Training and Education
The training program will primarily consist of direct research training in the laboratory, although there will also be formal didactic instruction, seminars, lectures, journal clubs, a program retreat and interaction with visiting scholars to enhance their training. In particular, postdoctoral fellows can take advantage of the formal courses in basic science as well as our newly developed course in drug abuse research that will provide a uniform and organized component to the training experience. We will also sponsor a lecture/visiting scholars’ series in drug abuse to provide close interaction with other established researchers in the field.
Trainees will be able to apply to and choose from a specific research theme among the five research themes that are based on the expertise of the faculty:
Signaling Mechanisms of Addiction
Mentors: Benson, Devi, Filizola, Iyengar, Nestler, Neves, Slesinger, Zachariou
In this area, trainees will study receptors and signaling pathways that mediate the effects of addictive drugs, with opportunities to apply a wide range of classical biochemical, cell biological, molecular biological and computational methods. One focus of interest in this training area is the role of epigenetic mechanisms in drug addiction. Another focus of interest is the emerging importance of opiate receptor dimerization, which adds a layer of complexity to opiate effects by shaping the pharmacology of opioid receptors and routing their signal outputs. Ongoing research also includes investigating the ability of the G-protein-coupled opiate and cannabinoid receptors to regulate channels, which promises to shed light on the modulatory effects of addictive drugs on neurotransmitter release. At the systems level, the effect of drug self-administration on activity in dopaminergic pathways is being studied through dialysis of brain regions that have been implicated in reward and addiction. The complementary interests of the investigators in this area, spanning cellular mechanisms from receptor-effector coupling to regulated gene expression, and involving multiple brain regions that are critical in addiction, will encourage trainees to formulate interdisciplinary projects that combine the expertise from multiple laboratories.
Adaptation, Plasticity and Memory in Drug Addiction
Mentors: Benson, Blitzer, Han, Morishita, Morrison, Russo, Schaefer
Trainees in this area will investigate fundamental processes that mediate adaptive responses to drugs of abuse; these will be analyzed at the synaptic, cellular, and behavioral levels, with an emphasis on molecular mechanisms. Combinations of transgenic, biochemical, immunocytochemical, electrophysiological, and behavioral techniques are used to study problems of relevance to addiction, including: (1) Transcriptional control mechanisms that are engaged by drug-reinforced learning and chronic drug exposure, particularly the roles of the transcription factors C/EBP and deltaFosB; (2) The contribution of BDNF-responsive TrkB receptors to cocaine-induced acute and adaptive responses; (3) The role of protein synthesis in the reconsolidation of recently recalled memories, and the control of dendritic translation during persistent forms of synaptic plasticity; and (4) Analysis of intracellular signaling initiated by cell adhesion molecules, which participate in neuronal development, plasticity, and potentially the developmental defects associated with prenatal exposure to drugs of abuse. Trainees who conduct research in this area will be encouraged to interact with members of the Systems Biology of Addiction group, both to generate signaling network models, and to design experiments that will improve the accuracy of those models.
Systems Biology of Drug Addiction
Mentors: Devi, Hurd, Iyengar, Ma’ayan, Neves
Trainees in this area will apply computational analyses of data from proteomic studies (such as those conducted by the Devi laboratory); and gene expression microarrays/RNA sequencing (such as those conducted by the Hurd, Nestler and Iyengar labs to study the functional alterations in cell-signaling and gene-regulatory networks due to drug abuse. Specifically, quantitative proteomics studies in the Devi lab compare changes in the presynapse proteome of rats addicted to morphine with their non-addicted littermates. RNA-seq analysis to examine gene expression changes in postmortem brains from heroin addicts has been applied by the Hurd lab. Gene expression analysis has been applied by the Nestler lab to compare the changes in expression profiles specifically activated by cocaine or morphine. These studies only provide lists of genes that change in their abundance levels under the addictive vs. normal states. The Ma’ayan and Iyengar labs use these genes as anchors to build networks based on careful literature mining, as well as integration with other large-scale studies. Graph-analysis algorithms and statistical tests are used to identify pathways and key regulators that could represent potential biomarkers and novel drug-targets. The Iyengar lab is building differential equation based dynamical models to understand the progression of molecular events during the onset of addiction. The Ma’ayan lab is focused on developing tools for extracting cell-signaling and gene-regulation pathways from neuroscience literature and developing mathematical approaches to integrate and analyze diverse datasets to construct novel hypotheses. Such tools are being used by Dr. Iyengar, Devi and Neves laboratories to integrate and analyze networks of proteins associating with synaptic signaling complexes.
Genomics and Epigenomics in Drug Addiction
Mentors: Goldstein, Hurd, Nestler, Russo, Schaefer
Under this strong interdisciplinary research topic, trainees will be able to investigate molecular and biochemical characterization of genes and their gene products in relation to genetic contributions to addiction disorders. Significant training will be obtained in molecular genetics of human disease, use of genetic animal models, genomics, and proteomics technologies. Current studies conducted by faculty within this program involve investigations into the mechanisms of transcription, gene expression, chromatin structure, and protein-protein interactions that regulate gene activity in relation to drug abuse disorders. These studies focus on epigenetic mechanisms (such as DNA methylation, histone modification, RNA editing and microRNA expression) relevant to the regulation of gene transcription and other cellular functions in the development and expression of addictive states. Investigators interact with the Genetics and Genomics Center and have strong collaborations with clinical teams in order to investigate genetic polymorphisms in clinical drug abuse cohorts as well as populations at risk for addiction disorders. Molecular and biochemical studies of the postmortem human brain as well as in vivo functional brain activity measures are also assessed in relation to individual genotype in attempts to identify discrete neurobiological correlates in the human brain directly associated with genetic polymorphisms associated with addiction. In addition to the possibility of combining genetics with the molecular neurobiological studies of the human brain, trainees will utilize mouse and other eukaryotic model systems to integrate basic genomic research with clinical and translational genetics.
Neuroimaging and Neurocognition in Addictive Disorders
Mentors: Goldstein, Hurd, Ivanov, Klein
This research topic offers the opportunity to investigate the neurobiology of substance abuse disorders directly in the living human brain. A major aspect of this research area is to apply findings from basic neuroscience to guide clinical research using imaging technologies such as functional magnetic resonance imaging (fMRI) and Positron Emission Tomography (PET) in order to investigate in vivo brain function in relation to addiction disorders. Current drug abuse research studies in this discipline are focused on examining the contribution of risk factors such as behavioral traits (e.g., inhibitory control deficit, sensation-seeking), genetics, environmental factors (e.g., stress), and early drug exposure on in vivo neural systems relevant to addiction disorders. Trainees will obtain state-of-the-art imaging equipment experience with neuroimaging technologies (fMRI, PET, DTI), neurocognitive psychology, and genetics. A number of faculty in this discipline have significant experience with studying children and adolescents, thus exploring CNS development in relation to addiction vulnerability is a significant theme of this research area. In vivo rodent PET studies are carried out in collaborations with the Brookhaven laboratory and Columbia School of Medicine and this training program is expected to be expanded in the future at Mount Sinai with the planned purchase of a mu-PET which will provide significant translational insights for bridging basic and clinical research.
Dr. Lakshmi A. Devi is Professor of the Pharmacology and Systems Therapeutics, Psychiatry and Neuroscience Departments. She is the Dean for Academic Development and Enrichment as well as Director of the Interdisciplinary Postdoctoral Training Program in Drug Abuse Research.
Dr. Yasmin L. Hurd is Professor in the Departments of Psychiatry, Pharmacology and Systems Therapeutics, and Neuroscience. She is the Chief of the Center of Excellence in Mood and Motivation in the Brain Institute. She also serves as Chair of the Minority Health Research Committee (MHRC). Dr. Hurd is the Director of the MSTP Program at Icahn School of Medicine.
Lakshmi A. Devi, PhD
Annenberg Building, Room 19-84
One Gustave L. Levy Place
New York, NY 10029