Physiology and Pharmacology

Sonia M. Najjar


Dr. Sonia M. Najjar

Frederick W. Hiss Endowed Professor in Diabetes Research
Professor, Department of Physiology and Pharmacology
Director, Center for Diabetes and Endocrine Research (CeDER)

Phone:   (419) 383-5196
             (419) 383-4183
FAX:      (419) 383-2871




  • B.A., Biochemistry, San Francisco State University, 1980
  • M.S., Chemistry, San Francisco State University, 1983
  • Ph.D., Physiology, Stanford University Medical School, 1989

Graduate Training

  • Student Research Assistant (I), Gastroenterology Department, University of California in San Francisco (Young Kim, MD, advisor),1980-1982
  • Student Research Assistant, Gastroenterology Division, Stanford University School of Medicine (Gary M. Gray, MD, advisor),1984-1989

Postgraduate Training

  • Intramural Research Training Assistant, Diabetes Branch, NIDDK, NIH, 1989-1994

Academic Appointment

  • Assistant Professor, Department of Pharmacology, UTCOM, 1980-1982
  • Teaching Assistant, Department of Chemistry, San Francisco State University, 1994-1999
  • Associate Professor with Tenure, Department of Pharmacology, UTCOM, 2000-2005
  • Adjunct Assoc. Professor of Medicinal Chemistry, University of Toledo, College of Pharmacy, 2002-2007
  • Professor with Tenure, Department of Physiology & Pharmacology, UTCOM, 2005-present

Administrative Appointment

  • Founding Director, Center for Diabetes and Endocrine Research (CeDER), 2006-present
  • Director, Molecular Basis of Disease Graduate Program, 2001-2007
  • Director, Cardiovascular and Metabolic Disease Graduate Track, 2007
  • Vice Director, Program in Bioinformatics and Proteomics/Genomic, 2001-2005

Research Interests
Dr. Najjar’s research focuses on identifying the genetic and environmental interactions underlying obesity, type 2 diabetes and their cardiovascular complications.

The laboratory pioneered the finding that CEACAM1 plays a key role in regulating insulin action by promoting insulin clearance in liver. By generating mouse models of loss- or gain-of function of this protein, the Najjar team observed that genetic inactivation/deletion of this protein causes insulin resistance, obesity and fatty liver disease, in addition to predisposing to type 2 diabetes and Non-alcoholic steatohepatitis (NASH) in response to high-fat diet. Current studies focus on the role of CEACAM1 in the pathogenesis of atherosclerosis and common types of cancer.

The Najjar laboratory also investigates the central role of CEACAM2 proteins in insulin secretion and energy balance.

Representative Publications

Journal Articles

Phan, D., Cheng, C.-J., Galfione, M., Vakar-Lopez, F., Tunstead, J., Thompson, N.E., Burgess, R.R., Najjar, S.M., Yu-Lee, L.-Y., and Lin, S.-H. (2004) Identification of Sp2 as a transcriptional repressor of CEACAM1 in tumorigenesis.  Cancer Res. 64:3072-3078.  PMID:  15126343  

McInerney, M.F., Najjar, S.M., Brickley, D., Lutzke, M., Abou-Rjaily, G.A., Reifsnyder, P., Haskell, B.D., Flurkey, K., Zhang, Y.J., Pietropaolo, S.L., Pietropaolo, M., Byers, J.P., and Leiter, E.H. (2004) Anti-insulin receptor autoantibodies are not required for type 2 diabetes pathogenesis in NZL/Lt mice, a New Zealand obese (NZO)-derived mouse strain.  Exp. Diabesity Res. 5:177-185  PMID:  15512785.  PMCID:  PMC2478629

Abou-Rjaily, G.A., Lee, S.J., May, D., Al-Share, Q.Y., DeAngelis, A.M., Ruch, R.J., Neumaier, M., Kalthoff, H., Lin, S-H., and Najjar, S.M. (2004) CEACAM1 modulates epidermal growth factor receptor-mediated cell proliferation.  J. Clin. Invest. 114:944-952.  PMID:  15467833.  PMCID:  PMC518664

Dai, T., Abou-Rjaily, G.A., Al-Share, Q.Y., Yang, Y., Fernstrom, M.A., DeAngelis, A.M., Lee, A.D., Sweetman, L., Amato, A., Pasquale, M., Lopaschuk, G.D., Erickson, S.K., and Najjar, S.M. (2004) Interaction between altered insulin and lipid metabolism in CEACAM1-inactive transgenic mice.  J. Biol. Chem. 279: 45155-45161.  PMID:  15316023

Wisloff, U., Najjar, S.M., Ellingsen, O., Haram, P.M., Swoap, S., Al-Share, Q., Fernstrom, M., Rezaei, K., Lee, S.J., Koch, L.G., and Britton, S.L. (2005) Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.  Science 307:418-420.  PMID:  15662013. 

Najjar, S.M., Yang, Y., Fernstrom, M.A., Lee, S.J., DeAngelis, M.A., Rjaily, G.A., Al-Share, Q.Y., Dai, T., Miller, T.A., Ratnam, S., Ruch, R.J., Smith, S., Lin, S.-H., Beauchemin, N., and Oyarce, A.M. (2005) Insulin acutely decreases hepatic fatty acid synthase activity.  Cell Metabolism 2:43-53.  PMID:  16054098 

Park, S.-Y., Cho, Y.-R., Kim, H.-J., Hong, E-G., Higashimori, T., Lee, S.J. Goldberg, I.J., Shulman, G.I., Najjar, S.M., and Kim, J.K. (2006) Mechanism of glucose intolerance in mice with dominant-negative mutation of CEACAM1.  Am. J. Physiol. Endocrinol Metab. 291:E517-E524.  PMID: 16638824

Nagaishi, T., Pao, L., Lin, S.-H., Iijima, H., Kaser, A., Qiao, S.-W., Chen, Z., Glickman, J., Najjar, S.M., Nakajima, A., Neel, B.G., and Blumberg, R.S. (2006) SHP1 phosphatase-dependent T cell inhibition by CEACAM1 adhesion molecule isoforms.  Immunity 25:769-781.  PMID:  17081782 

Wisløff, U., Støylen, A., Loennechen, J.P., Bruvold,M., 
Rognmo, Ø., Haram, P.H., Tjønna, A.E., Helgerud, J., Slørdahl, S.A., Lee, S.J., Videm, V., Bye, A., Smith, G.L., Najjar, S.M., Ellingsen, Ø., and Skjaerpe, T. (2007) Superior cardiovascular
 effect of aerobic interval training versus moderate continuous training 
in elderly heart failure patients: A randomized study.
  Circulation 115:3086-3094.  PMID:  17548726

Bye, A., Langaas, M., Høydal, M.A., Kemi, O.J., Heinrich, G., Koch, L.G., Britton, S.L., Najjar, S.M., Ellingsen, O., and Wisloff, U. Aerobic capacity-dependent differences in cardiac gene expression. (2008) Physiol. Genomics. 33:100-109.  PMID: 18171719

Bye A, Sørhaug S, Ceci M, Høydal MA, Stølen T, Heinrich G, Tjønna AE, Najjar SM, Nilsen OG, Catalucci D, Grimaldi S, Contu R, Steinshamn S, Condorelli G, Smith GL, Ellingsen O, Waldum H, and Wisløff U. (2008) Carbon monoxide levels experienced by heavy smokers impair aerobic capacity and cardiac contractility and induce pathological hypertrophyInhal. Toxicol. 20:635-646.  PMID: 18464052

Schjerve, I.E., Tyldum, G.A., Tjønna, A.E., Stølen, T.O., Loennechen, J.P., Hansen, H.E., Haram, P.M., Heinrich, G., Bye, A., Najjar, S.M., Smith, G.L., Slørdahl, S.A., Kemi, O.J., and Wisløff, U. (2008) Both aerobic endurance and strength training programs improve cardiovascular health in obese adults.  Clin. Sci. (Lond). 115:283-293.  PMID: 18338980.

Tjonna, A.E., Lee, S.J., Rognmo, O., Stolen, T.O., Bye, A., Haram, P.M., Loennechen, J.P., Al-Share, Q.Y., Skogvoll, E., Slordahl, S.A., Kemi, O.J., Najjar, S.M., and Wisloff, U. (2008) Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome a pilot study. Circulation 118:346-354.  PMID:  18606913

DeAngelis, A.M., Heinrich, G., Dai, T., Bowman, T.A., Patel, P.R., Lee, S.J., Hong, E.G., Jung, D.Y., Assmann, A., Kulkarni, R.N., Kim, J.K., and Najjar, SM, (2008) CEACAM1: A link between insulin and lipid metabolism.  Diabetes 57:2296-303.  PMID:  18544705.  PMCID:  PMC2518480  

Lee, S.J., Heinrich, G., Fedorova, L., Al-Share, Q.Y., Ledford, K.J., Fernstrom, M.A., McInerney, M.F., Erickson, S.K., Gatto-Weis, C., and Najjar, S.M. (2008) Development of nonalcoholic steatohepatitis in insulin-resistant liver-specific S503A carcinoembryonic antigen-related cell adhesion molecule 1 mutant miceGastroenterology 135:2084-2095.  PMID:  18848945.  PMCID:  PMC2784638

Haram, P.M., Kemi, O.J., Lee, S.J., Bendheim, M.Ø., Al-Share, Q.Y., Waldum, H.L., Gilliam, L.J., Koch, L.G., Britton, S.L., Najjar, S.M., and Wisloff, U. (2009) Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity.  Cardiovascular Res. 81:723-32.  PMID:  19047339.  PMCID:  PMC2642601

Gayen, J.R., Saberi, M., Schenk, S., Biswas, N., Vaingankar, S.M., Cheung, W.W., Najjar, S.M., O'Connor, D.T., Bandyopadhyay, G., and Mahata, S.K. (2009) A novel pathway of insulin sensitivity in chromogranin a null mice:  a crucial role for pancreastatin in glucose homeostasis.  J. Biol. Chem. 284:28498-509. PMID: 19706599.  PMCID:  PMC2781393 

Huang, S., Kaw, M., Harris, M.T., Ebraheim, N., McInerney, M.F., Najjar, S.M., and Lecka-Czernik, B. (2010) Decreased osteoclastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1.  Bone 46:1138-45.  PMID:  20044046.  PMCID:  PMC2862391

Warrier, M., Hinds, T.D., Jr., Ledford, K.J., Cash, H.A., Patel, P.R., Bowman, T.A., Stechschulte, L.A., Yong, W., Shou, W., Najjar, S.M. and Sanchez, E.R. (2010) Susceptibility to diet-induced hepatic steatosis and glucocorticoid resistance In FK506-binding protein 52-deficient mice.  Endocrinology 151:3225-36. PMID: 20427484.  PMCID:  PMC2903936

Heinrich, G., Ghosh, S., DeAngelis, A.M., Schroeder-Gloeckler, J.M., Patel, P.R., Castaneda, T.R., Jeffers, S., Lee, A.D., Jung, D.Y., Zhang, Z., Opland, D.M., Myers, M.G., Jr., Kim, J.K. and Najjar, S.M. (2010) Carcinoembryonic antigen-related cell adhesion molecule 2 controls energy balance and peripheral insulin action in mice.  Gastroenterology 139:644-52.  PMID:  20381490.  PMCID:  PMC2910848

Ghosh, S., Kaw, M, Patel, P.R., Ledford, K.J., Bowman, T.A., McInerney, M.F., Erickson, S.K., Bourey, R.E., and Najjar, S.M. (2010) Mice with null mutation of Ceacam1 develop nonalcoholic steatohepatitis.  Hept. Med. 2:69–78. PMID:  21949477,  PMCID: PMC3177946

Hinds, T.D., Jr., Ramakrishnan, S., Cash, H.A., Stechschulte, L.A., Heinrich, G., Najjar, S.M., and Sanchez, E.R. (2010) Discovery of glucocorticoid receptor-β in mice with a role in metabolism.  Mol. Endocrinol. 24:1715-1727.  PMID:  20660300.  PMCID:  PMC2940475

Bowman, T.A., Ramakrishnan, S.K., Kaw, M., Lee, S.J., Patel, P.R., Golla, V.K., Bourey, R.E., Haram, P.M., Kock, L.G., Britton, S.L., Wisloff, U., Lee, A.D., and Najjar, S.M. (2010) Caloric restriction reverses hepatic insulin resistance and steatosis in rats with low aerobic capacity.  Endocrinology 151:5157-5164. PMID: 20861239.  PMCID:  PMC2954714.

Wuescher, L., Angevine, K., Hinds, T., Ramakrishnan, S., Najjar, S.M., and Mensah-Osman, E.J. (2011) Insulin regulates menin expression, cytoplasmic localization and interaction with FOXO1.  Am. J. Physiol. Endocrinol. Metab. 301:E474-83.  PMID:  21693693.  PMCID:  PMC3275149 

Tiano, J.P., Delghingaro-Augusto, V., Le May, C., Liu, S., Kaw, M.K., Khuder, S.S., Latour, M.G., Bhatt, S.A., Korach, K.S., Najjar, S.M., Prentki, M., and Mauvais-Jarvis, F. (2011) Estrogen receptor activation reduces lipid synthesis in pancreatic islets and prevents β cell failure in rodent models of type 2 diabetes. J. Clin. Invest. 121:3331-42.  PMID:  21747171.  PMCID:  PMC3148728 

Hinds, T.D., Jr., Stechschulte, L.A., Cash, H.A., Whisler, D., Banerjee, A., Yong, W., Khuder, S.S., Kaw, M.K., Shou, W., Najjar, S.M., and Sanchez, E.R. (2011) Protein phosphatase 5 mediates lipid metabolism through reciprocal control of glucocorticoid receptor and peroxisome proliferator-activated receptor-γ (PPARγ). J. Biol. Chem. 286:42911-22.  PMID:  21994940.  PMCID:  PMC3234872

Patel, P.R., Ramakrishnan, S.K., Kaw, M.K., Raphael, C.K., Ghosh, S., Marino, J.S., Heinrich, G., Lee, S.J., Bourey, R.E., Hill, J.W., Jung, D.Y., Morgan, D.A., Kim, J.K., Rahmouni, K., and Najjar, S.M. (2012) Increased metabolic rate and insulin sensitivity in male mice lacking the carcino-embryonic antigen-related cell adhesion molecule 2.  Diabetologia 55:763-72.  PMID:  22159884.  PMCID:  PMC3272352

Gupta, S., Yan, Y., Malhotra, D., Liu, J., Xie, Z., Najjar, S.M., and Shapiro, J.I. (2012) Ouabain and insulin induce sodium pump endocytosis in renal epithelium. Hypertension 59:665-72.  PMID: 22311908.  PMCID: PMC3336087 

Chen, X.Y., Gu, X.T/, ‎Saiyin, H., Wan, B., ‎Zhang, Y.J., Li, J., Wang, Y.L., Gao, R., Wang, Y.F., Dong, W.P., Najjar, S.M., Zhang, C.Y, Ding, H.F., Liu, J.O. and Yu, L. (2012) Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic β-cells. J. Biol. Chem. 287:30368-75.  PMID:  22798068.  PMCID: PMC3436288

Friedman, T.C., Sinha-Hikim, I., Parveen, M., Najjar, S.M., Liu, Y., Mangubat, M., Shin, C.S., Lyzlov, A., Ivey, R., Shaheen, M., French, S.W., Sinha-Hiki, A.P. (2012) Additive effects of nicotine and high-fat diet on hepatic steatosis in male mice.  Endocrinology 153:5809-20.  PMID: 23093702.  PMCID:  PMC3512067 

Huang, J., Ledford, K.J, Pitkin, W.B., Russo, L., Najjar, S.M., and Siragy, H.M. (2013) Targeted deletion of murine CEACAM1 activates PI3K-Akt signaling and contributes to the expression of (Pro)renin receptor via CREB family and NF-κB transcription factors.  Hypertension 62:317-323.  PMID: 23734002.  PMCID: PMC3793251 

Najjar, S.M., Ledford, K.J., Abdallah, S.L., Paus, A., Russo, L., Kaw, M.K., Ramakrishnan, S.K., Muturi, H.T., Raphael, C.K., Lester, S.G., Heinrich, G., Pierre, S.V., Benndorf, R., Kleff, V., Jaffa, A.A., Levy, E., Vazquez, G., Goldberg, I.J., Beauchemin, N., Scalia, R., Ergün, S. (2013) Ceacam1 deletion causes vascular alterations in large vessels.  Am. J. Physiol. Endocrinol. Metab. 305:E519-29. PMID: 23800882.

Najjar, S.M. and Russo, L. (2014) CEACAM1 loss links inflammation to insulin resistance in obesity and non-alcoholic steatohepatitis (NASH).  Semin Immunopathol. 36:55-71.  PMID: 24258517.  PMCID:  PMC3946532

Kim, J.H., Meyers, M.S., Khuder, S.S., Abdallah, S.L.,  Muturi, H.T., Russo, L., Tate, C.R., Hevener, A.L., Najjar, S.M., Leloup, C., and Mauvais-Jarvis, F. (2014) Tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice.  Mol Metab. 3:177-90.  PMID: 24634829.  PMCID: PMC3953695

Ebke, L.A., Nestor-Kalinoski, A.L., Slotterbeck, B.D., Al Dieri, A.G., Ghosh-Lester, S., Russo, L., Najjar, S.M., von Grafenstein, H., and McInerney, M.F. (2014) Tight association between macrophages and adipocytes in obesity:  implications for adipocyte preparation.  Obesity 22:1246-55.  PMID: 24376179.  PMCID: PMC3980195

Gable, M.E., Abdallah, ‎S.L., Najjar, S.M., Liu, L., and Askari A. (2014) Digitalis-induced cell signaling by the sodium pump:  on the relation of Src to Na+/K+-ATPase.  Biochem. Biophys. Res. Commun. 446:1151-4.  PMID: 24667596.

Pereira, S., Park, E., Mori, Y., Haber, C.A., Han, P., Uchida, T., Stavar, L., Oprescu, A.I., Koulajian, K., Ivovic, A., Yu, Z., Li, D., Bowman, T.A., Dewald, J., El-Benna, J., Brindley, D.N., Gutierrez-Juarez, R., Lam, T.K., Najjar, S.M., McKay, R.A., Bhanot, S., Fantus, I.G., and Giacca, A. (2014) FFA-induced hepatic insulin resistance in vivo is mediated by PKCδ, NADPH oxidase, and oxidative stress.  Am. J. Physiol. Endocrinol. Metab.  PMID: 24824652

Stechschulte, L.A., Hinds, T.D., Jr., Khuder, S.S., Shou, W., Najjar, S.M. and Sanchez, ER. (2014) FKBP51 controls cellular adipogenesis through p38 kinase-mediated phosphorylation of GRα and PPARγ.  Mol. Endocrinol. 28:1265-75.  PMID:  24933247.  PMCID:  PMC4116587

Stechschulte, L.A., Hinds, T.D., Jr., Ghanem S.S., Shou, W., Najjar, S.M., and Sanchez, E.R. (2014) FKBP51 reciprocally regulates GRα and PPARγ activation via the Akt-p38 Pathway.  Mol. Endocrinol. 28:1254-64.  PMID:  24933248.  PMCID:  PMC4116593

Alshahrani, M.M., Yang, E., Yip, J., Ghanem, S.S., Abdallah, S.L., DeAngelis, A.M., O'Malley, C.J., Moheimani, F., Najjar, S.M., and Jackson, D.E. (2014) CEACAM2 negatively regulates hemi (ITAM-bearing) GPVI and CLEC-2 pathways and thrombus growth in vitro and in vivo.  Blood 124:2431-41.  PMID: 25085348.  PMCID:  PMC4192753

Book Chapters and Invited Review Papers

  1. Najjar SM. (1983) Effect of sodium butyrate on collagen synthesis in human epithelial tumor cells. MS Thesis
  2. Najjar SM. (1989) Altered intestinal hydrolase glycoproteins in Diabetes Mellitus. PhD Thesis
  3. Taylor SI, Kadowaki T, Accili D, Cama A, Kadowaki H, McKeon C, Moncada V, Marcus-Samuels B, Bevins C, Ojamaa K, Frapier C, Beitz L, Perrotti N, Rees-Jones R, Margolis R, Imano E, Najjar SM, Courtney F, Arakaki R, Gorden P, and Roth J. (1991) Mutations of the insulin receptor gene in genetic forms of insulin resistance. Recent Progress in Hormone Research. 46: 185-217
  4. Taylor SI, Najjar SM, Cama A, and Accili D. (1991) Structure and function of the insulin receptor. In: “Insulin-like Growth Factors: Molecular and Cellular Aspects”, (D. LeRoith, ed.) CRC Press, pp.221-244
  5. Najjar SM, and Weintraub B. (1993) Radioimmunoassay: Past, Present and Future. In " Handbook of Endocrine Research Techniques" (De Pablo, F., Scanes, C., and Weintraub, B. eds.) Academic Press, Inc., Orlando, Fl., pp: 3-23
  6. Najjar SM, Philippe N, Accili D, and Taylor SI. (1993) pp120, an endogenous substrate of the insulin receptor tyrosine kinase, is an ecto-ATPase. In " New Perspectives in Endocrinology" (Ares Serono Symposia eds.) Raven Press, New York, Volume 99, pp: 389-394
  7. Accili D, and Najjar SM. (1997) Il meccanismo d’azione dell’insulina. In: “Diabete Mellito. Principi e pratica”. (A.V.Greco, G.Ghirlanda, Eds.) Verduci, Rome, pp. 41-47
  8. Najjar SM. (1997) pp120/C-CAM: genomic cloning and role in insulin action and metabolism. In "Ecto-ATPases: Recent Progress on Structure and Function" (L. Plesner, T.L. Kirley, and A.F. Knowles, eds) Plenum Publishing Corporation, New York, pp 261-265
  9. Najjar SM. (2000) Insulin Action: Molecular Basis of Diabetes. In: Encyclopedia of Life Sciences, Nature Publishing Group: London,
  10. Najjar SM. (2010) Nonalcoholic fatty liver disease. In: “Metabolic Basis of Obesity”. (Rexford S. Ahima, Ed) World Scientific Publishing Co., published by Spriger-Verlag.
  11. Bourey RE, Kaw MK, Lesler SG, Ghanem SS, and Najjar SM. (2013) Diabetes. In: “Diet, Exercise, and Chronic Disease: The Biological Basis of Prevention”. (C. Murray Ardies, Ed). CRC Press; pp76-96. 
Last Updated: 6/26/15