Cancer Cell Biology
Area of interest
Recent studies have brought the lymphatic system to the forefront as an important route of tumor metastasis1,2, the major cause for treatment failure and decreased survival in cancer patients. The spread of cancer cells to the lymph nodes serves as an early indicator of metastatic disease and contributes to the staging of cancer3. Furthermore, expression of lymphangiogenic growth factors, including VEGFC and VEGFD, in various animal tumor models is often correlated with enhanced lymphatic metastasis4,5. Therefore, the targeting the lymphatic vascular system to slow or prevent metastasis in some forms of cancer has become an area of intense and robust investigation.
Our laboratory has recently demonstrated that the angiogenic factor adrenomedullin (AM) and its associated receptors are required for normal lymphatic vascular development6,7. AM also plays a role
in tumor progression by promoting tumor angiogenesis and proliferation and inhibiting apoptosis8. Elevated expression of AM is associated with an increase in tumor neovascularization in pancreatic carcinoma9, xenografted endometrial tumors10 and renal cell carcinoma11. Finally, AM ranks as the proangiogenic gene most tightly correlated with VEGFA expression in gliomas12. Taken together, these studies suggest that therapeutic modulation of AM signaling in some tumors may represent a novel pharmacological approach for slowing or preventing tumor metastasis through the lymphatic vasculature13.
Our current studies make use of in vitro cell culture approaches and sophisticated genetic mouse models to further elucidate the function of AM and its receptors in the growth and function of the lymphatic vasculature. Since the AM receptor is one of the first identified GPCRs involved in lymphangiogenesis13, we are interested in developing and launching a high throughput, small molecule interrogator screen aimed at identifying compounds that selectively target the AM receptor
for modulation of lymphatic endothelial cell growth and permeability. Eventually, we hope to use AMtargeted therapies in preclinical animal tumor models for the inhibition of tumor lymphangiogenesis and distal metastasis.
Awards and Honors
- NIH Individual National Research Service Award, Postdoctoral Training Fellowship, 1999
- American Heart Association Postdoctoral Fellowship- Awarded but declined, 2000
- Recipient of Burroughs Wellcome Fund Career Award in the Biomedical Sciences, 2001
- Irvine H. Page Young Investigator Research Award, American Heart Association, Finalist, 2008
- Jefferson Pilot Fellowship Award in Academic Medicine, 2008
- American Heart Association, Established Investigator Award, 2008