The Golub lab brings together a scientific community focused on understanding the basic molecular mechanisms of cancer and applying this knowledge to transform the practice of cancer medicine. The work includes systematic and comprehensive elucidation of cancers in terms of DNA alterations, RNA profiles, proteomic signatures, and functional responses. Scientists in the lab share ideas and launch collaborative projects to tackle key challenges. In addition, several associate members are working at the Broad in addition to their primary labs on cancer-related projects, collaborating with scientists both in the Cancer Program as well as the scientific platforms across the institute.
Major areas of focus include:
Cancer is a complex disease of genomic alteration, exploiting many different molecular mechanisms. Fighting cancer will ultimately require a comprehensive classification of cancers according to their genomic basis. Projects include: systematic studies of genome-wide loss and amplification; targeted resequencing to identify mutant genes in key pathways; and discovery of cancer-specific biomarkers. Several associate members, including Bill Sellers and Matt Meyerson of the Dana-Farber Cancer Institute, actively lead aspects of this initiative.
Kinase activation in cancers
An emerging theme in cancer biology is that many, if not all, cancers are caused by the aberrant activation of a class of enzymes known as kinases. This project seeks to develop methods for measuring molecular signatures of kinase activation in cancer cells. By systematically activating and inactivating all kinases in the human genome, program scientists will learn to recognize which kinases are activated in which cancer patients. Because many anti-kinase drugs are now in pharmaceutical development, this work will play an important role in determining which patients should receive which anti-kinase drugs — a crucial step toward the goal of personalized medicine.
Achilles' heels of cancer
Cancer cells rely for their survival on the expression of a limited number of specific genes. Identifying these genes would yield, for the first time, a comprehensive catalog of the potential therapeutic targets for cancer. Projects include systematic use of RNA interference (RNAi) to identify such Achilles' heels of cancers. Associate member Bill Hahn of the Dana-Farber Cancer Institute leads part of this effort.
Signature-based chemical screening
Genomic signatures provide a powerful way to recognize the effects of chemical compounds, both to understand cancer biology and to develop new therapeutics. Program activities include: Gene-Expression High-Throughput Screening (GE-HTS) to identify compounds that can induce specific developmental changes in cancer (for example, to cause leukemias to differentiate into normal cells), and the Connectivity Map, led by Justin Lamb of the Broad Institute, to generate a comprehensive compendium of genomic signatures for all FDA-approved drugs.
Other efforts include molecular pathology studies to map gene expression patterns to actual tumor architecture, integrating molecular signatures to predict cancer prognosis and treatment response, and developing robust computational biology tools to analyze and interpret the data generated across the large range of projects underway.