Research Faculty

Michael S. Rogers, PhD

Department Vascular Biology Program
Hospital Title Research Associate
Academic Title Assistant Professor
Department of Surgery
Harvard Medical School
Phone 617-919-2252
Fax 617-730-0002
Email Michael S. Rogers
Location Karp Family Research Laboratories
Room 11.211
300 Longwood Avenue
Boston, MA 02115

Research Overview

Dr. Rogers early work at Children's Hospital Boston focused on the identification of thalidomide analogs that exhibit improved anti-cancer activity. This work was critical to the initiation of clinical trials with the thalidomide analog 3-aminothalidomide (Actimid).

Currently one major focus of his research is the elucidation of the genetics differences that affect angiogenesis and their control of tumor growth. This work began with the characterization of differential angiogenic responsiveness in inbred mouse strains and the identification of quantitative trait loci (QTLs) controlling that responsiveness. 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. Recently, he has discovered that genes that control melanin production affect angiogenic response. In addition, he has identified a strong single candidate, a Hey2 enhancer polymorphism, as responsible for AngVq3. 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. The identification of additional regulators of angiogenic response and the characterization of their physiologic effects is ongoing.

Another major facet of his research has been the role of the anthrax toxin receptors in angiogenesis. In recently published work, he collaborated with Dr. Ken Christensen and Dr. John Collier to demonstrate that the Protective Antigen subunit of anthrax toxin is a potent anti-angiogenic agent. 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. In addition, his lab collaborates with the National Screening Laboratory for the Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases (NSRB) facility to identify small molecules that bind to the anthrax toxin receptors and inhibit its interaction with Protective Antigen. Such molecules are likely to serve as good leads for both anthrax-protective agents as well as anti-angiogenic agents. Future work on this project will include the identification of downstream mediators of anthrax toxin receptor signaling, as well as the identification and refinement of small molecule inhibitors of these receptors. It is hoped that these molecules will serve as leads for antiangiogenic drugs.

Key Publications:

  • D'Amato RJ, Lentzsch S, Anderson KC, Rogers MS. Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma. Seminars in Oncology 2001;28:597-601.
     
  • Lentzsch S*, Rogers MS*, LeBlanc R, Birsner AE, Shah JH, Treston AM, Anderson KC, D'Amato RJ. S-3-amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice. Cancer Research 2002;62:2300-5.
     
  • Rogers MS, D'Amato, RJ. The effect of genetic diversity on angiogenesis. Experimental Cell Research 2006;312:561-74.
     
  • Shaked Y, Bertolini F, Man S, Rogers MS, Cervi D, Foutz T, Rawn K, Voskas D, Dumont DJ, Ben-David Y, Lawler J, Henkin J, Huber J, Hicklin DJ, D'Amato RJ, Kerbel RS. Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell 2005;7:101-11.
     
  • Nakai K*, Rogers MS*, Baba T, Funakoshi T, Birsner AE, Luyindula DS, D'Amato RJ. Genetic Loci that Control the Size of Laser-induced Choroidal Neovascularization. FASEB Journal 2009.
     
  • Rogers MS, Christensen KA, Birsner AE, Short SM, Wigelsworth DJ, Collier RJ, D'Amato RJ. Mutant anthrax toxin B-moiety (protective antigen) inhibits angiogenesis and tumor growth. Cancer Research 2007;67:9980-5.