Department of Cancer Biology
The Department of Cancer Biology focuses on fundamental problems
in biology of relevance to cancer.
Research goals and themes
Thomas Roberts, PhD, Co-Chair 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).
Departmental growth
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.
Structural biology
Charles Stiles, PhD, Co-Chair 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.
Systems biology
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.
Chemical biology
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.
Neurobiology
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.
Women's cancers
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
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 the next generation of scientists
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.