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Related Research Units

Rogers Laboratory Research
Vascular Biology Program Research

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. 

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.

Publications

  1. M2 Macrophages are Major Mediators of Germline Risk of Endometriosis and Explain Pleiotropy with Comorbid Traits. bioRxiv. 2024 Nov 22. View Abstract
  2. Nociceptor-to-macrophage communication through CGRP/RAMP1 signaling drives endometriosis-associated pain and lesion growth in mice. Sci Transl Med. 2024 Nov 06; 16(772):eadk8230. View Abstract
  3. Targeting NGF but not VEGFR1 or BDNF signaling reduces endometriosis-associated pain in mice. J Adv Res. 2024 Aug 12. View Abstract
  4. Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-?B and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms. Front Immunol. 2023; 14:949407. View Abstract
  5. Vaccines Alone Cannot Slow the Evolution of SARS-CoV-2. Vaccines (Basel). 2023 Apr 16; 11(4). View Abstract
  6. AZIN1 RNA editing alters protein interactions, leading to nuclear translocation and worse outcomes in prostate cancer. Exp Mol Med. 2022 10; 54(10):1713-1726. View Abstract
  7. RvD1 disrupts nociceptor neuron and macrophage activation and neuroimmune communication, reducing pain and inflammation in gouty arthritis in mice. Br J Pharmacol. 2022 09; 179(18):4500-4515. View Abstract
  8. Capillary morphogenesis gene 2 (CMG2) mediates growth factor-induced angiogenesis by regulating endothelial cell chemotaxis. Angiogenesis. 2022 08; 25(3):397-410. View Abstract
  9. Rapid relaxation of pandemic restrictions after vaccine rollout favors growth of SARS-CoV-2 variants: A model-based analysis. PLoS One. 2021; 16(11):e0258997. View Abstract
  10. Controlling long-term SARS-CoV-2 infections can slow viral evolution and reduce the risk of treatment failure. Sci Rep. 2021 11 19; 11(1):22630. View Abstract
  11. Nonsurgical mouse model of endometriosis-associated pain that responds to clinically active drugs. Pain. 2020 06; 161(6):1321-1331. View Abstract
  12. A Canstatin-Derived Peptide Provides Insight into the Role of Capillary Morphogenesis Gene 2 in Angiogenic Regulation and Matrix Uptake. ACS Chem Biol. 2020 02 21; 15(2):587-596. View Abstract
  13. Galloyl Carbohydrates with Antiangiogenic Activity Mediated by Capillary Morphogenesis Gene 2 (CMG2) Protein Binding. J Med Chem. 2019 04 25; 62(8):3958-3970. View Abstract
  14. Developing a novel FRET assay, targeting the binding between Antizyme-AZIN. Sci Rep. 2019 03 15; 9(1):4632. View Abstract
  15. A paradoxical method to enhance compensatory lung growth: Utilizing a VEGF inhibitor. PLoS One. 2018; 13(12):e0208579. View Abstract
  16. Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy. Angiogenesis. 2018 11; 21(4):837-848. View Abstract
  17. Identification of Padi2 as a novel angiogenesis-regulating gene by genome association studies in mice. PLoS Genet. 2017 Jun; 13(6):e1006848. View Abstract
  18. Spontaneous reversion of the angiogenic phenotype to a nonangiogenic and dormant state in human tumors. Mol Cancer Res. 2014 May; 12(5):754-64. View Abstract
  19. Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment. J Clin Invest. 2014 Jan; 124(1):425-36. View Abstract
  20. Pomalidomide is strongly antiangiogenic and teratogenic in relevant animal models. Proc Natl Acad Sci U S A. 2013 Dec 10; 110(50):E4818. View Abstract
  21. 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. View Abstract
  22. 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. View Abstract
  23. The albino mutation of tyrosinase alters ocular angiogenic responsiveness. Angiogenesis. 2013 Jul; 16(3):639-46. View Abstract
  24. Common polymorphisms in angiogenesis. Cold Spring Harb Perspect Med. 2012 Nov 01; 2(11). View Abstract
  25. Phenolic compounds as antiangiogenic CMG2 inhibitors from Costa Rican endophytic fungi. Bioorg Med Chem Lett. 2012 Sep 15; 22(18):5885-8. View Abstract
  26. 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. View Abstract
  27. The classical pink-eyed dilution mutation affects angiogenic responsiveness. PLoS One. 2012; 7(5):e35237. View Abstract
  28. Targeting the anthrax receptors, TEM-8 and CMG-2, for anti-angiogenic therapy. Front Biosci (Landmark Ed). 2011 01 01; 16(4):1574-88. View Abstract
  29. Genetic loci that control the size of laser-induced choroidal neovascularization. FASEB J. 2009 Jul; 23(7):2235-43. View Abstract
  30. Mutant anthrax toxin B moiety (protective antigen) inhibits angiogenesis and tumor growth. Cancer Res. 2007 Oct 15; 67(20):9980-5. View Abstract
  31. The mouse cornea micropocket angiogenesis assay. Nat Protoc. 2007; 2(10):2545-50. View Abstract
  32. Thalidomide for multiple myeloma. N Engl J Med. 2006 Jun 01; 354(22):2389-90; author reply 2389-90. View Abstract
  33. The effect of genetic diversity on angiogenesis. Exp Cell Res. 2006 Mar 10; 312(5):561-74. View Abstract
  34. Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell. 2005 Jan; 7(1):101-11. View Abstract
  35. Genetic loci that control the angiogenic response to basic fibroblast growth factor. FASEB J. 2004 Jul; 18(10):1050-9. View Abstract
  36. Genetic loci that control vascular endothelial growth factor-induced angiogenesis. FASEB J. 2003 Nov; 17(14):2112-4. View Abstract
  37. Antiangiogenic therapy and p53. Science. 2002 Jul 26; 297(5581):471; discussion 471. View Abstract
  38. S-3-Amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice. Cancer Res. 2002 Apr 15; 62(8):2300-5. View Abstract
  39. Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma. Semin Oncol. 2001 Dec; 28(6):597-601. View Abstract
  40. Human calmodulin-like protein is an epithelial-specific protein regulated during keratinocyte differentiation. Exp Cell Res. 2001 Jul 15; 267(2):216-24. View Abstract
  41. 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. View Abstract
  42. Loss of immunoreactivity for human calmodulin-like protein is an early event in breast cancer development. Neoplasia. 1999 Aug; 1(3):220-5. View Abstract
  43. 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. View Abstract
  44. Application of a chimeric green fluorescent protein to study protein-protein interactions. Biotechniques. 1997 Nov; 23(5):864-6, 868-70, 872. View Abstract
  45. An improved washing apparatus for nucleoside phosphorylation assays. Biotechniques. 1993 Sep; 15(3):402-4, 406. View Abstract

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