James J. Tomasek

David Ross Boyd Professor, Department of Cell Biology
Dean, Graduate College

EDUCATION

B.S., University of Illinois, Urbana, Illinois 
Ph.D., State University of New York, Albany, New York

MEMBERSHIPS

American Association of Anatomists
American Society for Cell Biology 
Wound Healing Society

RESEARCH SUMMARY

The formation and function of myofibroblasts is critical for normal wound closure. Aberrant formation and function of myofibroblasts is believed to be responsible for the tissue and organ distortions that occur in pathological contractures; such as burn scar contractures, hypertrophic scars, Dupuytren's contracture, and organ constrictures. 
Regulation of Myofibroblast Formation and Function
The major long-term goal of research in this laboratory is to elucidate cellular and molecular mechanisms that control the formation and function of myofibroblasts during wound healing and tissue contraction and in tissue engineering. We have demonstrated that for fibroblasts to transition into myofibroblasts requires an alteration in the extracellular environment such that the stiffness of the extracellular matrix is increased and the presence of Transforming Growth Factor-b1 (TGF-b1). The following diagram depicts our working model for myofibroblast formation.

We are currently working to understand how the mechanical environment and TGF-b1 work together to promote the fibroblast-to-myofiboblast transition. Our working model is that a set of contractile genes that contain CArG elements in their promoter are mechanoregulated via the transcription factor myocardin related transcription factor-A (MRTF-A). The transcriptional activity of MRTF-A is regulated by its cytoplasmic-nuclear localization via actin dynamics as illustrated in the following diagram.

We are using animal mouse models, tissue culture models, cell and molecular biology techniques to examine the hypotheses for fibroblast-to-myofibroblast transition and the role of the myofibroblast in wound healing and tissue contraction.

SELECTED PUBLICATIONS

Hinz, B., Celetta, G., Tomasek, J.J., Gabbiani, G., and Chaponnier, C. (2001). Alpha-smooth muscle actin expression up-regulates fibroblast contractive activity. Mol. Biol. Cell 12:2730-2741.

Tomasek, J.J., Gabbiani, G., Hinz B., Chaponnier C., and Brown, R.A. (2002). Myofibroblasts and mechano-regulation of connective tissue remodeling. Nature Reviews Molecular Cell Biology 3: 349-363.

Mirastschijski, U., Haaksma, C.J., Tomasek, J.J., and Ågren, M.S. (2004). Matrix metalloproteinase inhibitor GM 6001 attenuates contraction and myofibroblast formation in skin wounds. Exp. Cell Res. 299:465-475.

Tomasek, J.J., McRae, J., Owens, G.K., and Haaksma, C.J. (2005). Regulation of Smooth Muscle a-Actin Expression in Granulation Tissue Myofibroblasts is Dependent on the Intronic CArG Element and the Transforming Growth Factor b-1 Control Element. Am. J. Pathol. 166:1343-1351.

Gallucci, R.M., Lee, E.G., and Tomasek, J.J. (2006). IL-6 modulates alpha-smooth muscle actin expression in dermal fibroblasts from IL-6-deficient mice. J. Invest. Dermatol. 126:561-568.

Tomasek, J.J., Vaughan, M.B., Kropp, B.K., Gabbiani, G., Martin, M.D., Haaksma, C.J., and Hinz, H. (2006). Contraction of myofibroblasts in granulation tissue is dependent on Rho/Rho kinase/myosin light chain phosphatase activity. Wound Repair Regen. 14:313-320.

Risinger, G.M., Jr., Updike, D.L., Bullen, E.C., Tomasek, J.J., and Howard, E.W. TGF-b suppresses the up-regulation of MMP-2 by vascular smooth muscle cells in response to PDGF-BB. (2010). Am. J. Physiol. 298: C191-C210. PMCID: PMC2806150

Mirastschiski, U., Schnabel, R., Claes, J., Schneider, W., Agren, M.S., Haaksma, C.J. and Tomasek, J.J. (2010). Matrix metalloproteinase inhibition delays wound contraction through attenuated transforming growth factor-b1 activation. Wound Repair Regen 18:223-234.

Haaksma,  C.J., Schwartz, R.J., and Tomasek, J.J. (2011). Myoepithelial cell contraction and milk ejection are impaired in mammary glands of mice lacking smooth muscle alpha-actin. Biol. Reprod. 85:13-21. PCID: PMC3123380

Crider, B.J., Risinger, G.M., Haaksma, C.J., Howard, E.W., and Tomasek, J.J. (2011). Myocardin-related transcription factors A and B are key regulators of TGF-β1-induced fibroblast to myofibroblast differentiation. J. Invest. Dermatol. 131:2378-2385. PMCID: PMC 3199034.

Howard, E.W., Crider, B.J., Updike, D.L., Bullen, E.C., Parks, E.E., Haaksma, C.J., Sherry, D.M., Tomasek, J.J. (2012). MMP-2 expression by fibroblasts is suppressed by the myofibroblast phenotype. Exp. Cell Res. 318:1542-1543.

Tomasek, J.J., Haaksma, C.J., Schwartz, R.J., and Howard, E.W. (2013). Whole animal knockout of smooth muscle alpha-actin does not alter excisional wound healing or the fribroblast-to-myofibroblast transition. Wound Repair Regen. 21:166-76. PMCID:PMC3540133 (Availble on 2014/1/1).


MAILING ADDRESS

University of Oklahoma Health Sciences Center
Department of Cell Biology
P.O. Box 26901
Oklahoma City, OK 73126-0901
Phone: (405) 271-8001 ext. 45505
Fax: (405) 271-3548

James-Tomasek@ouhsc.edu