Education:
BSc 1981 Medical Sciences - Hebrew University-Hadassah Medical School, Israel
MD 1985 Medicine - Hebrew University-Hadassah Medical School, Israel
PhD 1987 Biochemistry - Hebrew University-Hadassah Medical School, Israel
Postdoctoral Research Fellowship:
1995-1999 Children's Hospital, Los Angeles, CA
Started at USC: 2000
Research Topics: Cell Death, Cancer Cell Biology, Signal Transduction
Research Description
As a physician-scientist, I am engaged in clinical care of children with brain tumors and neuroblastoma side-by-side with bench research to better understand the biology of these tumors and develop novel treatments based on this biology. Currently, brain tumors are the most common cause of cancer-related death in children. I believe that better cancer therapy can only come from improved understanding of the molecular mechanisms driving growth of tumors.
My major area of interest is angiogenesis and the tumor microenvironment, and especially in the context of brain tumors. The tumor microenvironment is comprised of many elements, including tumor cells, supporting cells such as astrocytes in the brain, inflammatory cells and other infiltrating cells, endothelial cells, and pericytes. These cells secrete cytokines, growth factors, proteolytic enzymes, and other factors, creating autocrine and paracrine loops, thereby altering the microenvironment, making it more hospitable to tumor growth and survival. Modulation and inhibition of such signaling loops will inhibit tumor growth and cause its regression.
Angiogenesis, the formation of new capillary blood vessels, is critical for tumor growth beyond 1-2 cubic mm. Thus, anti-angiogenic therapy may improve tumor response to current cancer therapy. Angiogenesis likely supports tumor growth not only by providing a blood supply, but probably also at the molecular level, by altering the microenvironment to be more favorable to tumor growth and survival.
The unique nature of the brain microenvironment is exemplified in two observations. 1) Glioblastoma tumors grown simultaneously in the brain and under the skin in mice frequently show different morphologies, even in the same mouse. 2) Treatment such as the anti ?v-integrin peptide that inhibits tumor growth inside the brain, is completely ineffective against tumors under the skin in the same mouse.
Our goal is to understand molecular mechanisms regulating angiogenesis and the tumor-promoting microenvironment in pediatric brain tumors and neuroblastoma. In the past few years our laboratory has initiated a new area in angiogenic integrin signaling, namely, ceramide metabolism in the apoptosis induced by inhibition of integrin ?v?3/?v?5 signaling (Erdreich-Epstein et al, Cancer Research, 2000; Erdreich-Epstein et al, Blood, 2005). We are currently investigating signal transduction pathways involved in this apoptotic function of ceramide and integrins. A second area of investigation is molecular mechanisms involved in the tumor-promoting effects of infiltrating cells in the microenvironment of the brain tumors. Methods used in these studies include tissue culture, molecular biology and signal transduction techniques, mouse brain tumor models with state of the art imaging modalities, and others. The environment at Childrens Hospital Los Angeles is highly conducive to these studies. The modern facilities and equipment, diverse expertise of the researchers, stimulating research interactions and collaborations, high-level research seminars, and close proximity to patients and the physicians caring for them, make research in the lab exciting and stimulating.
Selected Publications
Rosenne E, Shakhar G, Melamed R, Schwartz Y, Erdreich-Epstein A, Ben-Eliyahu S. - Inducing a mode of NK-resistance to suppression by stress and surgery: A potential approach based on low dose of poly I-C to reduce postoperative cancer metastasis. - Brain Behav Immun [ 2007 ] May;21(4):395-408 . PubMed
Finlay JL, Erdreich-Epstein A, Packer RJ. - Progress in the treatment of childhood brain tumors: no room for complacency. - Pediatr Hematol Oncol [ 2007 ] Jan-Feb;24(1):79-84 . PubMed
Erdreich-Epstein A, Ganguly AK, Shi XH, Zimonjic DB, Shackleford GM. - Androgen inducibility of Fgf8 in Shionogi carcinoma 115 cells correlates with an adjacent t(5;19) translocation. - Genes Chromosomes Cancer [ 2006 ] Feb;45(2):169-81 . PubMed
Sohara Y, Shimada H, Minkin C, Erdreich-Epstein A, Nolta JA, DeClerck YA. - Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cells. - Cancer Res [ 2005 ] Feb 15;65(4):1129-35 . PubMed
Erdreich-Epstein A, Tran LB, Cox OT, Huang EY, Laug WE, Shimada H, Millard M. - Endothelial apoptosis induced by inhibition of integrins alphavbeta3 and alphavbeta5 involves ceramide metabolic pathways. - Blood [ 2005 ] Jun 1;105(11):4353-61 . PubMed
Jubran RF, Erdreich-Epstein A, Butturini A, Murphree AL, Villablanca JG. - Approaches to treatment for extraocular retinoblastoma: Children's Hospital Los Angeles experience. - J Pediatr Hematol Oncol [ 2004 ] Jan;26(1):31-4 . PubMed
Stins MF, Pearce D, Di Cello F, Erdreich-Epstein A, Pardo CA, Sik Kim K. - Induction of intercellular adhesion molecule-1 on human brain endothelial cells by HIV-1 gp120: role of CD4 and chemokine coreceptors. - Lab Invest [ 2003 ] Dec;83(12):1787-98 . PubMed
Perelman N, Selvaraj SK, Batra S, Luck LR, Erdreich-Epstein A, Coates TD, Kalra VK, Malik P. - Placenta growth factor activates monocytes and correlates with sickle cell disease severity. - Blood [ 2003 ] Aug 15;102(4):1506-14 . PubMed
