Kenneth Cowan, MD Ph.D
Professor & Director
Director, Eppley Institute
Director, Fred & Pamela Buffett Cancer Center
Professor of Oncology
Academic office mailing address:
UNMC Eppley Cancer Center
986805 Nebraska Medical Center
Omaha, NE 68198-6805
B.A. - University of Rochester, Chemistry
MD, PhD - Case Western Reserve University, Pharmacology
Kenneth H. Cowan, MD, PhD, became the director of the Fred & Pamela Buffett Cancer Center (formerly the UNMC Eppley Cancer Center) and the Eppley Institute for Research in Cancer and Allied Diseases in August 1999. The Fred & Pamela Buffett Cancer Center, created in 1983, is an NCI-designated clinical cancer center, uniting cancer researchers throughout the UNMC campus into a larger single entity. The Eppley Institute was founded in 1961. Dr. Cowan is the sixth director in the institute’s 40 year history. The Eppley Institute for Research in Cancer and Allied Diseases is a division of the University Of Nebraska Medical Center with 27 basic science laboratories headed by principal investigators focused on cancer research.
Prior to this, since completing his residency training at Texas Southwestern Affiliated Hospitals in Dallas, Dr. Cowan spent 21 years in the Public Health Service at the National Cancer Institute. Since 1988, he served as Chief of the Medical Breast Cancer Section, Medicine Branch. In his NCI position, he was responsible for overseeing laboratory researchers and clinical staff involved in basic and clinical research in breast cancer.
A New York City native, Dr. Cowan earned his undergraduate degree at the University of Rochester in Rochester, NY, and his medical and doctorate degrees from Case Western Reserve University in Cleveland. He has authored more than 240 papers for scientific journals and has been an invited guest lecturer at numerous scientific conferences.
Our laboratory is interested in understanding the role of tumor suppressor genes in the development of human tumors. We have constructed a series of recombinant viral vectors to study the effects of overexpression of tumor suppressor genes on the biology of breast cancer and for use in gene therapy of human tumors. Recombinant non-replicating adenoviral vectors are useful for these studies for several reasons; 1) human breast cancer cells (as well as many other normal and transformed human cell lines) contain high levels of adenoviral receptors and are readily infected by adenoviral vectors; 2) adenoviral vectors infect both replicating and quiescent cells; and 3) high levels of intracellular transgene expression is detected within 12 hours following infection with adenoviral vectors.
We have constructed a series of adenoviral vectors, including a vector that expresses the wild type breast cancer tumor suppressor gene BRCA1, and have studied the effects of tumor suppressor gene overexpression on cell cycle regulation and apoptosis in human breast cancer cells both in vitro and in vivo.
Our laboratory has also been involved in identifying the mechanisms associated with development of multi-drug resistance and the regulation of expression of drug resistance genes in human tumor cells. We have isolated a series of drug resistant human breast cancer cell lines, studied their pharmacological characteristics, and identified the genes associated with resistance in each cell line. We are also examining the ability to transfer drug resistance genes into hematopoietic stem cells in clinical trials in patients with breast cancer patients treated with high dose chemotherapy and hematopoietic stem cell rescue. The goal of these studies is to determine whether patients can be reconstituted long term with gene modified hematopoietic cells and whether the expression of drug resistance genes in hematopoietic progenitor cells will permit treatment with higher doses of chemotherapy and overcome clinical drug resistance in patients with breast cancer.
Dixon, K.H., Lanpher, B.C., Chiu, J., Kelley, K., and Cowan, K.H.: A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport-deficient cells. J. Biol. Chem. 269(1):17-20,1994.
Morrow, C., Nakagawa, M., Goldsmith, M.E., Madden, M.J., and Cowan, K.H.: Reversible transcriptional activation of mdr1 by sodium butyrate treatment of human colon cancer cells. J. Biol. Chem. 269(14):10739-10746,1994.
Goldsmith, M.E., Gudas, J.M., Schneider, E., and Cowan, K.H.: Wild type p53 stimulates expression from the human multidrug resistance promoter in a p53-negative cell line. J. Biol. Chem. 270(4):1894-1898,1995.
Dunbar, C., Cottler-Fox, M., O'Shaughnessy, J.A., Doren, S., Carter, C., Berenson, R., Brown, S., Moen, R., Greenblatt, J., Stewart, F.M., Leitman, S., Wilson, W., Cowan, K.H., Young, N.S., and Neinhuis, A.R.: Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contributed to long-term engraftment after autologous transplantation. Blood 85:3048-3057,1995.
Gudas, J., Nguyen, H., Li, T., Hill, D., and Cowan, K.H.: Effects of cell cycle, wild type p53 and DNA damage on p21CIPI/WafI expression in human breast epithelial cells. Oncogene 11:253-261,1995.
Moscow, J.A., He, R., Gong, M., Sgagias, M., Dixon, K.H., Anzick, S., Meltzer, P.S., and Cowan, K.H.: Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis of its expression in transport-deficient methotrexate-resistant human breast cancer cells. Cancer Res. 55(17):3790-3794,1995.
Gudas, J.M., Nguyen, H., Li, T., and Cowan, K.H.: Hormone dependent regulation of BRCA1 in human breast cancer cells. Cancer Res. 55:4561-4565,1995.
O'Shaughnessy, J.A., Tolcher, A., Riseberg, D., Venzon, D., Zujewski, J., Noone, M., Gossard, M., Danforth, D., Jacobson, J., Chang, V., Goldspiel, B., Keegan, P., Giusti, R., and Cowan, K.H.: Prospective, randomized trial of 5-fluorouracil, leucovorin, doxorubicin, and cyclophosphamide chemotherapy in combination with the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein (PIXY321) versus GM-CSF in patients with advanced breast cancer. Blood 87(6):2205-2211,1996.
Emmons, R.V.B., Doren, S., Zujewski, J., Cottler-Fox, M., Carter, C.S., Hines, K., O=Shaughnessy, J.A., Leitman, S.F., Cowan, K., and Dunbar, C.E.: Retroviral gene transduction of adult peripheral blood or marrow decreased CD34+ cells for 6 hours without growth factors or an autologous stroma does not improve making efficiency assessed?in vivo. Blood,89:4040-4046, 1997.
Craig, C., Wersto, R., Kim, M., Ohri, E., Li, Z., Katayose, D., Lee, S-J., Trepel, J., Cowan, K., and Seth, P.: A recombinant adenovirus expressing p27Kip1?induces cell cycle arrest and loss of cyclin-cdk activity in human breast cancer cells. Oncogene, 14:2283-2290, 1997.
Additional Publications at PubMed.Gov: https://www.ncbi.nlm.nih.gov/pubmed