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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 extensively in grant support, independent faculty appointments, personnel, and research direction. Collectively, the research support portfolio grew to more than $32.6 million for fiscal year 2015. Six new faculty joined the department since 2015, expanding the department to a total of 25 independent laboratories with over 300 members. In addition, as of 2016 the department is under new leadership with the appointments of co-chairs Rosalind Segal, MD, PhD, and Thomas Roberts, PhD.
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. Stephen Blacklow, MD, PhD, investigates the Notch pathway in the pathogenesis of T-cell acute lymphocytic leukemia and uses structural and other approaches to inhibit it. Eric Fischer, PhD, studies the pathways and protein complexes at the crossroads of fundamental cellular disposal systems using structural biology approaches. Hari Arthanari, PhD, is developing nuclear magnetic resonance methods to investigate the atomic level structures of protein surfaces that mediate molecular interactions important in disease pathways.
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. Suzanne Gaudet, PhD, takes a quantitative approach to measuring and analyzing the response of single cells to drugs and other extracellular signals. And Rameen Beroukhim, MD, PhD, develops genomic analysis methods to identify previously unrecognized oncogenic mutations that can serve as focal points for developing therapies.
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. Nathanael Gray, PhD, 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. Sara Buhrlage, PhD, is developing small molecules for therapies targeting deubiquitylating enzymes (DUBs) that inhibit the degradation of oncogenic proteins. Jun Qi, PhD, is designing small molecule inhibitors of epigenetic protein targets with therapeutic potential. And Justin Kim, PhD, is exploring novel strategies to synthesize complex molecular architectures that provide opportunities for new therapeutic approaches.
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. David Livingston, MD, who is also deputy director of DF/HCC, defines the functions of breast cancer susceptibility genes, BRCA1 and BRCA2. Jean Zhao, PhD, who is also co-director of the DF/HCC Breast Cancer Program, and Thomas Roberts, PhD, utilize both mouse models and chemical biology to determine the specific roles of various kinases, including the catalytic isoforms of PI3K in both normal physiology and cancer. Peter Sicinski, MD, PhD, characterizes the roles of cell cycle regulators in cancer, and Sasha Gimelbrant, PhD, probes the mechanisms of epigentic silencing of gene expression.
Energy homeostasis is the area of investigation for Bruce Spiegelman, PhD, Nika Danial, PhD, Pere Puigserver, PhD, and Edward Chouchani, PhD. 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. Chouchani innovates metabolomics technologies to address mitochondrial and metabolic pathways in normal and disease states.
Teaching is an important complement to our research activities. Collectively, the Department has trained 305 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.
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