Heads of Laboratories
Senior Attending Physician
Patrick E. and Beatrice M. Haggerty Professor
Laboratory of the Biology of Addictive Diseases
Mary.Jeanne.Kreek@rockefeller.edu
An estimated 25 to 33 percent of people who take a short-acting opiate drug — usually heroin — develop an addiction to it. This suggests that some people are naturally more vulnerable to addiction than others and that genetics may play a role along with direct drug-induced effects and environmental and psychological factors. Dr. Kreek investigates how genetic factors, as well as neurobiological alterations, factor into addictive diseases such as opiate addiction, nicotine addiction, cocaine dependency and alcoholism.
Dr. Kreek investigates the biological basis of addictive diseases as well as existing and novel treatments for these conditions. Her lab also researches the medical complications of drug abuse, such as hepatitis C and AIDS. This clinical and lab-based experimental approach led her lab to discover in 1983–84 that the second most common risk group for HIV-1/AIDS is parenteral drug users.
Dr. Kreek’s research, both clinical and experimental, focuses on the endogenous opioid system, the part of the body that manages stress and pain, and the roles that specific opioid peptides and their receptors play in both normal and abnormal circumstances. Heroin and morphine — which mimic the action of endogenous peptides — as well as cocaine and alcohol activate these opiate receptors, directly or indirectly. By comparing how these receptors and peptides function in healthy animals that are not given drugs with how they function in animals that are given or are allowed to self-administer a drug of abuse in either chronic or acute doses, Dr. Kreek and her colleagues study how chronic and acute exposure impacts or alters the brain’s neurochemistry, molecular neurobiology and circuitry and how these effects differ from the impacts of potential treatment agents. The lab further studies the genetic, physiological and behavioral effects of these drug administrations on the endogenous opioid system and related signaling networks. The scientists also use microdialysis in rats and mice to conduct dynamic studies of neurotransmitter release and peptide processing in specific brain regions.
Using microarray technology and a variety of other molecular approaches, Dr. Kreek’s lab conducts gene expression studies in both animal models and human tissue, measuring the expression of opioid receptors, opioid peptides and related proteins and transporters in specific brain regions. Dr. Kreek’s laboratory also identifies naturally occurring variations in gene sequences called genetic polymorphisms in postmortem human brain tissue and peripheral cells. In work that explores the medical complications of addictions, Dr. Kreek’s lab has shown that former injection-drug users with past hepatitis B infection who lack a particular antibody may have a silent form of the disease, a finding with epidemiological and medical implications.
With the goal of identifying specific and different components underlying the neurobiology of addictive disorders, clinical studies look at how select neuropeptides affect cocaine and heroin addicts, recovering and former opiate addicts maintained on methadone or other treatments and patients dependent on alcohol, nicotine or both. Her lab examines patients for polymorphisms in and outside of the coding regions of genes that may play a role in addiction and in genes that may alter responses to medications (pharmacogenetics) and affect normal physiology (physiogenetics). Her recent work has shown that a functional single nucleotide polymorphism in the 
-opioid receptor may impart a greater likelihood of developing an addiction to a person exposed to opioids and that it significantly alters stress responsivity in healthy subjects. Examinations of different ethnic populations have also revealed that specific polymorphisms may have a greater association with addictive disorders.
Dr. Kreek is well known for her pioneering work in the development of methadone maintenance therapy for heroin addiction in the 1960s, a therapy that has become common practice in many parts of the United States and other countries. She also was one of the first to document that drugs of abuse significantly alter expression of specific genes in specific brain tissues and alter normal functions that lead to perceptions of reward and dysphoria.
CAREER
Dr. Kreek received her B.A. from Wellesley College in 1958 and her M.D. from Columbia University College of Physicians and Surgeons in 1962. She (and also the late Marie Nyswander) joined Rockefeller in the laboratory of Vincent Dole in 1964.
Dr. Kreek received a Laurea ad Honorem in Farmacia from the University of Bologna in 2010, an honorary doctorate from Tel Aviv University in 2007, the Gold Medal for distinguished achievements in academic medicine from the Columbia University College of Physicians and Surgeons Alumni Association in 2004, an honorary doctorate from the University of Uppsala in 2000 and the Nathan B. Eddy Memorial Award for Lifetime Excellence in Drug Abuse Research and the R. Brinkley Smithers Distinguished Scientist Award in 1999. She received a Specific Recognition Award for Research in the Science of Addiction from the Executive Office of the President in 1998, and in 1996 she was given the Betty Ford Award.
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