Tumorigenesis and vasculopathies

The acquisition of unlimited proliferation potential (immortalization) is a critical step, but insufficient, in the transformation of a normal cell into a cancer cell. We are interested in uncovering genes mediating neoplastic progression beyond the immortalization step and have identified numerous genes expressed differentially between tumor and immortal cells.

Cardiovascular diseases are among the primary causes of death in the developed world. Atherosclerosis, aneurysm, and restenosis are all associated to extensive vascular wall remodeling. Angiotensin II (AngII) and vascular smooth muscle cells (VSMCs) play essential roles in vascular wall remodeling through relatively unknown mechanisms. While investigating these processes, we have uncovered a huge number of genes regulated by AngII in VSMCs.

To determine the contribution of some of these genes to tumor formation and invasion or to pathological vascular wall remodeling, we are employing genetically modified mice and cell models; transcriptomic (RNAseq) and proteomics analysis; lentivirus for gene overexpression, knockdown (siRNA and shRNA) or knockout (Crispr/Cas9); and numerous experimental approaches based in molecular biology, biochemistry and cell biology.

These studies may perhaps identify genes critically involved in tumor formation and invasion or in cardiovascular pathologies that may become targets for the development of more efficient and less toxic therapies than those currently used.