Principal Investigator
Goldyne Savad Institute of Gene Therapy
Phone: 972-2-677-8732
Fax: 972-2-6430982
Email: axelrod@hadassah.org.il
Affiliation
Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Education
1987-1990 Postdoctoral Fellow The Salk Institute, La Jolla, CA., Prof. Inder M. Verma, Area of Interest: Retroviral Vectors and Gene Therapy of Hemophilia B.
1982-1987 Ph.D., Dept. of Biol. Chemistry, Weizmann Institute of Science, Rehovot. Advisor: Prof. R. Miskin. Thesis Title: Human Plasminogen Activators: cDNA Cloning, Effect on Tumor Growth and Metastasis, and Study of Some Regulatory Aspects.
1979-1982 M.Sc., Dept. of Biol. Chemistry, Weizmann Institute of Science, Rehovot.
1976-1978 B.A., Biochemistry, Pomona College, Claremont, CA., USA
Research interests
Protein and gene therapy in the treatment of liver failure and neoplasia; prevention and treatment of viral hepatitis; primary liver tumors and liver transplantation.
Selected Original Articles
Arad U, Axelrod J, Ben-Nun-Shaul O, Oppenheim A, Galun E. 2004. Hepatitis B virus enhances transduction of human hepatocytes by SV40-based vectors. J Hepatology 40:520-526.
Sonza S, Mutimer HP, O'Brien K, Ellery P, Howard JL, Axelrod JH, Deacon NJ, Crowe SM, Purcell DF. 2002. Selectively reduced tat mRNA heralds the decline in productive human immunodeficiency virus type 1 infection in monocyte-derived macrophages. J Virol 76(26):12611-21.
Hecht N, Pappo O, Shouval D, Rose-John S, Galun E, Axelrod JH. 2001. Hyper-IL-6 gene therapy reverses fulminant hepatic failure. Mol Ther 3:683-7.
Axelrod JH, Honigman A. 1999. A sensitive and versatile bioluminescence bioassay for HIV type 1 based on adenoviral vectors. AIDS Res Hum Retroviruses 15:759-67.
Review Articles and Chapters in Books
Galun E, Axelrod J.H. 2002. The role of cytrokines in liver failure and regeneration: potential new molecular therapies. Biochim Biophys Acta Nov. 11; 1592(3):345-58.
Patent Applications:
IL-6/SIL-6R complex for promotion of liver functions. Invectors: Eithan Galun, Stephan Rose-John, Malte Peters and Jonathan H. Axelrod. PCT application No. US99/11877, Publication date 9/12/99, Publication No. WO 00\\99/62534.
Research group
Nechemia, Yael, M.Sc. Phone: 677-8883
Orfaig, Carmit, M.Sc. Phone: 677-8883/8887
Anat Shriki, M.Sc.
Daniel Barkan, M.D.
Collaborators
Prof. Stefan Rose-John, Christian-Albrechts-Universitat zu Kiel
RESEARCH SUMMARY
IL-6 is a plieotropic cytokine that has diverse physiological roles. In the liver, IL-6 is an important factor for the normal progression of tissue regeneration following injury. Hyper-IL-6 (HIL-6) is a super agonistic fusion protein consisting of IL-6 and the soluble form of the IL-6R (sIL-6R).
Previous studies from our laboratory have shown that treating animals with HIL-6 as opposed to IL-6, dramatically enhances hepatocyte proliferation and significantly enhances survival following induction of liver injury. Furthermore, we have shown that the delivery of HIL-6 via an adenoviral (Ad) vector based gene therapy strategy can also be used to treat acute liver failure, perhaps with even greater efficiency than by protein therapy.
In a second topic involving HIL-6 gene therapy, we are investigating the utility of our HIL-6 Ad vector, Ad.HIL6gfp, as an anti-neoplastic therapeutic agent. This area of investigation is based on previously published observations in some tumor-derived cell lines, that the presence of a complete IL-6 autocrine arc induces cellular factors that complement the adenoviral E1A function. In such tumor cells, E1-deficient adenoviral vectors are able to propagate and kill the cells. Because the Ad.HIL6 vector can endow the infected tumor cell with a complete IL-6 autocrine arc, we have speculated that such vectors may be useful oncolytic agents for tumor cells that do not naturally express IL-6 or IL-6R. Furthermore, because of the pro-inflammatory activity of HIL-6, Ad.HIL6 infection of the tumor cells may also enhance attraction of immune cells to the site of the tumor, and enhance immune mediated tumor rejection.