Philipp E. Scherer, Ph.D

Professor, Department of Cell Biology Chanin Bldg., Room 414 718 430-2928 scherer@aecom.yu.edu Biosketch Laboratory home page Complete list of publications

Research interests The Role of the Adipocyte in Energy Homeostasis and Inflammation The main focus in our laboratory is the identification and physiological characterization of adipocyte-specific gene products and the elucidation of pathways that are an integral part of the complex set of reactions that drive adipogenesis. The hope is to unravel novel mechanisms and identify novel proteins that could serve as potential links between the adipocyte and the process of whole body energy homeostasis, thereby defining novel targets for pharmacological intervention and further define the role of adipose tissue as an endocrine tissue. Until recently, adipose tissue has been considered to be a mere storage compartment of triglycerides. It is now becoming clear that adipocytes are highly responsive to extracellular stimuli, play a central role in overall energy homeostasis and are also essential for certain aspects of the immune system.  A major effort in our studies seeks to identify the molecules specifically secreted from adipocytes and to define their physiological role. Acrp30/adiponectin and resistin are both adipocyte-specific secretory proteins that have profound effects on systemic insulin sensitivity through direct action of these proteins on liver and muscle. We characterize the biogenesis of these molecules in adipocytes, analyze the interacting factors in serum, identify candidate receptor molecules and study signal transduction events in the target cell induced by these hormones. The long-term goal of another project in the laboratory aims at understanding the significance of adipose tissue in the elevation of systemic levels of acute-phase reactants and the general increase in the inflammatory state in Non Insulin Dependent Diabetes Mellitus (NIDDM). We propose that adipose tissue is a major contributor towards the overall increased inflammatory state observed in NIDDM and may therefore be at the center of the pathogenic sequelae of NIDDM. In this context, we are focusing on the relationship between adipocytes and the innate immune response. Adipocytes are highly responsive to bacterial endotoxin and secrete a number of inflammatory cytokines. The signaling pathways and transcriptional events leading to the upregulation of these inflammatory cytokines are being studied.  We address these questions with a wide range of techniques involving biochemistry, molecular and cellular biology at the tissue culture level, as well as genetic and physiological approaches in mice.

Selected Publications 2005/2006 Combs, T.P., Nagajyothi, Mukherjee, S., de Almeida C.J.G., Jelicks, L., Schubert, W., Lin, Y., Jayabalan, D.S., Zhao, D., Braunstein, V.L., Landskroner-Eiger, S., Cordero, A., Factor, S.M., Weiss, L.M., Lisanti, M.P., Tanowitz, H.B. and P. E. Scherer. 2005. The Adipocyte as an Important Target Cell for Trypanosoma cruz Infection. J. Biol. Chem., 280(25), 24085-24094. Pajvani, U.B., Trujillo, M.E., Combs, T.P., Iyengar, P., Jelicks, L., Roth, K.A., Kitsis, R.N. and P. E. Scherer. 2005. FAT Apoptosis Through Targeted Activation of Caspase8 (FAT-ATTAC) a novel mouse model of inducible and reversible lipoatrophy. Nat. Med, 11(7):797-803 Iyengar, P., Espina, V., Berry, D., Williams, T., Jelicks, L.A., Lee, H-K., Temple, K., Graves, R., Pollard, J., Chopra, N., Russell, R.G., Sasisekharan, R., Trock, B.J., Lippman, M., Calvert, V.S., Petricoin E.F., Liotta, L., Dadachova, E., Pestell, R.G., Lisanti, M.P., Bonaldo, P. and P. E. Scherer. 2005. Adipocyte-Derived Collagen VI Affects Early Mammary Tumor Progression in vivo: A Novel Interaction in the Tumor / Stroma Microenvironment. J. Clin. Inv., 115(5):1163-1176 Nawrocki, A.R., Rajala, M.W., Tomas, E., Pajvani, U.B., Saha, A.K., Trumbauer, M.E., Pang, Z., Chen, A.S., Ruderman, N.B., Chen, H., Rossetti, L. and P. E. Scherer. 2005. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to PPARgamma-agonists. J. Biol. Chem., 281(5): 2654-2660 Recent Reviews Nawrocki, A. and Scherer, P.E.. 2005. The Adipocyte as a Drug Discovery Target. 2005. Keynote Review. Drug Discovery Today, 10 (18): 1219-1230 Trujillo, M.E., Pajvani, U.B. and P. E. Scherer. 2005. . Apoptosis through Targeted Activation of Caspase8. Novel mouse models of inducible and reversible tissue ablation. . Cell Cycle, 4:9 e135-e139 Thematic Series in Circulation Research: Adipocyte Signaling in the Cardiovascular System Guest Editor: Philipp E. Scherer Berg, A.H. and P.E. Scherer. 2005. Adipose Tissue, Inflammation and Cardiovascular Disease Circ Res., 96:939-949. Trujillo, M.E. and P. E. Scherer. 2005. Adiponectin: Journey from an Adipocyte Secretory Protein to Biomarker of the Metabolic Syndrome J. Internal Med., 257(2):167-75 Bouskila, M., Pajvani, U.B. and P.E. Scherer. 2005. Adiponectin ? A Relevant Player in PPARgamma Agonist Mediated Improvements in Hepatic Insulin Sensitivity? Int J Obes Relat Metab Disord, 29 Suppl 1:S17-23 P. E. Scherer. 2006. Adipose Tissue: From Lipid Storage Compartment to Endocrine Organ. Outstanding Scientific Achievement Award Lecture. 2006. Diabetes, 55: 1537-1545 Recent Collaborative Efforts Fisher, F.F., Trujillo, M.E., Hanif, W., Barnett, A.H., McTernan, P.G., Scherer, P.E. and S. Kumar. 2005. Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia, 48(6):1084-1087. Halperin, F., Beckman, J.A., Patti, M.E., Trujillo, M.E., Garvin, M., Creager, M.A., Scherer, P.E. and A.B. Goldfine. 2005. The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes. Diabetologia, in press. Watson, E., Hahm, S., Mizuno, T.M., Windsor, J., Montgomery, C., Scherer, P.E., Mobbs, C.V. and S.R. Salton. 2005. VGF Ablation Blocks the Development of Hyperinsulinemia and Hyperglycemia in Several Mouse Models of Obesity. Endocrinology, in press Jurgens, H., Haass, W., Castaneda, T.R., Schurmann, A., Koebnick, C., Dombrowski, F., Otto, B., Nawrocki, A.R., Scherer, P.E., Spranger, J., Ristow, M., Joost, H.G., Havel, P.J. and M.H. Tschop. 2005. Consuming fructose-sweetened beverages increases body adiposity in mice. Obes Res., 13(7):1146-56. Graveleau, C., Zaha, V.G., Mohajer, A., Banerjee, R.R., Dudley-Rucker, N., Steppan, C.M., Rajala, M.W., Scherer, P.E., Ahima, R.S., Lazar, M.A. and ED Abel. 2005. Mouse and human resistin impair glucose transport in primary mouse cardiomyocytes and oligomerization is required for this biological action. J Biol Chem., 280: 31679-31685. Satoh, H., Nguyen, M.T., Trujillo, M., Imamura, T., Usui, I., Scherer, P.E. and J.M. Olefsky. 2005. Adenovirus-mediated adiponectin expression augments skeletal muscle insulin sensitivity in male Wistar rats. Diabetes, 2005, 54(5):1304-1313. Vasseur, F., Helbecque, N., Lobbens, S., Vasseur-Delannoy, V., Dina, C., Clement, K., Boutin, P., Kadowaki, T., Scherer, P.E. and P. Froguel. 2005. Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding (ACDC) gene promoter variants in morbid obesity: evidence for a role of ACDC in diabesity. Diabetologia, 48(5):892-9. Capozza, F., Combs, T.P., Cohen, A.W., Cho, Y.R., Park, S.Y., Schubert, W., Williams, T.M., Brasaemle, D.L., Jelicks, L.A., Scherer, P.E., Kim, J.K., and M.P. Lisanti. 2005. Caveolin-3 (-/-) Knockout Mice Show Increased Adiposity and Whole-Body Insulin Resistance, with Ligand-Induced Insulin Receptor Instability in Skeletal Muscle. Am J Physiol Cell Physiol. 288(6):C1317-1331. Bonuccelli, G., Sotgia, F., Frank, P.G., Williams, T.M., de Almeida C.J., Tanowitz, H..B., Scherer, P.E., Hotchkiss, K.A., Terman, B.I., Rollman, B., Alileche, A., Brojatsch, J. and M.P. Lisanti. 2005. Anthrax Toxin Receptor (ATR/TEM8) is Highly Expressed in Epithelial Cells Lining the Toxin's Three Sites of Entry (Lung, Skin, and Intestine). Am J Physiol Cell Physiol. 288(6):C1402-1410. Bouatia-Naji, N., Meyre, D., Lobbens, S., Seron, K., Fumeron, F., Balkau, B., Heude, B., Jouret, B., Scherer, P.E., Dina, C., Weill, J. and P. Froguel. 2006. ACDC/Adiponectin Polymorphisms Are Associated With Severe Childhood and Adult Obesity. Diabetes, 55(2):545-550. Schattenberg, J.M., Singh, R., Wang, Y., Lefkowitch, J.H., Rigoli, R.M., Scherer, P.E. and M.J. Czaja. 2005. Jnk1 but not jnk2 promotes the development of steatohepatitis in mice. Hepatology, 22;43(1):163-172 Hertzel, A.V., Smith, L.A., Berg, A.H., Cline, G.W., Shulman, G.I., Scherer, P.E. and D.A. Bernlohr. 2005. Lipid Metabolism and Adipokine Levels in Fatty Acid Binding Protein Null and Transgenic Mice. Am J Physiol Endocrinol Metab. in press

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