Bernard W Futscher, PhD
Professor; Assistant Research Scientist; Investigator, Center For Toxicology
Department:
Pharmacology and Toxicology
(520) 626-4646
Fax:
(520) 626-5462
E-mail:
Location:
Pharmacy 236
Bio / Research:
My laboratory focuses on the molecular origins of human cancer. More specifically, my laboratory has 3 inter-related research objectives based on the underlying concept that developing an in-depth understanding of epigenetic mechanisms that govern cell fate will allow for the development of more effective strategies for the prevention, treatment, and cure of cancer.
First, we wish to identify which epigenetic mechanisms participate in the transcriptional control of genes important to growth and differentiation. Second, we seek to determine how these epigenetic mechanisms, and therefore epigenetic homeostasis, become compromised during oncogenesis. Third, using our new and more complete understanding of epigenetic control of the genome, we are developing rational new therapeutic strategies that seek to repair these defects in the cancer cell and transcriptionally reprogram the malignant cancer cell to a benign state.
To reach our objectives, a variety of in vitro models of cancer have been developed to address emerging hypotheses that are inferred from the literature in basic and clinical science as well as our own data. Results from these in vitro studies are then translated to the clinical situation to determine their meaning in the actual clinical face of the disease. Similarly, we attempt to take information obtained from the genome-wide assessment of clinical specimens in order to help guide our thinking and develop new hypotheses that can be tested experimentally in our in vitro models.
An example of how this approach can work is provided below.
Publications:
Futscher B.W., Oshiro M.M., Wozniak R.J., Holtan N., Hanigan C.L., Duan H., & Domann F.E.: Role for DNA methylation in the control of cell type-specific maspin expression. Nature Genetics, 31:175-179, 2002 (Associated commentary on pgs 123-4).
Nouzova M., Holtan N., Oshiro M.M., Isett R.B., Munoz-Rodriguez J.L., List A.F., Narro M.L., Miller S.J., Merchant N.C., & Futscher B.W.: Epigenomic changes during leukemia cell differentiation: Analysis of histone acetylation and cytosine methylation using CpG island microarrays. Journal Pharmacology & Experimental Therapeutics, 311:3, 968-1032, 2004.
Wozniak R.J., Klimecki W.T., Lau S.S., Feinstein Y., Futscher B.W.: 5-Aza-2’-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene, 2006, doi:10.1038/sj.onc.1209763.
Novak P., Jensen T., Oshiro M.M., Wozniak R.J., Nouzova M., Watts G.S., Klimecki W.T., Kim C., & Futscher, B.W.: Epigenetic Inactivation of the HOXA Gene Cluster in Breast Cancer. Cancer Res, 66(22):10664-10670, 2006.