Department of Biology & Biotechnology Center

Western Kentucky University

Research Interests:

I. Molecular and Cellular Mechanism of Myofibroblast Differentiation

In my work, I am interested in understanding the molecular and cellular characteristics of myofibroblasts and determining the
intracellular mechanisms responsible for their growth and function. Myofibroblasts are unique mesenchymal cells from a variety of organ
systems that are involved in normal tissue development, remodeling and repair. Their recruitment during inflammation is accompanied by a
transition from a quiescent to an activated state in response to various cytokines and growth factors. This activated state of the
myofibroblast is characterized by an increase in a -smooth muscle actin expression, extracellular matrix (ECM) protein expression,
proliferation, and contractility. During injury however, the continued and unchecked proliferation of these cells has implicated them in
several disease states including pulmonary fibrosis and lymphangioleiomyomatosis (LAM). LAM is a rare but devastating lung
disease in young women characterized by the abnormal proliferation of ?LAM cells? which share many common features with myofibroblasts.
Ultimately, I am interested in understanding how myofibroblasts contribute to the pathogenesis of LAM and other interstitial diseases.

II. Genetic Regulation of Phosphorylase-b Kinase Expression

A second area of research involves understanding the transcriptional regulation of the complex oligomeric enzyme phosphorylase b kinase
(PhK). PhK, the first kinase discovered, is a regulatory enzyme involved in the cascade activation of glycogenolysis. In liver, these
reactions allow for the maintenance of blood glucose, and in muscle, they lead to energy production to sustain contraction. PhK is the
largest and most complex protein kinase known. It is a hexadecamer of four copies of four different subunits with a stoichiometry of (abgd)4
and total mass of 1.3 x 106 Da. While much work has been done on elucidating the catalytic mechanism and structural organization of
this protein, understanding its genetic regulation has lagged significantly. In my lab we are focused on determining those
mechanisms that function in complex coordination of PhK transcription by studying the promoter region for each PhK gene and elucidating
those cis- and trans-acting elements responsible for regulating gene expression. Such information will provide tremendous insights into
understanding how the precise temporal and spatial expression (muscle vs. liver vs. heart) of PhK is coordinated. Furthermore, an analysis
of the sequence variation in PhK promoter regions among species will aid in understanding how evolutionary adaptations in these genes have
led to alterations in gene expression and function.

 

Classes I Teach:

Bio 411-001 Cell Biology
Bio 560-501 Advanced Cell Biology