Dr. James Bradner of the Dana Farber Cancer Institute and Harvard Medical School, spoke on “Disruption of Super Enhancers” for Pharmacology’s 20th Avery Steelman Lecture, held May 19, 2015.
On May 19, 2015 the Department of Pharmacology had the distinct honor of hosting Dr. James Bradner as its distinguished Steelman Lecturer. The audience, anticipating a fun and engaging seminar, based on Dr. Bradner’s reputation as a dynamic performer with a keen intellect, was surely not disappointed. During his seminar, Dr. Bradner discussed seminal scientific discoveries that sit squarely at the crossroads of chemistry, biology and disease. Trained as an oncologist, and with a specialization in medicinal chemistry and pharmacological development, Dr. Bradner has been instrumental in contributing to our understanding of chromatin based signaling, how these signaling nodes can be targeted therapeutically, and the clinical promise these discoveries hold for improving the lives of patients with cancer. Dr. Bradner presented a “stacked” seminar, taking the audience through a tour de force of biological insight gleaned from his lab in the last half-decade.
He began by touching on the motivation for targeting a bromodomain protein called Brd4, which he predicted would stop cancers that divide uncontrollably. From there, he discussed his labs efforts to develop the first ever small molecule inhibitor of a Brd4. He followed this by presenting on studies of the Brd4 inhibitor JQ1, and the insight it has provided into Brd4 function. These discoveries gave way to his labs description of DNA elements termed Super Enhancers, which are involved in specifying cell identity and driving cell proliferation in cancer. He demonstrated his ability to selectively target super enhancers with JQ1, and similar drugs, to disrupt super enhancers and halt the growth of cancer in animals, and the promise this shows in patients. His lab, almost single handedly, has catalyzed a worldwide effort to develop JQ1 like compounds. This was in large part due to the innovative open source approach he adopted, distributing the compound to hundreds of labs around the world.
Overall, Dr. Bradner’s seminar left a lasting impression on graduate students, postdocs and seasoned faculty alike. The productivity and success of the Bradner team over the last 7 years is unmatched in academia, and it is clear that the deep and long lasting implications of this research are just now being realized both in the lab and the clinic for the treatment of patients with cancer.
Dr. James Bradner is a staff physician in the Division of Hematologic Malignancies at the Dana-Farber Cancer Institute as well as an Associate Professor in Medicine at the Harvard Medical School. He is associated with Cancer Biology, Chemical Biology and Therapeutics Program, the Department of Biochemistry and Molecular Pharmacology, as well as the Harvard Stem Cell Institute, in addition to being a member of the Broad Institute.
A little bit about Dr. Bradner
Dr. Bradner graduated from Harvard University in 1994 and received an MD from the University of Chicago. He then returned to Boston for his internship and residency at Brigham and Women’s Hospital followed by a fellowship in Medical Oncology and Hematology at Dana-Farber Cancer Institute. He then undertook the unusual step of doing a postdoc for 4 years in Stuart Schrieber’s lab at the Broad institute, studying the use of small molecules to probe biological processes involved in human disease.
The success of this path is evident in the fact that he has authored more than 100 papers in the last 6 years alone. In addition, in the spirit of the Steelman, Dr. Bradner is bridging academic discovery based research, and molecular pharmacology with clinical application. He has been involved in the development of many small molecules that are seeing their way into the clinic and is founder or advisory board member at several companies, including acetylon, SHAPE, agios, and tensha.
In recognition of this work he has been the recipient for many awards including those from Burroughs Welcome, and the Damon Runyon Innovation Award.
He holds patents for the discovery and development of numerous small molecules, but he is most known for the discovery of small molecule inhibitor JQ1 that targets a bromodomain containing protein Brd4. Bromodomains bind to acetylated lysines, most notably on chromatin to modulate the transcriptionally output of the genome.
More recently, in collaboration with Rick Young at the Whitehead institute at MIT, he discovered a phenomenon termed “super enhancers” which can be thought of as highly activated transcriptional subprograms that differ between cells in the body and cancer types, and contribute to cell identity and disease pathology. Therapeutic manipulation of super enhancers was the subject of his Steelman Lecture.
About the Avery Steelman Lecture Series
This prestigious Lectureship was established in 1992 by Dr. Sanford Steelman (the former director of international clinical pharmacology and endocrine research at Merck) to honor his father, Avery, who wished to attend medical school but did not have the opportunity to complete his education.
The Steelman lecturers have all been highly distinguished scientists including three Nobel laureates and many members of the National Academy. It has been customary to invite a distinguished scientist working in the broad area of endocrinology.