Saez Lab

Enrique Saez

Associate Professor
Department of Chemical Physiology TSRI - 2006

Joint Appointments

Department of Cell Biology

Education

Ph.D. Harvard University, 1995
A.B. Princeton University, 1990

Awards & Activities

1986-1989 The Allen Williamson Talley Memorial Scholarship, Princeton University
1989-1990 Richard B. Carter Trust Fellowship, Harvard University
1995-1996 American Diabetes Association Postdoctoral Fellowship
1997-2000 Susan G. Komen Breast Cancer Foundation Postdoctoral Fellowship
2008-2013 American Diabetes Association Career Development Award

Research Focus

Our lab is interested in two broad themes related to the regulation of energy balance in mammals:

Nuclear receptors as nutrient sensors - Nuclear receptors are ligand-activated transcription factors that sense dietary components such as lipids, vitamins and cholesterol derivatives. We are interested in identifying novel nutrient signaling pathways that involve nuclear receptors. Using high-throughput cell based and biochemical screens as well as a variety of animal models we hope to discover diet-derived physiological signaling pathways.

Genetic regulation of energy storage - Excess energy is stored in adipose tissue. We are using genomic and chemical approaches to identify novel genetic regulators of adipose tissue formation and to examine their role in metabolic disease.

By enhancing our understanding of how diet influences gene expression and the genetic regulation of energy balance, we aim to uncover novel therapeutic targets for the treatment of metabolic diseases such as obesity and diabetes.

Selected References

Mitro, N., Mak, P., Vargas, L., Godio, C., Hampton, E., Molteni, V., Kresuch, A. and Saez, E. The nuclear receptor LXR is a glucose sensor. Nature 2007, 445: 219-23.

Waki, H., Park, K.W d., Mitro, N., Pei, L., Damoiseaux, R., Wilpitz, D.C., Reue, K., Saez, E. and P. Tontonoz. The Small Molecule Harmine Is an Antidiabetic Cell-Type-Specific Regulator of PPARγ Expression. Cell Metabolism 2007, 5: 357-70.

Commerford, S.R., Vargas, L., Dorfman, S.E., Mak, P.A., Mitro, N., Rocheford, E.C., Li, X., Kennedy, P., Mullarkey, T.L., and Saez, E. Dissection of the anti-diabetic effect of liver X receptor ligands. Molecular Endocrinology 2007, 21(12):3002-1.

Molteni, V., Li, X., Nabakka, J., Liang, F., Wityak, J., Koder, A., Vargas, L., Romeo, R., Mitro, N., Mak, P.A., Seidel, H.M., Haslam, J.A., Tuntland, T., Spalding, T.A., Brock, A., Bradley, M., Castrillo, A., Tontonoz, P. and Saez, E. N-Acylthiadiazolines, a new class of liver X receptor agonists with selectivity for LXRβ. The Journal of Medicinal Chemistry 2007 50(17):4255-9.

Joseph, S.B., Bradley, M., Castrillo, A., Bruhn, K., Mak, P., Pei, L. Hogenesch, J., O'Connell, R.M., Cheng, G., Saez, E., Miller, J. and P. Tontonoz. LXR-dependent gene expression is important for macrophage survival and the innate immune response to bacterial pathogens. Cell 2004, 119: 299-309.

Saez, E., Rosenfeld, J.R., Livolsi, A., Olson, P., Lombardo, E., Nelson, M.C., Banayo, E., Cardiff, R.D., Izpisua/Belmonte, J.C. and R.M. Evans. PPARγ signaling exarcebates mammary gland tumor development. Genes and Development 2004, 18: 528-540.

Laffitte, B.A., Chao, L.C., Li, J., Walczak, R., Hummasti, S., Joseph, S.B., Castrillo, A., Wilpitz, D.C., Mangelsdorf, D.J., Collins, J.L., Saez, E. and P. Tontonoz. Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. PNAS 2003, 100: 5419-5424.

Saez, E., Nelson, M.C., Eshelman, B., Banayo, E., Koder, A., Cho, G.J., and R.M. Evans. Identification of ligands and coligands for the ecdysone-regulated gene switch. PNAS 2000, 97: 14512-14517.

Saez, E., Tontonoz, P., Nelson, M.C., Alvarez, J.G., U, T-M., Baird, S.M., Thomazy, V.A., and R.M. Evans. Activators of the nuclear receptor PPARγ enhance colon polyp formation. Nature Medicine 1998, 4:1058-1061.