A key aspect of signal transduction is the ability of cells to translate an extracellular signal into an intracellular one, enabling cells to respond to their environment. The initial response of cells to growth factors and hormones is facilitated by interaction with cell surface receptors; this interaction then leads to the activation of intracellular signaling pathways. These pathways often require a series of sequential protein kinase reactions that ultimately regulate many cellular processes including growth, matrix production, contractility and ion transport.
Our interests concern the regulation of the kinase signaling pathways by neurohormonal agents and reactive oxygen species in the cardiovascular system. Utilizing both intact tissue and cell culture models, our laboratory has concentrated on elucidating the role that kinases may play in modulating ion transport, matrix remodeling, sarcomere assembly, and contractility and cell growth. Representative current projects include: (1) Role of oxidative and nitrosative stress in the pathogenesis of heart failure; (2) Altered matrix remodeling in pressure and volume-overload heart failure with particular emphasis on cardiac fibroblasts; (3) Regulation of vascular smooth muscle cell growth by hypertrophic and hyperplastic factors. (4) Regulation of vascular smooth muscle function by kinase signaling pathways in vivo using two model systems: A carotid artery wire injury model (growth) and resistance vessel preparations (contractility). A combination of antisense, adenoviral and transgenic technologies are used to downregulate and manipulate expression/activation of key components of signaling cascades. 5) Alterations in myocyte Ca2+ homeostasis and sarcomeric assembly in pressure vs. volume overload.
Amy Gearica - Research Assistant
Amy graduated from Ohio Wesleyan University in May 2008 with a BA in Zoology and Pre-Medicine and a minor in Chemistry. As an undergraduate student she worked to characterize Caenorhabditis elegan mutants defective in cell division. After graduation, she spent a year working at The Ohio State University in a molecular biology laboratory studying the endogenous Wnt inhibitor Dickkopf-1 (DKK1) and its role in breast cancer to bone metastases. As a research assistant in Dr. Pamela Lucchesi’s lab she is assisting others in their projects investigating volume-overload heart failure as well as diabetes-induced coronary structural remodeling.
Anu Guggilam , Ph.D - Postdoctoral Fellow
Dr. Guggilam completed her studies of Veterinary Medicine at the College of Veterinary Sciences, Hyderabad, India, and earned her Doctoral degree in cardiovascular pathophysiology from the Louisiana State University, Baton Rouge, LA. Her graduate studies involved studying the role of TNF induced oxidative stress in the autonomic regulatory centers of the brain in the progression of ischemic heart failure. The main focus of her postdoctoral research in the Lucchesi lab is to understand the role of hemodynamic and neurohormonal stresses on in vivo and in vitro cardiac dysfunction in a volume overload model of heart failure. Her research aims are to understand the myocyte sarcomere assembly and Ca++ homeostasis as well as cell-cell communication in volume overload heart failure model. This project will help delineate the precise functional and structural alterations the myocytes undergo in congestive heart failure.
Kirk Hutchinson - Ph.D Candidate
Kirk is from New Orleans, Louisiana and left hurricane country with his wife and two little girls to work with Dr. Pamela Lucchesi at Nationwide Children’s. He is currently a graduate student working on his Ph.D in Pharmacology. His research involves determining the extent to which reactive oxygen species regulate cardiac fibroblasts and how this affects heart function in volume overload heart failure. He uses isolated cells as well as in vivo functional assessments to correlate the contributions of fibroblasts to heart function.
Paige Katz - Ph.D Candidate
Paige is a graduate student in the Department of Physiology at LSU Health Sciences Center and moved to Columbus to finish her research with Dr. Pamela Lucchesi. Currently, she is studying how type 2 diabetes affects coronary artery remodeling in the db/db mouse model. She utilizes in vivo, in vitro and molecular studies to identify the possible mechanisms involved in diabetes-induced coronary artery remodeling.
Aaron J. Trask , Ph.D. - Postdoctoral Fellow
Dr. Trask earned his PhD in physiology and pharmacology from Wake Forest University under the tutelage of Dr. Carlos M. Ferrario studying the involvement of new components of the renin-angiotensin system (RAS) in hypertension and cardiac hypertrophy. He joined Dr. Pamela Lucchesi at Nationwide Children’s Hospital as a postdoctoral fellow to expand his training and interests in the heart by studying the actions of advanced-glycation end products (AGEs), a major problem in diabetic cardiomyopathy, on coronary artery structure and function. A secondary interest of his is how the actions of AGEs ultimately affect global cardiac function. These studies will utilize both cell/molecular techniques, as well as in vivo experiments to discern the involvement of AGEs and components of the RAS in cardiac dynamics during both the normal and diabetic states.
T. Aaron West , M.S. - Research Associate / Laboratory Manager
Aaron received his Masters of Science and Bachelors of Science from Purdue University where his thesis concentration was Renal Physiology and Cell Biology. Specifically, he investigated how the Epithelial Sodium Channel (ENaC) and the Cystic Fibrosis Transmembrane Regulator (CFTR) in kidney distal tubule cells are hormonally regulated, and how the Thiazolidinedione (TZD) class of drugs used to treat Type II Diabetes alters their regulation. Before coming to Nationwide Children’s Hospital, he worked for a contract research organization coordinating clinical research for pharmaceutical companies. Currently, in addition to managing the Lucchesi laboratory and coordinating clinical studies, he works on multiple rodent model projects relating to volume overload heart failure as well as coronary artery remodeling in diabetes performing the biochemical assays, immunohistochemistry and immunofluorescence.