Dr. M. Teresa Sáenz-Robles

Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
W. Saunders
B. Stronach
S. Tonsor
R. Wood

Microbiology
J. Boyle
G. Hatfull
R. Hendrix
J. Lawrence
J. Pipas
M. Popa
R.L. Duda
S. Godfrey
V. Oke

Molecular Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh

Plant Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw

Science Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg

Structural Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark

Former Faculty

Photo of Dr.
Sáenz-Robles

Molecular Mechanisms of Cell Growth and Proliferation

Research Assistant Professor

Dr. Sáenz-Robles received her Ph. D. in 1985 with Juan Pedro Garcia Ballesta at the Universidad Autónoma de Madrid, performed postdoctoral studies with Pat Simpson at the CNRS (France), Tom Korberg at UCSF (San Francisco), Matt Scott at Stanford University and Terry Van Dyke at the University of Pittsburgh, served as Director for Transgenic Mouse Facility at the University of Pittsburgh, and joined the Department in 1997.

Currently, Dr. Sáenz-Robles is not accepting graduate students in her laboratory. Dr. Sáenz-Robles is accepting undergraduate researchers, and does sponsor students in other laboratories.

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of M. Teresa Sáenz-Robles

I joined the laboratory of James Pipas in 1997, aiming to contribute to the general understanding of mechanisms controlling cell growth and cellular differentiation during animal development. I have pursued the characterization of several mouse transgenic and mutant systems, focusing in particular on the mouse intestinal epithelium. The intestine constitutes an excellent material on which to analyze the properties of actively growing and differentiating cells, as well as to study the mechanisms governing tumor induction. The villi, finger-like projections lining the small intestine and responsible of absorbing nutrients, are mainly composed of growth-arrested, differentiated cells, the absorptive enterocytes. These cells function for a few days and are then replaced by new cells that migrate up the villus from the intestinal crypts. The crypts contain stem cells that are constantly dividing and that repopulate the epithelium. Since the stem and differentiated cell populations are in physically distinct compartments, they can be separated and isolated to determine protein activity or gene expression. We are using these techniques in wild type and mutant/transgenic mice to characterize the molecular properties distinguishing "resting" and "proliferating" cells, both during normal development and in cases of altered morphology and/or proliferation of the intestine.

We use a model system where murine intestines develop hyperplasia and dysplasia after T antigen, an oncoprotein from the Simian Virus 40, is expressed in the enterocytes. T antigen alters several molecular pathways and, at least in part, induces tumorigenesis by targeting and inactivating the retinoblastoma family of tumor suppressors, a pathway that we have studied extensively (see publications). More recently, our results from gene microarray experiments have revealed other pathways altered in hyperplastic intestinal tissue. In particular, the expression of SV40 TAg in intestinal epithelial cells results in a significant decrease in the levels of mRNAs encoding several drug metabolizing/detoxifying enzymes and transporters from the P450 pathway. The corresponding proteins of this pathway are responsible of the metabolization, processing and final elimination of toxic compounds, including carcinogens and drugs. Components of this pathway are normally expressed in the liver and small intestine, and their levels increase after exposure to different chemical agents. We have found that TAg blocks both the endogenous levels of P450 components as well as the induction of these mRNAs by chemical substances. Furthermore, this ability seems to be related to the ability of T antigen to inactivate the retinoblastoma (Rb) family of tumor suppressors (Sáenz Robles et al, 2007). These results have profound implications, as they indicate that a functional retinoblastoma pathway in the intestine is necessary for the expression of the detoxification system used to clear carcinogens. The loss of either retinoblastoma or other members of its molecular pathway occurs in most human cancers, and our results indicate that the genetic composition of a particular tissue and/or individual might change its susceptibility to chemical injury and tumor progression. We are actively investigating the connection between pRb, tumorigenesis and the P450 detoxification pathway and its possible significance in the metabolism and mechanism of action of both carcinogens and prescription drugs.

Publication Archive
17 Citations
13 Abstracts
1 PDFs

Recent Publications of M. Teresa Sáenz-Robles

Sáenz-Robles, M.T., J.A. Markovics, J.L. Chong, R. Opavsky, R.H. Whitehead, G. Leone, and J.M. Pipas (2007) Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2. J. Virol. 81:13191-13199

Rathi, A.V., M.T. Sáenz-Robles, and J.M. Pipas (2007) Enterocyte proliferation and intestinal hyperplasia induced by simian virus 40 T antigen require a functional j domain. J Virol 81:9481-9489

Sáenz-Robles, M.T., D. Toma, P. Cantalupo, J. Zhou, H. Gong, C. Edwards, J.M. Pipas, and W. Xie (2007) Repression of Intestinal Drug Metabolizing Enzymes by the SV40 Large T Antigen. Oncogene :In Press

Markovics, J.A., P.A. Carroll, M.T. Sáenz-Robles, H. Pope, C.M. Coopersmith, and J.M. Pipas (2005) Intestinal dysplasia induced by simian virus 40 T antigen is independent of p53. J. Virol. 79:7492-7502

Sáenz-Robles, M.T., C.S. Sullivan, and J.M. Pipas (2001) Transforming functions of Simian Virus 40. Oncogene 26:7899-7907

Rempel, R.E., M.T. Sáenz-Robles, R. Storms, S. Morham, S. Ishida, A. Engel, L. Jakoi, M.F. Melhem, J.M. Pipas, C. Smith, and J.R. Nevin (2000) Loss of E2F4 activity leads to abnormal development of multiple cellular lineages. Mol. Cell 6:293-306

How to Contact M. Teresa Sáenz-Robles

US Mail
University of Pittsburgh
Department of Biological Sciences
578 Crawford Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 624-4322
Lab : (412) 624-4322
FAX : (412) 624-4759
Email : msaenz+@pitt.edu
Web :

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