Welcome to our lab!

The research in our lab focuses on identifying and targeting small phospholipid molecules that regulate the development and progression of human ovarian, breast and prostate cancers. We previously identified a novel growth-promoting activity present in ascites of ovarian cancer patients mediated by lysophosphatidic acid (LPA). Like many other biomediators, LPA interacts with cells through specific cell surface receptors (G protein-coupled receptors). Recent studies indicate that in many types of human malignancies, LPA production is increased through overexpression of an LPA-synthesizing enzyme called autotaxin/Lyso-PLD, suggesting that amplification of LPA signaling represents a common step of human carcinogenesis.

 

LPA has multiple biological effects on human cancer cells including stimulation of cell proliferation, survival, drug resistance, and motility. We have recently demonstrated that LPA dramatically induces expression of multiple pro-angiogenic factors such as vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), interleukin (IL-6), and growth related oncogene 1 (Gro-1). These factors are important mediators of cancer progression. For example, VEGF increases vascular permeability, a critical step in ascites formation in ovarian cancer. IL-6 and IL-8 levels are elevated in ovarian, breast and prostate cancer patients. The increased concentrations of IL-6 and IL-8 correlate with poor response to chemotherapy or poor prognosis. Thus LPA may exert its detrimental effect through promoting tumor angiogenesis. The hypothesis is also consistent with the migration-stimulating activity of LPA. We are developing various approaches to modulate LPA production or its receptor expression in vitro and in vivo. An ability to manipulate the functionality of LPA could potentially lead to novel and effective therapies for cancer intervention.