Recent research emphasis in Dr. Mieyal’s laboratory (closed in 2018) was focused on mechanisms of alterations in redox regulation in Parkinson’s disease and cardiovascular diseases, both prevalent among the elderly. He continues to serve as a reviewer for multiple scientific journals. Dr. Mieyal is recognized internationally for advancing knowledge of redox regulation and signal transduction in health and disease, especially involving the glutaredoxin and thioredoxin enzyme systems. Professor Mieyal has been a featured speaker at many international symposia on Redox Regulation and Thiol Homeostasis in recent years, including those sponsored by the American Society of Biochemistry and Molecular Biology, the International Redox Network, and the International Gordon Conferences. He has served on scientific review boards for the National Institutes of Health, the American Heart Association, and the Department of Veterans Affairs; and he recently was guest editor for a special Forum Issue of the premier journal Antioxidants and Redox Regulation. Besides recognition for his research, Dr. Mieyal has won several University awards for his medical and graduate school teaching and mentorship, most recently the first annual Inamori Award for Excellence in Mentoring, and he has served on the Pharmacology Committee of the National Board of Medical Examiners. Dr. Mieyal has mentored numerous MS, PhD, MD/PhD., and postdoctoral trainees. Nineteen of the former trainees are engaged in academic research careers, five hold positions in industrial research, and several are pursuing clinical careers.
Research Information
Research Interests
Modulation of the thiol-disulfide status of critical cysteine residues on proteins is becoming recognized as an important mechanism of oxidative signal transduction as well as an important consequence of oxidative stress associated with aging and various disease states, including cardiovascular and neurodegenerative diseases, diabetes, AIDS, and cancer. Within these various contexts, a prevalent form of cysteine modification is reversible formation of protein mixed disulfides (protein-SSG) with intracellular glutathione (GSH).
Research Projects
Our laboratory is focused on the molecular mechanisms and physiological implications of enzymes that catalyze thiol-disulfide oxidoreductase (TDOR) reactions. In particular, we have characterized glutaredoxin (thioltransferase) as the TDOR enzyme that displays specificity and high catalytic efficiency for protein-SSG substrates, including hemoglobin-SSG, NF1-SSG, HIV-protease-SSG, and actin-SSG. This realization has placed made glutaredoxin a focal point in advancing understanding of protein-S-glutathionylation as a regulatory mechanism akin to phosphorylation of proteins. We are employing a range of cellular, molecular, and structural biology approaches to delineate the molecular basis for glutaredoxin catalysis and its role in regulation of fundamental cellular processes like proliferation, differentiation and apoptosis. A key objective in our research program is to characterize also the mechanisms of formation of specific protein-SSG intermediates and identify the enzymes responsible for catalyzing these reactions within cells. We are also focused on delineating changes in the regulation of protein-SSG status of specific effector proteins associated with the various disease states that involve oxidative stress.
Publications
Gallogly MM, Shelton MD, Qanungo S, Pai HV, Starke DW, Hoppel CL, Lesnefsky EJ, and Mieyal JJ (2010), , Antioxidants & Redox Signaling, [Epub Nov. 25, 2009], in press.
Shelton MD, Distler AM, Kern TS, Mieyal JJ. (2009), , J Biol Chem. 284, 4760-4766.
Gallogly, M.M., D.W. Starke, and J.J. Mieyal, , invited forum review article in Antioxidants & Redox Signaling, 11, 1059-1081 (2009).
Zhu X, Gallogly MM, Mieyal JJ, Anderson VE, Sayre LM, , Chem. Res. Toxicol. 22,1050-1059 (2009).
Park JW, Mieyal JJ, Rhee SG, Chock PB. (2009) . J Biol Chem. 284, 23364-23374.
Mieyal JJ, Gallogly MM, Qanungo S, Sabens EA, and Shelton MD, , invited comprehensive review in Antioxidants & Redox Signaling 10, 1941-1988 (2008).
Shelton, M.D., T.S. Kern & J.J Mieyal, , J. Biol. Chem., 282, 12467-12474 (2007).
Gallogly, M.M., D.W. Starke, A.K. Leonberg, S.M. Ospina, and J.J. Mieyal,, Biochemistry 47, 11144 -11157 (2008).
Pai, H.V., D.W. Starke, E.J. Lesnefsky, C.L. Hoppel, and J.J. Mieyal, Antioxidants & Redox Signaling, 9, 1-7 (2007).
, Curr Opin Pharmacol.7, 381-391 (2007).
Qanungo S., D.W. Starke, H.V. Pai, J.J. Mieyal, Nieminen AL., . J Biol Chem. 282, 18427-18436 (2007).
Jao, S.-C., S. M. English Ospina, C.B. Post, A.J. Berdis, D.W. Starke and J.J. Mieyal (2006), , Biochemistry, 45, 4785-4796.
Asmis R, Wang Y, Xu L, Kisgati M, Begley JG, Mieyal JJ. (2005), , FASEB J. 19, 1866-1868.
M.D. Shelton, P.B. Chock & J.J Mieyal , invited Forum Review in Antioxidants & Redox Signaling , K. Nose, Ed., Mary Ann Liebert, Inc., Larchmont, NY, Vol. 7, ps. 346-364 (2005).
Starke, D.W., P.B. Chock, and J.J. Mieyal (2003), , J.Biol. Chem ., 278, 14607-14613.
Jun Wang, Ephrem Tekle, Hammou Oubrahim, John J. Mieyal , Earl R. Stadtman, and P. Boon Chock (2003), , Proc. Nat'l. Acad. Sci. U.S.A . 100 , 5103-5106.
C.A. Chrestensen, D.W. Starke, and J.J. Mieyal , , J. Biol. Chem. 275 , 26556-26565 (2000).
Y. Yang Æ’ , S.-C. Jao Æ’ , S. Nanduri, D. W. Starke, J J. Mieyal *, and J. Qin*, , Biochemistry 37 , 17145-17156 (1998).
U. Srinivasan, P.A. Mieyal, and J.J. Mieyal , , Biochemistry 36 , 3199-3206 (1997).
S.A. Gravina and J.J. Mieyal , Biochemistry 32 , 3368-3376 (1993).