Margaret M. Briehl, PhD

Professor of Pathology

E-Mail Address: 
Phone Number: 
(520) 626-6827
Fax: 
(520) 626-1027
Short Bio: 

Dr. Margaret Briehl received her BS in Microbiology and PhD in Molecular and Cellular Biology from the University of Arizona in 1981 and 1988, respectively. She conducted postdoctoral research at the The University of Arizona Cancer Center and the Swiss Institute for Experimental Cancer Research in Lausanne, Switzerland. In 1994 she joined the Department of Pathology as a Research Assistant Professor. Dr. Briehl was promoted to the tenure-track in 1997. She achieved the rank of Associate Professor in 2003 and full Professor in 2009. Dr. Briehl's research laboratory has been funded by the DOD and the NIH to study mechanisms by which the redox environment of cancer cells control therapy-induced apoptosis.

Dr. Briehl's teaching contributions include co-directing the Pathology 515 Human Pathology Course for PhD students in the biomedical sciences, directing a student research seminar series in Cancer Biology Graduate Interdisciplinary Program and teaching in the Foundations, Aging and Cancer Blocks of the AzMed curriculum. She has been the dissertation advisor for five doctoral students and served on the dissertation committee of an additional 42 graduate students. Dr. Briehl has reviewed grants for the DOD and NIH, and manuscripts for numerous journals. She is currently the Vice President of Finance for the Society of Free Radical Biology and Medicine.

Research Information
Research Program: 
1. Therapeutic Development
Member Status: 
Member
Summary of Research Activity: 

Dr. Briehl’s laboratory's is investigating the mechanisms by which the redox state of cancer cells causes resistance to therapy-induced apoptosis. Cellular redox state is determined by the sum of prooxidants (e.g., the levels of reactive oxygen species) and antioxidants (e.g., proteins like catalase and small molecules like vitamin E) in the cell. Cancer cells have frequently undergone changes consistent with an altered ability to handle oxidative stress. Genetic differences in proteins that protect cells against oxidative stress have been associated with an increased risk of cancer. Epidemiological studies suggest that a diet rich in fruits and vegetables confers a lower risk of cancer. One idea is that the high antioxidants content of fruits and vegetables is protective, although definitive studies to prove this have not yet been conducted. Another untested idea is that cancer patients should avoid taking antioxidant supplements while undergoing chemotherapy, as the antioxidants may oppose the action of the anticancer drugs.

Based on their research with model systems for lymphoma, breast and skin cancer, they have accumulated evidence that a cell's ability to handle oxidative stress influences its susceptibility to apoptosis. Lymphoma cells that have acquired resistance to oxidative stress simultaneously acquire resistance to chemotherapy-induced apoptosis. The basic metabolism of the resistant cells is also fundamentally altered. These findings clearly have implications for the development and treatment of cancer. They potentially have a broader impact, since dysregulation of apoptosis and cellular redox state are common to other major diseases.

Dr. Briehl’s laboratory is now working to determine how an altered cellular redox state contributes to the control of apoptotic signaling, and to identify molecules that sense oxidative stress, are involved in the mechanism of apoptosis and may be dysfunctional in cancer cells. Other research projects in the laboratory are using gene expression and tissue microarrays, and SNP analyses of lymphoma patient samples to investigate whether the expression of antioxidant enzymes predicts response to therapy. Additional studies in the laboratory are exploring the use of novel redox-active agents as chemosensitizers in the treatment of lymphoma. Understanding how key processes like apoptosis are affected by resistance to oxidative stress will make an important contribution towards teasing out key relationships between genetics, diet, control of oxidative stress and effective cancer prevention and treatment.

Selected Publications: 
Tome, M.E., Briehl, M.M. and Lutz, N.W. (2005) Increasing the antioxidant defense in WEHI7.2 cells results in a more tumor-like metabolic profile. Int. J. Mol. Med. 15:497-501
 
Tome, M.E., Johnson, D.B.F., Rimsza, L.M., Roberts, R.A., Grogan, T.M., Miller, T.P., Oberley, L.W., Briehl, M.M. (2005) A redox signature score identifies diffuse large B-cell lymphoma patients with a poor prognosis. Blood 106:3594-3601
 
Tome, M.E., Johnson, D.B.F., Samulitis, B., Dorr, R.T., Briehl, M.M. (2006) Glucose 6-phosphate dehydrogenase overexpression models glucose deprivation and sensitizes lymphoma cells to apoptosis. Antioxid Redox Signal 8:1315-1327
 
Jaramillo, M.C., Frye, J.B., Crapo, J.D., Briehl, M.M., Tome, M.E. (2009) Increased manganese superoxide dismutase expression or treatment with a manganese porphyrin potentiates dexamethasone-induced apoptosis in lymphoma cells. Cancer Res. 69: 5450-5457
 
Skalska, J., Brookes, P.S., Nadtochiy, S.M., Hilchey, S.P., Jordan, C.T., Guzman, M.L., Maggirwar, S.B., Briehl, M.M., Bernstein, S.H. (2009) Modulation of cell surface protein free thiols: a potential novel mechanism of action of the sesquiterpene lactone parthenolide. PLoS ONE 4:e8115
 
Wilkinson, S.T., Johnson, D.B.F., Tardif, H.L., Tome, M.E., Briehl, M.M. (2010) Increased cytochrome c correlates with poor survival in aggressive lymphoma. Oncol Letts 1:227-230
 
Tome ME, Jaramillo MC‡‡, Briehl MM. Hydrogen peroxide signaling is required for glucocorticoid-induced apoptosis in lymphoma cells. Free Radical Biol. Med. 51:2048-59, 2011.
Collaborative Research: 

Lisa Rimsza, M.D., Department of Pathology, Expression of antioxidant enzymes as a predictor of treatment response in lymphoma

Steven Bernstein, Ph.D., University of Rochester, Optimizing redox modulation as a therapeutic strategy for non-Hodgkin lymphoma

Jani Ingram, Ph.D., Northern Arizona University, Uranium as an Environmental Risk Factor for Cancer

Christine Ambrosone, Ph.D., Roswell Park Cancer Institute, Pharmacogenomics of oxidative stress-related genes in lymphoma

Bio sketch: 
What prompted you to get into cancer research?: 

I have been fascinated by science since the time that I was a child. My first distinct memory is getting ‘hooked’ happened in 8th grade, looking through a microscope for the first time.

We had collected water from a pond next to the school. The teacher instructed us to place a drop of the water onto a microscope slide to check if there was anything there. Seeing a universe of exotic creatures I never knew existed was incredibly exciting.

My interests in science later narrowed down to cancer research. As a senior in high school, I recall a conversation with a guy at a party during which I declared my career goal: "to cure cancer."

We laughed together at the outlandishness of this goal, but it was a moment of self-discovery for me. I had just tapped into a deep desire to do something about the problem of cancer.

Professional Information
Professional Affiliations: 

American Association for Cancer Research

Society for Free Radical Biology & Medicine

Academic Information
Doctorate: 
University of Arizona, 1988
Undergraduate School: 
University of Arizona, B.S., 1981