CB 399: Cancer Epigenetics Fall 2014

Cancer Epigenetics

Course Instructors: Brad Bernstein MD PhD (Course Director), Charles Roberts MD PhD, Myles Brown MD, Jay Bradner MD, Curtis Keith PhD

Curriculum Fellow: Meg Mittelstadt PhD, megan_mittelstadt@hms.harvard.edu

Central roles for epigenetic dysregulation in oncogenesis are now well established. They may encompass genetic mutations of chromatin regulators, purely epigenetic alterations as well as intratumoral transcriptional heterogeneity.  These lines of evidence implicate a wide range of processes, ranging from aberrant DNA methylation to histone modification changes to defective chromatin remodeling. Importantly, unlike genetic mutations, epigenetic modifications are quite plastic and therefore hold particular promise for therapeutic intervention. In this nanocourse, we will discuss mounting evidence for and specific examples of epigenetic contributions to malignancy, and implications for therapy.



First Session: Monday, September 15, 2014, 1 - 4 PM 
Location: Building C, Cannon Room

Second Session: Wednesday, September 24, 2014: 9 – 11 AM
Location: TMEC 448

DROP DEADLINE: Monday, September 8, 2014



Assignment for Second Session: Biotech Strategies for Cancer Epigenetic Therapeutics, 9-11am Wednesday, September 24th

Written Assignment (Due by 9am Fri, September 19th via email to megan_mittelstadt@hms.harvard.edu)

Students will work together in groups (4 groups total, 3-4 students per group) to complete a written mini-proposal, one document submitted per group. Your proposal should be for a mechanism-based therapeutic opportunity in any disease indication with a clearly defined patient population. Any therapeutic strategy/approach related to chromatin biology is acceptable. Course faculty will be available following the first session to answer any questions you have regarding your written proposals.

Written proposals should be no longer than 2 pages single-spaced and include:

-Concept Title

-Definition of the idea/concept

-Novelty/Innovation of the idea

-Concept and Scientific Rationale

And should briefly address:

-Potential Challenges and Roadblocks in the development of this therapeutic

-Contributions of each team member

Proposal Pitch (Due 9am Wed, September 24th - presentations in class)

During the second session, each student group will pitch their proposal to a panel of experts: Jay Bradner, Brad Bernstein, Matt Freedman, Myles Brown, and Curtis Keith. Each group member should be prepared to answer questions regarding the group’s proposal. Presentations should have no more than 10 slides. Teams will be given 30 minutes to pitch their proposal: 15 minutes of presentation time (you will be timed) plus 15 minutes discussion. Groups should begin with a 30 second elevator pitch during their title slide, then move on to give the background and concept. Do not simply read from your group’s proposal – quickly convey your concept and be persuasive.

Recommended reading:

  • For first session: Epigenetic reprogramming in cancer (Suva et al Science 2013)
  • Selective inhibition of BET bromodomains (Filippakopoulos et al Nature 2010)
  • EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations (McCabe et al Nature 2012)
  • Broad-spectrum therapeutic suppression of metastatic melanoma through nuclear hormone receptor activation (Pencheva et al Cell 2014)
  • Epigenetic protein families: a new frontier for drug discovery (Arrowsmith et al Nature Reviews Drug Discovery 2012)