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The Department of Cancer Biology focuses on fundamental problems in biology of relevance to cancer.
The overarching goal of the Department is to translate laboratory findings into the development of new therapeutic strategies. Departmental strengths in the leading-edge technologies of structural, systems, and chemical biology facilitate the translation of biology-based investigations in neurobiology, women's cancers, and energy homeostasis. Expertise in signal transduction and cell cycle control has contributed directly and indirectly to a new generation of targeted therapeutics for cancer (a.k.a. "smart drugs"), such as imatinib (Gleevec) and gefitinib (Iressa).
The Department has grown over the past three years, as measured both by grant support and number of independent faculty. Collectively, the research support portfolio grew to more than $30 million for fiscal year 2008, compared to $28 million for 2005. Seven new faculty have joined the department since 2006, bringing the number of independent department faculty to 21. Ulrike Eggert, PhD, and Nathanael Gray, PhD, were recruited as part of the Dana-Farber strategic plan initiative in Cancer Chemical Biology. The addition of Alexander (Sasha) Gimelbrant, PhD, and Jean Zhao, PhD, adds to a growing research focus in women's cancers. Suzanne Gaudet, PhD, augments the Department's systems biology expertise, while Pere Puigserver, PhD, rounds out the energy homeostasis group. Stephen Blacklow, MD, PhD recently joined our structural biology group, having moved his laboratory to the department from Brigham and Women’s Hospital in 2010.
Michael Eck, MD, PhD, specializes in X-ray crystallography of kinases. In collaboration with investigators from Dana-Farber/Harvard Cancer Center's Lung Cancer Program, Eck has determined the structure of patient-derived EGFR mutants to propose mechanisms of tumor response to therapy and drug resistance. Jarrod Marto, PhD, develops mass spectroscopy techniques to optimize detection and characterization of phosphoproteins. William Shih, PhD, constructs nanoscale objects and nanomechanical devices based on DNA molecules. He uses these to interrogate and modulate the operation of cells. Blacklow investigates the Notch pathway in the pathogenesis of T-cell acute lymphocytic leukemia and uses structural and other approaches to inhibit it.
Marc Vidal, PhD, director of Dana-Farber's Center for Cancer Systems Biology, uses powerful techniques in genetics and computational biology to map the genetic and protein networks that control cell behavior. He applies this information in a predictive manner to identify new pathways for therapeutic intervention. Gaudet takes a quantitative approach to measuring and analyzing the response of single cells to drugs and other extracellular signals.
The chemical biology group brings departmental expertise in early-stage drug discovery and translates insights on protein structure and function into entry-level screens for new cancer therapeutics.
Eggert identifies new drug targets through the parallel approaches of small-molecule and genome-wide RNAi screening. Gray develops libraries of small-molecule kinase inhibitor compounds and collaborates widely with disease program investigators. Their goal is to use these libraries to define therapeutic targets in tumors.
Another group of Cancer Biology faculty focuses on the genetics of brain development. Qiufu Ma, PhD, identifies and characterizes transcription factors that regulate the formation of sensory neurons and create neural networks for the perception of pain. Charles Stiles, PhD, focuses on genes that direct the formation of the glial lineages in the brain, while Rosalind Segal, MD, PhD, describes interactions between cells in the brain that lead to cell proliferation or migration. The outcomes of these studies will lead to new insights about treatments for brain cancer, one of the most deadly and untreatable forms of cancer.
The biology of women's cancers, particularly breast cancer, is another area of focus for faculty in the Department. J. Dirk Iglehart, MD, works to translate basic science findings into new clinical treatments for breast cancer. David Livingston, MD, who is also deputy director of DF/HCC, defines the functions of breast cancer susceptibility genes, BRCA1 and BRCA2. Thomas Roberts, PhD, and Zhao determine the specific roles of PI3K isoforms in diverse cellular pathways such as growth, metabolism, and transformation. Peter Sicinski, MD, PhD, characterizes the roles of cell cycle regulators in cancer, and Gimelbrant probes the mechanisms of epigentic silencing of gene expression.
Energy homeostasis is the area of investigation for Bruce Spiegelman, PhD, Nika Danial, PhD, and Puigserver. Spiegelman defines the transcriptional programs governing development of adipocytes, as well as their roles in regulating energy balance and homeostasis. Danial determines the functions of BCL2 family proteins that operate at the intersection of metabolic and cell death pathways. Puigserver identifies the transcriptional mechanisms that regulate metabolic and longevity pathways.
Teaching is an important complement to our research activities. Collectively, the Department has trained 307 postdoctoral fellows and graduate students during the past three years. Students from many Harvard-based graduate programs – including Biomedical and Biological Sciences, Biophysics, Virology, and Neurobiology – complete their doctoral theses in the Department's many laboratories. Graduate students and postdoctoral fellows participate in informal weekly seminars and the annual departmental retreat. Stiles and Segal also co-direct a Harvard-wide training grant in cancer biology from the National Cancer Institute.
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