My Work
We want to understand specific cell types, focusing mostly on cells in the body. In my lab we use tools and techniques that allow us to probe the normal function of skin cells and examine how cells become specialized. We also examine what happens when skin cells stop behaving normally. When cells stop performing their function properly, it can lead to cancer and other diseases.
There are two approaches to determining why a cell becomes specialized, genetic and biochemical. In the genetic approach we study how individual genes communicate with each other when a cell divides. We look at what happens when we turn genes off or on, focusing on what happens to the normal process of how a cell divides, how it differentiates and becomes specialized. This is the basis of gene therapy, if we understand where the defect came from, we can alter the gene to correct the problem. My focus is finding the mechanism that leads to the effect.
In the biochemical approach we try to understand the molecular mechanism by which different compartments in the cell talk to each other. My ultimate goal is to understand the biology of normal cell function. This will lead to cures of diseases such as cancer.
My Research
Our research interests are centered on the biology of epithelial cells. Epithelia are a fundamental component of tissues and are the major cell type found in numerous organs. Examples include the outer surface of the body (skin epithelium), the inner lining of the gastro-intestinal tract (esophagus, stomach, intestines) and the respiratory tract (lungs and trachea).
The growth, division and differentiation of epithelial cell types are critical to the physiological function of tissues and organs and hence are regulated in a fine-tuned fashion. Divergent signals result in the expression of a specific subset of genes that govern epithelial cell function during both development and adult life. This unique gene signature is thought to bestow specific morphological and physiological features upon epithelial cell types that in turn dictate their various functions. Naturally, aberrancy in epithelial development has dire consequences.
The most common forms of cancer, called carcinomas, originate from epithelial cells. Like all cancers, they result from a breakdown in the normally tight controls over cell proliferation and differentiation, which leads to uncontrolled growth. Hence, understanding the molecular mechanisms that govern these processes is an important area of biomedical research.
We want to understand the process that dictates the unique gene signature of epithelial cells and we use skin epithelium as our model system. For this purpose we apply a wide array of powerful molecular, genetic and biochemical techniques to study skin cells primarily in transgenic mouse models. Because skin epithelium is visible to the eye, it is easy to detect defects and physiological alterations in mice. Often, these phenotypes in mice have often been correlated with skin conditions in human patients. The intricate regulation of epithelial cells is governed in part by transcription factors, which are specialized proteins that control the molecular destiny of a cell by turning genes on and off.
We have developed several mouse models where the levels of critical transcription factors can be altered in the skin epithelium in a controlled fashion. These models allow us to study the underlying mechanisms that control the homeostasis of the skin epithelium and to analyze the changes that lead to altered differentiation and development of skin diseases including cancer.