Christopher R. Chitambar, MD, FACP
Professor of Medicine Division of Hematology/Oncology
Department of Medicine
Medical College of Wisconsin
9200 W. Wisconsin Avenue
Milwaukee, WI 53226
Phone: (414) 805-4600
Fax: (414) 805-4604
e-mail: chitambr@mcw.edu
Education
MD - Christian Medical College, Panjab University, India Residency in Internal Medicine: Brackenridge Hospital, Austin TX Fellowship in Hematology/Oncology: University of Colorado Health Sciences Ctr, Denver, CO
Research Focus
Dr. Chitambar's research encompasses both basic and clinical investigation. His laboratory is investigating the role of iron and iron transport and storage proteins (transferrin, transferrin receptor, hemochromatosis protein, ferritin, iron regulatory proteins), mitochondrial iron proteins and iron-dependent DNA synthesis (ribonucleotide reductase) in the growth of malignant cells. A major emphasis of his work is to develop strategies to modulate iron-dependent malignant cell growth, induce apoptosis and enhance the efficacy of cancer chemotherapy by perturbing iron homeostasis in cells. The cytotoxicity of chemotherapeutic drugs such as ribonucleotide reductase inhibitors (e.g. hydroxyurea, gemcitabine) and anthracyclines (e.g. doxorubicin) are affected by changes in iron homeostasis in tumors. Gallium complexes, antibodies against the transferrin receptor, iron chelators, and genetic manipulation of the hemochromatosis (HFE) gene are among the therapeutic strategies being investigated to inhibit tumor growth. Additional investigation is in progress to determine whether HFE gene mutations result in altered tumor growth and sensitivity to chemotherapy. Dr. Chitambar's research will lead to a better understanding of iron metabolism in malignant cells and will generate the development of novel cancer treatment strategies directed at targeting iron-dependent tumor cell growth.
Selected Publications
Chitambar CR
, Wereley JP, Heinman T and O'Brien WJ. Cellular adaptation to downregulated iron transport: Effects on the expression of the gene for ribonucleotide reductase. Biochemical Journal, 345:681-685, 2000.
Chitambar CR and Wereley JP. Iron transport in a lymphoid cell line with the hemochromatosis C282Y mutation. Blood, 97:2734-2740, 2001.
Green DA, Antholine WE, Wong SJ, Richardson DR, and Chitambar CR. Inhibition of Malignant Cell Growth by 311, a Novel Iron Chelator of the Pyridoxal Isonicotinoyl Hydrazone Class: Effect on the R2 subunit of Ribonucleotide Reductase. Clinical Cancer Research,7:3574-3579, 2001.
Kotamraju, S, Chitambar CR, Kalivendi SV, Joseph J, and Kalyanaraman B. Transferrin receptor-dependent iron uptake is responsible for doxorubicin-mediated apoptosis in endothelial cells – Role of oxidant-induced iron signaling in apoptosis. Journal of Biological Chemistry. 277:1719-1787, 2002.
Tampo Y, Kotaraju S, Chitambar CR, Keszler A, Joseph J, and Kalyanaraman B. Oxidative stress-induced iron signaling is responsible for peroxide-dependent oxidation of dichlorodihydrofluorescein in endothelial cells – The role of transferrin receptor-dependent iron uptake in apoptosis. Circulation Research, 92:56-63, 2003.
Chitambar CR. Gallium nitrate revisited. Seminars in Oncology 30: 1-4, 2003.
Chitambar CR and Wereley JP. Expression of the Hemochromatosis (HFE) gene modulates the cellular uptake of 67Ga. Journal of Nuclear Medicine 44:943-946, 2003.
Kotamraju S, Tampo Y, Keszler A, Chitambar CR, Joseph J, Haas AL and Kalynaraman B. Nitric oxide inhibits peroxide-induced transferrin receptor dependent iron uptake, oxidative damage and apoptosis in endothelial cells: Role of ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. USA. 100:10653-10658, 2003.
Kotamraju S, Kavlivendi SV, Konorev E, Chitambar CR, Joseph J and Kalyanaraman B. Oxidant-induced iron signaling in Doxorubicin-mediated apoptosis. Methods in Enzymology 378:362-382, 2004.
Kotamraju S, Tampo Y, Kalivendi SV, Joseph J, Chitambar CR, Kalyanaraman B. Nitric oxide mitigates perioxide-induced iron signaling, oxidative damage, and apoptosis in endothelial cells: Role of proteosomal function? Archives of Biochemistry and Biophysics, 423:74-80, 2004.
Chitambar CR. Gallium nitrate for the treatment of non-Hodgkin's lymphoma. Expert Opinion on Investigational Drugs, 13:531-541, 2004.
Chitambar CR. Gallium compounds as antineoplastic agents. Current Opinion in Oncology, 16: 547-552. 2004.
Chitambar CR. Apoptotic mechanisms of gallium nitrate. Basic and clinical investigations. Oncology 18: 29-44, 2004.
Chitambar CR. Gallium compounds as antineoplastic agents. Curr Opin Oncol. 16: 547-52, 2004.
Chitambar CR. Cellular iron metabolism: mitochondria in the spotlight. Blood. 105: 1844-5, 2005.