Thomas P. Zwaka, MD, PhD

Assistant Professor Center for Cell and Gene Therapy Department of Molecular and Cellular Biology Baylor College of Medicine

 

 

 

Contact Information:
tpzwaka@bcm.tmc.edu
713-798-1272

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Education:
Medical School – University of Ulm
Postdoctoral – University of Ulm
Postdoctoral – University of Wisconsin, Madison

Research Interests:
The nature of embryonic stem cell pluripotency

Pluripotency is the potential of a cell to develop into nearly every mature cell type in the body. This remarkable biological status is restricted to cells in the early embryo and to germ cells. The underlying concept of pluripotency provides not only a unique basis for our understanding of the molecular processes involved in the cellular specification of the early embryo in vivo, but also for our understanding of the basic biology of pluripotent cell lines derived from mammalian pre-implantation embryos in vitro. In particular, embryonic stem (ES) cell lines have attracted interest because of their potential usefulness for cellular therapies. ES cells have been derived from pre-implantation embryos of different mammalian species. These cells demonstrate remarkable properties in cell culture: they can be expanded without limit and are pluripotent. Although several genes essential for maintaining pluripotency have been identified in ES cells, little is known about why some cells are pluripotent while others are restricted in their developmental potential.

The long-term goal of our laboratory is to develop a greater understanding of ES cell pluripotency in mouse and human ES cells, which offer unlimited materials for investigating the molecular mechanisms of pluripotency. This knowledge is of great value, as it may allow us to develop strategies for reprogramming other cell types into pluripotent cells. This would allow the use of reprogrammed cells in medical settings, thus bypassing many of the ethical concerns surrounding the use of ES cells. In addition, an in-depth examination of ES cell pluripotency may improve our understanding of adult stem cell types and cancer stem cells, which share some features with ES cells.

Our current investigations are focused on determining how undifferentiated cells decide when to undergo programmed cell death and when to differentiate. We are developing strategies to identify novel molecular targets of the programmed cell death pathway and differentiation machinery in ES cells, and will then examine the mechanisms by which these molecules control the chromatin changes associated with pluripotency. Our future work will include investigations into the true origin of ES cells, which is currently unknown. Identification of the cell type in the pre-implantation embryo that most closely resembles ES cells will provide new insights into pluripotency.

In this way, our laboratory hopes to make important new advances towards a greater understanding of pluripotency and its use in medical and nonmedical settings.

 

Selected Publications

Zwaka, T. P. and Thomson, J. A. (2005). Differentiation of human embryonic stem cells occurs through symmetric cell division. Stem Cells, in press.

Zwaka, T. P. and Thomson, J. A. (2005). Homologous recombination in human embryonic stem cells. In Essentials of Stem Cell Research, (ed. R. P. Lanza). San Diego: Elsevier Science (USA).

Zwaka, T. P. and Thomson, J. A. (2005). A germ cell origin of embryonic stem cells? Development132, 227-233.

Zwaka, T. P. and Thomson, J. A. (2004). Homologous recombination in human embryonic stem cells. In HANDBOOK OF STEM CELLs, Volume 2: Embryonic Stem Cells , (ed. R. P. Lanza). San Diego: Elsevier Science (USA).

Greiner, J., Wiehe, J., Wiesneth, M., Zwaka, T. P., Prill, T., Schwarz, M., Bienek-Ziolkowski, M., Schmitt, M., Dohner, H., Hombach, V. et al. (2004). Transient Genetic Labeling of Human CD34-Positive Hematopoietic Stem Cells Using Nucleofection. Transfusion Medicine and Hemotherapy31, 136-141.

Draper, J. S., Smith, K., Gokhale, P., Moore, H. D., Maltby, E., Johnson, J., Meisner, L., Zwaka, T. P., Thomson, J. A. and Andrews, P. W. (2004). Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol22, 53-4.

Zwaka, T. P., Torzewski, J., Hoeflich, A., Dejosez, M., Kaiser, S., Hombach, V. and Jehle, P. M. (2003). The terminal complement complex inhibits apoptosis in vascular smooth muscle cells by activating an autocrine IGF-1 loop. Faseb J17, 1346-8.

Zwaka, T. P. and Thomson, J. A. (2003). Homologous recombination in human embryonic stem cells. Nat Biotechnol21, 319-21.

Xu, R. H., Chen, X., Li, D. S., Li, R., Addicks, G. C., Glennon, C., Zwaka, T. P. and Thomson, J. A. (2002). BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat Biotechnol20, 1261-4.

Zwaka, T. P., Manolov, D., Ozdemir, C., Marx, N., Kaya, Z., Kochs, M., Hoher, M., Hombach, V. and Torzewski, J. (2002). Complement and dilated cardiomyopathy: a role of sublytic terminal complement complex-induced tumor necrosis factor-alpha synthesis in cardiac myocytes. Am J Pathol161, 449-57.

Zwaka, T. P., Hombach, V. and Torzewski, J. (2001). C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation103, 1194-7.

Torzewski, M., Rist, C., Mortensen, R. F., Zwaka, T. P., Bienek, M., Waltenberger, J., Koenig, W., Schmitz, G., Hombach, V. and Torzewski, J. (2000). C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler Thromb Vasc Biol20, 2094-9.

Engers, R., Zwaka, T. P., Gohr, L., Weber, A., Gerharz, C. D. and Gabbert, H. E. (2000). Tiam1 mutations in human renal-cell carcinomas. Int J Cancer88, 369-76.

 

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(Modified:August 15, 2006- SM)