Research

 
 
REGULATION OF THE ADENOVIRAL GENE EXPRESSION PROGRAM
 
 
Adenoviruses were recognized as an invaluable tool for investigating mammalian molecular biology since 1953, the year of their isolation. Studies of these viruses have contributed to the molecular understanding of many fundamental cellular processes such as the control of cell cycle progression and pre-mRNA splicing. At present, the adenovirus represents more than just a versatile eukaryotic model system; in recent years, several of its distinguishing features have made it the preferred vehicle for gene transfer and transgene expression in mammalian cells. New insights into adenoviral gene expression program are expected to facilitate the efforts to improve the safety and efficacy of clinical approaches that utilize adenoviral vectors. In recent years, a rapidly developing field of research has exploited the potential use of adenoviruses in anti-cancer therapy. To this end, advances in our understanding of the mechanisms that ensure efficient replication of adenoviruses are critical to identify effective strategies for the design of adenovirus-based anti-cancer agents. The overall focus of our studies is the regulatory mechanism by which transcription of adenoviral genes coordinates with viral DNA synthesis for a successful infectious cycle.
 
 
Temporal expression of adenovirus genes
 
In our lab we employ two human adenoviruses, serotype 2 (Ad2) and serotype 5 (Ad5). We have extensive knowledge about their tropism, gene expression, host cell interactions, and transforming capabilities. However, several important facets of adenovirus biology remain poorly understood. One such aspect is the regulation of the early-to-late switch in the adenoviral gene expression. As part of this temporally phased program, most regulatory proteins (early) are produced before the onset of viral DNA synthesis, while structural proteins (late) are made following the initiation of viral DNA synthesis. It has been known for some time that activation of late genes is accompanied by a diminished transcription of early genes, but whether these changes occur through passive gene activity or active gene repression has not been conclusively determined. Study of such regulatory mechanisms is crucial for the understanding of how successful progression through the adenoviral reproductive cycle is achieved. Our research aims to elucidate how transcription from two adenoviral late promoters, IVa2 and E2L, is regulated.

STEM CELL DIFFERENTIATION IN BIOMATERIALS USED FOR TISSUE REGENERATION

This is a recent project carried out in collaboration with Dr. Jennifer Vernengo and Dr. Jennifer Kadlowec from the College of Engineering. More details to come.