George Kunos, M.D., Ph.D. Scientific Director

More than 10 million Americans suffer from alcoholism, a disease that results in more than 100,000 deaths annually and is estimated to have an annual cost of $ 185 billion in the United States. The mission of our intramural research program is to identify the causes and consequences of alcoholism and excessive drinking, and to understand the underlying biological processes at the molecular, cellular and whole organism levels. We address these questions by using a broad range of research approaches, including clinical investigations using state-of-the-art brain imaging techniques, studies of alcohol-drinking behavior in primate models, analyses of drug and alcohol action at the cellular and molecular levels, and genetic studies aimed to identify genes that increase or decrease our vulnerability to develop alcoholism. In doing this work we interact extensively and closely with scientists in other institutes that make up the intramural research program of the National Institutes of Health. This broad-based interactive approach offers an outstanding training environment for young scientists interested in gaining expertise in a variety of biological disciplines. We would be more than happy to answer any further questions you may have about our research program and training opportunities.

The Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism has as its overall goals understanding the biological basis of alcohol use disorders and alcohol-induced morbidities, and developing novel strategies and tools for the prevention and treatment of these disorders. Research is conducted at multiple levels: cellular/molecular, animal studies in rodents and non-human primates, human studies of the genetics and epidemiology of alcoholism and co-morbidities, and validation of novel molecular targets for alcohol use disorders. Collaborations among the various units and between these units and investigators from other NIH institutes or extramural institutions reflect the integrative, multidisciplinary nature of ongoing research. Research into the causes and consequences of alcoholism is not a discipline in its own right, rather it relies on and employs the tools of a wide range of biological disciplines. The outstanding scientists heading the various research units of our intramural program are recognized for their contributions to their chosen research fields, be it molecular biology, neuroscience, biochemistry, physical chemistry, physiology, genetics, epidemiology or psychiatry, and apply their expertise to answer questions related to alcohol use disorders.

There are ten intramural NIAAA Laboratories made up of a total of 25 sections/units, each headed by a principal investigator, each of whom provides a detailed description of their ongoing research in this volume. The Laboratory of Clinical and Translational Studies (LCTS) is the only clinical laboratory of our intramural program. It focuses on developing novel pharmacologic treatments for alcohol use disorders, through a combination of preclinical studies aimed to discover and validate new molecular targets using rodent and primate models, and clinical proof-of-concept studies that test these novel targets through the use of therapeutic agents directed against such targets. This work also takes advantage of state-of-the-art functional brain imaging techniques. Due to budgetary constraints, the primate research program had to be closed down in FY07. The Laboratory of Membrane Biochemistry and Biophysics (LMBB) explores the relationship between alcohol-induced changes in membrane structure and function, and investigates the biological functions of polyunsaturated fatty acids, with special emphasis on docosahexaenoic acid (DHA). The Laboratory of Neuroimaging (LNI) uses in vivo brain imaging to gain insight into the neurochemical basis of addictive disorders, including drug-seeking behavior, alcoholism and alcohol dependence. The Laboratory of Neurogenetics (LNG) aims to identify genes that predispose to or protect from alcoholism and comorbid disorders. Their approach combines functional genomics in in vitro systems, large scale analyses of gene expression, and linkage analyses including both candidate gene and genome-wide approaches. The Laboratory of Epidemiology and Biometry (LEB) designs, conducts and analyzes the collected data from national epidemiologic surveys on alcohol use disorders and related conditions, in order to gain insight into their prevalence, co-morbidities, prevention, treatment needs and societal costs. The unifying theme of research in the Laboratory of Integrative Neuroscience (LIN) is forebrain mechanisms of cognition and behavioral control that play a role in addiction, which are investigated using a combination of electrophysiological, cell and molecular biological and whole animal behavioral techniques and paradigms. The Laboratory of Molecular Signaling (LMS) explores the signaling pathways involved in the effects of polyunsaturated fatty acids on neuronal survival and their modulation by ethanol, using a combination of cell biological and mass spectrometry-based proteomic approaches. Research in the Laboratory of Physiologic Studies (LPS) focuses on neuroendocrine mechanisms that regulate appetitive functions, including alcohol drinking behavior, on liver biology and on mechanisms of oxidative and nitrosative stress. A shared interest among the three sections of this Laboratory is the role of the endocannabinoid system in the above functions. The Laboratory of Metabolic Control (LMC) studies how the flux through various metabolic pathways is involved in controlling cellular energy status, with particular emphasis on the metabolism of ketone bodies and its therapeutic implications. Finally, the Laboratory of Molecular Physiology (LMP) investigates cellular, subcellular and molecular mechanisms underlying synaptic transmission in the nervous system, using electrophysiological and advanced cellular imaging techniques, as well as zebrafish genetics.

Tough economic times require creative measures for maintaining the viability of our research program. One approach is to explore and take advantage of extramural funding sources. Our investigators have been exceptionally successful in this regard: research support was obtained from the Defense Advanced Research Projects Agency (DARPA; Richard Veech, Joe Hibbeln), Sanofi-Aventis (fellowship support for Pal Pacher), the Korean government (B.J. Song), the Jain Foundation (Steve Vogel), the Department of Commerce (Joe Hibbeln), the U.S./Israel Binational Science Foundation (Andrew Holmes) and cooperative research and development agreements (CRADAs) with Eli Lilly & Co. and with Johnson & Johnson (Markus Heilig). Another approach is to join forces with other NIH institutes in recruiting talented investigators. We currently have two such joint appointments: Dr. Kenner Rice heads the Chemical Biology Research Branch, jointly sponsored by NIDA and NIAAA, and Dr. Veronica Alvarez was recruited as a tenure-track investigator in 2008 jointly by NINDS and NIAAA to set up a Section on Neuronal Structure. The key to continued success, however, lies in the creative ingenuity and hard work of our investigators who are guided by the principle enunciated by the Nobel laureate, Albert Szent-Györgyi:

“Discovery consists in seeing what everyone else has seen and thinking what no one else has thought”


Updated: May 2009