Research News

Cleveland Clinic’s Northern Ohio Alcohol Center (NOAC) launched ten years ago to address alcohol-associated liver disease and explore the impact of alcohol on other organs.

Laura Nagy, PhD, the director of the NOAC, applied for initial grant funding from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), a branch of the National Institutes of Health, because she saw an important, multidisciplinary opportunity for researchers to take on a critical public health issue.

“When I first joined Cleveland Clinic, very few people were studying alcohol-associated organ injury, yet there were many expert investigators in the areas that are susceptible to alcohol injury,” Dr. Nagy says. “By bringing together my group’s expertise in different preclinical models, I believed we could expand our range of studies in alcohol research.”

Researching new angles, seeking solutions

Alcohol-associated liver disease (AALD) develops when frequent, heavy alcohol use damages the liver. It is considered a major public health concern because of its prevalence and severity. The problem is growing because alcohol contributes to a substantial portion of liver-related deaths, and AALD can progress to more serious conditions.

Alcohol is also associated with injuries to other organs – even if a person is not considered a heavy drinker. Currently, there is no treatment or cure for AALD other than eliminating alcohol. Cleveland Clinic’s researchers want to find more solutions.

Over the past 10 years, multiple labs have expanded their work to include alcohol-associated research. These studies have resulted in many high-impact publications, including the sample listed below:

• J. Mark Brown, PhD, who studies the influence of the gut microbiome on disease progression. His lab’s discovery of an association between trimethylamine (TMA) and AALD is the first proof-of-concept that targeting microbial enzymes can improve disease outcomes – a finding that has broad implications for drug discovery.
• Srinivasan Dasarathy, MD, whose research focus areas include sarcopenia, which is the gradual age-related loss of muscle mass, strength and function.
• Dimitrios Davalos, PhD, whose interest in microglia and in vivo imaging work has enhanced studies connected to AALD.
• Dr. Nagy, whose lab work includes studies on how alcohol affects innate immune function.

Supporting future AALD research

Multiple research components and associated cores in the NOAC support scientists and encourage innovation. In addition to an administrative core that sponsors speakers and retreats, and resource cores that provide cell and preclinical models, the NOAC also includes a clinical core. This core, connected to Cleveland Clinic’s BioRepository, grants researchers access to biological samples from healthy individuals, heavy drinkers, people with AALD and people with metabolic liver disease.

A pilot core provides funding for one or two projects per year. Some pilot award recipients have gone on to get R01 (independent) research funding and started their own labs, either at other research institutions or within Cleveland Clinic – including Gail Cresci, PhD, and Dr. Brown.

Over the past decade, 10 trainees associated with the NOAC have received additional research grants from the NIAAA – a statistic that highlights the importance of the researchers' ongoing work.

“I received a pilot grant as a young investigator, which started my lab’s maiden voyage into alcohol-focused research,” Dr. Brown says. “The NOAC is designed to bring together expertise to tackle hard scientific questions, and also plays a role in the education and training of young scientists across Cleveland Clinic Research.”

For trainees and young scientists, opportunities to present their work and attend conferences – in addition to working alongside principal investigators and researchers across disciplines – are particularly valuable.

“My involvement with the NOAC has been an important part of my scientific training and development at Cleveland Clinic,” says Venkateshwari Varadharajan, research associate in Dr. Brown’s lab. “The center has provided me with a strong environment for collaboration, mentorship and research presentations as I engage in work focused on understanding molecular mechanisms that contribute to alcohol-associated liver injury.”

More work to do

Funding for the NOAC has just been renewed for a third five-year cycle. The P50 grant, which supports a broadly based, multidisciplinary, often long-term research project focused on a specific theme, will maintain the NOAC’s objective to uncover mechanisms related to alcohol and tissue injury.

“As our work continues for the next five years and beyond, we hope to identify and develop treatments that help patients prevent or recover from the impacts of alcohol-associated diseases,” Dr. Nagy says. “With the way the NOAC reflects Cleveland Clinic’s approach to team science and focus on patient outcomes, I’m optimistic that we’ll continue to expand the breadth and depth of alcohol research.”