Koch Institute Clinical Investigator
M.D., Ph.D. 2002, Yale University
Current Cancer Area of Interest:
Brain tumors, Glioblastoma, Epigenetics, DNA damage response, Radiotherapy
"Our laboratory is focused on finding improved strategies for cancer therapy. Currently, over half of all cancer patients receive radiation therapy as part of cancer treatment. For patients with brain tumors, radiation therapy is particularly important because many chemotherapies do not enter the brain well. Therefore, nearly all brain tumor patients receive radiation therapy. Although often effective, radiation therapy can have serious side effects and does not work for all tumors. We are therefore interested in finding new drugs and drug targets that improve radiation treatment, in particular for brain tumors. We are also working to find molecular markers that can predict whether tumors are sensitive or resistant to radiation therapy."
Dr. Floyd studied molecular biology and music at Vanderbilt University in Nashville, Tennessee, then graduated from Yale University's MD/PhD program with doctoral thesis work investigating connections between autoimmune neurological syndromes and cancer. Dr. Floyd completed his internal medicine internship at the Hospital of St. Raphael in New Haven, Connecticut, and the Harvard Radiation Oncology Program, a combined residency training at Massachusetts General Hospital, Brigham and Women’s Hospital, Children’s Hospital, Beth Israel Deaconess Medical Center, Boston Medical Center and the Dana Farber Cancer Institute. He first came to MIT's Koch Institute in 2005 as an American Board of Radiology Holman Pathway Research Fellow working in the laboratory of Prof. Michael Yaffe on modifiers of the DNA damage response. Dr. Floyd joined the staff of Boston's Beth Israel Deaconess Medical Center in 2007, where he specializes in the treatment of both primary and metastatic central nervous system tumors in the Beth Israel Deaconess Brain Tumor Center and Department of Radiation Oncology. In 2012, Dr. Floyd joined the Koch Institute as a Clinical Investigator. His laboratory is focused on genes and drugs that modulate chromatin structure and function and affect the cellular response to DNA damage.
Cancer cells are deficient in their ability to effectively repair DNA damage. This can trigger genomic instability and further mutations that lead to more aggressive tumors, metastasis, and resistance to therapy. Many current cancer therapies take advantage of this deficiency—killing tumors by damaging cancer cell DNA. However, these chemotherapy and radiation therapy treatments can also damage the DNA of normal, healthy cells, resulting in side effects such as hair loss, nausea, bone marrow toxicity, neurological damage, and secondary tumor formation. Dr. Floyd has seen the devastating effects of cancers and the inadequacy of current therapies first-hand through his work as a practicing radiation oncologist specializing in brain tumors. The aim of his research is to gain a better understanding of how cells repair damage in their DNA, and to discover molecules that modulate the DNA repair process. Ultimately, Dr. Floyd hopes that this work will lead to better treatment for deadly brain cancers, particularly glioblastoma and brain metastases.
Radiotherapy plays a critical role in the current treatment for glioblastoma, a deadly brain cancer where median survival is only one year after diagnosis. A growing number of studies indicate that epigenetic modifications that regulate the chromatin state are critical regulators of the DNA damage response (DDR). The Floyd laboratory has developed discovery platforms to interrogate chromatin structure and the DDR using automated microscopy and digital image analysis coupled to small molecule and RNAi libraries in order to find novel chromatin-active DDR modulators.
Through their discovery platform, Dr. Floyd and colleagues have identified the tandem bromodomain protein Brd4 as a novel regulator of the DDR. This reader of epigenetic marks has a role in several cancers, including glioblastoma. The overall goal of the Floyd lab is to elucidate the relationship between epigenetic changes in chromatin structure and DNA damage signaling, from both basic science and clinical perspectives. The group is actively studying Brd4 and other chromatin-active targets in vitro and in vivo to establish new methods of enhancing tumor treatment.
1. Floyd SR, Pacold ME, Huang Q, Clarke SM, Lam FC, Cannell IG, Bryson BD, Rameseder J, Lee MJ, Blake EJ, Fydrych A, Ho R, Greenberger BA, Chen GC, Maffa A, Del Rosario AM, Root DE, Carpenter AE, Hahn WC, Sabatini DM, Chen CC, White FM, Bradner JE, Yaffe MB. “The bromodomain protein Brd4 insulates chromatin from DNA damage signaling.” Nature, 2013, Jun. 13;498(7453):246-50.
2. Weingeist DM, Ge J, Wood DK, Mutamba JT, Huang Q, Rowland EA, Yaffe MB, Floyd S, Engelward BP. “Single cell microarray enables high throughput evaluation of DNA double strand breaks and DNA repair inhibitors.” Cell Cycle, 2013, Mar. 15;12(6):907-15.
3. Floyd SR, Kasper EM, Uhlmann EJ, Fonkem E, Wong ET, Mahadevan A. “Hypofractionated radiotherapy and stereotactic boost with concurrent and adjuvant temozolomide for glioblastoma in good performance status elderly patients – Early results of a Phase II trial.” Frontiers in Oncology, 2012, Oct.;2:122 Epub Oct. 16.
4. Wang CC, Floyd SR, Chang CH, Warnke PC, Chio CC, Kasper EM, Mahadevan A, Wong ET, Chen CC. “Cyberknife hypofractionated stereotactic radiosurgery (HSRS) of resection cavity after excision of large cerebral metastasis: efficacy and safety of an 800 cGy × 3 daily fractions regimen.” Journal of NeuroOncology, 2012, Feb;106(3):601-10.
5. Mahadevan A, Floyd S, Wong E, Jeyapalan S, Groff M, Kasper E. “Stereotactic body radiotherapy reirradiation for recurrent epidural spinal metastases.” International Journal of Radiation Oncology, Biology, Physics, 2011, Dec. 1;81(5):1500-5.