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Scholar Retreat

September 12–15, 2013

Chaired By

 Carl D. Novina MD, PhD of Dana-Farber Cancer Institute

Meeting Description

The Scholar Retreat held annually, invites scholars and mentors to attend a 3-day meeting. This meeting focuses on bringing junior scientists together from various areas of cancer research. The collaborations and innovative ideas that come from this meeting have been numerous and outstanding. The mentors provide great guidance regarding science and career for these junior scientists.

At the Retreat, the Scholars share their research with the other Scholars and Mentors. Each Scholar will participate in four sequential retreats, with all expenses paid by WGFRF. The opportunity for Scholars to connect and form relationships with researchers from completely different areas of cancer research and to have a sort of peer review is one of the most valuable roles of the Retreat. Through the Mentors, the Retreat offers Scholars guidance on practical career issues such as writing grants and preparing successful scientific publications.

Each year, the Scholar Retreat coincides with the Foundation’s annual ‘Blue Jean Ball’ fundraiser. All Scholars attend this event, providing them an opportunity to meet with families whose lives have been directly affected by cancer. This experience resonates particularly with scientists who, unlike clinicians, do not have contact with patients, by putting a human face on cancer.

Meeting Summary

The meeting began on Thursday evening with cocktails and dinner followed by a keynote ad- dress by Keith Yamamoto (UCSF, San Francisco) which provided an expansive view of science, science practice, and science policy. Keith made seminal discoveries in steroid hormone receptor-induced transcription and has been honored with numerous awards including membership in the National Academy of Sciences and Institute of Medicine. He is also Dean and Vice Chancellor at UCSF Medical School, an Obama Advisor and consultant to the NIH. Keith drew from these experiences to describe how science is changing to integrate biology, chemistry, physics, mathematics, engineering, computer science, and public health. He presented a changing science practice in which each of these areas are not discrete disciplines, but rather is simultaneously incorporated into the discovery and educational processes. Keith then provided an example of an integrated approach to biological discovery. Joe DeRisi’s lab at UCSF Medical School developed a miniaturized microfluidic “lab-on-a-chip” to sequence samples from an outbreak of respiratory infections which led to the identification and molecular characterization of the SARS virus in affected populations. Notably, the curriculum at UCSF Medical School has been re-vamped to teach new investigators integrated science to prepare the next generation of leaders for scientific discovery. This keynote address provided insights into the current practice of science, provided a glimpse of a new way of teaching and doing science and set the tone for a meeting filled with exciting discussions.

The scientific sessions on Friday focused on brain tumors and cancer genomics. Many cancers demonstrate a phenomenon called “oncogene addiction” which may be targeted for therapy. Clark Chen (UCSD Medical Center, San Diego) described an interesting phenomenon of “non-oncogene addiction” in glioblastoma which may be revealed in model systems when cells are subjected to stress. Understanding non-oncogene addiction may have value in clarifying the biology of glioblastoma and possibly can be exploited for therapy. Oren Brecher (Duke University, Durham) described the molecular pathogenesis of pediatric glioma which is a brainstem cancer. Oren listed many of the usually suspected genes that are mutated in this cancer. However, some unusual suspects also appeared including 20% of cases with mutations in BMP (bone morphogenic protein) receptor. Similarly, Sharon Diskin (Children’s Hospital of Philadelphia) examined the genetics of neuroblastoma and found genetic variants associated with susceptibility and treatment response. For example, some neuroblastomas have a loss of part of one chromosome (16p11.2) which increases their risk for developing the disease. Others contain variation in a gene that normally protects cells from oxidative damage (perioxiredoxin), and these cancers might be particularly susceptible to chemotherapies that generate reactive oxygen species. These examples show that studying the underlying genetics of cancers is critically important not only to discover suspects in cancers but also to discover an Achilles heal for treatment of particular cancers.

The scientific sessions on Saturday focused on epigenetics and tumor metabolism. Epigenetics are the chemical marks to the DNA and the proteins that bind to DNA. These chemical marks determine which genes are turned on or turned off in particular cells. We previously saw that that mutating critical genes can cause cancer. Epigenetics has shown us that changing the expression pattern of normal genes – too much or too little of an unmutated gene or expression of a normal gene in the wrong place or at the wrong time—can also play critical roles in cancer formation. Gary Hon (UCSD; San Diego) described how the loss of certain activities (Tet2) that remove inhibitory marks on DNA (methylation) can promote leukemias. He and Alvaro Rada-Iglesias (Stanford University Medical Center) provided examples of how alterations of enhancers (regions of the DNA which determine which genes are turned on or turned off) can also play important roles in human diseases. Kathryn Wellen (University of Pennsylvania, Philadelphia) described how glucose can promote activation of genes by putting a chemical mark (acetylation) on the proteins that bind DNA. Activating genes in this way can be sustained during nutrient stress which may be observed in cancers. Julie-Aurore described how a normal enzyme in our cells called (isocitrate dehydrogenase) can generate an unusual intermediate in cancers (R-2-hydroxyglutarate) called an “onocometabolite”. This oncometabolite can inhibit Tet2 which allows methylation and repression of tumor suppressor genes. These lessons teach us how cancers can hijack normal function of epigenetics and metabolism to make cells grow out of control.

This short summary of highlights from the recent Forbeck Retreat does not convey the excitement of the scientific talks and depth of interactions that occur at a typical retreat. The Scholar Retreat format focuses discourse on organizing concepts. The lively and intense interplay between speakers and audience during the scientific sessions leads to specific and constructive comments that have tactical and strategic impact on Scholars’ research directions. These interactions provide insights that cross disciplines and that might not occur as readily in traditional meetings focused around one scientific theme. Additionally, Scholars and Mentors have many opportunities to talk at relaxed social events. The scenic views of Lake Geneva during hikes and meals also facilitate conversation and accentuate the relaxed atmosphere of the Retreat. Finally, this will be the last time the Forbeck Scholar Retreat will be held at George Williams College of Aurora University. While we will miss the hospitality and beautiful views from George Williams College and its proximity to Yerkes Observatory, we look forward to a new venues and new perspectives around Lake Geneva.

Forum Participants

Scott Armstrong, MD, PhD
Memorial Sloan Kettering Cancer Center
 Retreat Mentor

Oliver Ayrault, PhD
Institute Curie
 Forbeck Scholar

Oren Becher, MD
Duke University
 Forbeck Scholar

Benjamin P. Berman, PhD
University of Southern California
 Forbeck Scholar

Grant Challen, PhD
Washington University
 Forbeck Scholar

Clark C. Chen, MD, PhD
University of California San Diego
 Forbeck Scholar

Derek Y. Chiang, PhD
"Novartis Institutes for BioMedical Research, Inc."
 Forbeck Scholar

Sharon J. Diskin, PhD
Children's Hospital of Philadelphia
 Forbeck Scholar

Gary Hon, PhD
University of California San Diego
 Forbeck Scholar

Mohit Jain, MD, PhD
Harvard Medical School
 Forbeck Scholar

Christopher J. Kemp, PhD
Fred Hutchinson Cancer Research Center
 Retreat Mentor

Chang-Hyuk Kwon, PhD
The Ohio State University
 Forbeck Scholar

Julie-Aurore Losman, MD, PhD
Dana-Farber Cancer Institute
 Forbeck Scholar

Carl D. Novina, MD, PhD
Dana-Farber Cancer Institute
 Retreat Mentor

Barry Polisky, PhD
"Marina Biotech, Inc."
 Retreat Mentor

Chris Putnam, PhD
Ludwig Institute for Cancer Research
 Forbeck Scholar

Alvaro Rada-Iglesias, PhD
Stanford University
 Forbeck Scholar

Chris Vakoc, MD, PhD
Cold Spring Harbor Laboratory
 Forbeck Scholar

Kathryn E. Wellen, PhD
University of Pennsylvania
 Forbeck Scholar

Jonathan E. Whetstine, PhD
Harvard Medical School
 Retreat Mentor

Hao Zu, MD
Harvard Medical School
 Forbeck Scholar