Biomedical Research Infrastructure Center

Jill Keith, Ph.D.

Jill Harp PhD photoDr. Jill Harp, a bioorganic chemist with postdoctoral training in pharmacology, and Dr. Sara Jones, a neurobiologist and electrochemist at Wake Forest University School of Health Sciences, are researching the development of pharmacotherapies to improve human health. They are focusing primarily on drug addiction, HIV-AIDS, and sickle cell. Cocaine and methamphetamine addiction has been the focus of research for the past several years. Unlike addictions to heroine, tobacco, and alcohol, there are no medications for addiction to cocaine. Behavioral programs have not been particularly successful, either. Dr. Harp is targeting the protein responsible for cocaine addiction, and his lab is synthesizing small molecules that are similar to cocaine's structure in an attempt to find a replacement therapy. This approach would allow the addict to be weaned from cocaine and eventually become drug free. After the compounds are made, further biological testing is done in collaboration with Drs. Sara Jones and Steven Childers. The lab has already identified compounds that warrant further study. The chronic use of illicit drugs is linked to an increased susceptibility to viral infections. Many findings confirm that there is a significant connection between cocaine exposure in vivo and the progression of HIV. The Harp lab hopes to uncover a therapy that would slow the progression of HIV replication in cocaine addicts infected with HIV. Researchers are also working to identify cocaine's role in enhancing this rate of replication. Teaming up with Dr. Dinesh Singh's lab has proven to be invaluable in this endeavor. Sickle cell anemia is a blood disorder that affects a protein found in red blood cells that help carry oxygen to all parts of the body. The disease arises from a genetic mutation that likely occurred in malaria-infested areas of Africa thousands of years ago. While normal blood cells have a life span of about four months, sickle shaped cells break down after about two weeks causing anemia. Dr. John Chapman of the Harp lab is synthesizing small molecules that will help increase the oxygen carrying capacity and life span of sickle shaped cells. This will alleviate the pain and suffering experienced by individuals with the disease.

Selected Publications

Gennady B. Lapa, Gary D. Byrd, Alla A. Lapa, Evgeny A. Budygin, Steven R. Childers, Sara R. Jones and Jill J. Harp. The synthesis and biological evaluation of dopamine transporter inhibiting activity of substituted diphenylmethoxypiperidines. Bioorg Med Chem Lett. 2005;15(22):4915-8.

Lapa GB, Mathews TA, Harp J, Budygin EA, Jones SR. Diphenylpyraline, a histamine H1 receptor antagonist, has psychostimulant properties. Eur J Pharmacol. 2005; 506(3):237-40

Bennett BA, Hollingsworth CK, Martin RS, Harp JJ. Alteration in dopamine transporter function after methamphetamine treatment. Br Res 1997; 782:219-227.

Porter NA, Su Q, Harp JJ, McPhail AT. The stereoselective synthesis of succinamide derivatives via enolate oxidative coupling. Tet Lett 1993; 4457-4460.

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