Carl Novina, MD, Ph.D., Dana-Farber Cancer Research Institute
Barry Polisky, Ph.D., Marina Biotech, Inc.
Christopher Kemp, Ph.D., Fred Hutchinson Cancer Research Center
Johnathan R. Whetstine, Ph.D., Harvard Medical School & Massachusetts General Hospital
Scott Armstrong, MD, Ph.D., Memorial Sloan-Kettering Institute
2009 Forbeck Scholars
Clark C. Chen, Ph.D., University of California San Diego
Oliver Ayrault, Ph.D., Institute Curie
Chang-Hyuk Kwon, Ph.D., Ohio State University
Oren Becher, MD, Duke University
2010 Forbeck Scholars
Derek Y. Chiang, Ph.D., Novartis
Benjamin Berman, Ph.D., USC Epigenome Center
Sharon J. Diskin, Ph.D., Children’s Hospital of Philadelphia
Chris Putnam, Ph.D., Ludwig Institute for Cancer Research
2011 Forbeck Scholars
Grant Challen, Ph.D., Washington University in St. Louis
Gary Hon, Ph.D., University of California San Diego
Alvaro Rada-Iglesias, Ph.D., University of Cologne
Chris Vakoc, MD, Ph.D., Cold Spring Habor
2012 Forbeck Scholars
Mohit Jain, MD, Ph.D., Harvard Medical School
Julie Aurore-Losman, MD, Ph.D., Dana-Farber Cancer Research Institute
Kathryn E. Wellen, Ph.D., University of Pennsylvania
Hao Zhu, MD, Children’s Hospital of Boston
The 9th annual Forbeck Scholar Retreat gathered scholars from the past 4 years of Forbeck Forums: The Biology and Treatment of Primary Brain Tumors (2009), Cancer Genomics (2010), Epigenetics (2011) and Tumor Metabolism (2012).
The meeting began on Thursday evening with cocktails and dinner followed by a keynote address 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 morning of Friday the 13th began with a presentation of unique opportunities for Forbeck Scholars and Mentors alike. Many clinicians and scientists have made basic discoveries that if properly developed could benefit patients in the near term. However, these discoveries often are not brought forward to clinical application for a variety of reasons. The Forbeck Foundation is considering a forward-thinking initiative which could accelerate the pace of translating basic discoveries in academia to clinical practice by partnering with Southeast TechInventures (STI). STI is a for-profit company that assists academics in forming companies, developing intellectual property and business plans, initiating business partnerships, and preparing Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants from the NIH which fund early stage companies. Karen LeVert (STI, Research Triangle Park, NC) presented a business model in which Universities, the Government, and the Forbeck Foundation would work with STI to knock down barriers to commercialization and bring the efficiencies of industry to bear on translating academic discoveries into drugs and devices. By leveraging Forbeck Foundation and STI resources, it is hoped that clinicians’ and scientists’ discoveries will accelerate towards clinical application.
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.
On Friday evening, Scholars and Mentors were treated to sky viewing and a tour of Yerkes Observatory by a colorful guide, Richard Dreiser. Sky viewing included detailed views of the moon though a telescope and identification of constellations using a high power laser pointer. Showing intellectual curiosity and a willingness to challenge paradigm, one of the 2012 Scholars, Julie- Aurore Losman (Dana-Farber Cancer Institute, Boston) had a spirited debate with Richard Dreiser over the exact location of the Andromeda Galaxy. We were next brought on a tour of Yerkes Observatory which is still part of the Department of Astromony and Astrophysics of the University of Chicago. Yerkes houses the largest refractor telescope in the world and is still used for research and teaching purposes. In addition to impressive telescopes and an amazing history in astronomy, the Yerkes itself is fascinating with intricate carvings sculpted into the building. Several caricatures of key people involved in establishing and maintaining the Yerkes as well as astronomers who worked at University of Chicago at the time of Yerkes construction in 1897 are memorialized in the Yerkes architecture. Indeed, scientists and builders back then had a robust sense of humor.
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.