RESEARCH INTERESTS

We are interested in the mechanisms that contribute to the initiation and progression of epithelial-derived tumors (carcinomas), especially aggressive, poorly differentiated tumors. Our research projects emphasize molecular cell biology but they derive from the analysis and clinical behavior of carcinomas. Researchers in our group are identifying mechanisms that account for the loss of differentiation and the highly aggressive behavior of these tumors, and exploiting these mechanisms to improve prognosis and therapy. A major focus of this work is to define mechanisms that control the genesis and function of cancer stem cells and understanding how these cells contribute to tumor initiation, progression and recurrence. Within this framework, major projects include studies on:

Regulation and Function of Integrins

The lab has pioneered studies on the α6 integrins (α6β1 and α6β4), which function as receptors for the laminins, a family of extracellular matrix proteins. We seek to understand how these integrins contribute to tumor initiation and progression with an emphasis on cancer stem cells and on the role of laminins in the cancer stem cell niche.

VEGF/Neuropilin Function and Signaling

A major interest of the lab is the ability of VEGF to target tumor cells directly, especially cancer stem cells and, consequently, contribute to tumor initiation, progression, and recurrence. This function of VEGF is independent of its role in angiogenesis and mediated primarily by neuropilins (NRPs), a class of VEGF receptors. We are studying how VEGF/NRP signaling impacts CSC function and targeting NRPs for therapy.

Ferroptosis Resistance

The survival of carcinoma cells in the tumor microenvironment is a problem of paramount importance in cancer biology and therapy. Aggressive carcinoma cells are dependent on mechanisms that resist ferroptosis, an iron-dependent form of regulated cell death characterized by the accumulation of lipid reactive oxygen species. We are pursuing studies on the cell biological mechanisms that contribute to ferroptosis resistance in carcinomas.