Mirajul Hoque Kazi, Ph.D.

Designation: Scientist & Ramalingaswami Fellow

Previous Positions:

Instructor of Medicine, John Hopkins University School of Medicine, Baltimore, MD, USA.
Postdoctoral Fellow, Johns Hopkins University
Postdoctoral Fellow, Yale University School of Medicine, New Haven, CT, USA.

Contacts

E-mail: kmh_niced@yahoo.co.in
Mobile: +91-801-722-6735
Office: +91-33-2363-3853/3373/3374
Fax: +91-33-2363-2398/2370-5066

Other homepage

http://myprofile.cos.com/kmhoque

Professional Experience & Research Interest:

Dr. Mirajul H. Kazi has recently joined as a Scientist & Ramalingaswami Fellow at the Molecular Pathophysiology Division. He obtained his doctoral degree in Gastrointestinal Physiology in 2003 from Jadavpur University, Kolkata. His Ph.D. work was done at NICED in Pathophysiological mechanisms of action of bacterial toxin in diarrhea. In 2003, he moved to the Digestive Diseases department, Yale University School of Medicine, New Haven, CT, USA for initial postdoctoral training with Prof. Henry Binder. While working at Yale, Dr. Kazi was the first scientist in the field to show the unequivocal physiologic evidence of anti-diarrheal mechanism of Zinc [Am J Physiol Gastrointest Liver Physiol. 2005 May;288(5):G956-63, Gastroenterology. 2006 Jun;130(7):2201-5]. This study advanced the use of zinc together with oral rehydration therapy for the treatment of acute diarrhea. He then moved to the gastroenterology division of the Johns Hopkins University headed by Prof. Mark Donowitz to work on the regulation of transport proteins involved in the pathobiology of diarrheal diseases. During his stay at Hopkins, he was independently driven to investigate a new mechanism of epithelial Cl- secretion involving Epac (Exchange protein directly activated by cAMP) which forms the basis of his current and independent research program here at NICED. He is currently investigating the role of Epac in epithelial ion transport (transcellular vs. paracellular) and tight junction function and its role in diarrhea. This is an emerging area that should allow to provide new insights understanding of intestinal ion transport. Preliminary findings indicate that the Protein kinase A (PKA) and Epac contribute concurrently (but separately) to cAMP and thus cholera toxin stimulated Cl- secretion via a non-CFTR Cl channels. (J Gen Physiol. 2010 Jan; 135 (1):43-58). This work would challenge whether CFTR is the only Cl channel involved in secretory diarrhea. Clearly this new dimension of epithelial transport will help to understand how intestinal ion transport is being regulated both normally as part of normal digestive physiology and how this becomes abnormal in diarrheal diseases. In future, using multiple approaches; knock down of specific signaling protein(s) by lenti siRNA, and over expression of dominant negative or constitutively active proteins, electrophysiological study in Ussing chamber and in patch clamp, two photon technology, Real Time PCR, his group will explore a better understanding of new targets involved in restitution of transport process and barrier function and the development of agents that specifically modify these targets would be of great value in alleviating patient suffering in gastrointestinal disorders such as diarrhea.

His other research interests include the interaction of enteric bacterial pathogens with host intestinal epithelial cells and the mechanisms by which epithelial function is altered as a result of these infections. Specific physiological functions that are being investigated include tight junction barrier function delineating the signal transduction pathways and membrane trafficking events of specific transport protein and protein-protein interaction underlying these effects. He is also interested in searching for super-super ORS for the treatment of diarrhea with the expectation of safety, selectivity of action and low cost.

Group Members

Awards & Recognitions

 
Editorial Activities (Peer review activities)

1. American Journal of Physiology
2. J Experimental Physiology
3. Gastroenterology Insights
4. World Journal of Physiology
5. Journal of Physiology

Funded Grant

1. Dept. of Biotechnology, Govt. of India sponsored Ramalingaswami Fellowship Grant of ~70 lakhs for 5 years (D.O.NO.BT/HRD/35/02/2006). (Role: Principle Investigator)
2. NIH Training Grant: 2T32DK00763221
3. NIH sponsored Pilot grant: Role of a non-CFTR Chloride Channel in Diarrhea & Digestive Diseases. Role: Principal Investigator.

Publications

1. Mendoza S., Hoque KM, Shaoguang Wu, Cynthia L. Sears, Xuhang Li., Isabel Romero-Clavo, Nicholas C. Zachos, Olga Kovbasnjuk, Mark Donowitz, Rakhilya Murtazina (2011). NHERF1 knockout mice have abnormal tight junction and increased severity of B. fragilis enterotoxin related colitis associated with reduced expression of claudin 2 and 4 Gastroenterology, 140(5), S-697.
    
2. Chatterjee T; Mukherjee D; Dey, S; Pal, A; Hoque K.M; and Chakrabarti P; (2011). Accessory cholera enterotoxin, Ace, from Vibrio cholerae: studies on structure, unforlding and virstatin binding. Biochem; J. 50(14): 2962-72.
    
3. Hoque K.M*., Owen wood., van Rossum D.B., Nickolas C. Zachos., Chen L. and Tse, C.M., (2010). Epac1 mediates Protein Kinase A independent mechanism of forskolin (FSK) stimulated Cl secretion in T84 cells. J. Gen. Physiol. 135(1): 43-58. *Co-corresponding author.
    
4. Chen L., Jennifer W. Tse, Hoque K.M., P. Muthu, George PH Leung and Chung-Ming Tse., (2010). Nucleobase Transport Systems of Intestinal HT-29-19A Cells: An adenine specific nucleobase transport and a broadly selective nucleobase transport mediated by ENT2 (revision in American Journal of Physiology).
    
5. Hoque K.M*, Sarker, R., Guggino S.E. and Tse, C.M. (2009) A New Insight into Pathophysiological Mechanism of Zinc in Diarrhea. Ann. N. Y. Acad. Sci. 1165: 279-284. * Corresponding author.
    
6. Hoque K.M., Linxi Chen, George PH Leung and Chung-Ming Tse (2008). A Novel purine-selective nucleobase/nucleoside transporter in PK15NTD cells. Am J Physiol Regul Integr Comp Physiol. 294(6): R1988-95.
    
7. Crane JK and Hoque KM. (2008). “Zinc for Infectious Diarrhea in Developed Countries: Should we be Sprinkling our own Lawns?" J Pediatr Gastroenterol Nutr 146(5): 484-485.
    
8. R. Murtazina, O. Kovbasnjuk, N. Zachos, X. Li, Y. Chen, A. Hubbard, B. Hogema, D. Steplock, U. Seidler, Hoque, K.M., M. Tse, H. De Jonge, E. Weinman, and M. Donowitz (2007). Tissue specific regulation of sodium-proton exchanger isoform 3 (NHE3) activity in Na/H exchanger regulatory factor 1 (NHERF1) null mice: cAMP inhibition is differentially dependent on NHERF1 and exchange protein directly activated by cAMP (EPAC) in ileum versus proximal tubule. J Biol Chem. 282(34): 25141-51.
    
9. Chen, L., Hoque K.M., Tse, C.M. (2007). Characterization of Na/H exchange systems in immortalized rat caput epididymal (RCE) cells. The FASEB Journal 21(6) A1336.
    
10. Hoque K.M. & Binder H. J. (2006). Zinc in the treatment of acute diarrhea: Current status and Assessment. Gastroenterology 130: 2201-2205.
     
11. Ghosh A., Saha, D.R., Hoque K.M., Saha, D.R., Asakuna, M., Yamazaki, S., Koley H., Das S. S., and Chakrabarti, M.K. (2006) Enterotoxicity of 45kDa matured and 35-kDa processed forms of hemagglutinin protease purified from a cholera toxin negative V. cholerae non-O1.non-O139 strain. Infect. Immun. 74: 2937-2946.
     
12. Hoque, K. M., Rajendran, V.M., Binder, H. J. (2005). Zinc inhibits cAMP-stimulated Cl secretion via basolateral K channel blockade in rat ileum. Am J. Physiol-Gastrointest Liver Physiol 288: G956-G963.
     
13. Chakrabarti M. K., Hoque K.M., Chakrabarty M., Mahalanabish D. (2005). Effect of reducing sodium or glucose concentration in a hypo-osmolar ORS (Oral Rehydration Salts) on absorption efficiency: Marker perfusion in rat jejunum. Dig. Dis. Sci. 50(2): 241-245.
     
14. Hoque, K. M., Saha, S., Chakrabarti, M. K. (2004). Role of nitric oxide induced store operated calcium influx in the mechanism of action of NAG-ST produced by Vibrio cholerae non-O1 in isolated rat enterocytes. Toxicology 201: 95-103.
     
15. Hoque, K. M., Pal, A., Chakrabarti, M. K. (2003). Translocation of Protein Kinase C with IP3 induced Calcium mobilization by heat-stable enterotoxin of Vibrio cholerae non-O1 in rat enterocytes. Int. J. Med. Microbiol. 293 (6): 413-420.
     
16. Hoque, K. M., Pal, A., Nair, G. B., Chattapadhyay, S. and Chakrabarti, M. K. (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 (1): 45-50.
     
17. Pal, A., Hoque, K. M., Neiyogi, S. K., Ramamurthy, T., Nair, G. B. and Chakrabarti. (2001). M. K. Rise in intracellular free calcium in HeLa cells infected with aggregative Klebsiellia pneumoniae strains isolated from cases of diarrhoea. Indian J. Med. Res. 113: 1-4.
     
18. Khaled, M. A., Mahalanabis, D., Jana, S., Chowdhury, A., Bhattacharya, M., Chakrabarti, M. K., Hoque, K. M. and Das, K. P. (2001). Zinc Supplementation and Lipid per-oxidation in children with measles and pneumonia. The FASEB Journal 15: A610.
     
19. Bhattacharya, J., Samanta, S., Hoque, K. M., Mukherjee, A. and Chakrabarti, M. K. (2001). Escherichia coli heat stable enterotoxin receptors and guanylyl cyclase activity in the intestinal brush border membrane of hamsters and guinea pig. Indian J. Med. Res. 113: 5-10.

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