Prof. Eli C Lewis

Prof. Eli C Lewis Profile

Professor
Ph.D. 2006
Residency: Denver, Colorado

Head of Department

Department : Clinical Biochemistry and Pharmacology
Room :
Phone :
Email : lewis@bgu.ac.il
Office Hours :  
inflammation, autoimmunity, diabetes, immunology,t cells, bio chemistry, pharmacology

Education

  • 2004-2006 Post-doctoral fellowship, University of Colorado Health and Science Center, laboratory of Prof. Charles A. Dinarello 1999-2003 Ph.D. Summa Cum Laude, Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer-Sheva. Title of Thesis: “The study of the role of IL-15 in transplant rejection”. Supervisor: Dr. Amos Douvdevani 1997-1999 M.Med.Sc. Magna Cum Laude, Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer-Sheva. Title of Thesis: “The design of an IL-15-antisense for the study of the role of IL-15 in renal transplant rejection”. Supervisors: Prof. Cidio Chaimovitz and Dr. Amos Douvdevani 1993-1997 B.Med.Sc., Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer-Sheva, Israel

Research Interests

  • Topics: Islet transplantation Immune tolerance T regulatory cells Beta-cell regeneration Vascularization Anti-inflammation IL-1 receptor antagonist IL-18 binding protein Alpha-1-antitrypsin Xenografting Techniques: Mouse islet isolation Mouse islet transplantation Introduction of siRNA into islets by portal vein inflation Gene profiling of explanted islet grafts Human pancreatic islet transplantation is a vital option for type-1 diabetes patients. Unlike whole-pancreas grafting, which similarly supplies tight regulation of endogenous insulin release, isolated islets contain no organ-related transplantation risks such as surgical complications, CMV transmission or excessive immunosuppression. In this procedure, globally performed in over 50 centers across Europe, USA, Canada and Japan, islets are collected from donors soon after death in a sterile laboratory, employing a 7-hour procedure. At the same time, a diabetic transplant candidate is reached and transplantation team recruited. The procedure of islet introduction is strikingly simplistic. Islets are introduced into the liver via a fine needle to the portal vein under local anesthesia, guided by non-invasive echo guidance. Covered by minimal non-diabetogenic immunosuppression, the patient is allowed to leave the hospital within less than an hour. Complete insulin independence is achieved in individuals after a second additional graft is performed. Unfortunately, five-year islet cell function follow-up studies reveal unacceptably high islet erosion. Probable elements that impede indefinite graft survival may include ineffective immunosuppression, as well as unrestrained ongoing inflammation. In addition, islet mass is rapidly reduced after engraftment by robust local inflammation, the inhibition of which is absent due to removal of steroids from immunosuppression protocol. There is, therefore, a demand for islet survival regimens that are safe, feasible and effective. Our group studies mouse and human islets, as well as relevant immune processes, in order to advance the understanding of islet survival during transplantation and islet restoration in diabetic pancreata. Experimental models include in vitro studies of islets that are subject to inflammatory agents, as well as an highly delicate in vivo model of engraftment of isolated islets into diabetic mice, followed by intensive follow-up and profiling of immune and islet responses in the live mouse. In collaboration with Rocky Mountain Human Islet Transplant Program, Colorado, human islets are similarly assessed to verify relevance of findings to diabetic patients. Inflammation, according to our findings, is the pivotal obstacle in optimal islet transplantation. We study anti-inflammatory therapies as potential treatments to accompany islet isolation and transplantation, with firm accordance to clinical relevance. Exciting findings in our lab reveal that immune-tolerance, the only condition in which a therapy can be withdrawn and the graft remain intact, has been attained by our group using a potent anti-inflammatory clinically available monotherapy. As a result, a compound currently used for various other indications in medical opractice was approved for clinical trial in type-1 diabetes patients in Colorado. Related studies in our laboratory include beta-cell regeneration, understanding of insulin responses in whole islets, xenotransplantation (animal to human) and gene delivery into islets.

Major expertise and techniques in the lab

  • Animal survival microsurgery, adoptive transfer experiments, chimera studies • Primary islets, lung epithelial cells and immune cells • Molecular biology, point-mutation studies • Culture and co-culture studies, including cell migration and angiogenesis

Publications and funding summary / representative publications and grants

  • Lewis EC. Review: Extended Clinical Indications for Alpha-1-Antitrypsin Therapy. Molecular Medicine , 18:957-970, 2012.
  • Twina, Guy; Sheiner,Eyal; Shahaf, Galit; yaniv salem, shimrit; Madar, Tamar; Baron, Joel; Wiznitzer, Arnon; Mazor, Moshe; Holcberg, Gershon; Lewis, Eli. Lower Circulating Levels and Activity of Alpha-1 Antitrypsin in Pregnant Women with Severe Preeclampsia The Journal of Maternal-Fetal & Neonatal Medicine 2012 (Jul 16. Epub ahead of print ).
  • Keren Bellacen, Noa Kalay, Eyal Ozeri, Galit Shahaf and Eli C. Lewis. Revascularization of Pancreatic Islet Allografts is Enhanced by Alpha-1-Antitrypsin Under Anti-inflammatory Conditions 2012 Cell Transplantation
  • Grants: 2010-2013 Israel Science Foundation (ISF), Bikura. Shared PI with Tel-Aviv and Bar-Ilan, $210,000.
  • 2011-2014 Joint Israel Science Foundation (ISF) and Juvenile Diabetes Research Foundation (JDRF) Biomedical research grant for type 1 diabetes, Single grant recipient: PI, Eli C Lewis NIS 1,521,000

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