NIAAA T32 Postdoctoral Training Grant
PRINCIPAL INVESTIGATORS
Dr. Marisa Roberto
Addiction is a chronic, relapsing illness and available treatments are insufficient. Studies in my laboratory aim to understand the specific brain circuits and neuronal mechanisms that underlie synaptic and/or molecular changes that influence the development of dependence on alcohol and other drugs of abuse using electrophysiological, pharmacological, and molecular methods. We have characterized several neuroadaptative changes that provide seminal insights into synaptic transmission which will be useful towards developing new therapeutic agents to alleviate drug dependence, and particularly alcohol dependence. In parallel, our studies are identifying key functional roles for neuropeptides and neuroimmune factors in the neurocircuits that mediate motivated behavior.
Dr. Eric Zorrilla
My laboratory seeks to understand the neural substrates of motivated behavior and of the regulatory control of energy balance using interdisciplinary molecular, biochemical, neuroanatomical, pharmacological, physiological, behavioral and statistical techniques. We are particularly interested in genetic, epigenetic and neuroadaptive differences in the neurobiology of reward and stress circuits that subserve the control of food intake as well as of other appetitive (reward-driven) and stress-related behaviors. Our work aims to be therapeutically relevant to the increased incidence of obesity, binge eating disorders, alcoholism and drug addiction, and stress-related psychiatric disorders of anxiety and depression in industrialized societies.
PROGRAM MENTORS
Dr. Candice Contet
My laboratory seeks to identify molecular and circuit mechanisms that causally contribute to the behavioral symptoms of alcohol use disorders. To achieve this goal, our projects combine behavioral models of excessive alcohol drinking in mice with genetic engineering methods enabling the manipulation of gene expression and neuronal activity. In addition to alcohol intake escalation, we aim to improve the modeling of negative affect in protracted abstinence and the influence of early life stress on the vulnerability to alcohol dependence vulnerability. Our mechanistic studies currently focus on BK channels, microtubule remodeling, and a cluster of CRF neurons located in the parasubthalamic nucleus. Candidates with expertise in neuronal morphology analysis, fiber photometry and/or 'omics data analysis are particularly encouraged to apply!
Dr. Ben Cravatt
Our research group aims to understand the roles that proteins play in human physiological and pathological processes and to use this knowledge to identify novel therapeutic targets and drugs to treat disease. To achieve these goals, we develop and apply new technologies that bridge the fields of chemistry and biology, ascribing to the philosophy that the most significant biomedical problems require creative multidisciplinary approaches for their solution. Our technological innovations address fundamental challenges in human physiology and disease that are beyond the scope of contemporary methods.
Dr. Cindy Ehlers
My lab conducts translational studies in the development of alcohol use disorders in rodents and in human populations. We use genetic techniques such as: whole genome sequencing, RNA seq, and epigenetics that we combines with endophenotypic measures such as: electrophysiology, sleep, and immune measures as well as extensive epidemiological and clinical assessments in humans, focusing on minority populations. In rodents we have a particular focus on sleep physiology as well as the neurotoxic effects of alcohol during adolescent development.
Dr. Sandra Encalada
Our research focuses on the characterization of the cellular and molecular mechanisms by which vesicular cargoes and organelles including mitochondria, undergo intracellular cytoskeleton-based transport in neurons, and how defective transport and endolysosomal pathways play a role in neurodegeneration and aging. We use a combination of cell biology, molecular genetics, biochemistry, proteomics, and high-resolution microscopy in mammalian neurons, mice, and in Caenorhabditis elegans. We generate models for various diseases including prion disorders, Alzheimer’s Disease and related tauopathies, and for the transthyretin (TTR) amyloid diseases, to identify and characterize the molecular mechanisms of neuronal toxicity. Our focus ranges from the dissection of subcellular-level pathways -to scrutinize the spreading of misfolded proteins and the role of liquid-liquid phase separation in disease-, to organismal/behavioral/neuronal brain circuit level questions. We develop quantitative high- and super-resolution imaging platforms to dissect subcellular-level mechanisms of protein movement and trafficking inside neurons. With these newfound mechanistic insights, we are actively screening small molecule compounds that ameliorate neurodegenerative phenotypes and behavioral outputs.
Dr. Olivier George
I have a major interest in the brain stress and cognitive systems in drug addiction. The main goals of my lab are to unveil the neurobiological mechanisms underlying the transition to drug addiction, and to develop novel pharmacological and non-pharmacological treatments to reduce compulsive drug seeking and taking. We have identified that activation of the CRF system in the extended amygdala and prefrontal cortex during withdrawal mediates excessive nicotine and alcohol intake. My lab has also demonstrated that escalation of cocaine, methamphetamine and alcohol intake produces a dysfunction of the prefrontal cortex leading to cognitive impairment. I have also pioneered the development of two novel animal models of escalation of nicotine intake and exposure to electronic cigarette. Current studies are exploring the role of the CRF, dynorphin, hypocretin and steroid systems in addiction to alcohol, nicotine, cocaine and prescription opiates.
Dr. Giordano De Guglielmo
Our program focuses on the neural circuits of addiction, with an emphasis on critical molecular and cellular mechanisms that are responsible for adverse behavioral outcomes that are associated with substance abuse and dependence. The de Guglielmo Lab is located in the department of Psychiatry at the UCSD School of Medicine and is part of the Preclinical Addiction Research Consortium (PARC) of UC San Diego.
Dr. Remi Martin-Fardon
My lab investigates the neurobiological basis of chronic vulnerability to relapse, with an emphasis on identifying neural substrates that are responsible the compulsive nature of drug- (i.e., cocaine, alcohol, opioids, nicotine) seeking behavior. Specifically, projects are focused on 1) characterization of neural mechanisms of reward, dependence, withdrawal and relapse using pharmacology, in vivo neurochemistry, and molecular approaches (e.g., AAV, DREADD); 2) behavioral analyses using animal models of binge-like drug consumption, escalation of drug intake which models compulsive consumption, negative reinforcement of drug taking during dependence, dysregulated stress responsivity and affect control during protracted withdrawal, impaired cognitive function (e.g. impulsivity, attentional capacity, cognitive flexibility, conditioned fear) and reinstatement of extinguished drug-seeking behavior.
Dr. Barbara Mason
My laboratory focuses on clinical research in medications development for alcohol use disorder and cannabis use disorder. We have conducted the seminal studies of nalmefene, which is now approved throughout the European Union for the treatment of AUD, I have served as Overall Principal Investigator for the U.S. multi-center study conducted in support of FDA-approval of acamprosate for the treatment of AUD, and I currently serve as Program Director for the translational Scripps Alcohol Research Center. My postdoctoral fellows gain experience in all facets of conducting human laboratory studies to screen potential pharmacotherapies for alcohol use disorder, and manuscript preparation. Prior trainees in my lab have obtained positions in industry, academia, and clinical practice.
Dr. Nobuyoshi Suto
Research in my lab is concerned with the neurobiological basis of motivation and learning, in particular, those related to alcoholism and drug addiction. We take advantage of a multidisciplinary approach combining well-established and novel animal models (transgenetic rats/mice) with cutting-edge molecular (FACS + NGS), chemogenetic (Daun02), optogenetic, neurochemical (microdialysis + mass spectrometry) and neuroanatomical (brain-wide 3D circuit analysis) techniques. Our ultimate research goal is to develop a novel anti-addiction medicine through neural activity-based behavioral/brain circuitry/neurochemical/gene expression profiling of behaviorally and/or environmentally-relevant brain mechanisms (neuronal ensembles/memory engrams).
Dr. Michael Taffe
Research in the Taffe Laboratory focuses on the effects of recreational or abused drugs on the brain and the resulting changes in behavior. We have a current interest in the compulsive use of drugs with a focus on factors involved in the transition from casual to repetitive drug use, as well as on novel therapeutic approaches using the immune system.
Dr. Friedbert Weiss
My research program is concerned with the neural basis of behavior controlled by the addictive actions of drugs of abuse, as well as the mechanisms responsible for the development of dependence and vulnerability to relapse. My group approaches these questions at the “systems level” by pinpointing neurochemical, neuroanatomical, and molecular substrates as well as adaptations in the functioning of these neural systems that develop as a result of chronic drug use and modify drug-seeking behavior.
Dr. John R Yates III
Research in the Yates Laboratory focuses on genomic and EST sequencing projects. These data along with mass spectrometry provide the cornerstone technologies fueling the proteomics revolution. Our group is focused on developing tools and strategies in proteomics to answer basic biological questions. By coupling the additional amino acid sequence information that can be obtained using peptide tandem mass spectrometry to "back-end" database searching and "front-end" separative techniques, we are able to directly analyze extremely complex protein mixtures. The applications for these technologies vary from analyzing purified protein complexes to studying host-pathogen interactions in diseases such as malaria or anthrax. We are further extending these applications to find post-translational modifications to the proteins within these same complex mixtures.