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Dr. Briehl is a tenured Professor of Pathology in the Department of Medicine and a member of the Arizona Cancer Center at the University of Arizona. She was trained as a basic scientist. Her research focus is redox regulation of apoptosis with an emphasis on understanding therapy resistance in lymphoma. Dr. Briehl participates in the Lymphoma Research Consortium and has collaborated with physician scientists to apply her research findings to lymphoma patients. She contributes to the education mission of the Arizona Cancer Center through her involvement in the Cancer Biology Graduate Interdisciplinary Program and the Partnership for Native American Cancer Prevention.
As a member of the Cancer Biology Graduate Interdisciplinary Program, Dr. Briehl established the graduate student research colloquium. This has become a very effective approach for disseminating information about ongoing research in the UACC and helping the graduate students develop oral communication skills and critical thinking. Since 2013, Dr. Briehl has served as Vice Chair of the Cancer Biology Graduate Program. Another of her roles is to lead the Training Core for the Partnership for Native American Cancer Prevention. Dr. Briehl’s activities in this role include recruiting students for the training program, introducing them to cancer research, planning activities that give the students exposure to American Indian role models (e.g., graduate students, postdocs, physicians and academic scientists) and helping the trainees develop their oral and written communication skills. Leading the Training Core has provided Dr. Briehl with invaluable insight into Native ways of knowing, historical perspectives on genetic research projects involving Native peoples and on cancer health disparities among Native Americans.
Dr. Briehl’s teaching contributions include co-directing the Pathology 515 Human Pathology Course for MS and PhD students in the biomedical sciences and co-directing one of the core courses in the Cancer Biology graduate program. In the AzMed curriculum, she teaches in the Foundations, Life Cycle and Cancer Blocks. Dr. Briehl has been the dissertation advisor for five doctoral students and served on the dissertation committees of an additional 49 graduate students.
Dr. Briehl’s serves on the Scientific Review Committee of the Arizona Cancer Center and the Academic Promotion and Tenure Committee in the College of Medicine. She is a member of the editorial board for two journals: Apoptosis and Redox Biology.
One focus of Dr. Briehl’s research has been to explore connections between the cellular redox environment and cancer cell phenotypes. Her laboratory’s studies have demonstrated that alterations seen in lymphoma cells made resistant to oxidative stress include: a more oxidized redox environment despite increased expression of antioxidant enzymes, enhanced net tumor growth, metabolic changes involving the mitochondria, and resistance to the mitochondrial pathway to apoptosis. Of particular importance, the cells show cross-resistance to multiple chemotherapeutic agents used to treat aggressive lymphomas. A clinical ramification of these studies is that chronic inflammation may promote the development of tumors that are particularly aggressive and resistant to therapy.
Working in collaboration with physician-scientists, Dr. Briehl’s research team has explored the clinical ramifications of her basic science studies. These collaborations led to the discovery of a worse prognosis for patients whose diffuse large B cell lymphomas have gene expression patterns consistent with a more oxidized redox environment. In multiple types of lymphoma, patients with the worst survival outcomes express increased levels of proteins involved in oxidative phosphorylation, including cytochrome c. This is consistent with these cells functioning as metabolic opportunists. Furthermore, these translational studies have provided evidence that the bcl-2 oncogene functions at least in part to confer resistance to apoptosis by altering the cellular redox state.
Another focus of Dr. Briehl’s research efforts has been to develop new therapeutic approaches that target the cellular redox environment. Proof-of-principle studies from her laboratory show enhanced killing using genetic and drug approaches that oxidize the cellular redox environment: increased expression of manganese superoxide dismutase, treatment with a manganoporphyrin that oxidizes the glutathione redox couple, or treatment with a copper chelator that inhibits superoxide dismutase and leads to peroxynitrite-dependent cell death. The latter approach effectively kills lymphoma cells that overexpress the anti-apoptotic protein BCL-2. As part of the Lymphoma SPORE with the University of Rochester, Dr. Briehl’s correlative studies for a Phase 2 clinical trial with imexon showed that the redox state in lymphoma cells predicts the patients’ response to treatment. Imexon is a redox-active drug that was developed in the Arizona Cancer Center.
- Jaramillo MC, Briehl MM, Batinic-Haberle I, Tome ME. Manganese (III) meso-tetrakis N-ethylpyridinium-2-yl porphyrin acts as a pro-oxidant to inhibit electron transport chain proteins, modulate bioenergetics, and enhance the response to chemotherapy in lymphoma cells. Free Radic Biol Med (2015) 83:89-100. PubMed PMID: 25725417
- Barr PM, Miller TP, Friedberg JW, Peterson DR, Baran AM, Herr M, Spier CM, Cui H, Roe DJ, Persky DO, Casulo C, Littleton J, Schwartz M, Puvvada S, Landowski TH, Rimsza LM, Dorr RT, Fisher RI, Bernstein SH, Briehl MM. Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma. Blood (2014) 124:1259-65. PubMed PMID: 25016003
- Gustafson HL, Yao S, Goldman BH, Lee K, Spier CM, LeBlanc ML, Rimsza LM, Cerhan JR, Habermann TM, Link BK, Maurer MJ, Slager SL, Persky DO, Miller TP, Fisher RI, Ambrosone CB, Briehl MM. Genetic polymorphisms in oxidative stress-related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma. Am J Hematol (2014) 89:639-45. PubMed PMID: 24633940
- Lee K, Briehl MM, Mazar AP, Batinic-Haberle I, Reboucas JS, Glinsmann-Gibson B, Rimsza LM, Tome ME. The copper chelator ATN-224 induces peroxynitrite-dependent cell death in hematological malignancies. Free Radic Biol Med (2013) 60:157-67. PubMed PMID: 23416365
- Jaramillo MC, Briehl MM, Crapo JD, Batinic-Haberle I, Tome ME. Manganese porphyrin, MnTE-2-PyP5+, Acts as a pro-oxidant to potentiate glucocorticoid-induced apoptosis in lymphoma cells. Free Radic Biol Med (2012) 52:1272-84. PubMed PMID: 22330065
- Tome ME, Frye JB, Coyle DL, Jacobson EL, Samulitis BK, Dvorak K, Dorr RT, Briehl MM. Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance. Exp Ther Med (2012) 3:845-852. PubMed PMID: 22529877
- Wilkinson ST, Johnson DB, Tardif HL, Tome ME, Briehl MM. Increased cytochrome c correlates with poor survival in aggressive lymphoma. Oncol Lett (2010) 1:227-230. PubMed PMID: 20798784
- Jaramillo MC, Frye JB, Crapo JD, Briehl MM, Tome ME. Increased manganese superoxide dismutase expression or treatment with manganese porphyrin potentiates dexamethasone-induced apoptosis in lymphoma cells. Cancer Res (2009) 69(13):5450-7. PubMed PMID: 19549914
- Tome ME, Johnson DB, Rimsza LM, Roberts RA, Grogan TM, Miller TP, Oberley LW, Briehl MM. A redox signature score identifies diffuse large B-cell lymphoma patients with a poor prognosis. Blood (2005) 106:3594-601. PubMed PMID: 16081686
- Tome ME, Baker AF, Powis G, Payne CM, Briehl MM. Catalase-overexpressing thymocytes are resistant to glucocorticoid-induced apoptosis and exhibit increased net tumor growth. Cancer Res (2001) 61:2766-73. PubMed PMID: 11289160
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
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.