Ram Ganapathi, Ph.D., is Director of the Clinical Pharmacology Program at the Taussig Cancer Institute, Cleveland Clinic.

The laboratory of clinical pharmacology within the Experimental Therapeutics Program of the Cleveland Clinic Taussig Cancer Institute was originally established in spring of 1982 with a laboratory program focused on mechanisms by which cancer cells evade chemotherapy. This program has been continuously supported by the National Cancer Institute and National Institutes of Health for more than 25 years, and it is built on the strong belief that rational and effective treatment of cancer requires a comprehensive understanding of the biology of the tumor being treated as well as an understanding of the mechanisms of action and pathways that regulate resistance to the anti-cancer drug.

This information is integrated in drug development and Phase I clinical trials that are focused on defining safety and toxicity of new drugs being tested in patients with cancer. Keeping these goals in perspective, promising experimental results from the laboratory and an understanding of regulation of genes in the cancer are actively pursued in translational studies for targeted therapy in kidney cancer, leukemia and ovarian cancer, to maximize efficacy and reduce toxicity of cancer chemotherapy.

Our studies in acute myeloid leukemia (AML), a form of leukemia commonly found in adults are focused on an enzyme called topoisomerase II that is essential for cell division and involved in cell differentiation in mammalian cells. Towards understanding the regulation of topoisomerases during cell growth and differentiation, our studies are focused on determining the regulatory function of topoisomerase IIa and ß as down stream effectors of all trans retinoic acid-induced effects on cell growth and differentiation in models of human AML and leukemia cells from patients with AML.

This enzyme is also a target for several anti-cancer drugs that are widely used to treat patients with leukemia, breast cancer and lung cancer, and our studies with topoisomerase II have revealed that the defective addition of phosphate at specific sites in the enzyme is a mechanism by which tumor cells evade chemotherapy. Using results from laboratory engineered model systems to understand how the addition of phosphate makes this enzyme vulnerable to drug treatment, leukemia cells from patients with AML are being tested to develop novel treatment strategies.

Our work in kidney cancer and ovarian cancer are focused on understanding how the screening for specific genes or mutations in a gene can be used to predict the effects of targeted therapy and treatment failure. Based on the recent identification of a few important genes in these cancers, we are studying their regulation to develop new paradigms for targeted therapy and novel treatment options when relapse from the cancer is a problem.

Doctorate - Massachusetts College of Pharmacy and Health Sciences - MA Campus

Boston, MA USA
1977

Undergraduate - Andhra University

India
1971

Fellowship - Dana-Farber Cancer Institute

Boston, MA USA

Fellowship - University of Miami Hospitals and Clinics

Miami, FL USA

• Principal Investigator, "Effect of Calmodulin Inhibitors on Adriamycin Resistance”. Period of support: 5/1/84 - 4/30/01 Supported by USPHS Grant 1 RO1 CA35331
• Principal Investigator, "Regulation of Topoisomerase II-Drug-DNA Ternary Complex”. Period of support: 1/1/99 - 8/31/08. Supported by USPHS Grant 1 RO1 CA74939.
• Co-Principal Investigator, ”Topoisomerases in Retinoid Induced Differentiation”. Period of Support: 2/1/00 - 1/31/05. Supported by USPHS Grant 1 RO1 DK56917.
• Principal Investigator, “Topoisomerase IIb in Myeloid Differentiation by Retinoids”. Period of Support: 7/1/06 - 6/30/11. Supported by USPHS Grant 1 RO1 CA117928.
• Co-Investigator, "Phase I Multiple-Dose Safety and Pharmacokinetic Clinical Trial of Sulindac Sulfone in APC Patients ". Period of Support: 6/30/95 - 6/29/98. Supported by USPHS Grant NO1-CN-55119.
• Co-Investigator, "Phase I Single and Multiple-Dose Safety and Pharmacokinetic Clinical Study of a Chemopreventive Agent". Period of Support: 6/30/96 - 12/31/02. Supported by USPHS Grant NO1-CN-55131.
• Co-Investigator, "Phase II Study of SERM3 vs. Tamoxifen vs. Placebo in Premenopausal Women with an Increased Risk for Breast Cancer. Period of Support: Oct. 1, 1999-June 30, 2003

• American Association for Cancer Research
• American Association for the Advancement of Science
• New York Academy of Sciences
• International Society for Analytical Cytology

• Clinical Pharmacology

Cleveland Clinic physicians and scientists report if they have any collaborations with the pharmaceutical or medical device industries as part of the Cleveland Clinic’s procedures. The Cleveland Clinic publicly discloses payments to its physicians and scientists for speaking and consulting of $5,000 or more per year, and any equity, royalties, and fiduciary relationships in companies with which they collaborate. In publicly disclosing this information, the Cleveland Clinic tries to provide information as accurately as possible about its doctors’ connections with industry and those of their immediate family members. As of 7/30/2008, Dr. Ganapathi has reported no financial relationship with industry that is applicable to this listing. Patients should feel free to contact their doctor about relationships with industry and how the relationships are overseen by the Cleveland Clinic. To learn more about the Cleveland Clinic’s policies on collaborations with industry and innovation management, go to our Integrity in Innovation page.

• English