The University of Toledo

Sonia M. Najjar

Professor Director, Center for Diabetes and Endocrine Research (CeDER) Phone: (419) 383-5196            (419) 383-4183 FAX:     (419) 383-2871 E-mail: sonia.najjar@utoledo.edu

Education

• 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., Cheung, 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.

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.

Abou-Rjaily, G.A., Lee, S.J., May, D., Al-Share, Q.Y., 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. Comments on Page 867.

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.

Wisloff, U.*, Najjar, S.M.*, Ellingsen, O., Haram, Per M., Swoap, S., Fernstrom, M.A., Lee, S.J., Rezaei, K., Al-Share, Q., Koch, L.G., and Britton, S.L. (2005) Metabolic syndrome X emerges from artificial selection for aerobic capacity. Science 207:418-420.  (*Shared First Authorship).
-Selected for press release and was accompanied by a preview in Science.
-Selected among the highly cited metabolic syndrome-related papers published in 2005 and chosen by leaders in the field among the notable advances: [Nature Med. 12 (1) (58-61), 2006].
-Also reviewed as News and Views by Bernal-Mizrachi, C and Semenkovich, C.F. Fast predators or fast food, the fit still survive. Nature Medicine, 12 (1): 46-47, 2006.

Najjar, S.M., Yang, Y., Fernstrom, M.A., Abou-Rjaily, G.A., Lee, S.J., DeAngelis, M.A., Al-Share, Q., Miller, T., Dai, T., Ratnam, S., 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. (Selected for press release and was accompanied by a preview).

Park, S.-Y., Choo, 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 with dominant-negative mutation of CEACAM1. Am. J. Physiol. Endocrinol Metab. 291(3): E517-E524. PMID: 16638824

Nagaishi, T., Pao, L., Lin, S.-H., Iijima, H., Kaser, A., Qiao, S.-W., Chen, D., Glickman, J., Najjar, S.M., Nakajima, A., Neel, B.G., and Blumberg, R.S. (2006) SHP1 Dependent T cell inhibition by CEACAM1 Isoforms Expressing a Long Cytoplasmic Domain. Immunity 25(5): 769-781. PMCID: PMC Journal-In Process

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 Skjærpe, T. (2007) Superior cardiovascular
 effect of aerobic interval-training versus moderate continuous training 
in elderly heart failure patients: A randomized controlled study.
 Circulation. 115(24): 3086-3094. PMID: 175487226

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. 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, Wisløff U.  (2008)  Carbon monoxide levels experienced by heavy smokers impair aerobic capacity and cardiac contractility and induce pathological hypertrophy.  Inhal Toxicol. May;20(7):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., Wisløff, U. (2008) Both aerobic endurance and strength training programs improve cardiovascular health in obese adults. Clin. Sci (Lond). 115: 283-293. PMID: 18338980.

Arnt Erik TjØnna, MSc; Sang Jun Lee, PhD;  Øivind Rognmo, MSc; Tomas O. StØlen, MSc; Anja Bye, MSc; Per Magnus Haram, PhD; Jan Pål Loennechen, PhD; Qusai Y. Al-Share, MSc; Eirik Skogvoll, PhD; Stig a SlØrdahl, PhD; Ole J. Kemi, PhD; Sonia M. Najjar, PhD; Ulrik WislØff, PhD. (2008) Aerobic Interval Training Versus Continuous Moderate Exercise as a Treatment for the Metabolic Syndrome A Pilot Study. Circulation, 118:346-354. PMCID: PMC2777731

DeAngelis AM, Heinrich G, Dai T, Bowman TA, Patel PR, Jun Lee S, Hong EG, Young Jung D, Assmann A, Kulkarni RN, Kim JK, Najjar, SM, (2008) CEACAM1: A Link Between Insulin and Lipid Metabolism.  Diabetes, Sept;57(9):2296-303. PMCID: PMC2518480 

Sang Jun Lee, Garrett Heinrich, Larisa Federova, Qusai Y. Al-Share, Kelly J. Ledford, Mats A. Fernstrom, Marcia F. McInerney, Sandra K. Erickson, Cara Gatto-Weis, Sonia M. Najjar. (2008) Development of Non-alcoholic Steatohepatitis in Insulin Resistant L-SACC1 Mice.  Gastroenterology, 135: 2084-2095. *Shared first authorship. 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. (2008) Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity. Cardiovascular Res. 2009 Mar 1;81(4):723-32. *Shared senior authorship. 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. A Novel Pathway of Insulin Sensitivity in Chromogranin A Null Mice: A Crucial Role for Pancreastatin in Glucose Homeostasis. J. Biol. Chem. PMCID: PMC2781393 

Huang S, Kaw M, Harris MT, Ebraheim N, McInerney MF, Najjar SM, Lecka-Czernik B. (2010) Decreased osteo-clastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1. Bone. 2010 Jan 5. PMCID: PMC2862391

Warrier M, Hinds TD, Jr, Ledford KJ, Cash HA, Patel PR, Bowman TA, Stechschulte LA, Young W, Shou W, Najjar SM* and Sanchez ER*. (2010) Susceptibility to Diet-induced Hepatic Steatosis and Glucocorticoid Resistance In FK506-Binding Protein 52-Deficient Mice. Endocrinology, 151:3225-36. *shared senior authorship. PMCID: PMC2903936

Heinrich G, Ghosh S, DeAngelis MA, Schroeder-Gloeckler JM, Patel PR, Castaneda TR, Jeffers S, Lee AD, Jung DY, Zhang Z, Opland DM, Myers MG, Jr, Kim JK and Najjar SM. (2010) A Role for CEACAM2 in the Central Control of Energy Balance and Peripheral Insulin Action. Gastroenterology 139: 644-652. PMCID: PMC2910848

Ghosh S*, Kaw M*, Patel PR, Ledford KJ, Bowman TA, McInerney MF, Bourey RE, Erickson, SK and Najjar SM. (2010) Null mutation of Ceacam1 causes Non-alcoholic Steatohepatitis. Hepatic Medicine: Research and Evidence. Hepatic Medicine: Research and Evidence 2: 69–78. PMID: 21949477; PMCID: PMC3177946

Hinds TD Jr, Ramakrishnan SK, Cash HA, Stechschulte LA, Heinrich G, Najjar SM and Sanchez ER. (2010) Discovery of Glucocorticoid Receptor-β in Mice with a Role in Metabolism. Molecular Endocrinology. 24(9):1715-1727. PMCID: PMC2940475

Bowman TA*, Ramakrishnan SK*; Kaw M, Lee SJ, Patel PR, Golla VK, Bourey RE, Haram PM, Kock LG, Britton SL, Wisloff U, Lee AD, and Najjar SM. (2010) Caloric restriction reverses hepatic insulin resistance and steatosis in rats with low aerobic capacity. Endocrinology 151: 5157-5164. PMCID: PMC2954714.

Wuescher LM, Angevine KR, Hinds T, Ramakrishnan SK, Najjar SM and Mensah-Osman EJ. Insulin regulates Menin expression, cytoplasmic localization and interaction with FOXO 1. (2011) Am. J. Physiol. Endocrinol. Metab. 301(3): E474-83. PMID: 21693693 

Tiano JP, Delghingaro-Augusto V, Le May C, Liu, S., KawMK, Khuder, S.S., Latour MG, Bhatt SA, Korach KS, Najjar SM, Prentki M, 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. Clinical Investigation. 121(8): 3331-42. PMCID: PMC3148728 

Hinds TD Jr, Stechschulte LA, Cash HA, Whisler D, Banerjee A, Yong W, Khuder SS, Kaw MK, Shou W, Najjar SM, Sanchez ER. (2011)Protein Phosphatase 5 mediates lipid metabolism through reciprocal control of glucocorticoid and PPARγ receptors. J. Biol. Chem. 286(50):42911-22. PMID: 21994940 

P. R. Patel; S. K. Ramakrishnan; M. K. Kaw; C. K. Raphael; S. Ghosh; J. S. Marino; G. Heinrich; S. J. Lee; R. E. Bourey; J. W. Hill; D. Y. Jung; D. A. Morgan; J. K. Kim; S. K. Rahmouni; S. M. Najjar. (2011) Increased metabolic rate and insulin sensitivity in male mice lacking the carcino-embryonic antigen-related cell adhesion molecule 2, Diabetologia, 55(3):861. PMID: 22159884.  Manuscript was chosen for “upfront review” by the Editor.

Gupta S, Yan Y, Malhotra D, Liu J, Xie Z, Najjar SM, and Shapiro JI. Ouabain and insulin induce sodium pump endocytosis in renal epithelium. (2012) Hypertension59(3): 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 SM, Zhang C-Y, Ding H-F, Liu JO and Yu L. Brain selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic -cells. (2012) J. Biol. Chem. 287(36): 30368-30375. PMID: 22798068.

Friedman TC, Sinha-HikimI, ParveenM, Najjar SM, Liu Y, Mangubat M, ShinC-S, LyzlovA, Ivey R, Shaheen M, FrenchSW, Sinha-Hiki, AP. Additive effects of nicotine and high-fat diet on hepatic steatosis in male mice. (2012) Endocrinology. 153(12): 5809-20. PMID: 23093702.

Huang J, Ledford KJ, Pitkin WB, Russo L, Najjar SM* and Siragy HM*. Targeted deletion of murine carcinoembryonic antigen-related cell adhesion molecule 1 activates PI3K-Akt signaling and contributes to the expression of (Pro) renin receptor via transcription factors CREB family and NF-κB transcription factors. (2013) Hypertension 62(2): 317-323. (*Shared Senior Authorship). PMID: 23734002.

Najjar SM, Ledford KJ, Abdallah SL, Paus A, Russo L, Kaw MK, Ramakrishnan SK, Muturi HT, Raphael CK, Lester SG, Heinrich G, Pierre SV, Benndorf R, Kleff V, Jaffa AA, Levy E, Vazquez G, Goldberg IJ, Beauchemin N, Scalia R, Ergün S. Ceacam1 deletion causes vascular alterations in large vessels. (2013) Am J Physiol Endocrinol Metab. 305(4): E519-29. PMID: 23800882.


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, www.els.net
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.