Enrique Saez, PhD
Scripps Research Joint Appointments
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.
Education
Ph.D. (Genetics), Harvard University, Department of Genetics, 1995A.B. (Molecular Biology), Princeton University, 1989
Professional Experience
2010-2017 Associate Professor, Chemical Physiology, Scripps Research2006-2010 Assistant Professor, Chemical Physiology, Scripps Research
2005-2006 Group Leader, Genetics, Genomics Institute of the Novartis Research Foundation (GNF)
2004-2005 Principal Investigator II, Lead Discovery, Genomics Institute of the Novartis Research Foundation (GNF)
2002-2004 Principal Investigator, Lead Discovery, Genomics Institute of the Novartis Research Foundation (GNF)
1996-2001 Postdoctoral Fellow, Salk Institute for Biological Studies
1995-1996 Postdoctoral Fellow, Dana-Farber Cancer Institute
1995-1996 Postdoctoral Fellow, Harvard University
1992-1992 Teaching Fellow, Harvard University
1987-1989 Research Fellow, Princeton University
1985-1985 Research Aide, Princeton University
Awards & Professional Activities
1986-1989 The Allen Williamson Talley Memorial Scholarship, Princeton University1989-1990 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
Selected References
Madhavan, A., Kok, B. P., Rius, B., Grandjean, J. M. D., Alabi, A., Albert, V., Sukiasyan, A., Powers, E. T., Galmozzi, A., Saez, E.*, Wiseman, R. L.* 2022. Pharmacologic IRE1/XBP1s activation promotes systemic adaptive remodeling in obesity. Nature Communications 13, 608. https://doi.org/10.1038/s41467-022-28271-2. (*co-corresponding authors)
KoK, BP., Ghimire, S., Kim, W., Chatterjee, S., Johns, T., Kitamura, S., Eberhardt, J., Ogasawara, D., Xu, J., Sukiasyan, A., Kim, S.M., Godio, C., Bittencourt, J.M., Cameron, M., Galmozzi, A., Forli, S., Wolan, D.W., Cravatt, B.F., Boger, D.L. and E. Saez. 2020. Discovery of small-molecule enzyme activators by activity-based protein profiling. Nature Chemical Biology online June 8 2020 doi: 10.1038/s41589-020-0555-4. Online ahead of print.
Galmozzi, A., Kok, B.P., Kim, A.S., Montenegro-Burke, J.R., Lee, J.Y., Spreafico, R., Albert, V., Cintron-Colon, R., Godio, C., Webb, W.R., Conti, B., Parker, C.G., Peluso, J.J., Pru, J.K., Suizdak, G., Cravatt, B.F. and E. Saez. 2019. PGRMC2 is an intracellular haem chaperone critical for adipocyte function. Nature 576:138–142.
Kok,B.P., Galmozzi, A., Albert, V., Godio, C., Kim, W., S.M., Kim, Fang, M., Bland, J.S., Grayson, N., Meyerhof, W., Siuzdak, G., Behrens, M. and E. Saez. 2018. Intestinal bitter taste receptor activation alters hormone secretion and imparts metabolic benefits. Molecular Metabolism 16: 76-87.
Parker, C.G., Galmozzi, A., Wang, Y., Correia, B.E., Sasaki, K., Joslyn, C.M., Kim, A.S., Cavallaro, C.L., Lawrence, M., Johnson, S.R., Narvaiza, I., Saez, E.*, Cravatt, B.F.* 2017. Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell 168:1-15. (*co-corresponding authors).
Parsons, W.H., Kolar, M.J., Kamat, S.S., Cognetta, A.B., Hulce, J.J., Saez, E., Khan, B., Saghatelian, A. and B.F. Cravatt. 2016. AIG1 and ADTRP are atypical integral membrane hydrolases that degrade bioactive FAHFAs. Nature Chemical Biology 12:367-72.
Chen, W., Dong, J., Plate, L., Mortenson, D.E., Brighty, G.J., Li, S., Liu, Y., Galmozzi, A., Lee, P.S., Hulce, J., Cravatt, B.F., Saez, E., Powers, E.T., Wilson, I.A., Sharpless, K.B., and J.W. Kelly. 2016. Arylfluorosulfates Inactivate Intracellular Lipid Binding Protein(s) through Chemoselective SuFEx Reaction with a Binding Site Tyr Residue. Journal American Chemical Society 138:7353-64.
Dominguez, E., Galmozzi, A., CHang, J.W., Hsu, K., Pawlak, J., Li, W., Godio, C., Thomas, J., Partida, D., Niessen, S., O'Brien, P.E., Russell, A.P., Watt, M.J., Nomira, D.K., Cravatt, B.F. and E. Saez. 2014. Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes. Nature Chemical Biology 10:113-121.
Galmozzi, A., Sonne, S.B., Keylin, S., Luijten, I., Chang, J.W., Sharp, L.Z., Cravatt, B.F., Saez, E.* and S. Kajimura.* 2014. ThermoMouse: an in vivo model to identify modulators of UCP1 expression in brown adipose tissue. Cell Reports 9:1584-93. (*co-corresponding authors)
Villanueva, C., Vergnes, L., Wang, J., Drew, B., Hong, C., Tu, Y., Hu, Y., Peng, X., Xu, P., Saez, E., Hevener, A., Reue, K., Loren Fong, L., Young, S. and P. Tontonoz. 2013. Adipose subtype-selective recruitment of TLE3 or Prdm16 by PPARγ specifies lipid-storage versus thermogenic gene programs. Cell Metabolism, 17:423–435.
Galmozzi, A., Mitro, N., Ferrari, A., Gers, E., Gilardi, F., Godio, C., Cermenati, G., Gualerzi, A., Donetti, E., Rotili, D., Valente, S., Guerrini, U., Caruso, D., Mai, A., Saez, E., De Fabiani, E. and M. Crestani. 2013. Inhibition of Class I Histone Deacetylases Unveils a Mitochondrial Signature and Enhances Oxidative Metabolism in Skeletal Muscle and Adipose Tissue. Diabetes, 62:732-42.
Jain, T., Papas, A., Jadhav, A. and E. Saez. 2012. In situ electroporation of surface-bound siRNAs in microwell arrays. Lab on a Chip, 12: 939-47.
Cermenati, G., Abbiati, F., Cermenati, S., Brioschi, E., Volonterio, A., Cavaletti, G., Saez, E., De Fabiani, E., Crestani, M., Garcia-Segura, L., Melcangi, R.C., Caruso, D. and Nico Mitro. 2012. Diabetes induced myelin abnormalities are associated with an altered lipid pattern: protective effects of LXR activation. Journal of Lipid Research, 53:300-10.
Villanueva, C.J., Waki, H., Godio, C., Nielsen, R., Chou, W.-L., Vargas, L., Wrobleski, K., Schemdt, C., Chao, L. C., Boyadjian, R., Mandrup, S., Hevener, S., Saez, E. and P. Tontonoz. 2011. TLE3 is a dual function transcriptional coregulator of adipogenesis. Cell Metabolism 3:413-27. (co-corresponding authors).
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., 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., Rocheford, E.C., Mitro, N., Li, X., Kennedy, P., Mullarkey, T.L. and E. Saez. 2007. Dissection of the anti-diabetic effect of Liver X Receptor ligands. Molecular Endocrinology 12: 3002-12.