Jeffrey M. Arbeit, M.D.

Urologic Surgery
Principal Investigator
Cell Biology and Physiology

Molecular Cell Biology Program
Molecular Genetics and Genomics Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-362-3222

  • 314-362-3236

  • 314-362-3246

  • 8242

  • 10103 Wohl Hospital


  • cancer, hypoxia, cell signaling, tumor biology, transcription, vascular biology

  • Molecular regulation of epithelial carcinogenesis

Research Abstract:

Solid tumors grow because of activation of signaling pathways regulating cell proliferation, and survival. Growth is crucially supported by tumor secretion of growth factors that induce angiogenesis of adjacent microvessels producing a new, “neovascular” network for oxygen and nutrient provision. Conversely, tumor neovascular endothelial cells secrete molecules that stimulate malignant cellular growth and survival. The goal of my laboratory is to understand both malignant cell autonomous and paracrine neovascular endothelial cell contribution to tumor growth. We continue to focus on the function of hypoxia inducible factors-1 and -2, mTOR signaling complexes, and angiogenesis signaling via VEGF. We are developing novel mouse models to interrogate signaling pathway disruption in tumor endothelial cells, new cellular reporters to interrogate tumor cellular functions in response to genetic or pharmacologic endothelial signaling disruption, and new tumor cellular screens for genes that enable cancers to evade angiogenesis inhibitor therapies. We are also investigating the function of selected signaling pathways in embryonic blood vessel development to glean additional functional insights relevant to tumor neovascularization. In collaboration with Lihong Wang’s lab, we are using a novel noninvasive microvascular imaging technique, photoacoustic microscopy, to functionally characterize how tumor microvessel anatomy, oxygen delivery, and oxygen consumption responds to pharmacological or genetic angiogenesis inhibition strategies. We have additional collaborations with investigators using MRI, PET, and nanotechnology, along with clinical oncologists with the goal of rapid translation of laboratory discoveries to cancer patient treatment.

Selected Publications:

Scortegagna M, Cataisson C, Martin RJ, Hicklin DJ, Schreiber RD, Yuspa SH, Arbeit JM. HIF-1α regulates epithelial inflammation by cell autonomous NFkappaB activation and paracrine stromal remodeling. Blood 2008 111: 3343-54.

Scortegagna M, Martin R, Kladney R, Neumann R, Arbeit JM. Hypoxia-inducible factor-1α suppresses squamous carcinogenic progression and epithelial mesenchymal transition. Cancer Research 2009 69(6): 2638–2646.

Garbow J, Santeford A, Anderson J, Engelbach J, Arbeit JM. Magnetic resonance imaging defines cervico-vaginal anatomy, cancer, and VEGF trap antiangiogenic efficacy in estrogen-treated K14-HPV16 transgenic mice. Cancer Research 2009 69(20): 7945–7952.

Lu ZH, Shvartsman MB, Lee AY, Shao JM, Murray MM, Kladney RD, Fan D, Krajewski S, Chiang GG, Mills GB, Arbeit JM. Mammalian target of rapamycin activator RHEB is frequently overexpressed in human carcinomas and is critical and sufficient for skin epithelial carcinogenesis. Cancer Research 2010 70: 3287-3298.

Kladney RD, Cardiff RD, Kwiatkowski DJ, Chiang GG, Weber JD, Arbeit JM, Lu ZH. Tuberous sclerosis complex 1: An epithelial tumor suppressor essential to prevent spontaneous prostate cancer in aged mice. Cancer Research 2010 70(21): 8937-47.

Oladipupo S, Hu S, Santeford AC, Yao J, Kovalski J, Shohet RV, Maslov K, Wang LV, Arbeit JM. Conditional HIF-1 induction produces multistage neovascularization with stage-specific sensitivity to VEGFR inhibitors and myeloid cell independence. Blood 2011 117: 4142-4153.

Oladipupo S, Hu S, Kovalski JR, Yao J, Santeford AC, Sohn RE, Shohet RV, Maslov K, Wang LV, Arbeit JM. VEGF is essential for hypoxia-inducible factor mediated neovascularization but dispensable for endothelial sprouting. PNAS 2011 108: 13264-13269.

Last Updated: 1/26/2012 8:33:25 AM

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