Robert D. Simari, M.D.

Long Term Research Aims:

To develop novel biological therapies for vascular disease through enhanced understanding of the molecular basis of vascular disease.

Mid-Term Research Aims:

To better define the coordinated regulation of thrombosis and angiogenesis.

To define the population of adult progenitor cells in the adult vasculature.

To design novel genetic, peptide and cell-based therapies for occlusive vascular disease.

To perform early (first in man or Phase 1) clinical trials of novel therapies for vascular disease.

Approach:

Our laboratory is based on the premise that through basic definition of the molecular basis for vascular disease, we can identify and develop novel therapeutics. Our aim is to define biological problems and to treat them with biological therapeutics. Our interests are broad and range from understanding the vascular response to injury and thrombosis to the development of novel peptide and cell-based therapies.

Ongoing projects

1. Our lab has established the importance of regulation of the tissue factor pathway in vascular disease. We have identified that tissue factor pathway inhibitor (TFPI) regulates arterial thrombosis in murine models. Surprisingly, we recently demonstrated that TFPI regulates lipoprotein metabolism through its interaction with heparin sulfate proteoglycans (Pan, Circ Res 2009). Additional studies are underway to define the role of TFPI in angiogenesis and endothelial cell function.
2. The family of natriuretic peptides regulates cardiac and vascular form and function. In 2009, we discovered an alternatively spliced form of b-type natriuretic peptide (BNP) (Pan, PNAS 2009). This variant is found in tissue from failing hearts. Using this variant as a template, our team designed a novel therapeutic which maintains the renal effects of BNP but lacks the vasoactive effects. This peptide is being developed for clinical use.
3. I have the honor of chairing the NHLBI-sponsored Cardiovascular Cell Therapy Research Network (http://ccct.sph.uth.tmc.edu/cctrn) that performs early Phase 1 and 2 trials of cell-based therapies for heart disease. We are currently performing three trials for acute and chronic left ventricular dysfunction.