Margaret M. Briehl, PhD

Research Interests: 

My laboratory’s research objective is to elucidate relationships between oxidative stress and disease processes, particularly cancer. Specifically, we are investigating the regulation of apoptosis by the redox state of the cell. 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 our research with model systems for lymphoma, breast and skin cancer, we have accumulated evidence that a cell’s ability to handle oxidative stress does influence its susceptibility to apoptosis. Lymphocytes that have acquired resistance to oxidative stress simultaneously acquire resistance to glucocorticoid-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. We are now working towards determining the mechanism by which an altered cellular redox state contributes to the control of apoptotic signaling and identifying molecules that sense oxidative stress, are involved in the mechanism of apoptosis and may be dysfunctional in cancer cells. Using gene expression and tissue arrays from lymphoma patient samples, we are investigating whether the expression of antioxidant enzymes predicts response to therapy. Understanding how key processes like apoptosis can be 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.

Degrees
  • PhD: University of Arizona, 1988

Select Publications

2017

Wair, A., JB. Weinstein, MM. Briehl, MJ. Holcomb, KA. Erps, A. Holtrust, G. Barker, and EA. Krupinski, "Second Flexner revolution--democratization of medical knowledge: Repurposing a medical school general pathology course into a set of interoperable medical science “gateway” courses for use at multiple education levels", J Acad Pathol, vol. 4, pp. 1-12, 2017.
Jim, V., C. LaViolette, MM. Briehl, and JC. Ingram, "Spatial distribution of uranium in mice kidneys detected by laser ablation inductively coupled plasma mass spectrometry", J Appled Bioanalysis, vol. 3, pp. 43-48, 2017.

2016

Briehl, MM., MA. Nelson, EA. Kupinski, KA. Erps, MJ. Holcomb, JB. Weinstein, and RS. Weinstein, "Flexner 2.0—Longitudinal Study of Student Participation in a Campus-Wide General Pathology Course for Graduate Students at The University of Arizona", Acad Pathol, vol. 3, pp. 1-13, 10/2016.

2015

Laurila, K., JC. Ingram, MM. Briehl, and RT. Trotter, "Weaving the Web: Evaluation strategies for successful navigation of Native American undergraduates in research.", Council on Undergrate Research, vol. 35, pp. 4-11, 2015.
Jaramillo, M. C., M. M. Briehl, I. Batinic-Haberle, and M. E. Tome, "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, vol. 83, pp. 89-100, 2015 Jun. PMCID: PMC4441837  PMID: 25725417
Briehl, M. M., "Oxygen in human health from life to death - An approach to teaching redox biology and signaling to graduate and medical students.", Redox Biol, vol. 5, pp. 124-139, 2015 Apr 11. PMCID: PMC4412967  PMID: 25912168
Laurila, K., J. C. Ingram, M. M. Briehl, and R. T. Trotter, "Weaving the Web: Evaluation Strategies to Help Native-American Undergraduate Research Training Programs Navigate Students to Success.", CURQ Web, vol. 35, issue 3, pp. 4-11, 2015 Spring. PMCID: PMC4671630  PMID: 26665169

2014

Briehl, M. M., M. E. Tome, S. T. Wilkinson, M. C. Jaramillo, and K. Lee, "Mitochondria and redox homoeostasis as chemotherapeutic targets.", Biochem Soc Trans, vol. 42, issue 4, pp. 939-44, 2014 Aug. PMID: 25109983
Barr, P. M., T. P. Miller, J. W. Friedberg, D. R. Peterson, A. M. Baran, M. Herr, C. M. Spier, H. Cui, D. J. Roe, D. O. Persky, et al., "Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma.", Blood, vol. 124, issue 8, pp. 1259-65, 2014 Aug 21. PMCID: PMC4141515  PMID: 25016003
Gustafson, H. L., S. Yao, B. H. Goldman, K. Lee, C. M. Spier, M. L. LeBlanc, L. M. Rimsza, J. R. Cerhan, T. M. Habermann, B. K. Link, et al., "Genetic polymorphisms in oxidative stress-related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma.", Am J Hematol, vol. 89, issue 6, pp. 639-45, 2014 Jun. PMCID: PMC4137041  PMID: 24633940
Lee, K., M. R. Hart, M. M. Briehl, A. P. Mazar, and M. E. Tome, "The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma.", Int J Oncol, vol. 45, issue 1, pp. 439-47, 2014 Jul. PMCID: PMC4079159  PMID: 24788952

2013

Lee, K., M. M. Briehl, A. P. Mazar, I. Batinic-Haberle, J. S. Reboucas, B. Glinsmann-Gibson, L. M. Rimsza, and M. E. Tome, "The copper chelator ATN-224 induces peroxynitrite-dependent cell death in hematological malignancies.", Free Radic Biol Med, vol. 60, pp. 157-67, 2013 Jul. PMCID: PMC3654089  PMID: 23416365

2012

Jaramillo, M. C., M. M. Briehl, J. D. Crapo, I. Batinic-Haberle, and M. E. Tome, "Manganese porphyrin, MnTE-2-PyP5+, Acts as a pro-oxidant to potentiate glucocorticoid-induced apoptosis in lymphoma cells.", Free Radic Biol Med, vol. 52, issue 8, pp. 1272-84, 2012 Apr 15. PMCID: PMC3331723  PMID: 22330065
Tome, M. E., K. Lee, M. C. Jaramillo, and M. M. Briehl, "Mitochondria are the primary source of the H(2)O(2) signal for glucocorticoid-induced apoptosis of lymphoma cells.", Exp Ther Med, vol. 4, issue 2, pp. 237-242, 2012 Feb. PMCID: PMC3404723  PMID: 22844350
Wilkinson, S. T., M. E. Tome, and M. M. Briehl, "Mitochondrial adaptations to oxidative stress confer resistance to apoptosis in lymphoma cells.", Int J Mol Sci, vol. 13, issue 8, pp. 10212-28, 2012. PMCID: PMC3431854  PMID: 22949856