Gene Response Section, CCR, NCI
has moved to: Georgetown University
the laboratory remains affiliated with NCI: Laboratory of Metabolism, CCR

Albert J. Fornace Jr., M.D.   positions available (see below)	Previous staff currently in CCR (2005) Galina Belova, Ph.D. Visiting Fellow M. Christine Hollander, Ph.D., Microbiologist  Ludmila Jirmanova, Ph.D. Visiting Fellow Christine Koch-Paiz, Biologist ALUMNI FELLOWS Sally Amundson, Sc.D., Associate Prof., Columbia University (2003) Insoo Bae, Ph.D., Assistant Prof., Albert Eistein College of Medicine        at Long Island Jewish Medical Center (2001) Dmitry V. Bulavin, M.D., Ph.D., Assistant Prof., Inst. of Cellular and Molecular       Biology, Univ. of Singapore (2004) France Carrier, Ph.D., Assistant Prof., Dept. of Biochemistry &       Molecular Biology, Univ. of MD Medical School (1999) I-Tsuen Chen, Ph.D., Associate Professor, Inst. Biotechnology       of Medical Technology, Taiwan (1997) Laura Henmeuller, Ph.D., Technology Transfer Specialist, NCI Technology      Transfer Branch, NIH (2000) Jeff Hildesheim, Ph.D., Technology Transfer Specialist, NCI Technology      Transfer Branch, NIH (2005) Oleg Kovalsky, Ph.D., Moscow, Russia (2001) H. Udo Kontny, M.D., Instructor, Pediatric Hematology/Oncology,       Children's Hospital of the Albert-Ludwigs-Universitaet,Freiburg, Germany (1998) Jesús Salvador, Ph.D., Assistant Professor, Consejo Superior de Investigaciones     Cientificas (CSIC), Department of Immunology and Oncology, National Center for     Biotechnology, Madrid (2005) M. Saeed Sheikh, M.D., Ph.D.,  Assistant Prof., Dept. of Pharmacology,         S.U.N.Y., Syracuse, N.Y. (2000); Associate Professor (2003); Professor (2006) Martin L. Smith, Ph.D., Assistant Professor, Indiana Univ. Cancer Center (2000);       Associate Professor (2004)  Stuart D. Tyner, Ph.D., Assistant Chief, Microbiology Division, Department of Pathology      and Area Laboratory Services, Landstuhl Regional Medical Center (2004) Qimin Zhan, M.D., Assistant Professor, Pittsburgh Cancer Center      and Dept. of Radiation Oncology, Univ. of Pittsburgh (1999); Associate Professor (2003);     Director and Professor, State Key Laboratory of Molecular Oncology, Cancer Institute,     Chinese Academy of Medical Sciences (2004) ALUMNI STUDENT FELLOWS Rania Awaad, Univ. of Virginia School of Medicine Class of 2009 Donald M. Ayers, Univ. of Chicago School of Medicine Class of 2001 Patricia Blank-DePaez, UCLA School of Public Health Khanh T. Do, George Washington University School of Medicine, Class of 2006 Will Ferguson, Agilent Technologies, Inc., Life Science Solution Unit, Wash., DC Bill Giasi, George Washington University Medical School, Class of 2003 David Gutkind, Kirksville College of Osteopathic Medicine, Class of 2004 Kate Kim, University of Chicago Law School, Class of 2003 Richard A. Lee, Drexel Univesity College of Medicine, Class of 2006 Thomas Molinaro, New Jersey Medical School, Class of 2002 Sarah Ogden, Columbia University Medical School, Class of 2001 Andrew Patterson, Graduate Student, NIH-GWU Robyn Philburn, Ph.D. program at Columbia University School of Public Health, 2004 Crissy Philips, Graduate Student, NIH-Johns Hopkins Matt Robertson, Univ. of Minnesota Medical School, Class of 2009 Sohrab Shabab, Eastern Virginia School of Medicine, Class of 2004 Lisa Vinikoor, Ph.D. program in Dept. of Epidemiology, Sch. of Public Health, Univ. of North Carolina, 2003 Sylvia Wong, Predoctoral Fellow, NHGRI Michelle Wyatt, Biological & Biomedical Sciences Ph.D. Program, Vanderbilt University, 2003 Kelly Yu,Yale School of Public Health

The Molecular Biology of Cellular Injury

The major focus of this research group is the study of responses to genotoxic stress in mammalian cells. Genotoxic stress and other adverse environmental conditions elicit a variety of stress-related signals that lead to the altered expression of multiple genes involved in cell-cycle control, programmed cell death, and in some cases DNA repair. Interestingly, key growth-control genes, such as the tumor suppressors p53 and RB, play central roles in some of these signaling pathways, and perturbations in their function in many human tumor cells have important implications in both carcinogenesis, radiobiology, and experimental cancer treatment.

Efforts in this laboratory have included the cloning and characterization of a variety of DNA-damage-inducible (DDI) genes and the role of the tumor suppressor p53 in their regulation. Studies have involved the gadd genes, CIP1/WAF1, BCL2, BAX, MCL1, BCLX, ß-polymerase, O6-methylguanine DNA methyltransferase, c-jun, c-fos, topoisomerases I and II, metallothionein, and ubiquitin. Understanding the role of DNA-damage responses in determining the cellular sensitivity to cytotoxic agents, such as used in cancer therapy, is a major objective. An important response to genotoxic stress in all cells are delays in cell cycle progression which are induced by DNA damage. These delays are mediated by various genes and probably include the GADD genes which are both DDI and growth-arrest inducible. The major portions of this project focus on: 1) the regulation of these genes with particular emphasis on p53-mediated features; 2) characterization of radiation-responsive genes using a functional genomics approach; 3) elucidation of the in vivo and in vitro functions of particular stress genes with emphasis on the use of targeted gene knockout approaches; and 4) the role of the GADD and related genes in cell-cycle control, genomic stability, and apoptosis. Of particular interest is our findings that the GADD45 gene is p53-regulated and the Gadd45 protein interacts with both proteins involved in both cell-cycle regulation and DNA repair. The regulation of such stress genes by p53 has important implications in cancer therapy considering that the majority of human tumors lack normal p53 function.