Our studies are focused on the revelation of WNT5A, a secreted glycoprotein. WNT5A belongs to the non-transforming class of WNTs, and upon binding to different receptors or co-receptor complexes (Frizzled, RYK, ROR1/2, LRP5/6 and CD146), it elicits non-canonical (β-catenin-independent) signaling. WNT5A act as both tumor promoter as well as tumor suppressor, depending on cell type. For example, in breast cancer loss of WNT5A protein is associated with poor survival. In contrast, WNT5A expression is associated with increased metastasis and reduced survival in melanoma patients. Our laboratory focusses on how WNT5A expression is regulated in these cancers and deciphering the WNT5A signaling pathways governing cancer cell migration and invasion.
On therapeutic front, we have developed a hexapeptide, Foxy5 (an agonist of WNT5A) which is currently in Phase1 clinical trial for breast cancer, prostate cancer and colon carcinoma (NCT02020291). Another peptide, Box5 (a WNT5A derived antagonist) is currently in pre-clinical trials for malignant melanoma.