The Department of Pediatric Surgery at the University of Texas Medical School at Houston
Department of Pediatrics
The Department of Pediatric Surgery

Faculty Biography

Program in Regenerative Medicine 


Pamela L. Wenzel, Ph.D.

Dr. Wenzel is an Assistant Professor in the Department of Pediatric Surgery and at the Brown Foundation Institute of Molecular Medicine, Center for Stem Cell and Regenerative Medicine. The current research in her lab centers on stem cell biology and mechanisms of their regulation.

Specifically, her research is designed to promote a better understanding of how biomechanical forces in the body regulate the cellular potential and function of various types of stem cells and their precursors, including cells within the embryo and adult, such as hematopoietic stem cells, mesenchymal stem cells, and cancer cells. The studies conducted in her lab will broaden our understanding of the types of signals, soluble and mechanical, that define the stem cell niche and will advance the field of regenerative medicine toward establishing alternative, high quality sources of stem cells that can be used for cellular therapies in the treatment of hematologic disorders, cancers, and neural injuries.

Curriculum Vitae

Current Research

Training

Dr. Wenzel began her training as a stem cell biologist at The Ohio State University with Dr. Gustavo Leone. Her doctoral studies there focused on the developmental defects caused by genetic mutations of two classes of genes renowned for their relevance to cancer, Rb and E2f. She identified a critical role for Rb in regulating proliferation and differentiation of trophoblast stem cells by generating Rb-deficient trophoblast (placental) stem cell lines and a placenta-specific Cre-expressing transgenic mouse, referred to as CYP19-Cre. With these genetic tools, she showed that ablation of Rb in the stem cell compartment of the placenta was sufficient to cause death of otherwise normal fetuses and that the lethal placental phenotype resulting from loss of Rb induced non-cell autonomous defects in fetal tissues such as the central nervous system and red blood cells.

In parallel, she developed complementary systems to address the requirement for the E2f1, E2f2, and E2f3 transcription factors, the primary mediators of Rb transcriptional regulation, in initiation of the cell cycle. Using genetic ablation in mice and derivation of embryonic and trophoblast stem cell lines triply-deficient for E2f1-3 she demonstrated that, in stark contrast to dogma established by fibroblast-based assays, E2F activators are not required for cell cycle progression. In fact, expression of cell cycle regulatory genes modulated by E2F activators were upregulated in triply-deficient cells and embryos, suggesting that E2F activators possess repressor-type functions in vivo.

Dr. Wenzel moved to Children's Hospital Boston and Harvard Medical School to complete her post-doctoral training, mentored by a true pioneer in the field of stem cell biology and reprogramming, Dr. George Q. Daley. There she focused on hematopoietic stem cell biology. She studied a number of extrinsic factors, including biomechanical force, soluble molecules, and pharmacological compounds that endow hematopoietic precursors with the ability to contribute to the adult blood system. Conversely, she also studied the inhibitory role that adipocytes play in hematopoiesis of the adult bone marrow and showed that expansion of fatty marrow interferes with recovery of hematopoietic progenitors following radiation therapy in animal models.

Selected Publications

  1. de Bruin, A., Wu, L., Saavedra, H.I., Wilson, P., Yang, Y., Rosol, T.J., Weinstein, M., Robinson, M.L., and Leone, G. 2003. Rb function in extraembryonic lineages suppresses apoptosis in the CNS of Rb-deficient mice. Proc Natl Acad Sci USA 100(11): 6546-6551.
  2. Wu, L., de Bruin, A., Saavedra, H.I., Starovic, M., Trimboli, A., Yang, Y., Opavska, J., Wilson, P., Thompson, J.C., Ostrowski, M.C., Rosol, T.J., Woollett, L.A., Weinstein, M., Cross, J.C., Robinson, M.L., and Leone, G. 2003. Extra-embryonic function of Rb is essential for embryonic development and viability. Nature 421(6926): 942-947.
  3. Mosaliganti, K., Pan, T., Sharp, R., Ridgway, R., Iyengar, S., Gulacy, A., Wenzel, P., de Bruin, A., Machiraju, R., Huang, K., Leone, G., and Saltz, J. 2006. Registration and 3D visualization of large microscopy images. Proc SPIE Int Soc Opt Eng 6144: 61442V.
  4. Chen, D., Opavsky, R., Pacal, M., Tanimoto, N., Wenzel, P., Seeliger, M.W., Leone, G., and Bremner, R. 2007. Rb-mediated neuronal differentiation through cell-cycle-independent regulation of E2f3a. PLoS Biol 5(7): e179.
  5. Sharp, R., Ridgway, R., Mosaliganti, K., Wenzel, P., Pan, T., de Bruin, A., Machiraju, R., Huang, K., Leone, G., and Saltz, J. 2007. Volume Rendering Phenotype Differences in Mouse Placenta Microscopy Data. Comput Sci Eng 9: 38-47.
  6. Wenzel, P.L. 2007. Role of the Rb tumor suppressor in regulation of stem cell proliferation. http://Scitizen.com.
  7. Mosaliganti, K., Janoos, F., Sharp, R., Ridgway, R., Machiraju, R., Huang, K., Wenzel, P., de Bruin, A., Leone, G., and Saltz, J. 2007. Detection and visualization of surface-pockets to enable phenotyping studies. IEEE Trans Med Imaging 26(9): 1283-1290.
  8. Wenzel, P.L. and Leone, G. 2007. Expression of Cre recombinase in early diploid trophoblast cells of the mouse placenta. Genesis 45(3): 129-134.
  9. Wenzel, P.L.*, Wu, L.*, de Bruin, A., Chong, J.L., Chen, W.Y., Dureska, G., Sites, E., Pan, T., Sharma, A., Huang, K., Ridgway, R., Mosaliganti, K., Sharp, R., Machiraju, R., Saltz, J., Yamamoto, H., Cross, J.C., Robinson, M.L., and Leone, G. 2007. Rb is critical in a mammalian tissue stem cell population. Genes & Development 21(1): 85-97. *Equal contribution.
  10. Mosaliganti, K., Pan, T., Ridgway, R., Sharp, R., Cooper, L., Gulacy, A., Sharma, A., Irfanoglu, O., Machiraju, R., Kurc, T., de Bruin, A., Wenzel, P., Leone, G., Saltz, J., and Huang, K. 2008. An imaging workflow for characterizing phenotypical change in large histological mouse model datasets. J Biomed Inform 41(6): 863-873.
  11. Adamo, L., Naveiras, O., Wenzel, P.L., McKinney-Freeman, S., Mack, P.J., Gracia-Sancho, J., Suchy-Dicey, A., Yoshimoto, M., Lensch, M.W., Yoder, M.C., Garcia-Cardeña, G., and Daley, G.Q. 2009. Biomechanical forces promote embryonic haematopoiesis. Nature459: 1131-1135.
  12. Naveiras, O., Nardi, V.*, Wenzel, P.L.*, Hauschka, P.V., Fahey, F., and Daley, G.Q. 2009. Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment. Nature 460: 259-263. *Equal contribution.
  13. Chong, J.-L.*, Wenzel, P.L.*, Saénz-Robles, M.T.*, Nair, V., Ferrey, A., Hagan, J.P., Gomez, Y.M., Sharma, N., Chen, H.-Z., Ouseph, M., Wang, S.-H., Trikha, P., Culp, B., Mezache, L., Winton, D.J., Sansom, O.J., Chen, D., Bremner, R., Cantalupo, P.G., Robinson, M.L., Pipas, J.M. and Leone, G. 2009.  E2F1-3 switch from activators in progenitor cells to repressors in differentiating cells Nature462: 930-934. *Equal contribution.
  14. Chen, D., Pacal, M., Wenzel, P., Knoepfler, P.S., Eisenman, R., Leone, G., and Bremner, R. 2009. Division and apoptosis of E2F-deficient retinal progenitors. Nature 462: 925-929.
  15. Wenzel, P.L.*, Chong, J.-L.*, Saénz-Robles, M.T., Ferrey, A., Hagan, J.P., Gomez, Y.M., Sharma, N., Chen, H.-Z., Robinson, M.L., and Leone, G. 2011. Cell Proliferation in the Absence of E2F1-3. Developmental Biology351:35-45. *Equal contribution.
  16. Ouseph, M.M., Li, J., Chen, H.-Z., Pecot, T., Wenzel, P.L., Thompson, J.C., Comstock, G., Chokshi, V., Byrne, B., Forde, B., Chong, J.-L., Huang, K., Machiraju, R., de Bruin, A., Leone, G. Atypical E2F Repressors and Activators Coordinate Placental Development. Developmental Cell. In press.

Faculty Biography

Charles Cox Jr, MD
  • Pamela L. Wenzel, Ph.D.
    Assistant Professor
    Program in Regenerative Medicine
  • Department of Pediatric Surgery
  • The University of Texas Medical School at Houston
    1825 Pressler Street, SRB 630A
    Houston, TX 77030
  • phone: (713) 500-3472
    fax: (713) 500-7296
    e-mail: Pamela.L.Wenzel@uth.tmc.edu

Administrative Contact

Research Interests