Marsha A. Moses, Ph.D.

Co-Director (Interim), Vascular Biology Program
Children's Hospital Boston
Professor, Harvard Medical School
Department of Surgery
Children's Hospital Boston and Harvard Medical School
Karp Family Research Laboratories, Rm 12.214
300 Longwood Avenue
Boston, MA 02115-5737
Tel: (617) 919-2207
Fax: (617) 730-0231
Email: marsha.moses@childrens.harvard.edu

Our laboratory has had a long standing interest in identifying the molecules and understanding the mechanisms that regulate angiogenesis. Using biochemical and molecular approaches, we have identified a number of endogenous regulators of neovascularization that function at both the transcriptional and translational level. Structure-function studies of some of these inhibitors have revealed distinct anti-angiogenic domains that regulate tumor growth and metastasis in vivo. Two of these are currently being developed for clinical use. We are also studying the control of new blood vessel formation from the earliest stages of the vascular program, ie. from the switch to the angiogenic phenotype through tumor growth and progression. We have developed tumor models that reliably recapitulate the angiogenic switch in vivo. Using these models, we have conducted transcriptional profiling studies and have identified and validated the unique cohort of genes that are differentially expressed during the transition from an avascular to a vascular tumor in this system. These and other results are being used to understand the mechanisms by which angiogenesis is regulated and to ultimately develop novel diagnostics/prognostics and therapeutics for use in those diseases which are characterized by dysregulated angiogenesis.

To complement these studies, we have established a Proteomics Initiative in our laboratory that has now led to the discovery of a panel of urinary cancer biomarkers that not only predict disease status in cancer patients but are also sensitive and specific predictors of disease progression and therapeutic efficacy of cancer drugs. Current studies are underway to determine whether the detection of some of these urinary cancer biomarkers can serve as non-invasive sentinels of the switch to the angiogenic phenotype during tumor progression as well.

References:

• Harper J, Yan L, Loureiro RM, Wu I, Fang J, D'Amore PA, Moses MA. Repression of vascular endothelial growth factor expression by the zinc finger transcription factor ZNF24. Cancer Res. 2007; 67(18):8736-41.
• Moses MA, Harper J, Folkman J. (2006) Doxycycline treatment of lymphangioleiomyomatosis with urinary MMP monitoring. N. Engl. J. Med., 354(24): 2621-2.
• Roy R, Wewer UM, Zurakowski D, Pories SE, Moses MA. (2004) ADAM 12 cleaves ECM proteins: correlation with cancer status and stage. J. Biol. Chem. 279(49):51323-30. (Epub 2004 Sep 20).
• Fernandez CA, Butterfield C, Jackson G and Moses MA. (2003) Structural and functional uncoupling of the enzymatic and angiogenic inhibitory activities of Tissue Inhibitor of Metalloproteinase-2 (TIMP-2), J. Biol. Chem. 2003; 278:40989-40995.