Training and Education

The Interdisciplinary Training Program in Drug Abuse Research consists primarily of direct research training in the laboratory, along with formal didactic instruction, seminars, lectures, journal clubs, a program retreat, and interaction with visiting scholars. Postdoctoral fellows can take advantage of the formal courses in basic science as well as our newly developed course in drug abuse research, which provide a uniform and organized component to the training experience. We also sponsor a lecture/visiting scholar series in drug abuse to provide close interaction with other established researchers in the field.

Trainees can apply to and choose from one of five research themes:

Trainees 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. We focus on the role of epigenetic mechanisms in drug addiction and 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, we look at the effect of drug self-administration on activity in dopaminergic pathways 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—encourage trainees to formulate interdisciplinary projects that combine expertise from multiple laboratories.

Mentors: Deanna Benson, PhD, Lakshmi Devi, PhD, Marta Filizola, PhD, Srinivas Iyengar, PhD, Eric Nestler, MD, PhD, Susana Neves, PhD, Paul Slesinger, PhD, Venetia Zachariou, PhD

Trainees in this area invesftigate fundamental processes that mediate adaptive responses to drugs of abuse at the synaptic, cellular, and behavioral levels, with an emphasis on molecular mechanisms. We use combinations of transgenic, biochemical, immunocytochemical, electrophysiological, and behavioral techniques to study problems related to addiction.

The topics we consider include:

  • 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
  • The contribution of BDNF-responsive TrkB receptors to cocaine-induced acute and adaptive responses
  • The role of protein synthesis in the reconsolidation of recently recalled memories, and the control of dendritic translation during persistent forms of synaptic plasticity
  • 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

We encourage trainees who conduct research in this area 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.

Mentors: Deanna Benson, PhD, Robert Blitzer, PhD, Ming-Hu Han, PhD, Hirofumi Morishita, PhDScott Russo, PhD, Anne Schaefer, MD

Trainees 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 laboratories) to study the functional alterations in cell-signaling and gene-regulatory networks due to drug abuse.

Specifically, quantitative proteomics studies in the Devi Laboratory compare changes in the presynapse proteome of rats addicted to morphine with their non-addicted littermates. The Hurd Laboratory is looking at using RNA-seq analysis to examine gene expression changes in postmortem brains from heroin addicts. The Nestler Laboratory is applying gene expression analysis to compare the changes in expression profiles specifically activated by cocaine or morphine. These studies document those genes that vary in levels of abundance under the addictive vs. normal states. The Ma’ayan and Iyengar laboratories use these genes as anchors to build networks based on careful literature mining, as well as integration with other large-scale studies.

We use graph-analysis algorithms and statistical tests to identify pathways and key regulators that could represent potential biomarkers and novel drug targets. The Iyengar Laboratory is building differential equation-based dynamical models to understand the progression of molecular events during the onset of addiction. The Ma’ayan Laboratory 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. The laboratories of Dr. Iyengar, Dr. Devi and Dr. Neves use these tools to integrate and analyze networks of proteins associating with synaptic signaling complexes.

Mentors: Lakshmi Devi, PhD, Yasmin Hurd, PhD, Srinivas Iyengar, PhD, Avi Ma’ayan, PhD, Susana Neves, PhD

As a trainee, you investigate molecular and biochemical characterization of genes and their gene products in relation to genetic contributions to addiction disorders. You receive significant training in molecular genetics of human disease, use of genetic animal models, genomics, and proteomics technologies.

Our faculty is currently studying 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 Department of Genetics and Genomic Sciences and collaborate with clinical teams in order to investigate genetic polymorphisms in clinical drug abuse cohorts as well as populations at risk for addiction disorders.

We also look at molecular and biochemical studies of the postmortem human brain, as well as in vivo functional brain activity measures in relation to individual genotype. We are working to identify discrete neurobiological correlates in the human brain directly associated with those genetic polymorphisms that are, in turn, associated with addiction. You use mouse and other eukaryotic model systems to integrate basic genomic research with clinical and translational genetics.

Mentors: Rita Goldstein, PhDYasmin Hurd, PhD, Eric Nestler, MD, PhD, Scott Russo, PhD, Anne Schaefer, MD

Researchers in this area investigate the neurobiology of substance abuse disorders directly in the living human brain. We 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 examine 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 (such as fMRI, PET, diffusion tensor imaging), neurocognitive psychology, and genetics. Vulnerability is a significant theme of this research area. We conduct in vivo rodent PET studies in collaborations with the Brookhaven National Laboratory and Columbia University College of Physicians and Surgeons. We expect to expand this training program with the purchase of a mu-PET, which will provide significant translational insights for bridging basic and clinical research.

Mentors: Rita Goldstein, PhD, Yasmin Hurd, PhD, Iliyan Ivanov, MD, Nelly Alia-Klein, PhD