Carmen R. Bergom, MD, PhD, MPhil
Instructor, Department of Radiation Oncology
Medical College of Wisconsin, MD (2008)
Medical College of Wisconsin, PhD (2006)
University of Cambridge, UK, MPhil (1999)
Members of the Rho, Rac, Ras, and Rap families of small GTPases regulate cancer development and progression. In addition, Ras and other small GTPases can alter the sensitivity of cancer cells to radiation and chemotherapy. Identifying new ways to suppress small GTPase activation in cancers may provide new treatment approaches. While most small GTPases promote cancer and are oncogenic, a few of the small GTPase family members are actually tumor suppressors. Our laboratory studies members of the small GTPase family which have tumor suppressor activities.
The DiRas family of small GTPases has the unique property of having tumor suppressive actions, rather than the tumor promoting actions common to most other small GTPases. DiRas1 and DiRas2 are poorly characterized thus far, with the literature consisting of only a few publications demonstrating tumor suppressor functions in central nervous system and esophageal malignancies. DiRas3 (ARHI) is the most studied of the DiRas proteins. DiRas3 is downregulated or lost in 40-70% of ovarian and breast cancers. Overexpression of DiRas1 inhibits Ras-mediated cellular transformation of NIH3T3 cells, and DiRas3 dramatically inhibits cells growth of breast and ovarian cancer cells. Our laboratory is currently studying the roles of DiRas signaling in breast cancer and other malignancies.
Our long-term goal is to understand how small GTPases can be manipulated to enhance cancer treatment. The knowledge obtained from our studies may help define novel signaling pathways that modulate the functions of pro-oncogenic small GTPases in the Ras family. We hypothesize that knowledge of DiRas family tumor suppressive signaling can identify new targets for cancer therapeutics and help to identify novel ways in which to abolish pro-oncogenic small GTPase signaling which is critical in the development and progression of a number of malignancies.
Gao C, Sun W, Christofidou-Solomidou M, Sawada M, Newman DK, Bergom C, Albelda SM, Matsuyama S, Newman PJ. PECAM-1 functions as a specific and potent inhibitor of mitochondrial-dependent apoptosis. Blood 102:169-179, 2003.
Maas M, Stapleton M, Bergom C, Mattson DL, Newman DK, Newman PJ. Endothelial cell PECAM-1 confers protection against endotoxic shock. AJP Heart Circ Physiol 288:159-64, 2005.
Bergom C, Gao C, Newman PJ. Mechanisms of PECAM-1-mediated cytoprotection and implications for cancer cell survival. Leuk Lymphoma 46:1409-1421, 2005. Review.
Bergom C, Goel R, Paddock C, Gao C, Newman DK, Matsuyama S, Newman PJ. The cell-adhesion and signaling molecule PECAM-1 is a molecular mediator of resistance to genotoxic chemotherapy. Cancer Biol Ther 5:1699-1707, 2006.
Bergom C, Paddock C, Gao C, Holyst T, Newman DK, Newman PJ. An alternatively spliced PECAM-1 isoform is expressed at high levels in human and murine tissues and reveals a novel role for the C-terminus of PECAM-1 in cytoprotective signaling. J Cell Sci 121:1235-1242, 2008.
Bergom C, Kelly T, Wagner J, Morrow N, Wilson JF, White J. Prone whole breast irradiation using 3-dimensional conformal radiotherapy in women undergoing breast conservation for early disease yields high rates of excellent-good cosmetic outcomes in patients with large-pendulous breasts. Int J Rad Biol Phys, 83:821-828, 2012.
Bergom C, Kainz K, Morrow N, Ahunbay E, Prior R, White J. Partial breast irradiation (PBI) in the prone position using image-guided IMRT: Preliminary results from a phase II study. Accepted, Radiotherapy and Oncology, May 2013.
Hauser AD, Bergom C, Schuld N, Lorimer EL, Li R, Mackinnon AC, Williams CL. The SmgGDS splice variant SmgGDS-558 is a key promoter of tumor growth and RhoA activation in breast cancer. Submitted July 2013.