Scientist Development Award recipient, American Heart Association, 2006 - present
Member, American Heart Association
Member, International Society for Stem Cell Research

My interest is to understand the role of the each pathway activated by Hedgehogs in biologically relevant processes. In particular, we have three areas of research:

1. Angiogenesis: The formation of new vessels from pre-existing ones involves coordinated proliferation, migration, and tubulogenesis of endothelial cells. Hedgehog promotes, and is required for, many types of angiogenesis. Our goals are to understand the Hedgehog signaling pathways involved in angiogenesis. A focus of this project is the crosstalk between Hedgehog signals and mitochondrial function to support endothelial cells proliferation.


2. Myocardial regeneration: Our objective is to understand the molecular mechanism/s underlying stem cell maintenance, proliferation, and specification into cardiac cell types. The regenerative potential of cardiomyocytes in vivo is very limited, leading to persistent function deficits in chronically or acutely ischemic injured hearts. Our long-term goal is to use mesenchymal stem cells (MSCs) isolated from adipose tissue to generate cardiac progenitors that can terminally differentiate into cardiomyocytes when transplanted back into the heart. To this end, MSCs will be manipulated in vitro with embryonic growth factors, with emphasis in Hedgehog, in an attempt to recapitulate embryonic cardiogenesis.

3. Cancer: hyperactivation of the Hedgehog signaling pathway is very common in human cancers. We are interested in evaluating the role of signal crosstalk between Hedgehog and other growth factors that activate PI3K/Akt and/or ERK in the control of cancer cell proliferation and survival.

The Hedgehog family of ligands regulates a plethora of biological processes involved in embryonic development, tissue homeostasis and regeneration, and cancer progression. The canonical Hedgehog pathway is based on a series of de-repression events mediated by the proteins Patched, Smoothened, and Su(Fu) that allow a tightly controlled activation of the downstream transcription factors Gli1, Gli2, and Gli3. We and others have recently shown that Hedgehog, signaling through Smoothened, also activates Gi proteins/GRK2/arrestin, PI3K/Akt, and ERK signaling pathways which may have physiological significance on their own. In addition, Patched directly regulates cell cycle progression in a Hedgehog-dependent manner. These newly discovered events are grouped into the so-called non-canonical Hedgehog pathway.

Hedgehog, angiogenesis, stem cells, G proteins, phosphorylation, signal transduction, cancer, regenerative medicine, cardiovascular biology.