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Primary Phone: (520) 6260240
Skaggs College of Pharmacy
1703 E Mabel
Tucson AZ 85721
Primary Phone: (520) 6260240
PhD, University of North Carolina at Chapel Hill, 1998, Microbiology/Immunology
BS, University of Arizona, Tucson, 1991, Microbiology/Immunology
P.D., Mayo Clinic, Arizona, 1998-2001, Biochemistry&Mol Biol
- College Of Pharmacy
Investigating the integration between extracellular matrix and growth factor receptor signaling during heart morphogenesis
Environmental Health Research & Expertise:
My research program centers upon developmental cardiovascular biology stemming from my good fortune to have trained in mouse genetic engineering and producing the first model for patent ductus arteriosus in the mouse(1). Our use of molecular and cellular techniques combined with mouse functional genomics is revealing novel discoveries in regards to heart and coronary vessel development. The significance of this work relates to the fact that cardiovascular-heart defects are the most common congenital defects diagnosed in infants in this country. A 2007 American Heart Association publication reports the incidence of congenital heart defects at 5% for births in the United States. In addition, we firmly propose that cardiovascular disease in adults has developmental origins. Therefore, we are not only defining developmental cardiac events and causes of congenital defects, but also etiology of cardiovascular connective tissue diseases. In this regard, we have identified that exposure to environmental arsenic in drinking water contributes to altered heart structures, hypertension, and cardiac hypertrophy. We are poised to decipher the molecular and cellular mechanisms of arsenic developmental cardiotoxicity as we have previously established the roles for TGFb(6,13), VEGF(5,9,11) and ErbB signaling(3,7) as well as hyaluronan matrix in heart structure formation and disease(4,7,11,14). We have recently discovered a signaling node through Map3-Kinases that integrates many of these signals to mediate the correct signal transduction for normal heart formation(12). We have also discovered that arsenic exposure disrupts developmental EMT impacting cardiac physiology (14,15). Our efforts will lead to improved diagnostics and be applied to develop novel repair strategies to improve the health of children and adults with congenital heart defects as well as risk reduction or prevention in arsenic vulnerable populations. My collective research program constitutes a critically important amalgamation of molecular and developmental biology, genetics, protein chemistry and eventually pediatric medicine. We have contributed several seminal papers to the field and are recognized as leaders in this area with the contribution of chapter 6 to the 2010 publication of the second edition of Heart Development and Regeneration.
- Cardiac Epithelial-Mesenchymal Transition Is Blocked by Monomethylarsonous Acid (III).
- HER2/HER3 regulates extracellular acidification and cell migration through MTK1 (MEKK4).
- Disruption of canonical TGFβ-signaling in murine coronary progenitor cells by low level arsenic.
- Arsenite activates NFκB through induction of C-reactive protein.
- Chronic low-level arsenite exposure through drinking water increases blood pressure and promotes concentric left ventricular hypertrophy in female mice.
- Transforming growth factor beta signaling in adult cardiovascular diseases and repair.
- The cytoplasmic domain of TGFβR3 through its interaction with the scaffolding protein, GIPC, directs epicardial cell behavior.
- Transforming growth factor Beta2 is required for valve remodeling during heart development.
- The relationship between bone, hemopoietic stem cells, and vasculature.
- ErbB signaling in cardiac development and disease.
- TGFβ2-mediated production of hyaluronan is important for the induction of epicardial cell differentiation and invasion.
- Arsenic exposure perturbs epithelial-mesenchymal cell transition and gene expression in a collagen gel assay.
- Involvement of the MEKK1 signaling pathway in the regulation of epicardial cell behavior by hyaluronan.
- Akt promotes endocardial-mesenchyme transition.
- An improved protocol for the isolation and cultivation of embryonic mouse myocytes.
- Size-dependent regulation of Snail2 by hyaluronan: its role in cellular invasion.
- MEKK3 initiates transforming growth factor beta 2-dependent epithelial-to-mesenchymal transition during endocardial cushion morphogenesis.
- An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart.
- Arsenic-induced decreases in the vascular matrix.
- Depolymerized hyaluronan induces vascular endothelial growth factor, a negative regulator of developmental epithelial-to-mesenchymal transformation.
- Has2 expression in heart forming regions is independent of BMP signaling.
- Form and function of developing heart valves: coordination by extracellular matrix and growth factor signaling.
- Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors. Previous years
- MAP3Ks as central regulators of cell fate during development.
- MUC1 alters beta-catenin-dependent tumor formation and promotes cellular invasion.
- Elevated glucose inhibits VEGF-A-mediated endocardial cushion formation: modulation by PECAM-1 and MMP-2.
- VEGF modulates early heart valve formation.
- Temporal and distinct TGFbeta ligand requirements during mouse and avian endocardial cushion morphogenesis.
- Hyaluronan: genetic insights into the complex biology of a simple polysaccharide.
- CD44 attenuates metastatic invasion during breast cancer progression.
- Critical parameters for genome editing using zinc finger nucleases.
- Differential growth and multicellular villi direct proepicardial translocation to the developing mouse heart.
- Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells.
- MEKK4 regulates developmental EMT in the embryonic heart.
- Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase.