Assistant Professor of Biochemistry
215-762-1898
michael.bouchard@drexelmed.edu

Education:
Ph.D. (1997) Microbiology,
Columbia University
 
Research Program

Liver cancer is one of the most common cancers worldwide, and 80% of liver cancers can be attributed to chronic infection with the Hepatitis B virus (HBV). The HBV X protein, HBx, is essential for HBV replication and thought to have a role in HBV-associated liver cancer. HBx is a multifunctional protein that influences cellular transcription pathways, cell cycling, apoptosis, and cellular signal transduction cascades involving proto-oncogenes such as Src kinases. However, the exact means by which HBx influences such diverse activities is not understood. Recently, we demonstrated that one activity associated with HBx expression in human liver cells is modulation of cellular calcium signaling which results in the activation of Pyk2 and Src kinases. These functions of HBx are essential for HBV replication, as well as HBx-induced cell cycling and transcription activation. Alterations in calcium signaling have many consequences for cellular metabolism and therefore, may explain many of the diverse functions that have been attributed to HBx. We are continuing to study HBx-induced calcium signaling as well as other activities associated with HBx expression to determine the precise mechanism through which this protein influences such a diverse array of cellular pathways. These studies are performed in established human liver cell lines, in cultures of primary mouse and rat hepatocytes, and in vivo through the use of adenovirus recombinants that can transduce HBV into the livers of mice. Such studies should help delineate how this protein and chronic infections with HBV can lead to the transformation of liver cells and the development of liver cancer.

Selected References

McClain, S., A. Clippinger, R. Lizzano and M. Bouchard. HBV replication is associated with an HBx-dependent mitochondrial-regulated increase in intracellular calcium levels. (Submitted)

M. Bouchard, L-H. Wang, and R. Schneider. (2006) Activation of focal adhesion kinase by hepatitis B virus HBx protein:  multiple functions in viral replication. J. Virol. 80: 4406-4414

M. Bouchard, and R. Schneider. (2004) The Enigmatic X Gene of the Hepatitis B virus. J. Virol.  78: 12725-12734.

M. Bouchard, R. Puro, L-H. Wang, and R. Schneider. (2003) Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in HBV replication. J Virol. 77: 7713-7719

M. Bouchard, L-H. Wang, and R. Schneider. (2001) Calcium signaling by HBx protein in Hepatitis B virus DNA replication. Science 294: 2376-2378

M. Bouchard, S. Giannakopoulos, E. Wang, N. Tanese, and R. Schneider. (2001) The hepatitis B virus X protein activates the cyclin A promoter in a Src-dependent manner. J. Virol. 75: 4247-4257.

N. Klein, M. Bouchard, L-H Wang, C. Korbarg, and R. Schneider. (1999) Src kinases involved in hepatitis B virus replication. EMBO J. 18: 5019-5027.