John G. Pastorino, Ph.D.

Assistant Professor

E-mail: pastorjg@umdnj.edu
Phone: 856 566-6041
Fax: 856 566-6291
Office: Science Center 316
Address:
Department of Molecular Biology
UMDNJ-SOM
2 Medical Center Drive
Stratford, NJ 08084

Research Interests

The work of my laboratory focuses on the role of mitochondria in cell injury and apoptosis. As such we have been able to investigate a wide range of research interests. The mitochondria have emerged as integral to the areas of cell death and survival. Mitochondria are noted as the primary source of energy generation in the cell. However in this capacity the mitochondria can also assimilate and respond to a number of signaling pathways. Our work has uncovered that mitochondria are central to the reaction of a cell to treatment with tumor necrosis factor (TNF). This is especially critical in the context of alcoholic liver disease (ALD) where the hepatocytes display a propensity to induction of cell killing in the form of apoptosis and necrosis when exposed to TNF. This in turn leads to the alterations in liver architecture and function that are characteristic of ALD. Additionally, the mitochondria are central to energy metabolism and as such, the work performed in my laboratory has uncovered how alterations to mitochondrial outer membrane proteins such as VDAC can influence insulin signaling, thereby having implications for diseases such as diabetes and non-alcoholic fatty liver disease, which have their genesis in metabolic abnormalities.

Our studies in mitochondria also impact the field of cancer research. As a central mediator of the cell death response, mitochondria have the potential to be exploited as a chemotherapeutic target. This is especially relevant in highly glycolytic tumors such as gliomas . Our studies have uncovered that hexokinase II (HXK II) in cancerous cells, a protein over-expressed in a number of malignancies, is bound to the mitochondria in a controlled fashion. The binding of HXK II to the mitochondria is mediated through an interaction between HXK II and VDAC, an outer mitochondrial membrane protein. In this configuration, HXK II prevents interaction of VDAC with pro-apoptotic proteins such as Bax and Bak . Treatment of cancer cells with exogenous agents that detach hexokinase II from the mitochondria greatly facilitate the ability of conventional chemotherapeutic agents to kill the transformed cells. Since the expression and binding of HXK II is so much greater in cancer than in normal cells, the influence of hexokinase II detachment on the viability of normal cells is nominal.

Study in the fields of apoptosis and mitochondria have increased dramatically in the past decade. Our work over the past 18 years has encompassed both of these areas and the interactions that occur between them. This places us in a unique position to study the myriad of diseases where apoptosis and mitochondria converge and have been implicated in the pathogenesis and progression of disease states.