Abdul Moshin Mian, Ph.D.
Professor of Medicine
Description of Research
Dr. Mian’s research focuses on the use of anti-viral nucleosides for the treatment of AIDS-associated lymphomas. Lymphomas in immunocompromised individuals are frequently associated with the herpes virus. Therapeutic outcomes of these lymphomas when treated with AZT depend on the presence of EBV and/or levels of BCL-2. The effects of AZT in EBV-positive lymphomas are mediated via apoptosis, whereas in EBV-negative lymphomas failed to induce apoptosis as determined by Annexin V staining methodology. Therefore, it seems EBV plays a role in inhibiting the tumor growth by this anti-viral drug in sensitive cells. However, AIDS lymphomas that over-express BCL-2 (an anti-apoptotic protein) even when EBV is positive are resistant to AZT-mediated apoptosis. Thus, absence of EBV infection and/or higher expression of BCL-2 render these lymphomas resistant to AZT treatment.
In order to improve the therapeutic outcome of these tumors, researchers in Dr. Mian’s laboratory are examining new and more effective congeners, as well as mechanism of growth inhibition, and the metabolism of the active anti-viral molecule(s). Thus, by utilizing the primary cultures from the responding and non-responding AZT treated patients as well as established culture lines, researchers are evaluating the new and modified anti-viral compounds for their growth inhibitory properties. These metabolism studies are being carried out in EBV positive and negative tissue cultures. Dr. Mian and his researchers aim to decipher the active metabolite(s) and establish the probable site of inhibition by AZT. Results from these experiments may provide better understanding and improved agents to combat this malignancy.
- Designed and synthesized new chemotherapeutic congeners with anti-viral and anti-cancer properties. In addition to being therapeutic agents, some of the nucleoside antimetabolites have helped in the understanding of biosynthetic pathways.
Selected Cancer-Related Publications
- Leclerc GJ, Mou C, Leclerc GM, Mian AM, Barredo JC. Histone deacetylase inhibitors induce FPGS mRNA expression and intracellular accumulation of long-chain methotrexate polyglutamates in childhood acute lymphoblastic leukemia: implications for combination therapy. Leukemia 24:552-62, 2010. Read more »
- Sandberg DI, Solano J, Petito CK, Mian A, Mou C, Koru-Sengul T, Gonzalez-Brito M, Padgett KR, Luqman A, Buitrago JC, Alam F, Wilkerson JR, Crandall KM, Kuluz JW. Safety and pharmacokinetic analysis of methotrexate administered directly into the fourth ventricle in a piglet model. J Neurooncol 100:397-406, 2010. Read more »