Joshua LaBaer, MD, PhD

2007-2008 BCRF Project:
Through the support of BCRF over the past several years, the Brugge and LaBaer laboratories have completed and exceeded the ambitious BC1000 project to identify, capture and verify a collection of more than 1000 human genes related to breast cancer (actual number is over 1300 genes). These clones are now stored in an automated freezer system and can be obtained by any scientist worldwide at http://plasmid.hms.harvard.edu.

During the last six months, the LaBaer group has continued to pursue studies to identify and characterize genes that regulate critical events involved in the initiation and progression of breast cancer. The BC1000 clones have been employed in the development and execution of high throughput unbiased screens, as well as biased analyses of specific candidate genes, to look for genes that contribute to drug resistance in breast cancer. The screens have identified several genes that reproducibly confer drug resistance on breast cancer cells in culture. These results will lead to important new findings relating to genes that are involved in breast development and breast cancer.

Last year, with BCRF support, the LaBaer team tested over 500 human kinases and identified a small subset that conferred resistance to Tamoxifen in breast cancer cell lines (MCF7) . In 2007-2008, they will characterize the functional role of these select kinases through protein interactions, transcriptional profiling and data modeling to better understand the molecular causative factors associated with Tamoxifen resistance. They will use similar methods to continue characterizing Tamoxifen/Faslodex sensitive and resistant MCF7 cell lines. Their preliminary data already suggests that activation of the ERK pathway, and interactions with proteins involved in apoptosis, cell growth and division may all participate in Tamoxifen resistance. Finally, they will optimize their methods to extend the testing to larger gene collections like the BC1000. Their goal is to identify proteins and their pathways for therapeutic intervention.

Mid-Year Progress Report:
During the last six months, the LaBaer group has continued to pursue studies to identify and characterize genes that regulate critical events involved in the progression of breast cancer and the understanding the development of resistance to anti-estrogen drug treatment. They have produced several matching drug sensitive and resistant breast cancer cultured cell lines that they can use to study the factors that lead to drug resistance. These cells provided a useful resource to study which genes are inappropriately regulated in the resistant state and which genes when added to the sensitive cells will make them resistant. Screens of these cells have identified several genes that reproducibly confer drug resistance on breast cancer cells in culture. In conjunction, the results will lead to important new findings relating to genes that are involved in breast development and resistance to hormonal treatment in breast cancer.

In addition, the LaBaer group has continued to develop, maintain and distribute a large gene collection, the BC1000, for studies by the breast cancer community. These clones have been employed in the development and execution of high throughput unbiased screens, as well as focused analyses of specific candidate genes, to look for genes that contribute to breast cancer development. This collection is available to all researchers in the scientific community at http://plasmid.hms.harvard.edu.

Bio:
Joshua LaBaer, MD, PhD, is a founder and Director of the Institute of Proteomics at Harvard Medical School. He attended the University of California at Berkeley as an undergraduate and completed medical school and graduate school at the University of California, San Francisco, where he studied steroid regulation of DNA transcription and protein-DNA interactions.

He completed his internship and residency at the Brigham and Women's Hospital and a clinical fellowship in Oncology at the Dana-Farber Cancer Institute in Boston. He also pursued research interests at the Massachusetts General Hospital in Boston in the areas of breast cancer, mammalian cell cycle regulation and cell cycle checkpoint genes.

He currently holds an academic appointment through the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. Dr. LaBaer is an associate editor of the Journal of Proteome Research, a member of the Scientific Advisory Committee for the Proteome Society and a founding member of the Human Proteome Organization.