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Researchers
  • Dr.  Yossi Tam
Dr Yossi Tam
 
Research Interests
The Obesity and Metabolism Laboratory is focused on uncovering the involvement of the peripheral endocannabinoid system in the pathogenesis of obesity and its metabolic complications, with therapeutic prospects for the development of an effective drug therapy.
 
During the last few decades, there has been an epidemic increase worldwide in the prevalence of obesity and its metabolic complications, including diabetes, changes in blood lipid profile and fatty liver disease, which, in turn, can lead to coronary disease, liver cirrhosisCombined drawing of a man with a sandwich and Central stomach with the cannabis plant and even cancer. There is no currently available medication that simultaneously targets all of the metabolic consequences of obesity, justifying the search for novel approaches. 
 
Endocannabinoids (eCBs) are lipid‐like signaling molecules present in the brain as well as peripheral tissues. They interact with the same cell surface receptors, CB1 and CB2, that can also recognize the psychoactive ingredient in marijuana, and produce similar effects, such as an increase in appetite and increased synthesis and decreased degradation of lipids. Using animal models of obesity we found that a novel class of chemical compounds that blocks the CB1 receptor in peripheral tissues but does not penetrate into the brain, improves all of the above deleterious consequences of obesity without causing untoward neurological side effects that would occur with similar, but brain‐penetrant compounds. Yet, for a successful translation of our preclinical findings to clinical practice, a better understanding of the involvement of the peripheral eCB system in the pathogenesis of obesity and its metabolic complications is still required, and is the main focus of the work done in our lab.
 
This question, and its implication for therapeutic potential, is pursued at multiple levels, from a single molecule through cell culture to transgenic and knockout mice, addressing the specific contribution of the peripheral eCB-CB1 signaling pathway to the development of obesity-induced leptin resistance, hepatic steatosis (fatty liver) and renal complications. Our work is expected to provide new insights into the pharmacological modulation of the peripheral eCB system as a potential target for therapeutic intervention in such diseases.
 
 
 
Research Projects
      Identifying the role of the peripheral eCB system in leptin resistance and obesity
 
     Exploring the signaling pathways activated by hepatic CB1 receptor in obesity-induced hepatic steatosis
 
     Elucidating the role of proximal tubular CB1 receptor in obesity-induced renal dysfunction
 
     Targeting proximal tubular CB1 receptor for the treatment of diabetic nephropathy
 
     Assessing the contribution of the peripheral eCB system to the development of obesity in Prader-Willi syndrome

     Deleneating the role of the peripheral endocannabinoid system in diabetes-induced osteoporosis  
 
 
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Lab Members
 
Dr Yossi Joseph Tam Rivka Hadar Liad Hinden Adi Drori
Dr. Yossi (Joseph) Tam
Principal Investigator
yossit@ekmd.huji.ac.il
Ms. Rivka Hadar
Lab Manager
rivka@savion.huji.ac.il
Liad Hinden
Postdoctoral Fellow
liad.hinden@mail.huji.ac.il
Adi Drori
Postdoctoral Fellow
adidr@ekmd.huji.ac.il
Shahar Azar Saja Baraghithy Shiran Udi Ibrahim Knani
Shahar Azar
Ph.D. Student
shahara@ekmd.huji.ac.il
Saja Baraghithy
Ph.D Student
saja.baraghithy@mail.huji.ac.il
Shiran Udi
M.Sc. Student
shiran.udi@mail.huji.ac.il
Ibrahim Knani
M.Sc. Student
Ibrahim.knani@mail.huji.ac.il
  
  
Available Positions
The Obesity and Metabolism Laboratory is looking for excellent Ph.D. students for leading research projects in the field of obesity, diabetes and the metabolic syndrome.
 
Job description: Research will be focused on elucidating the mechanisms of action in obesity and diabetes pathogenesis using complete metabolic and phenotypic analyses of transgenic and knockout mice. A wide variety of biochemical, biological and metabolic experiments in animal models and cultured cells will be utilized.
 
Qualifications: Candidates with an outstanding master in medical sciences (or similar), hands-on experience in molecular biology, cell culture techniques and animal experiments are especially encouraged to apply. Applicants should have the ability to work independently and in a team environment, show flexibility, innovative and creative thinking. Previous knowledge and experience in the area of obesity, diabetes and metabolic disorder is prioritized.
 
We offer: A dynamic, innovative, well equipped, and scientifically stimulating environment, with excellent mentoring and training program and possibility to participate in national and international meetings.
Please send your complete application including cover letter, CV and references by E-mail to: yossit@ekmd.huji.ac.il
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Brief CV
Senior Lecturer (2014-present)
Institute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem
 
Staff Scientist (2011-2014)
Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute of Health (NIH)
 
Postdoctoral Fellow (2009-2011)
Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute of Health (NIH)
Advisor: Dr. George Kunos
 
Ph.D. 2009 Summa Cum Laude
Bone laboratory, The Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem
Advisors: Prof. Itai Bab, Prof. Esther Shohami
 
Advanced Education in General Dentistry Residency (2004-2005)
Department of Prosthodontics, Faculty of Dental Medicine, The Hebrew University of Jerusalem
 
D.M.D. 2005
Faculty of Dental Medicine, The Hebrew University of Jerusalem
 
M.Sc. 2005
Bone laboratory, The Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem
 
B.Med.Sc. 2002 Cum Laude
Faculty of Dental Medicine, The Hebrew University of Jerusalem
 
  
Publications
Ofek, O., Karsak, M., Leclerc, N., Fogel, M., Frenkel, B., Wright, K., Tam, J., Attar-Namdar, M., Kram, V., Shohami, E., Mechoulam, R., Zimmer, A. and Bab, I. (2006). Peripheral CB2 Cannabinoid Receptor Regulates Bone Mass. Proc.Natl.Acad.Sci U.S.A, 103:696-701.
 
Tam, J., Ofek, O., Fride, E., Ledent, C., Gabet, Y., Müller, R., Zimmer, A., Mackie, K., Mechoulam, R., Shohami, E. and Bab, I. (2006). Involvement of Neuronal Cannabinoid Receptor, CB1, in Regulation of Bone mass and Bone Remodeling. Mol.Pharmacol., 70:786-792.
 
Yirmiya, R., Goshen, I., Bajayo, A., Kreisel, T., Feldman, S., Tam, J., Trembovler, V., Csernus, V., Shohami, E. and Bab, I. (2006). Depression Induces Bone Loss through Stimulation of the Sympathetic Nervous System. Proc.Natl.Acad.Sci U.S.A, 103:16876-16881.
 
Tam, J., Trembovler, V., Di Marzo, V., Petrosino, S., Leo, G., Alexandrovich, A., Regev, E., Casap, N., Shteyer, A., Ledent, C., Karsak, M., Zimmer, A., Mechoulam, R., Yirmiya, R., Shohami, E. and Bab, I. (2008) The Cannabinoid CB1 Receptor Regulates Bone Formation by Modulating Adrenergic Signaling. FASEB J, 22:285-294.
 
Bab, I., Ofek, O., Tam, J., Rehnelt, J., Zimmer, A. (2008). Endocannabinoids and the Regulation of Bone Metabolism. J Neuroendocrinol, 20 Suppl 1:69-74.
 
Noh, T., Gabet, Y., Cogan, J., Shi, Y., Tank, A., Sasaki, T., Criswell, B., Dixon, A.,  Lee, C, Tam, J., Kohler, T., Segev, E., Kockeritz, L., Woodgett, J., Müller, R., Chai, Y., Smith, E., Bab, I. and Frenkel, B. (2009). Lef1 Haploinsufficient Mice Display a Low Turnover and Low Bone Mass Phenotype in a Gender- and Age-Specific Manner. PLoS One, 4:e5438.
 
Tam, J., Vemuri, V.K., Liu, J., Bátkai, C., Mukhopadhyay, B., Godlewski, G., Osei-Hyiaman, D., Ohnuma, S., Ambudkar, S.V., Makriyannis, A. and Kunos, G. (2010). Peripheral CB1 Cannabinoid Receptor Blockade Improves Cardiometabolic Risk in Mouse Models of Obesity. J Clin. Invest., 120:2953–2966.
• Highlighted in J Clin. Invest., (2010) 120:2646-8.
 
Smoum, R., Bar, A., Tan, B., Milman, G., Attar-Namdar, M., Ofek, O., Stuart, J.M., Bajayo, A., Tam, J., Kram, V., O’Dell, D., Walker, M.J., Bradshaw, H.B., Bab, I. and Mechoulam, R. (2010). Oleoyl-serine, an Endogenous N-acyl Amide Modulates Bone Remodeling and Mass. Proc.Natl.Acad.Sci U.S.A, 107:17710-17715.
 
Godlewski, G., Alapafuja, S.O., Bátkai, S., Nikas, S.P., Cinar, R., Offertáler, L., Osei-Hyiaman, D., Liu, J., Mukhopadhyay, B, Harvey-White, J., Tam, J., Pacak, K., Blankman, J.L., Cravatt, B.F., Makriyannis, A. and Kunos, G. (2010). Inhibitor of Fatty Acid Amide Hydrolase Normalizes Cardiovascular Function in Hypertension without Adverse Metabolic Effects. Chem.Biol., 17:1256–1266.
 
Tam, J., Liu, J., Mukhopadhyay, B., Cinar, R., Godlewski, G. and Kunos, G. (2011). Endocannabinoids in Liver Disease. Hepatology, 53:346-355.
 
Mukhopadhyay, B., Cinar, R., Yin, S., Liu, J., Tam, J., Godlewski, G., Harvey-White, J., Mordi, I., Cravatt, B.F., Lotersztajn, S., Gao, B., Yuan, Q., Schuebel, K., Goldman, D. and Kunos, G. (2011). Hyperactivation of anandamide synthesis and regulation of cell-cycle progression via cannabinoid type 1 (CB1) receptors in the regenerating liver. Proc.Natl.Acad.Sci U.S.A, 108:6323-6328.
• Highlighted in Proc.Natl.Acad.Sci U.S.A, (2011) 108: 6339-40.
 
Kunos, G. and Tam, J.  (2011). The Case for Peripheral CB1 Receptor Blockade in the Treatment of Visceral Obesity and its Cardiometabolic Complications. Br J Pharmacol., 163: 1423-1431.
 
Liu, J., Zhou, L., Xiong, K, Godlewski, G., Mukhoadhyay, B., Tam, J., Yin, S., Gao, P., Shan, X., Pickel, J., Bataller, R., O’Hare, J., Scherer, T., Buettner, C. and Kunos, G. (2012). Hepatic Cannabinoid Receptor 1 Mediates Diet-induced Insulin Resistance via Inhibition of Insulin Signaling and Clearance in Mice, Gastroenterology, 142:1218-1228.
• Highlighted in Gastroenrerology, (2012) 142:1063-6.
• Selected for Faculty of 1,000. http://f1000.com/prime/716247804
 
Srivastava, S., Kashiwaya, Y., King, M.T., Baxa, U., Tam, J., Niu, G., Chen, X., Clarke, K. and Veech, R.L. (2012). Mitochondrial Biogenesis and Increased Uncoupling Protein 1 in Brown Adipose Tissue of Mice Fed a Ketone Ester Diet. FASEB J., 26:2351-2362.
 
Tam, J.*, Cinar, R., Liu, J., Godlewski, G., Wesley, D., Jourdan, T., Szanda, G., Mukhopadhyay, B., Chedester, L., Liow, J.S., Innis, R.B., Cheng, K., Rice, K.C., Deschamps, J.R., Chorvat, R.J., McElroy, J.F. and Kunos, G. (2012). Peripheral Cannabinoid-1 Receptor Inverse Agonism Reduces Obesity by Reversing Leptin Resistance. Cell Metab., 16:167-179.
• Appeared on the August 2012 cover page of Cell Metabolism.
• Featured in Nature Review in Endocrinology, (2012) 8:564.
• Featured in Nature Review in Drug Discovery, (2012) 11:749.
• * Corresponding Author
 
Silverman, M.N., Mukhopadhyay, P., Belyavskaya, E., Tonelli, L.H., Revenis, B.D., Doran, J.H., Ballard, B.E., Tam, J., Pacher, P. and Sternberg, E.M. (2013). Impaired Glucocorticoid Receptor Dimerization Exacerbates LPS-induced Inflammation, Sickness Behavior and Metabolic Alterations in Mice. Mol. Psychiatry, 18:1006-1017.
 
Jourdan, T., Godlewski, G., Cinar, R., Bertola, A., Szanda, G., Liu, J., Tam, J., Han, T., Mukhopadhyay, B., Ju, C., Kunos, G. (2013). Endocannabinoid Activation of Nlrp3 Inflammasome in Infiltrating Macrophages Mediates β-cell Loss in Type II Diabetes. Nat. Med., 19:1132-1140.
• Featured in Nature Review in Endocrinology, (2013) 9:626.
 
Cinar, R., Godlewski, G., Liu, J., Tam, J., Jourdan, T., Mukhopadhyay, B., Harvey-White, J., Kunos, G. (2013). Hepatic CB1 receptors mediate diet-induced insulin resistance by increasing de novo synthesis of long chain ceramides. Hepatology, 59:143-153.
 
Tam, J*., Godlewski, G., Earley, B.J., Zhou, L., Jourdan, T., Szanda, G., Cinar, R., Kunos, G. (2014). Role of Adiponectin in the Metabolic Effects of Cannabinoid Receptor-1 Blockade in Mice with Diet-Induced Obesity. Am J Physiol Endocrinol Metab306:E457-468. 
• * Corresponding Author
 
Jourdan, T., Szanda, G., Rosenberg, A.Z., Tam, J., Earley, B., Godlewski, G., Cinar, R., Liu, Z., Liu, J., Ju, C., Pacher, P., Kunos, G. (2014). Overactive Cannabinoid 1 Receptor in Podocytes Drives Type-2 Diabetic Nephropathy. Proc.Natl.Acad.Sci U.S.A., 111:E5420-5428. ​

Wasserman, E., Tam, J., Mechoulam, R., Zimmer, A., Maor, G., Bab, I. (2015). CB1 cannabinoid receptors mediate endochondral skeletal growth attenuation by Δ9-tetrahydrocannabinol.Ann N Y Acad Sci, 1335:110-119.

Park, O., Ki, S.H., Xu, M., Wang, H., Feng, D., Tam, J., Osei-Hyiaman, D., Kunos, G., Gao, B.​ (2015). Biologically active, high levels of interleukin-22 inhibit hepatic gluconeogenesis but do not affect obesity and its metabolic consequences.​ Cell Biosci. 5: 25.

Tam, J. (2015)​. The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases. J Basic Clin Physiol Pharmacol. doi: 10.1515/jbcpp-2015-0055.
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Keywords
Endocannabinoids, Peripheral CB1 receptor, Diet-induced Obesity, Diabetes, Metabolic Syndrome, Leptin Resistance, Diabetic Nephropathy, Syndromic Obesity, Prader-Willi Syndrome, Fatty Liver (Hepatic Steatosis), Hepatic SIRT1& PPAR-alpha signaling, Osteoporosis, Drug design,  Endocrinology, Pharmacology, Metabolism
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