RESEARCH INTERESTS

We are a talented group of molecular cell biologists interested in understanding the mechanisms that contribute to the initiation and progression of carcinomas and exploiting these mechanisms to improve prognosis and therapy.  Our research projects emphasize molecular cell biology, but they derive from the analysis and clinical behavior of carcinomas, especially breast and prostate carcinoma.  Currently, we are identifying mechanisms that enable carcinoma cells, especially metastatic cells, to evade ferroptosis, a form of cell death caused by iron-dependent lipid peroxidation of cell membranes.  Other projects include investigating the role of VEGF signaling in carcinomas cells mediated by neuropilin-2, a pathway that we have shown is amenable to therapeutic intervention.  We also have a long-standing interest in the role of integrins in carcinoma biology, especially the a6 integrins (a6b1 and a6b4).  Current projects focus on the role of these integrins in the interaction of carcinoma cells with immune effector cells. 

Within this framework, major projects include studies on:

Mechanisms of 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, especially metastatic 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.

Function of Integrins in Immune Cell Interactions

The lab pioneered studies on the contribution of the a6 integrin laminin receptors (a6b1 and a6b4) to the biology of carcinomas. We now seek to understand how these integrins contribute to the ability of carcinoma cells to interact with immune effector cells.

Therapeutic Targeting of VEGF/Neuropilin-2 Signaling

A major interest of the lab has been 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 neuropilin-2, a VEGF receptor.  We are currently studying how VEGF/NRP-2 signaling impacts the behavior of carcinoma cells and developing approaches to inhibit the interaction of VEGF with NRP2 as a therapeutic approach for breast and prostate carcinoma.