Tulane Cancer Center

Biographical Narrative:
Dr. Dash received his Ph.D from the All India Institute of Sciences, New Delhi, India in 1991. His graduate work involved characterizing a putative receptor of Hepatitis B virus envelope protein on human liver cells. Dr. Dash moved to Tulane as a post-doctoral fellow under Professor Michael A. Gerber. There he finished six years of post-doctoral training, working on Hepatitis C in the Department of Pathology and Laboratory Medicine. In 1995 Dr. Dash was promoted to Research Assistant Professor in the Department of Pathology.

Research Interests:
The liver is the largest solid organ of the human body and is often affected by primary malignant tumors such as hepatocellular carcinoma and cholangiocarcinoma. This organ is also more frequently affected by secondary malignant diseases derived from a variety of cancers such as colorectal carcinoma, carcinomas of the stomach, pancreas, lungs, breast and malignant melanomas. According to the National Cancer Institute, hepatocellular carcinoma (HCC) is the 4th most common cancer in the world. It is also called primary liver cancer because it arises from hepatocytes, which are the major cell type of the liver. The cause of hepatocellular carcinoma is unknown but contributing factors include viral hepatitis (hepatitis B and hepatitis C), cirrhosis, hemochromatosis, and toxins (especially aflatoxins) found in foods in parts of Africa and Asia. In the United States hepatitis C virus infection is the leading cause of hepatocellular carcinoma and liver transplantation. During the last few years our focus has been to prevent HCV-related hepatocellular carcinomas by developing effective strategy to inhibit virus replication and production. A significant proportion of chronic hepatitis C patients who can not get rid of the virus infection by interferon therapy experience long-term inflammation of liver and scarring of liver tissue. Those patients with liver cirrhosis usually have increased risk of developing liver cancer. The molecular details of why some patients do not respond to standard interferon therapy are not known. This could be partly related either to specific hepatitis C viral strains that show persistent infection in the liver by inhibiting interferon response or defects in host cell response to interferon signaling. We have been able to successfully grow hepatitis C virus outside the liver in cell culture. We demonstrated that this culture is infectious since viral particles derived from HCV-cell culture cause persistent infection in a chimpanzee model. HCV-cell culture models are currently being utilized in our laboratory to understand the antiviral action of interferon alpha and mechanisms of interferon resistance. We have developed alternative therapeutic strategies for chronic HCV infection based on intracellular immunization with genetically engineered recombinant human antibodies targeting to the viral helicase. In the future, our research will lead to an effective gene therapy approach for chronic hepatitis C patients who are not responding to interferon therapy. This will reduce the incidence of hepatocellular carcinomas due to hepatitis C. My laboratory is actively involved in developing oncolytic adenoviruses, which can be used for the treatment of primary and secondary liver tumors. The significance of these accomplishments has been recognized by my peers through the publication records and continuous support from the National Cancer Institute for the laboratory.

Selected Publications:

• Hiramatsu N, Dash S, Gerber MA. Development of an efficient HCV cDNA transfer in vitro. J Viral Hepatitis 4: 61-67 (1997)
• Sullivan D, Dash S, Du H, Hiramatsu H, Aydin F, Koll J, Blanchard J, Baskin G, Gerber MA. Liver directed gene transfer in Non-Human Primates. Human Gene Therapy 8: 1195-1206 (1997)
• Lu H, Ye MQ, Thung S, Gerber MA, Dash S. Hepatitis C virus RNA sequences in cholangiocarcinoma. Chinese J Medicine 113: 1138-1141 (2000)
• Kalkeri G, Garry RF, Dash S. HCV expression induces apoptosis in HepG2 cells. Virology 282(1): 26-37 (2001)
• Dash S, Kalkeri G, McClure HM, Garry RF, Clejan S, Thung SN, Murthy K. Transmission of HCV to a chimpanzee using virus particles produced in an RNA-transfected HepG2 cell culture. J Med Virol (in press). (2001)
• Myung J, Kalkeri G, Garry RF, Dash S. Replication and assembly of Hepatitis C virus from a full-length cDNA clone pMO9.6-T7 using an adenovirus that expresses T7 RNA polymerase. J Virological Methods (in press) (2001)
• Lu H, Sullivan D, Dash S, Gerber MA. Adenovirus induced acute hepatitis in non-human primates after liver-directed gene therapy. Chinese J Medicine (in press) (2001)