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Paula Hoffman, Ph.D.

Paula Hoffman headshot
Paula L. Hoffman, Ph.D.
is a professor in the Department of Pharmacology at the University of Colorado Denver. Dr. Hoffman recently won the RSA Distinguished Researcher Award at the Research Society on Alcoholism’s 36th annual meeting during June 2013 in Orlando, Florida.

Writer Sherry Wasilow interviewed Dr. Hoffman from her office at the University of Colorado Denver.

SW: What is your current research focus?

PLH: The influence on the risk for developing alcohol addiction is about equally divided between genetic and environmental factors. Our research is primarily aimed at learning about the genetic differences in individuals that contribute to that risk.

We study behaviors that are important for the development of addiction, but are more easily modeled in animals. Levels of alcohol drinking are genetically influenced, and a large number of paula hoffman quotegenes contribute to even this relatively simple behavior. Instead of focusing on a particular gene or protein, we take an unbiased approach to determine – through experimental and computational techniques – the combinations of genes that help regulate alcohol drinking. These studies of the systems that underlie risk for complex traits help bridge the gap that exists in human studies, that is, the gap between finding genetic differences, and determining which of these differences contribute(s) to the risk of alcohol addiction.

SW: How did you begin your work in the field of alcohol studies?

PLH: When I began graduate work, I was interested in endocrinology, how hormones work at the molecular level.
This led me to study the structure of peptide or small protein hormones, and how they interact with their receptors, the binding proteins on the cell surface that recognize the hormones. Toward the end of my graduate work, I was looking at the functional effects of peptide hormones on learning and memory. When I moved to the University of Illinois, Chicago, I became interested in studying alcohol tolerance, which may – like learning – represent an adaptation of the brain to external stimuli. My colleagues and I showed that peptide hormones did affect alcohol tolerance in a manner similar to their effects on learning and memory. This was the beginning of my research on brain adaptations that are key to the development of alcohol addiction.

SW: Why are you committed to, or why did you choose, this research focus?

PLH: Our prior studies of alcohol tolerance led us to the question: What does alcohol, which is a simple molecule without specific receptors, do to brain neurochemistry? Some researchers believed that alcohol affects the lipid components of brain cell membranes. We hypothesized that alcohol would affect the interactions of proteins that reside within the cell membranes, including the interactions of cell surface receptors with proteins that mediate the effects of neurotransmitters on intracellular signaling processes.

After moving to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Intramural Program, we eventually found that a subtype of glutamate receptor, the N-methyl-D-aspartate receptor (NMDA) receptor, is very sensitive to perturbation by alcohol (click for link). This work again led us back to the study of adaptation to alcohol, since the NMDA receptor is important for learning and memory processes, as well as tolerance, and also plays a key role in the neuronal hyperexcitability that can lead to alcohol withdrawal seizures, which are a sure sign of physical dependence on alcohol.

After moving to the University of Colorado, I became interested in the genetic basis of alcohol adaptation, utilizing lines of mice selectively bred for differences in alcohol sensitivity and tolerance. We began to initiate “systems” analysis of the genetic basis for alcohol-related traits, an approach requiring collaboration with colleagues skilled in molecular biology, as well as biostatisticians and bioinformaticians.


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