Research

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Michael S. Rogers, PhD

Michael S. Rogers, PhD
Program:
Vascular Biology Program
Hospital Title:
Research Associate
Academic Title:
Assistant Professor Department of Surgery Harvard Medical School

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. 

Publications

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  1. Rogers MS, Novak K, Zurakowski D, Cryan LM, Blois A, Lifshits E, Bø 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 nonangiogenic and dormant state in human tumors. Mol Cancer Res. 2014 May; 12(5):754-64.
  2. 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 Dec 10; 110(50):E4818.
  3. 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 Jul; 18(6):714-25.
  4. Cryan LM, Bazinet L, Habeshian KA, Cao S, Clardy J, Christensen KA, Rogers MS. 1,2,3,4,6-Penta-O-galloyl-ß-D-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2. J Med Chem. 2013 Mar 14; 56(5):1940-5.
  5. Rogers MS, Adini I, McBride AF, Birsner AE, D'Amato RJ. The albino mutation of tyrosinase alters ocular angiogenic responsiveness. Angiogenesis. 2013 Jul; 16(3):639-46.
  6. Rogers MS, D'Amato RJ. Common polymorphisms in angiogenesis. Cold Spring Harb Perspect Med. 2012 Nov 01; 2(11).
  7. 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 Sep 15; 22(18):5885-8.
  8. 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(6):e39911.
  9. Rogers MS, Boyartchuk V, Rohan RM, Birsner AE, Dietrich WF, D'Amato RJ. The classical pink-eyed dilution mutation affects angiogenic responsiveness. PLoS One. 2012; 7(5):e35237.
  10. 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 Jul; 23(7):2235-43.
  11. Show all
  12. 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 Oct 15; 67(20):9980-5.
  13. Rogers MS, Birsner AE, D'Amato RJ. The mouse cornea micropocket angiogenesis assay. Nat Protoc. 2007; 2(10):2545-50.
  14. Folkman J, Rogers MS. Thalidomide for multiple myeloma. N Engl J Med. 2006 Jun 1; 354(22):2389-90; author reply 2389-90.
  15. Rogers MS, D'Amato RJ. The effect of genetic diversity on angiogenesis. Exp Cell Res. 2006 Mar 10; 312(5):561-74.
  16. 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 Jan; 7(1):101-11.
  17. Rogers MS, Rohan RM, Birsner AE, D'Amato RJ. Genetic loci that control the angiogenic response to basic fibroblast growth factor. FASEB J. 2004 Jul; 18(10):1050-9.
  18. Rogers MS, Rohan RM, Birsner AE, D'Amato RJ. Genetic loci that control vascular endothelial growth factor-induced angiogenesis. FASEB J. 2003 Nov; 17(14):2112-4.
  19. Browder T, Folkman J, Hahnfeldt P, Heymach J, Hlatky L, Kieran M, Rogers MS. Antiangiogenic therapy and p53. Science. 2002 Jul 26; 297(5581):471; discussion 471.
  20. 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 Apr 15; 62(8):2300-5.
  21. D'Amato RJ, Lentzsch S, Anderson KC, Rogers MS. Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma. Semin Oncol. 2001 Dec; 28(6):597-601.
  22. Rogers MS, Kobayashi T, Pittelkow MR, Strehler EE. Human calmodulin-like protein is an epithelial-specific protein regulated during keratinocyte differentiation. Exp Cell Res. 2001 Jul 15; 267(2):216-24.
  23. Rogers MS, Strehler EE. The tumor-sensitive calmodulin-like protein is a specific light chain of human unconventional myosin X. J Biol Chem. 2001 Apr 13; 276(15):12182-9.
  24. Rogers MS, Foley MA, Crotty TB, Hartmann LC, Ingle JN, Roche PC, Strehler EE. Loss of immunoreactivity for human calmodulin-like protein is an early event in breast cancer development. Neoplasia. 1999 Aug; 1(3):220-5.
  25. Qian H, Rogers MS, Schleucher J, Edlund U, Strehler EE, Sethson I. Sequential assignment of 1H, 15N, 13C resonances and secondary structure of human calmodulin-like protein determined by NMR spectroscopy. Protein Sci. 1998 Nov; 7(11):2421-30.
  26. Garamszegi N, Garamszegi ZP, Rogers MS, DeMarco SJ, Strehler EE. Application of a chimeric green fluorescent protein to study protein-protein interactions. Biotechniques. 1997 Nov; 23(5):864-6, 868-70, 872.
  27. Cryan LM, Rogers MS. Targeting the anthrax receptors, TEM-8 and CMG-2, for anti-angiogenic therapy. Front Biosci (Landmark Ed). 2011 Jan 01; 16:1574-88.
  28. Borrowman A, Rogers MS, O'Neill KL. An improved washing apparatus for nucleoside phosphorylation assays. Biotechniques. 1993 Sep; 15(3):402-4, 406.
  29. 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 Jan; 124(1):425-36.
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