Dr. Robert Nabi
Professor
Cellular & Physiological Sciences
Current Research Focus
The Nabi lab focuses on cell biology and its relation to disease, in particular cancer. The expression of cellular domains, ranging from cell polarity to organelle biogenesis to membrane microdomain organization, plays an important role in regulating cell function. Domain localization is critical to the regulation of receptor activation and our work has elaborated on the functional significance of various cellular domains in receptor function in cell motility.
Example Project(s)
“Caveolin-1 Regulation of Focal Adhesion Tension and the Breast Cancer Cell Response to Matrix Stiffness” Poor outcomes in aggressive breast and prostate cancer are associated with increased stiffness of the extracellular matrix (ECM), The ECM is a collection of molecules outside of cells that provides support to the surrounding cells. Indeed, the association of mammography density with more aggressive breast cancers is based on the increased organization and stiffness of the ECM of these cancers. Focal adhesions are structures on the surface of cells responsible for the attachment of cells to the ECM and mediate the response of cancer cells to the stiffness of the ECM. We have identified a protein called caveolin-1 that regulates focal adhesion mediated tension between the cells and ECM. This protein is also associated with breast and prostate cancer malignancy. We will now determine how caveolin-1 controls focal adhesion mediated tension, and whether its role as a regulator of focal adhesions is responsible for its association with malignant cancers. This work will advance our understanding of highly aggressive breast cancers and could help us identify new mechanisms and molecules that can be targeted to treat these cancers.
Specific projects include:
• The role of autocrine motility factor receptor (AMFR, also gp78), a cancer-associated receptor and E3 ubiquitin ligase in endoplasmic reticulum associated degradation (ERAD) and ER-mitochondria interaction.
• Development of novel anti-cancer therapeutics based on the raft-dependent endocytosis of autocrine motility factor (AMF), the gp78/AMFR ligand.
• The role of plasma membrane domains and their effectors, including galectin-3 and caveolin-1, in receptor signaling and focal adhesion dynamics in metastatic cancer cells.
• Characterization of the proteome and transcriptome of tumor cell pseudopodia and the regulation of tumor cell migration and metastasis.
Research Keywords
Breast Cancer, Fluorescent Microscopy, Mitochondrial Dynamics, Tumor Progression, Metastasis, Single Molecule Localization Microscope, Super Resolution Microscopy