National Institute of Cholera and Enteric Diseases

Indian Council of Medical Research
Department of Health Research, Ministry of Health and Family Welfare, Government of India
WHO Collaborating Centre for Research and Training on Diarrhoeal Diseases

NICED : Scientists

Dr. Amit Pal

Dr. Amit Pal

Dr. Amit Pal is a Scientist D at the Division of Pathophysiology, National Institute of Cholera and Enteric Diseases (NICED) in Kolkata. He joined NICED in March 1999 as a Senior Research Officer. He did his Bachelors and Masters in Physiology from Kolkata University. He completed his doctoral thesis related to enteric toxins at Division of Microbiology, NICED in 1992. He did his postdoctoral research on molecular characterization of V. cholerae O1 strains under Dr Y Takeda at the Department of Microbiology, Kyoto University from 1992 to 1994. He was a Research Associate at the Department of Molecular Biology at the Indian Institute of Chemical Biology, Jadavpur, Kolkata from 1994 to 1995. He did his next postdoctoral research from 1995 to 1997 at the National Children's Hospital, Tokya, Japan under Dr T. Takeda working on molecular epidemiological studies on E. coli O157:H7 strains. He was a pool officer at the Department of Microbiology, NICED from 1997-1999. Since 1999 he has joined NICED working as a Senior Research Officer at the Division of Pathophysiology. He has been working on the enterotoxigenicity of cholera toxin gene negative V. cholerae non-O1, non-O139 strains. He has three Ph. D students working under him. At present he is working as a visiting researcher at the Department of Molecular Biology Umea University, Sweden. He is also the main partner in the Swedish Foundation for International Cooperation in Research and Higher Education along with Dr Sun Nyunt Wai, Associate Professor, Department of Molecular Biology, Umea University. The STINT project is related to work on molecular pathogenesis of V. cholerae O1 strains.

General Information
Name Dr. Amit Pal
Educational Qualification M.Sc., Ph.D.
Designation Scientist F
Division Pathophysiology
Specialization Molecular Pathogenesis
Date of joining ICMR 5th March 1999
Email : pala@icmr.org.in

Profile

Professional Experience

B. Sc in Physiology from Kolkata University from 1983-86

M. Sc in Physiology from Kolkata University from 1986-88

Ph. D in Physiology at the National Institute of Cholera and Enteric Diseases (NICED), Kolkata, India from 1989-92

Monbusho fellowship at the Department of Microbiology, Faculty of Medicine, Kyoto University, Kyoto, Japan from 1992-1994

Research Associate (CSIR) at the Molecular Biology Laboratory, Indian Institute of Chemical Biology, Kolkata 1994-1995

Science and Technology Associate (STA) at the National Children's Medical Research Center, Tokyo, Japan from (October) 1995-(April) 1996

Pool Officer (CSIR) at NICED, Kolkata from 1997-1999

Research Scientist at the International Medical Research Center of Japan, Tokyo from (July) 1996-(July) 1997

Senior Research Officer at the National Institute of Cholera and Enteric Diseases (NICED), Kolkata, India from 1999-2004

Assistant Director at the National Institute of Cholera and Enteric Diseases (NICED), Kolkata, India from 2004 till date

Research Interests

Studies on enterotoxigenicity of 45-kDa matured and 35-kDa processed forms of hemagglutinin protease purified from a cholera toxin gene negative Vibrio cholerae non-O1, non-O139 strain.

Cholera toxin gene negative Vibrio cholerae non-O1, non-O139 strain PL-21 is the etiologic agent of cholera like syndrome. Hemagglutinin protease (HAP) is one of the major secretary proteins of PL-21. The 45-kDa matured and the 35-kDa processed forms of HAP were purified in the presence and absence of EDTA from culture supernatants of PL-21. Enterotoxigenicities of both forms of HAP were tested in the rabbit ileal loop (RIL), Ussing's chamber and tissue culture assay. The 35-kDa HAP showed hemorrhagic fluid response in a dose-dependent manner in the RIL assay. Histopathological examination of 20 µ g of purified protease treated rabbit ileum showed presence of erythrocytes and neutrophils in the upper part of the villus lamina propria. The 35-kDa HAP, when added to the luminal surface of rat ileum loaded in Ussing's chamber, showed a decrease in the intestinal short circuit current and a cell rounding effect on HeLa cells. The mature 45-kDa form of HAP showed an increase in intestinal short circuit current in Ussing's chamber and a cell distending effect on HeLa cells. These results show that HAP may play a role in the pathogenesis of PL-21.

Pathogenesis and outer membrane vesicle mediated transport of hemagglutinin protease of Vibrio cholerae O1.

Hemagglutinin protease (HAP), a major secreted proteolytic enzyme, was purified from the culture supernatant of Vibrio cholerae O1 strain C6709 after removal of outer membrane vesicles (OMVs) using a single step ion-exchange chromatography. The purified HAP or the culture supernatant of C6709 when injected subcutaneously into suckling mouse, showed distinct in vivo hemorrhagic response and histopathological changes including presence of moderate number of erythrocytes diffusely scattered throughout the skin, capillary necrosis, acute myofiber degeneration and necrosis of muscle layer. However, when the culture supernatant of an isogenic ?hapA strain CHA6.8 was used the hemorrhagic effects in suckling mouse was not detectable.

Themajor protein components, laminin and collagen, of basement membrane comprising of vascular endothelial cells, are degraded by HAP and this may cause destruction of the basement membrane, breakdown of capillary blood vessels and leakage of erythrocytes. Purified HAP or OMVs of C6709 showed cell distending and rounding effects on Int407 cells. In this study we show that the HAP may be exported through OMVs. Confocal microscopical studies indicated that OMVs of C6709 bind to the cell surface of Int407 followed by release of HAP in the cytoplasm.

Projects

  • Intramural: Studies on enterotoxigenicity of a cholera toxin gene negative V. cholerae non-O1, non-O139 strain in an in-vitro rat intestinal mode
  • Extramural Studies on role of accessory toxins in pathogenesis of Vibrio cholerae in animal models. Okayama University Project

Pre-doctoral and Post-doctoral Students

  • Amit Ghosh, Aurelia Syngron, Elluri Sridhar

Memberships

  • Indian Science Congress

Fellowships

  • Pool Officer (CSIR) at NICED, Kolkata from 1997-1999
  • Research Scientist at the International Medical Research Center of Japan, Tokyo from (July) 1996-(July) 1997
  • Science and Technology Associate (STA) at the National Children's Medical Research Center, Tokyo, Japan from (October) 1995-(April) 1996
  • Research Associate (CSIR) at the Molecular Biology Laboratory, Indian Institute of Chemical Biology, Kolkata 1994-1995
  • Monbusho fellowship at the Department of Microbiology, Faculty of Medicine, Kyoto University, Kyoto, Japan from 1992-1994
  • Junior Research Fellow (CSIR) at the Department of Microbiology, National Institute of Cholera and Enteric Diseases, Kolkata from 1989-1992

Publications

2016

  1. Ray T, M. K.Chakrabarti, A.Pal. 2016. Hemagglutinin protease secreted by V. cholerae induced apoptosis in breast cancer cells by ROS mediated intrinsic pathway and regresses tumor growth in mice model. Apoptosis 21:143-154 Pubmed
  2. Ray T, A. Pal. 2016. PAR-1 mediated apoptosis of breast cancercells by V. choleraehemagglutinin protease.Apoptosis21:609-620 Pubmed
  3. Mondal A, R. Tapader, N. S. Chatterjee, A. Ghosh, R. Sinha, H.Koley, D. R.Saha, M. K.Chakrabarti, S. N.Wai,A. Pal. 2016. Cytotoxic and inflammatory responses induced by outer membrane vesicles associated biologically active proteases fromVibrio cholerae. Infect Immun.84:1478-1490 Pubmed
  4. Syngkon, A., S. Elluri, H. Koley, P. K. Romikuntal, D. R. Saha, M. K. Chakrabarti, R. K. Bhadra, S. N. Wai and A. Pal. 2010. Studies on a novel serine protease of a del hapA del prtV Vibrio cholerae O1 strain and its role in hemorrhagic response in rabbit ileal loop model. PloS ONE, 5(9), pii: e13122 Pubmed

2010

  1. Syngkon, A., S. Elluri, H. Koley, P. K. Romikuntal, D. R. Saha, M. K. Chakrabarti, R. K. Bhadra, S. N. Wai and A. Pal. 2010. Studies on a novel serine protease of a del hapA del prtV Vibrio cholerae O1 strain and its role in hemorrhagic response in rabbit ileal loop model. PloS ONE, 5(9), pii: e13122 Pubmed

2008

  1. Saha, S., P. Chowdhury, A. Pal, P. Das, M. K. Chakrabarti. 2008. Role of Yersinia enterocolitica heat-stable enterotoxin (Y-ST) on differential regulation of nuclear and cytosolic calcium signaling in rat intestinal epithelial cells Cell Biol Toxicol. 25: 297-308 Pubmed
  2. Saha, S., P. Chowdhury, A. Pal, M. K. Chakrabarti 2008. Downregulation of human colon carcinoma cell (COLO-205) proliferation through PKG-MAP kinase mediated signaling cascade by E. coli heat-stable enterotoxin (STa), a potent anti-angiogenic and anti-metastatic molecule. J.  Appl Toxicol. 28: 475-83. Pubmed

2006

  1. Ghosh, A., D. R. Saha, K. M. Hoque, M. Asakuna, S. Yamasaki, H. Koley, S. S. Das, M. K. Chakrabarti and A. Pal. 2006. Enterotoxigenicy of Mature 45-kilodalton and Processed 35- kilodalton forms of Hemagglutinin Protease Purified from a cholera toxin gene negative Vibrio cholerae non-O1, non-O139 strain. Infect. Immun. 74: 2936-2946. Pubmed

2003

  1. Hoque, K. M., A. Pal and M. K. Chakrabarti. 2003. Translocation of protein kinase C with IP3 mediated calcium mobilization by heat stable enterotoxin of Vibrio cholerae non-O1 in isolated rat enterocytes. Int. J. Med. Microbiol. 293: 1-8. Pubmed

2002

  1. Khan, A., S. Yamasaki, T. Sato, T. Ramamurthy, A. Pal, S. Dutta, N. R. Chowdhury, S. C. Das, A. Sikdar, T. Tsukamoto, S. K. Bhattachrya, Y. Takeda and G. B. Nair. 2002. Prevalence and genetic profiling of virulence determinants of non-O157 Shiga toxin-producing Escherichia coli isolated from cattle, beef, and humans, Calcutta, India. Emerg. Infect. Dis. 8: 54-62. Pubmed

2001

  1. Hoque, K. M., A. Pal, G. B. Nair, S. Chattapadhyay and M. K. Chakrabarti. 2001. Evidence of calcium influx across the plasma membrane depends upon the initial rise of cytosolic calcium with activation of IP3 in rat enterocytes by heat-stable enterotoxin of Vibrio cholerae non-O1. FEMS. Microbiol. Lett. 196: 45- 50. Pubmed
  2. Pal, A., K. M. Hoque, S. K. Niyogi, T. Ramamurthy, G. B. Nair and M. K. Chakrabarti. 2001. Rise in intracellular free calcium in HeLa cells infected with aggregative Klebsiellia pneumoniae strains isolated from cases of diarrhoea. Ind. J. Med. Res. 113: 1-4. Pubmed

1999

  1. Pal, A., P. K. Saha, G. B. Nair, S. Yamasaki, T. Takeda, Y. Takeda, S. K. Bhattacharya and T. Ramamurthy. 1999. Clonal analysis of non-toxigenic Vibrio cholerae O1 associated with an outbreak of cholera. Indian J. Med. Res. 109: 208-11. Pubmed
  2. Pal, A., S. Ghosh, T. Ramamurthy, S. Yamasaki, T. Tsukamoto, S. K. Bhattacharya, G. B. Nair and Y. Takeda. 1999. Shiga-toxin producing Escherichia coli from healthy cattle in a semi-urban community in Calcutta, India Indian J. Med. Res. 109: 208-11. Pubmed

1996

  1. Takeda, T., K. Yoshino, T. Ramamurthy, H. Uchida, E. Matsuda and A. Pal. 1996. Molecular epidemiology of infections with enterohemorrhagic E. coli O157 in Japan. Japan J. Bacteriol. 51: 1037-1042. Pubmed
  2. Singh, D. C., A. Tikoo, A. Pal and S. C. Sanyal. 1996. Cholera toxin, zonula occludens and accessory cholera enterotoxin gene negative V. cholerae non-O1 strains produce new cholera toxin. Current Science. 70: 1041-1043.

1995

  1. Kurazono, H., A. Pal, P. K. Bag, G. B. Nair, T. Karasawa, T. Mihara and Y. Takeda. 1995. Distribution of genes encoding cholera toxin, zonula occludens toxin, accessory cholera toxin and El Tor hemolysin in V.cholerae of diverse origins Microb. Pathog. 18: 231-235. Pubmed

1994

  1. Nair, G. B., T. Shimada, H. Kurazono, J. Okuda, A. Pal, T. Karasawa, T. Mihara, Y. Uesaka, Y. Shirai, S. Garg, P. K. Saha, A. K. Mukhopadhyay, A. K. Ohashi, T. Tada, J. Nakayama, S. Fukushima, T. Takeda and Y. Takeda. 1994. Characterization of phenotypic, serological and toxigenic traits of V.cholerae O139 Bengal. J. Clin. Microbiol. 32: 2775-2779. Pubmed

1993

  1. Ramamurthy, T., A. Pal, S. K. Bhattacharya, G. B. Nair, H. Kurazono, S. Yamasaki, T. Takeda and Y. Takeda. 1993. Detection of cholera toxin gene by the polymerase chain reaction in stool specimens: Comparison with the CT bead ELISA and with culture methods for laboratory diagnosis of cholera. J. Clin Microbiol. 31: 3068-70. Pubmed
  2. Ramamurthy, T., S. Garg, R. Sharma, S. K. Bhattacharya, G. B. Nair, T. Shimada, T. Takeda, T. Karasawa, H. Kurazono, A. Pal and Y. Takeda.1993. Emergence of novel strain of Vibrio cholerae with epidemic potential in Southern and Eastern India. Lancet 341: 703-704. Pubmed

1992

  1. Bhattacharya, S. K., M. K. Bhattacharya, T. Ramamurthy, A. Pal, P. K. Bag, T. Takeda, T. Shimada and S. Chakraborti. 1992. Acute secretary diarrhoea caused by V. cholerae non-O1 which does not produce cholera like and heat-stable enterotoxins. J. Diarrhoeal. Dis. Res. 10: 161-163. Pubmed
  2. Pal, A., T. Ramamurthy, R. K. Bhadra, T. Takeda, T. Shimada, Y. Takeda, G. B. Nair, S. C. Pal and S. Chakraborti. 1992. Reassessment of the prevalence of heat-stable enterotoxin among environmental V.cholerae non-O1 isolates using a NAG-ST DNA probe. Appl. Environ. Microbiol. 58: 2485-2489. Pubmed
  3. Ramamurthy, T., A. Pal, M. K. Bhattacharya, S. K. Bhattacharya, A. Chowdhury, Y. Takeda, T. Takeda, S. C. Pal and G. B. Nair. 1992. Serovar, biotype, phagetype, toxigenicity and antibiotic susceptibility patterns of V.cholerae isolated during two consecutive cholera seasons (1989-92) in Calcutta. Indian J. Med. Res. 95: 125-129. Pubmed
  4. Ramamurthy, T., A. Pal, S. C. Pal and G. B. Nair. 1992. Taxonomical implications of emergence of high frequency of occurrence of 2,4, diamino-6-7-diisopropylpteridine-resistant strains of V.cholerae from clinical cases of cholera in Calcutta, India. J. Clin. Microbiol. 30: 742-743. Pubmed
  5. Pal, A., T. Ramamurthy, A. R. Ghosh, S. C. Pal, Y. Takeda and G. B. Nair. 1992. Virulence traits of Aeromonas strains in relation to species and source of isolation. Zentralblatt fur Bakteriologic Mikrobiologie and Hygiene. 276: 418-428. Pubmed

1990

  1. Ramamurthy, T., A. Pal, G. B. Nair, S. C. Pal, T. Takeda and Y. Takeda. 1990. Experience with toxin Bead-ELISA in cholera outbreak. Lancet. 336: 375-376. Pubmed

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