Cheryl Rockwell, Ph.D.
Pharmacology & Toxicology
Dr. Cheryl Rockwell
B205 Life Sciences
1355 Bogue Street
East Lansing, MI 48823
Fields of Interest: The Rockwell lab studies the mechanisms that regulate immune cell polarization and activation as well as the subsequent downstream immune responses.
- 1994 - B.S., Biology, University of Michigan
- 2005 - Ph.D., Pharmacology & Toxicology, Michigan State University
- 2005-06 - Research Associate, University of Missouri Kansas City
- 2006-11 - Postdoctoral Fellow, University of Kansas Medical Center
- 2011-17 - Assistant Professor, Pharmacology & Toxicology, Michigan State University
- 2017-Present - Associate Professor, Pharmacology & Toxicology, Michigan State University
The overall aim of my research is to determine the mechanisms that modulate immune cell polarization and function. Specifically, I am interested in the effects of xenobiotic sensors on the regulation of lymphocyte function. It is my overall hypothesis that, in general, xenobiotic sensors serve to limit lymphocyte response to reactive xenobiotics thus averting exaggerated or inappropriate immune responses that might otherwise cause autoimmunity or other types of inflammatory conditions. My current research focuses on the role of the stress-activated transcription factor, nuclear factor erythroid 2 related factor 2 (Nrf2), on T cell function and T cell-dependent immune responses.
Recent studies demonstrate that Nrf2 plays a critical cytoprotective role in countering oxidative and electrophilic cellular stresses. Nrf2 is activated by a variety of chemicals, including environmental contaminants such as arsenic, cadmium, cigarette smoke and diesel exhaust. In addition, several widely used food preservatives also activate Nrf2. Thus, Nrf2 activators are widely disseminated in the environment and in our food. Several recently-published papers describe the suppressive effects of Nrf2 in innate immunity. In addition, the development of lupus-like pathology in Nrf2-null mice suggests that Nrf2 also plays an important role in adaptive immunity, but the role of Nrf2 in regulating lymphocyte function is not well characterized.
Our preliminary data demonstrate that activated Nrf2 modulates CD4+ T cell differentiation. Specifically, we have shown that Nrf2 inhibits Th1 differentiation and promotes Th2 differentiation in isolated murine CD4+ T cells (Rockwell et al., 2012). We found that activation of Nrf2 inhibits Th1 cytokine production and increases Th2 cytokine production, in wild-type, but not Nrf2-null, CD4 T cells. In addition, activation of Nrf2 inhibited the activity of the Th1 transcription factor, T-bet, but promoted the activity of the Th2 transcription factor, GATA-3. We are currently conducting studies to determine whether these effects also occur in vivo. Recently, we have also shown that the Nrf2 activator, tBHQ, inhibits some of the early events following T cell activation (Zagorski et al., 2013). Specifically, we found that tBHQ inhibits IL-2 production and CD25 induction in Jurkat T cells
Because numerous environmental contaminants and commonly used synthetic food preservatives have been shown to activate Nrf2, the effects of Nrf2 activation on different organ systems should be fully characterized. This is particularly pertinent for the immune system in which the effects of Nrf2 on adaptive immunity are largely unknown.
- 03/2008 - Post-doctoral presentation award, Immunotoxicology Specialty Section, Society of Toxicology, 2008 Annual Meeting, Seattle, Washington
- 2009-2010 - Kansas Idea Network of Biomedical Research Excellence Postdoctoral Fellowship, "Mechanisms of impaired T cell cytokine production and immune response by Nrf2."
- 2009 - Best postdoctoral presentation, Post-doctoral Fellow Research Day, University of Kansas Medical Center
- 2010-2015 - K99/R00 Pathway to Independence Transitional Grant, "Role of Nrf2 in immunotoxicity by food additives and environmental contaminants, Impact score: 28.- K99 awarded 05/01/2010 – 04/30/2012 R00 phase: 05/2012 – 04/2015
Memberships in Professional Societies
- American Association of Immunologists, 2001-Present
- American Society for Pharmacology and Experimental Therapeutics, 2003-Present
- Society of Toxicology, 2004-Present
- Michigan Society of Toxicology, 2012-Present
Offices in Chapters and Committees
- Michigan Regional Chapter, Society of Toxicology, Councilor, 2013 - 2014
- Awards Committee, Immunotoxicology Specialty Section, Society of Toxicology, 2012-2013
- O'Brien, K.M., Allen, K.A., Luyendyk, J.P., Rockwell, C.E., Copple, B.L., "Interleukin-17A synergistically enhances bile acid-induced inflammation during obstructive cholestasis," In press, American Journal of Pathology (2013), PMID: 24012680
- Zagorski, J.W., Turley, A.E., Dover, H.E., Vandenberg K.R., Compton, J.R., Rockwell, C.E., "The Nrf2 activator, tBHQ, differentially affects early events following stimulation of Jurkat cells," In press Toxicological Sciences (2013), PMID: 23945499
- Rockwell, C.E., Cheng, X., Fields, P.E., Klaassen, C.D., "Acute immunotoxic effects of perfluorononanoic acid in C57BL/6 mice," In press Clinical and Experimental Pharmacology (2013), S4:002. doi: 10.4172/2161-1459.S4-002
- Sullivan, B.P., Kopec, A.K., Cline, H., Joshi, N., Bishop, S.C., Kassel, K.M., Rockwell, C.E., Mackman, N., Luyendyk, J.P., "Role of mouse hepatocyte tissue factor in coagulation cascade activation," Blood (2013), 121(10):1868-74, PMID: 23305736
- Rockwell, C.E., Monaco, J.J., Qureshi, N., "A critical role for the inducible proteasomal subunits, LMP7 and MECL1, in cytokine production by activated murine splenocytes," Pharmacology (2012), 89(3-4):117-126, PMID: 22398747