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Abstract
Grant Number: 1R43DK064468-01 PI Name: LARRICK, JAMES W. PI Email: calvarez@pano.com PI Title: PRESIDENT AND SCIENTIFIC DIRECTOR Project Title: A Novel Hepatokine Abstract: DESCRIPTION (provided by applicant): Hepatokines are hepatocyte-derived autocrine or paracrine growth and survival factors. Preliminary data described below demonstrates the identification of a novel hepatokine (HK-1) originally isolated from fetal hepatocytes and patented by this laboratory. The overall goal of the present project is to produce sufficient quantities of recombinant HK-1 to evaluate its capacity to enhance pancreatic islet cell survival and transplantation. HK-1 is mitogenic for hepatocytes and hepatocyte cell lines and promotes the survival of fetal pancreas and hepatocytes. Highly purified HK-1 protects mice from acute CCI4-induced liver cell injury and augments the success of fetal pancreas transplantation. In phase I we will express the cDNA for HK-1 and purify sufficient quantities of protein for biological studies, evaluate he activity of HK-1 using in vitro assays of apoptosis, growth and differentiation and study the in vivo activity of HK-1 in an animal model of diabetes mellitus. In Phase II we will carry out more in-depth studies of HK-1 in conjunction with allogeneic pancreas transplantation. Depending upon the success of these studies, HK-1 will be produced under GMP conditions, subjected to formal toxicology and preclinical studies in preparation for submission of an IND.
Thesaurus Terms:
drug design /synthesis /production, growth factor, liver cell, pancreatic islet function, pancreatic islet transplantation, protein structure function
apoptosis, autocrine, biotherapeutic agent, cell differentiation, cell growth regulation, pancreas transplantation, paracrine
laboratory mouse, molecular cloning, protein purification
Institution: PANORAMA RESEARCH, INC. 2462 WYANDOTTE ST MOUNTAIN VIEW, CA 94043 Fiscal Year: 2003 Department: Project Start: 01-JUL-2003 Project End: 30-JUN-2004 ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES IRG: ZRG1