensitivity to drugs of abuse, adolescent and old age, trait impulsivity, risky behaviors, as well as comorbid disorders such as HIV. She was the PI on NIH-funded R03 grant investigating the role of the HIV-related Tat protein in nicotine dependence. In this project, Dr. Semenova will be investigating the combined effects of chronic METH exposure, HIV-related gp120 and Tat proteins, and aging on cognitive function.
Project 5: Behavior & Neural Networks
Marcus Kaul, Ph.D. (Associate Professor, Infectious and Inflammatory Disease Center at the Sanford-Burnham-Prebys Medical Discovery Institute; Associate Professor (Adjunct) Department of Psychiatry at UCSD; Director, Project 5) is interested in cellular and molecular mechanisms of infectious and inflammatory diseases, as well as in the role of co-morbidity factors that contribute to the development of neuronal injury such as it occurs in the setting of HIV infection and use of METH. He was previously the PI of an NINDS-funded R01 award that studied the role of chemokine receptor signaling in the neuropathology of HIV-1 infection. He is currently also the PI of an NIMH-funded R01 award investigating the neuroprotective effect of interferon-beta in AIDS.