Heads of Laboratories
Mary Jeanne Kreek, M.D.
Senior Attending Physician
Patrick E. and Beatrice M. Haggerty Professor
Laboratory of the Biology of Addictive Diseases
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 to 1984 that the second most common risk group for HIV-1/AIDS is parenteral drug users.
Dr. Kreek’s research focuses on the endogenous opioid system, which manages stress and pain, and the roles that specific opioid peptides and their receptors play in normal and abnormal circumstances. Heroin and morphine, which mimic endogenous peptides, as well as cocaine and alcohol activate these opiate receptors, directly or indirectly. Dr. Kreek and her colleagues examine receptor and peptide function in animals that are given or are allowed to selfadminister a drug of abuse in chronic or acute doses to study how this exposure impacts the brain’s neurochemistry, molecular neurobiology and circuitry and how these effects compare to potential treatments. The lab also studies genetic, epigenetic, physiological and behavioral effects of drug administration on the endogenous opioid system and related signaling networks. The scientists use microdialysis in rats and mice to conduct dynamic studies of neurotransmitter release and peptide processing in the brain.
Using molecular approaches of diverse types, Dr. Kreek’s lab conducts gene expression studies in both animals and humans, measuring the expression of opioid receptors, opioid peptides and related proteins and transporters in specific brain regions. The lab also identifies naturally occurring variations in gene sequences called genetic polymorphisms in postmortem human brain tissue and peripheral cells. Exploring the medical complications of addictions, the lab found 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 the components underlying the neurobiology of addictive disorders, clinical studies look at how select neuropeptides affect cocaine and heroin addicts, former opiate addicts maintained on methadone or other treatments and patients dependent on alcohol, nicotine or both. Patients are examined for polymorphisms near 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 work identified and characterized a functional single nucleotide polymorphism in the μ-opioid receptor, which increases the likelihood of addiction in a person exposed to opioids and significantly alters stress responsivity in healthy subjects. Her more recent work identified functional polymorphisms of the dynorphin gene. Examinations of different ethnic populations have also revealed that other 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 throughout the world. 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 perceptions of reward and dysphoria.
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 the Wellesley Alumnae Achievement Award in 2012, 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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