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Jeffrey E. Green, M.D.

Laboratory of Cancer Biology and Genetics Head, Transgenic Oncogenesis and Genomics Section Senior Investigator Building 37, Room 4054C 37 Convent Drive Bethesda, MD 20892 Phone:   301-435-5193 Fax:   301-496-8395 E-Mail:   jegreen@nih.gov Link: Other Homepage

Biography

Dr. Green received his undergraduate degree in history and philosophy of science from Princeton University and was awarded a fellowship to continue his studies at the University of Munich. After receiving his M.D. from McGill University, Montreal, he completed a pediatric residency at the Children’s Hospital of Philadelphia. He came to the NCI as a clinical genetics fellow, studied gene regulation with George Khoury, and joined the Laboratory of Cell Regulation and Carcinogenesis as head of the Transgenic Carcinogenesis Group in 1997.

Research

Transgenic Models for Prostate and Mammary Carcinogenesis

The research objectives of my lab are to 1) understand the biology of breast and prostate cancer, from initiation through its progressive stages, including tumor cell dormancy and metastases; 2) relate the biologic changes during tumor progression to genomic changes that occur, including alterations in gene copy number, gene transcription, non-coding RNAs, and protein levels; 3) process this information into an integrated systems understanding of cancer genetic networks and epigenetic regulatory influences; and 4) utilize this network analysis to identify new molecular targets to treat cancer.

Understanding how particular oncogenic events may specify the development of particular sub-types of breast and prostate cancer has been a focus of our work. Mouse models of human cancers offer particular advantages in uncovering such relationships since specific genetic alterations can be utilized to induce tumorigenesis and variability in genomic changes can be minimized using mice with well-defined genetic backgrounds.

Our work has included the development and utilization of novel approaches to integrate microarray data from both human cancer and corresponding mouse cancer models. These studies have demonstrated that specific mouse models of mammary cancer can be classified with human basal or luminal tumors according to the initiating oncogenic event. By performing the first supervised analysis comparing mouse and human breast cancers according their estrogen-receptor status, we have identified a robust and highly gene network related to breast cancer tumor lineage and estrogen receptor function that could not be uncovered using only human array data. Interestingly, this ER network is operative during normal mammary development, thus indicating that ER+ positive tumors utilize an existing signaling system found in normal mammary epithelium. We have also discovered an intrinsic oncogene signature for SV40 T/t-antigens in multiple epithelial transgenic tumors. This unique signature defines a highly integrated network related to DNA damage and repair, cell cycle regulation, proliferation and apoptosis. Importantly, this signature predicts poor prognosis and metastases in human breast, prostate and lung cancers, suggesting that targets identified by this network may be vital for tumor maintenance. These findings provide new opportunities for devising targeted therapies and testing them in mouse models validated for this purpose.

We have also made important observations related to cancer prevention and therapeutic intervention. Our group is the first to demonstrate that muscadine grape skin extract contains unique compounds that inhibit growth of transformed prostate cancer cells at least in part through inhibition of the Akt survival pathway. We are currently attempting to isolate the active compound(s) for further evaluation and development, and are conducting in vivo tumor studies.

In order to understand how tumor cells switch from a dormant state to a proliferative metastatic state, we have developed that first in vitro predictive model system to study this phenomenon. We have discovered that the dormant state can be dependent upon the extracellular environment and that proteins determining the intracellular architecture of the cell are critical in regulating the switch from dormancy to proliferative metastatic growth. This system is being exploited to further understand mechanisms of dormancy and proliferative outbreak from dormancy. New insights from these studies may be extremely valuable in devising new strategies to kill dormant tumor cells or maintain their dormant phenotype, thus preventing metastatic recurrence.

Currently, I serve as the Principal Investigator of the NCI Mouse Models of Mammary Cancer Collective, which is part of the national NCI Mouse Models of Human Cancer Consortium. The NCI Mouse Collective is composed of 25 NIH investigators who have assembled into a highly interactive community to advance the understanding of breast cancer through the use of animal models. Additionally, I am a Captain in the US Public Health Service.

For additional information about the laboratory, as well as useful links, go to http://rex.nci.nih.gov/RESEARCH/basic/lc/jg.htm

This page was last updated on 6/11/2008.