Photo of Michael S. Rogers,  PhD

Michael S. Rogers, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2252
Fax: (617) 730-0002


michael.rogers@childrens.harvard.edu

Michael S. Rogers, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Surgery, Harvard Medical School
  • Research Associate, Vascular Biology Program, Boston Children's Hospital

Research Abstract

My early work at Children’s Hospital Boston has 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) and resulted in two publications.

The major focus of my research has been elucidation of the genetics of angiogenesis and its 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. I have 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, I have identified the albino allele as the polymorphism responsible for AngVq4. In addition, I have identified a strong single candidate, a Hey2 enhancer polymorphism, as responsible for AngVq3. In collaboration with Dr. Robert Kerbel, we have demonstrated that circulating endothelial cells may serve as a surrogate marker of angiogenic responsiveness that can be measured in humans. This work has resulted in several papers and the AACR-AstraZeneca Scholar-in-Training award. My preliminary data suggest that the major effect of differences in angiogenic responsiveness is on tumor latency rather than subsequent growth rates. The identification of additional regulators of angiogenic response and the characterization of their physiologic effects is ongoing.

Another major facet of my research has been the role of the anthrax toxin receptors in angiogenesis. I 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. Dr. Christensen and I are continuing this collaboration to clarify the role of each of the two anthrax toxin receptors in angiogenesis. In addition, we are collaborating 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. This work forms the basis of my currently funded R01, and my recently completed DOD BCRP Synergistic Idea Award. 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. I anticipate that these molecules will serve as leads for antiangiogenic drugs.

 

Publications

Powered by Harvard Catalyst
  • Rogers MS, Novak K, Zurakowski D, Cryan L, Blois A, Lifshits E, Bo TH, Oyan AM, Bender ER, Lampa M, Kang SY, Naxerova K, Kalland KH, Straume O, Akslen LA, Watnick RS, Folkman J, Naumov GN. Spontaneous Reversion of the Angiogenic Phenotype to a Non-angiogenic and Dormant State in Human Tumors. Mol Cancer Res 2014. PubMed
  • Adini I, Ghosh K, Adini A, Chi ZL, Yoshimura T, Benny O, Connor KM, Rogers MS, Bazinet L, Birsner AE, Bielenberg DR, D'Amato RJ. Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment. J Clin Invest 2014; 124:425-36. PubMed
  • D'Amato RJ, Lentzsch S, Rogers MS. Pomalidomide is strongly antiangiogenic and teratogenic in relevant animal models. Proc Natl Acad Sci U S A 2013; 110:E4818. PubMed
  • Cryan LM, Bazinet L, Habeshian KA, Cao S, Clardy J, Christensen KA, Rogers MS. 1,2,3,4,6-Penta-O-galloyl-硫-D-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2. J Med Chem 2013; 56:1940-5. PubMed
  • Cryan LM, Habeshian KA, Caldwell TP, Morris MT, Ackroyd PC, Christensen KA, Rogers MS. Identification of Small Molecules That Inhibit the Interaction of TEM8 with Anthrax Protective Antigen Using a FRET Assay. J Biomol Screen 2013. PubMed
  • Rogers MS, Adini I, McBride AF, Birsner AE, D'Amato RJ. The albino mutation of tyrosinase alters ocular angiogenic responsiveness. Angiogenesis 2013. PubMed
  • Cao S, Cryan L, Habeshian KA, Murillo C, Tamayo-Castillo G, Rogers MS, Clardy J. Phenolic compounds as antiangiogenic CMG2 inhibitors from Costa Rican endophytic fungi. Bioorg Med Chem Lett 2012; 22:5885-8. PubMed
  • Rogers MS, Cryan LM, Habeshian KA, Bazinet L, Caldwell TP, Ackroyd PC, Christensen KA. A FRET-based high throughput screening assay to identify inhibitors of anthrax protective antigen binding to capillary morphogenesis gene 2 protein. PLoS ONE 2012; 7:e39911. PubMed
  • Rogers MS, D'Amato RJ. Common polymorphisms in angiogenesis. Cold Spring Harb Perspect Med 2012. PubMed
  • Cryan LM, Rogers MS. Targeting the anthrax receptors, TEM-8 and CMG-2, for anti-angiogenic therapy. Front Biosci 2011; 16:1574-88. PubMed
  • 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 J 2009; 23:2235-43. PubMed
  • 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 Res 2007; 67:9980-5. PubMed
  • Rogers MS, Birsner AE, D'Amato RJ. The mouse cornea micropocket angiogenesis assay. Nat Protoc 2007; 2:2545-50. PubMed
  • Folkman J, Rogers MS. Thalidomide for multiple myeloma. N Engl J Med 2006; 354:2389-90; author reply 2389-90. PubMed
  • Rogers MS, D'Amato RJ. The effect of genetic diversity on angiogenesis. Exp Cell Res 2006; 312:561-74. PubMed
  • 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. PubMed
  • Rogers MS, Rohan RM, Birsner AE, D'Amato RJ. Genetic loci that control the angiogenic response to basic fibroblast growth factor. FASEB J 2004; 18:1050-9. PubMed
  • Rogers MS, Rohan RM, Birsner AE, D'Amato RJ. Genetic loci that control vascular endothelial growth factor-induced angiogenesis. FASEB J 2003; 17:2112-4. PubMed
  • Browder T, Folkman J, Hahnfeldt P, Heymach J, Hlatky L, Kieran M, Rogers MS. Antiangiogenic therapy and p53. Science 2002; 297:471; discussion 471. PubMed
  • 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 Res 2002; 62:2300-5. PubMed
Hide