Paul Stemmer, Ph.D.

Wayne State University
Associate Professor, Institute of Environmental Health Sciences
Core Leader, Protein Interactions and Proteomics Facility Core, EHS Center

Tel.

(313) 961-7634

Fax.

(313) 577- 0082

Email:

pmstemmer@wayne.edu

Address:

Institute of Environmental Health Sciences

Wayne State University
2727 Second Avenue, Room 4000
Detroit, MI 48201-2654
     
Research Interests:    
Immunosuppression: The drugs that made organ transplantation possible are immunosuppressants that inhibit Calcineurin Phosphatase activity. The mechanism of action of those drugs, Cyclosporin-A and Tacrolimus, remains an active area of research. The integration of regulatory mechanisms to control phosphates activity and drug action is studied in my laboratory using manufactured proteins and assays directed at the five mechanisms regulating calcineurin activity.

 

 

Regulation of Calcineurin Phosphatases: Calcineurin is an enzyme regulating many aspects of cellular function and tissue, organ and organism development. There are five mechanisms that contribute to regulation of the enzyme: calmodulin, calcineurin-B, redox state, targeting or inhibitory proteins and enzyme structure. The emphasis of this laboratories work has been the integration of these five regulatory mechanisms. We have used a site-directed mutagenesis approach to make novel proteins with slightly differing functions and in so doing, have generated new knowledge about the integration of regulatory mechanisms controlling calcineurin.

Proteomic Analysis: Proteins are the major working component of all cells and protein modifications are central to all cellular regulatory mechanisms. We have adopted a two dimensional chromatography approach to profiling proteomes as exemplified by the PF-2D chromatography system. Protein identification and modifications that change enzyme function are examined by mass spectrometry.
     
Select Publications:    

Feng, B. and Stemmer, P.M.:  Interactions of Calcineurin A, Calcineurin B, and Ca(2+). Biochemistry 38:12481-12489, 1999.

 

Persechini, A., Yano, K. and Stemmer, P.M.:  Ca2+ binding and energy coupling in the calmodulin-myosin light chain complex.  J. Biol. Chem. 275: 4199-204, 2000.

 

Sommer, D. and Stemmer, P.M.:  Modulation of calcineurin activity by oxidants and antioxidants.  Eur. J. Biochem.,  267: 2312-2322, 2000.

 

Stemmer, P.M., Ledyard, T.H. and Watanabe, A.M.:  Protein dephosphorylation rates in myocytes after isoproterenol withdraw.  Biochem. Pharmacol.,  59: 1513-1519, 2000.

 

Feng, B. and Stemmer, P.M.:  Ca2+-binding site 2 in calcineurin-B modulates calmodulin-dependent calcineurin phosphatase activity.  Biochemistry,  40: 8808-8814, 2001.

 

Persechini, A and Stemmer, P.M.:  Calmodulin is a Limiting Factor in the Cell.  Trends in Cardiovascular Med., 12: 32-37, 2002.

 

Sommer, D., Coleman, S., Swanson, S.A. and Stemmer, P.M.:  Differential Susceptibilities of Serine/Threonine Phosphatases to Oxidative and Nitrosative Stress, Arch Biochem Biophys.,  404: 271-278, 2002.

 

Ohashi, I., Pohoreki, R., Morita, K. and Stemmer, P.M.:  Alcohols increase calmodulin affinity for Ca2+ and decrease target affinity for calmodulin. Biochimica et Biophysica Acta. 1691: 161-167, 2004.

 

Rai, A.J., Stemmer, P.M., Zhang, Z., Morgan, B., Caffrey, B.R., Podusk, V., Leung, E.H.C.: Analysis of HUPO-PPP Reference Specimens using SELDI-TOF Mass Spectrometry: Multi-Institution Correlation of Spectra and Identification of Biomarkers. Proteomics, In Press.