The Intramural Division–A Core Component of NIAAA’s Research Program

As the lead Federal agency for research on alcohol and health, NIAAA is structured in a way that captures all areas of alcohol science. Through an integrated and multidisciplinary program of basic and applied research, NIAAA investigates everything from the causes, consequences, prevention, and treatment of alcohol use disorder to the potential benefits of moderate drinking. In some cases, NIAAA staff scientists in the Division of Intramural Clinical and Biological Research (DICBR) conduct the research directly; in others, NIAAA’s extramural divisions support researchers across the country and around the world.

DICBR is NIAAA’s “in-house” research program. With a combination of clinical and basic research (from genetics to molecular biology to neuroimaging), DICBR studies the ways that alcohol produces intoxication, dependence, and damage to vital organs, and the potential tools to prevent and treat those processes.

“At NIH, we have the largest concentration of world-class programs and scientists in the world,” says George Kunos, M.D., Ph.D., and Scientific Director of DICBR, speaking of the NIH intramural program broadly. “With nearly 1,000 senior investigators NIH-wide, NIH is an amazing environment in which to conduct basic scientific and clinical research.”

The intramural program at NIH also offers unique research opportunities. “We have the ability to do high-risk, high-reward work, which often cannot be done in the extramural community,” explains Dr. Kunos. But he is quick to emphasize that the aim of intramural research is “not to compete with extramural research, but to complement it by engaging in innovative approaches.”

DICBR’s twelve intramural laboratories, some of which are divided into sections, conduct research on many levels, including cellular/molecular studies, animal studies in rodents, human studies of the genetics and epidemiology of alcoholism and co-morbidities, and validation of novel molecular targets for alcohol use disorders.

Each lab and section is headed by a principal investigator, tenured or tenure track. Others on the lab teams include staff scientists, staff clinicians, visiting scientists, postdoctoral or pre-doctoral fellows, and graduate students.

One of these, the Laboratory of Neurogenetics (LNG), studies the inherited factors contributing to people’s vulnerability to alcoholism and addiction, as well as related behaviors and psychiatric pathologies. David Goldman, M.D., who has served as Chief of LNG since 1991, values the flexibility that intramural research, as opposed to grant-based research, promotes.

“When you don’t have to sell people an attractive package to secure a grant, it allows researchers to try something a little different, a little more risky,” says Dr. Goldman. However, NIAAA’s Board of Scientific Counselors reviews all intramural research at least every four years and tenure track scientists are reviewed every two years.

DICBR also seeks to facilitate multidisciplinary work between labs and Institutes. “We collaborate across labs and that gives us access as needed to different tools and types of expertise. In a center like DICBR, we have so many different tools available, you can put together all the different pieces you need,” Dr. Goldman says.

For example, LNG collaborates with the NIAAA neuroscience lab and Laboratory of Physiologic Studies (LPS), as well as with labs at the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH).

These unique collaborations facilitate the kinds of programs Dr. Goldman believes are key to his lab’s success. Specifically, he says an emphasis on the “big data” of genomics and on functional genetics allow for exceptional types of discoveries.

“By sequencing genes, large parts of the genome, and genomes, we can identify genetic variants that influence alcohol use disorders and alcohol related behaviors in humans and animal models,” explains Dr. Goldman, “and then build on those discoveries.”

Collaborations like these are a priority for the Collaborative Research on Addiction at NIH (CRAN) program, the trans-NIH substance use, abuse, and addiction functional integration initiative formally established by NIH Director Dr. Francis Collins in 2012. NIAAA, along with NIDA and NCI, is a primary contributor to this initiative.

“The CRAN structure is often better able to address the issues of addiction in general,” said Dr. Kunos. “It allows for economies of scale in our intramural program—we’re sharing resources so we can do things even in tight budget times that we wouldn’t otherwise be able to do.”

Other DICBR collaborative programs with NIDA include a shared institutional review board (IRB) for all human research protocols, a joint center in addictions genomics, and a joint section on clinical psychoneuroendocrinology and neuropsychopharmacology, which runs translational and clinical studies on human patients to identify possible novel medications for addiction. There is also a joint optogenetic core that develops state-of-the art tools to study brain neuronal function in vivo, and a joint medicinal chemistry core that can synthesize and provide chemical substances if research requires it. In addition, about three years ago, Dr. Goldman and Dr. Kunos developed a joint scientific review committee with NIDA that scores every new NIAAA and NIDA human protocol for merit.

Over the years, NIAAA’s intramural program has produced numerous significant advances that are recognized across the alcohol research field. For example, Dr. Andrew Holmes’ laboratory of Behavioral and Genomic Neuroscience recently published a study in Molecular Psychiatry demonstrating a potential therapeutic approach for post-traumatic stress disorder. This approach is based on the lab’s discovery that endocannabinoids in the amygdala region of the brain play a role in the extinction of aversive or unpleasant memories. Drs. David Lovinger, Rui Costa, and Steven Vogel published a high profile paper in Nature that introduced a novel technique to study the interaction among different neurons in freely moving and behaving mice.

In fact, the number of articles that DICBR contributes to the esteemed Nature series of journals testifies to its scientific reputation. Relative to our size, NIAAA would need to publish two and a half papers in Nature journals to support NIH’s overall ranking. “In 2013, we had eight papers published, so we are doing more than our fair share to contribute to NIH’s reputation,” explained Dr. Kunos.

DICBR’s contribution to NIH’s reputation is also reflected in the number of prestigious awards that DICBR scientists have earned. Dr. Holmes recently received the Society for Neuroscience’s Waletzky Award for excellent research in neuroscience and substance abuse. He also received the Bennett Award from the Society of Biological Psychiatry for his basic research.

Dr. Lovinger received an NIH Director’s Award for “discovering novel forms of synaptic plasticity, providing outstanding leadership in the neuroscience of addiction, and demonstrating exemplary skills as a mentor.”

And, Drs. Pal Pacher and Kunos were both selected as Thomson Reuters Highly Cited Researchers in Pharmacology/Toxicology based on highly cited papers published between 2002 and 2012. Furthermore, last year, research by six different DICBR scientists was cited 1,000 or more times in the scientific literature and was published in the top ranking journals.

All told, NIAAA’s robust intramural research program, under the leadership of Dr. Kunos, has made significant progress in clinical and basic research, and continues to complement the work of the extramural scientists we support around the world.