1991 - 1995 Post-Doctorate
Tulane University School of Medicine
Department of Pathology
New Orleans, Lousiana

Teaching Specialty:
Molecular virology of hepatitis viruses
Mechanism of immune injury: Hypersensitivity

Director of Pathology Hepatitis Research Laboratory

Post Docs:
Ahkter, Shamin, MBBS
Hernandez, Cynthia
Nangle, Sara
Panebra, Alfredo, Ph.D.
Prabhu, Ramesh, Ph.D.
Sidhartha Hazari, Ph.D

Phone: 504-988-2519

FAX: 504-988-7389

•  Dash S , Kalkeri G, McClure HM, Garry RF, Clejan S, Thung SN and Murthy K. Transmission of HCV to a chimpanzee using virus particles produced in an RNA-transfected HepG2 cell culture. Journal of Medical Virology , 2001; 65:276-281.

•  Kalkeri G, Khalap N, Garry R, Fermin CD and Dash S . Hepatitis C virus protein expression induces   apoptosis   in HepG2 cells. Virology, 2001; 282(1):26-37.

•  Myung J, Khalap N, Kalkeri G, Garry R and Dash S . Inducible model to study negative strand RNA synthesis and assembly of hepatitis C virus from a full-length cDNA clone. Journal of Virological Methods, 2001; 94 (1-2): 55-67.

•  Kalkeri G, Khalap N, Garry R, Fermin C and Dash S . Hepatitis C viral proteins   affect cell viability and membrane permeability. Experimental and Molecular Pathology, 2001 , 71; 194-208.

•  Lu H, Sullivan D, Gerber MA and Dash S . Adenovirus   induced   acute   hepatitis   in non-human   primates   after liver directed gene   therapy. Chinese Medical Journal , 2002: 115(5): 726-731.

•  Gaglio PJ, Liu H, Dash S , Cheng S, Dunne B, Raterree M, baskin G, Blanchard J, Bohm R, theise N and Labrecque   D.   Liver regeneration   investigated   in a non-human primate   model. J Hepatology , 2002, 37(5): 625-632.

•  Sullivan D, Mondelli M U, Curiel DT, Krasnykh V, Mikheeva G, Gaglio P, Morris CB, Dash S and Gerber MA. Construction and characterization of an intracellular single-chain human antibody to hepatitis c virus nonstructural 3 protein. J Hepatology, 2002, 37 (5): 660-668.

•  Qi Z, Kalkeri G, Hanible J, Prabhu R, Bastian F, Garry RF and Dash S . Stem-loop structures   (II-IV) of the 5' untranslated    sequences    are   required   for   the expression of the   full-length hepatitis   C virus genome.   Archives   of Virology, 2003 148(3):449-467.

•  Akhter S, Liu H,   Prabhu R, DeLuca   C, Bastian F, Garry RF, Thung SN and Dash S . Epstein-Barr   virus   and human   hepatocellular   carcinoma.   Cancer Letters, 2003 20;192 (1):49-57.

•  Robert Garry and Srikanta Dash . Proteomics computational analysis suggests that hepatitis C virus E1 and pestivirus E2 envelope glycoproteins are truncated class II fusion protein. Virology, 2003, 307(2):255-265.

•  Prabhu R, Garry RF, Bastian F, Haque S, Regenstein F, Thung SN and Dash S . Interferon alpha-2b inhibits negative strand RNA and protein expression from a full-length HCV1a clone. Experimental and Molecular Pathology 2004, 76 (3): 242-252 .

•  Frank O Bastian, Srikanta Dash and Robert F Garry. Linking chronic wasting disease to scrapie by comparison of Spiroplasma mirium   ribosomal DNA sequences. Experimental and Molecular Pathology , 2004,77:49-56.

•  Prabhu R, Khalap N, Burioni R, Clementei M, Garry RF and Dash S . Inhibition of hepatitis C virus non structural protein, helicase activity and viral replication by a recombinant human antibody clone. Am J Pathology 2004 , 165:1163-1173.

•  Buza N, Lagarde DC, Dash S and Haque S. Langerhans cell histiocytosis: report of a single organ involment in a child . J Cell Mol Med 2004; 8(3): 397-401.

•  Dash S , Prabhu R, Hazari S, Luo G, Bastian F, Garry RF, Zou W, Haque S, Joshi B, Regenstein FG and Thung SN.   Interferon alpha, beta, gamma each inhibits hepatitis C virus replication at the levels of internal ribosome entry site mediated translation. Liver International, 2005 (in press).

•  Mirabel R. S. M. Pai, Ramesh Prabhu, Alfredo Panebra, Sarah Nangle, Frank Bastian, Robert Garry, Krishna Agrawal, Steve Goodbourn and   Srikanta Dash . Activation of interferon stimulated response element in a Huh-7 cell line replicating hepatitis C virus sub-genomic RNA. Intervirology 2005 (in press)

The liver is the largest solid organ of the human body 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 4 th 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.