Researcher | Research Overview
Dr. Rogers early work at Boston Children's Hospital focused on the identification of thalidomide analogs that exhibit improved anti-cancer activity. His work was critical to the initiation of clinical trials with the thalidomide analog S-3-amino-phthalimido-glutarimide. This compound, which is now known as pomalidomide, has been FDA approved for the treatment of multiple myeloma and is in clinical trials for several other cancers.
Currently his research focuses on using genetic differences in the host’s ability to vascularize tissue to identify new target pathways for cancer therapy. This work began the identification of quantitative trait loci (QTLs) controlling new vessel formation in inbred strain crosses. He has identified several QTLs regulating differential response to VEGF and bFGF in C57BL/6J x DBA/2J strain crosses and have used new bioinformatics techniques to narrow down the number of candidates in some of these regions to a few genes. In collaboration with Dr. Robert Kerbel, he has demonstrated that circulating endothelial cells may serve as a surrogate marker of angiogenic responsiveness that can be measured in humans. Recently, he has discovered that genes that control melanin production affect vessel growth, in part by regulating the production of fibromodulin. This may partially explain differences in disease susceptibility among different human patient populations and identifies several new targets for tumor therapy. The identification of additional regulators of angiogenic response and the characterization of their physiologic effects is ongoing, with a strong interest in identifying sex-related differences in tissue neovascularization. These studies will focus on faster new mapping methods that promise to reduce the time spent identifying novel targets five-fold.
One important outgrowth of Dr. Rogers genetic research has been identification of the anthrax toxin receptors as important players in tumor vessel growth. As a result of his genetic work, Dr. Rogers collaborated with Dr. Kenneth Christensen and Dr. John Collier to demonstrate that the protective antigen (PA) subunit of anthrax toxin potently inhibits the growth of new blood vessels and lung and mammary tumors. This establishes the anthrax toxin receptors as new targets for antiangiogenic therapy. His lab is continuing this collaboration with the goal of understanding role of each of the two anthrax toxin receptors in angiogenesis. His has collaborated with the National Screening Laboratory for the Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases (NSRB) to identify small molecules that bind to the anthrax toxin receptors and inhibit its interaction with PA. Such molecules are likely to serve as good leads for both anthrax-protective agents as well as anti-tumor agents. Ongoing work on this project includes the identification of downstream mediators of anthrax toxin receptor signaling, as well as the refinement of small molecule inhibitors of these receptors. The latter will serve as leads for new anti-tumor drugs, which Dr. Rogers hopes will be as effective in treating patients as the thalidomide analogs that began his career at Children’s.
Researcher | Research Background
Dr. Rogers received his Ph.D. from the Mayo Clinic where his thesis work focused on the role of the calmodulin-like protein gene (CALML3) in human cancer and myosin regulation. His postdoctoral work focused on identifying thalidomide analogs with increased activity against multiple myeloma and one of these (pomalidomide) is now FDA approved. He now focuses on identifying and validating targets for the treatment of multiple angiogenesis-dependent diseases, including endometriosis, cancer, and corneal neovascularization.
A key component of his appointment at Harvard Medical School is high-quality teaching of medical students. These efforts resulted in multiple teaching awards. It also resulted in his selection to the core faculty for Foundations in 2015. In that role, he worked along with other core faculty members to adapt the MCM curriculum to the needs of the new case-based flipped classroom aproach to teaching. These efforts included portions of the cancer curriculum focusing on angiogenesis that he developed. Throughout his teaching efforts, he has routinely received outstanding evaluations and has recently been selected as a peer mentor to assist other HMS instructors in adapting to the requirements of this new approach.