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Expert Profile

Dr SK Panda

Professor of Pathology,
AIIMS, New Delhi

Education:

M.B.B.S: Utkal University (1977)
M.D. (Pathology): All India Institute of Medical Sciences (1981)
Post Doc. Fellow: London School of Tropical (Molecular Virology)
with Prof. Arie Zuckerman: Medicine and Hygiene (1987)

Field of Specialization: Pathology (Liver Pathology), with special interest in molecular virology of hepatitis viruses.

Research Experience:

Dr Panda has 18 years research experience and is leading one of the major groups in Asia working on viral Hepatitis and has mostly contributed papers on the hepatitis viruses B, C and E.

Hepatitis E virus (HEV):

He developed the first Rhesus monkey model for enteric hepatitis virus (HEV) which now has made possible HEV research in many developing countries (Hepatology 1989; J.Med. Virol. 1992: 32: 263-270). In most other types of viral hepatitis the major problem that scientists face is the lack of an animal model which can be used to test vaccines, therapy, diagnostic tests and drugs as most of these grow in chimpanzees, not available to scientists in many parts of the world. Afterwards his group characterised the transmission pattern, the disease development and replication of the virus in liver cells using strand specific PCR (J.Med.Virol. 1994, 42: 237-240,). In the meantime they had shown the epidemiological pattern of this disease and demonstrated HEV as the major cause of sporadic acute hepatitis in India and associated with more than 27% of the acute liver failure seen in this country (J.Med.virol. 1994, 42:133-137; J. Med.virol. 1995; In Press).
Their group has cloned the HEV and expressed all the viral genes (ORF1, ORF2 and ORF3) (J.Clin.Microbiol. 1995; 33; 2653-2659, J. Med virol, 2000, 60, 275-283) and eukaryotic cells (J. Virology. 1996; 70, 207-216, & J. Virology.1997; 71, 9045-9053)and non structural proteins of the virus (ORF1- J. Med virol, 2000, 60, 275-283)). They have also produced for the first time an infectious cDNA clone of HEV (J.Virol, 2000,in press). The in-vitro produced RNA transcripts on transfection to HepG2 cells undergo replication, transcription and translation. All the viral proteins could be metabolically labelled and immuno precipitated from RNA transfected cells. The culture supernatant of such cells are infectious to experimental animals (J.Virol, 2000,74,2430-2437). They have developed a diagnostic test for acute HEV infection by detection of anti HEV-IgM in patients' serum and demonstrated protracted viraemia in patients (Gastroenterol. 1995; 108; 225-230). They are working towards developing a vaccine for the HEV by use of naked DNA immunization method/ immunisation expressed proteins.

He is presently investigating the transcriptional and replicational regulation of the HEV genome by use of infectious RNA and has identified the sites for replication initiation by RdRp-RNA interaction (under publication). In recognition of this work, the Council of Scientific and Industrial Research (CSIR) has awarded him the Shanti Swarup Bhatnagar prize. This award is regarded as the highest scientific honour in India.

Hepatitis B virus (HBV):

He has worked on several areas of hepatitis B virus infection like epidemiology, vaccine trials, receptor identification, carcinogenesis, drug development. This work can be briefly summarized as follows.
Epidemiology:

He and his colleagues were the first in India to carry out a large scale epidemiological study of maternal-child transmission of hepatitis B virus in India (J.Med.Virol. 1986:21:137-145). This was followed by the evaluation of both plasma derived and yeast recombinant vaccine in India (J.Med.Virol. 1991; 35:297-302). These studies have contributed significantly to a policy of vaccination of HBV in India. In addition they have studied the epidemiology of HBV infection in various clinical conditions and population settings (Lancet 1986: 919-920; J. Gastroenterol. & Hepatol. 1987; 2:333-345; Tropical Gastroenterol 10:106-110; J. Gastroenterol. & Hepatol. 1989; 4:345-352).

Receptor Identification:
The mode of attachment of the hepatitis B virus to liver cells is still being actively pursued as this may provide insight into preventing the virus entry into the liver cells. Both direct attachment of the virus to liver cells and polymerised albumin mediated attachment have been suggested to be the possible mechanisms. His group has convincingly showed that polymerised albumin mediated attachment is insignificant in HBV attachment to liver cells (Hepatology 1990; 13:134-142; J. Gastroenterol & Hepatol. 1990; 5:16-24). They also identified and isolated the receptor for the pre-S1 region of the HBV envelope protein as a 34 kilodalton protein (J.Med.Virol. 1992:37:116-121) which has now been shown to be endonexin.
Immunology and Vaccine development:

Dr Panda along with Dr. K.V.S. Rao from the ICGEB (International Centre for Genetic Engineering and Biotechnology, New Delhi) have generated information on immune response to hepatitis B virus infection and developed a Self-oligomerising peptide candidate vaccine for which we have applied for international patent. In addition, using synthetic peptides to pre-S1, pre-S2 and S regions of HBV envelope protein they investigated the dynamics of the appearance and disappearance of both humoral and cellular immune response at various stages of HBV infection. From this they concluded that the acute liver damage is mediated by immune response to envelope protein whereas the chronic liver damage is due to CTL response against the core protein (J. Clin. Exp. Immunol. 1992: 90: 194-198). In the mean time they detected the self-oligomerisation of a synthetic envelope peptide S (aa.124-147) and identified both B cell and more than two T cell epitopes on this peptide using various derivitised peptides and overlapping peptides. This peptide was found to be immunogenic with alum as an adjuvant (J. Immunol. 1992: 148,4006-4011, 148:4012-4020; 149:2082-2088; Vaccine 1992: 10: 204-208; 1993: 11: 366-371; Immunology 1993: 79: 362-367).

Hepatocellular carcinoma:

The association of hepatitis B virus with hepatocellular carcinoma is well known. However, no one mechanism explains all cases of carcinogenesis. They investigated the HBV in hepatocellular carcinoma tissue using multiple overlapping polymerase chain reaction covering the whole viral genome. They identified a small fragment of surface antigen genome in 92% of hepatocellular carcinoma. On functional analysis it was found to be a new undescribed transactivator (J. Gen. Virol.1994, 75,327-334, J.Hepatol 1993, 19, 319-320). They then carried out mutational analysis of this fragment and identified the very region responsible for transcriptional transactivation. On further analysis they observed this protein to be a universal transactivator acting through direct DNA binding (J.Med.virol. 2000, in press).

Method of Screening for anti hepadna drugs:

The duck hepatitis B virus resembles and belongs to the same family as the hepatitis B virus. My group cloned the Indian strain of duck hepatitis virus by a method using microquantity serum method developed by us (Nucleic Acid Research, 1992: 20: 2023). The virus has been entirely sequenced by our group (Gene Bank accessions no. X74623). Using this virus I and Dr. Raj Mehrotra (KGMC, Lucknow) developed a chronic DHBV carrier Pekin duck colony and analysed a few potential plant derived anti hepadnavirus drugs like Phyllanthus amarus, Phyllanthus maderaspatensis, Picrorhiza kuroo, Eclipta alba (J. Med. Virol. 1993: 40: 53-58 & 41: 275-281).

Hepatitis C virus (HCV):

Our group has developed a RT-PCR assay for HCV and has demonstrated that it is responsible for a large number of cases of chronic hepatitis in India. We have also demonstrated the inefficiency of the available commercial ELISA tests to detect HCV infection in India (J. Gastroenterol. Hepatol 1992, 7,393-395. J.Med.Virol 1994: 44,176-179). This is possibly due to the wide strain variation shown all over the world. To avoid this problem we have cloned the core, envelope and part of the non structural region of the virus from several Indian isolates (EMBL acc. no. X91297-91307 & X91416-91423). In sequence analysis we could identify a new subtype of HCV in Indian patients. This has been labelled as type 3g (J. Med. Virol.1996, 48, 191-196). We have developed a diagnostic assay system based on synthetic peptides, which is in routine use for screening blood donors and liver disease patients for HCV infection at the AIIMS. We have worked extensively on the epidemiology of hepatitis C virus infection in India (J. Med. Virol,1997,51: 167-174 ). For this work, we have been awarded the International Ranbaxy Science Foundation Award on applied medicine. In addition we were the first ones to detect HGV infection in India (Lancet, 1996; 348: 1319) and genotype the strains from India (J.Hepatol. Gastroenterol. 1998; In press). We have also developed a PCR based diagnostic test for detection of yersinia pestis specific genes in historical material (Current Science, India 1996, 71,794-799). They have cloned, sequenced and expressed the f1 and pla gene of Y.pestis, which are immuno reactive. These have been used to develop serological tests for plague.

Other Activities:
I have been characterising the morphological pattern of liver diseases in India. More specifically related to:
  • Viral hepatitis- acute, sub-acute, fulminant and chronic hepatitis.
  • Aetiology of cholestatic hepatitis.
  • Morphological changes in portal venous outflow tract obstruction.
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