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Name:
Dr. Neeraj Khatri
Expertise:
Veterinary Sciences & Animal Husbandry B.V.Sc. & A. H M. V. Sc. (Veterinary Medicine), PhD (Biotechnology)

Contact Address:

Senior Scientist & In-charge,

Assistant Professor, AcSIR

Experimental Animal Facility,

Institute of Microbial Technology,

(CSIR, Government    of INDIA),

Sector 39-A, CHANDIGARH - 160 036, INDIA
Phone: 91-172-2690694 Ext. 341(O), 522 (R), Mobile: 09417371055
FAX: 91-172-2690585/2690632
E-mail: neeraj@imtech.res.in, khatrineeraj28us@gmail.com


Write-up of research and development interests/focus, past and present goals:

The primary interest of my research group is to develop animal models of various disease conditions and to study the therapeutic efficacy of test compounds against these models. During the last few years, we have been studying the therapeutic role of plasma gelsolin (pGSN) in different diseases. Several reports in literature suggest that exogenous administration of GSN leads to improvement of condition in sepsis and burn in various rodent models advocating the need for “gelsolin replacement therapy”. 

I. Analgesic and anti-inflammatory properties of gelsolin in acetic acid-induced writhing, tail immersion and carrageenan-induced paw edema in mice

This study was planned to examine the analgesic and anti-inflammatory activity of exogenous gelsolin in mice models of pain and acute inflammation. Administration of gelsolin not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects but also exhibited analgesic property intail immersion test in mice as compared to placebo-treated mice. Additionally, the anti-inflammatory function of gelsolin was confirmed in the carrageenan induced paw edema where the inflammation was measured by vernier caliper and fluorescent tomography imaging. Interestingly, carrageenan groups pretreated with gelsolin or the anti-inflammatory drug diclofenac sodium showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Analysis of cytokines and histo-pathological examinations of tissue revealed that administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6.

II. Role of gelsolin and its truncated versions in improving type II diabetes in mice 

In this study we reported for the first time that pGSN values decline in type II diabetic humans and mice models. Administration of recombinant pGSN and its truncated forms could decrease blood sugar levels in diabetic mice as tested by oral glucose tolerance test when treated daily for one week. Results of this study propose that gelsolin level monitoring and replacement of F-actin severing capable gelsolin(s) should be considered in the management of diabetes.

III. Therapeutic role of thrombolytic proteins in thrombosis / stroke models of mice and rats

This ongoing project is part of IMTECH’s BIODISCOVERY project in collaboration with Dr. Girish Sahni, DG, CSIR (for testing streptokinase and its derivatives in animals) and with Dr. Ashish (for testing efficacy of gelsolin). In CSIR-IMTECH, Dr. Sahni has done extensive research for the discovery of new and improved versions of thrombolytic drugs (Streptokinase and its mutants) leading to development of novel clot busters with clot specific and anti-thrombotic properties. 

Gelsolin levels have been reported to decrease in many diseases and exogenous administration leads to improvement of conditions in rodent models of sepsis, burn, diabetes, acute inflammation etc. It is also showing anti-thrombotic activities in preliminary animal experimentations done by us in IMTECH. 

Objectives of the projects: 

Standardization and characterization of  animal models of thrombosis and middle cerebral artery occlusion (MCAO) model of stroke and Insight into the molecular mechanism and patho-physiology of stroke using state of the art animal  MRI

Evaluation of the efficacy of thrombolytic drugs developed in IMTECH (new derivatives of SK / tPA / gelsolin) to study the thrombolytic effect of new improved bio-generics of streptokinase / tPA / gelsolin



Significant recognition: Awards, fellowships, international funding of distinction, technologies transferred/licensed etc.:

  • Awarded Raman Research Fellowship 2015-16 by Council of Scientific and Industrial Research (CSIR), Government of India
  • Contributed in an institutional research project which was licensed to Nostrum Pharmaceuticals, USA, on 23 February, 2009 to develop and commercialize Caerulomycin A, and its proprietary derivatives and analogues (“Caerulomycin”) for their novel indication of immuno-suppression. The license was obtained from Institute of Microbial Technology (IMTECH), Chandigarh.


Papers Presented in National/International Conferences:

 

  • Khatri N, Gandhi S and Suri CR (2009).   Refinement and reduction in use of animals: Use of egg yolk antibodies for development of enzyme-linked immunoassay for morphine. Poster presented in National Symposium on “Animal Models in Biomedical Research: Ethical & Welfare Issues, CDRI, Lucknow,  February 25-26, 2009, p. 132.

  • Khatri N, Nichani AK, Sharma RD and Khatri M (1999). Attempts to preserve in vitro propagated Theileria annulata schizonts at 4*C in media containing gelatin. In proceeding: International conference on “ Sustainable Animal Production Health and Environment – Future Challenges”, CCS HAU, Hisar, 24-27 November, 1999, p. 129.

  • Singh S, Nichani AK, Khatri N, Sharma RD, Malhotra DV and Aneja DR (1999). Antibody titres in animals vaccinated with the Theileria annulata (Hisar) cell culture vaccine under field conditions. In proceeding: XVII Annual convention of Indian Society for Veterinary Medicine, Orissa University of Agriculture & Technology, Bhubneswar, 5-7 February, 1999, p.11-12.

  • Nichani AK, Manuja A, Khatri N, Singh S, Beniwal RK and Sharma RD (1998). Epidemiology and control of tropical theileriosis in Northern India. In proceeding: Fifth International Veterinary Immunology Symposium, PAU Ludhiana, November 8-13, 1998 p.149.

Radio Talks:

  • Pashoun me muh va khur rog avam roktham. (In Hindi) Delivered at All India Radio, Udaipur, Rajasthan.
  • Varsha ritu me hone vali bimariyan avam roktham. (In Hindi) Delivered at All India Radio, Hisar, Haryana.

Selected list of Publications and Patents:

Papers Published

1.   Ravindra Gujar, Neeraj Maurya, Vinod Yadav, Mamta Gupta, Saurabh Arora, Neeraj Khatri and Pradip Sen (2016). c-Src suppresses dendritic cell antitumor activity via T cell Ig and mucin protein-3 receptor. Journal of Immunology (in press). 

2.   Gautam A, Nanda JS, Samuel JS, Kumari M, Priyanka P, Bedi G, Nath SK, Mittal G, Khatri N, Raghava GP. Topical Delivery of Protein and Peptide Using Novel Cell Penetrating Peptide IMT-P8. Sci Rep. 2016 May 18;6:26278. doi: 10.1038/srep26278.

3.  Baindara P, Chaudhry V, Mittal G, Liao LM, Matos CO, Khatri N, Franco OL, Patil PB, Korpole S. Characterization of the Antimicrobial Peptide Penisin, a Class Ia Novel Lantibiotic from Paenibacillus sp. Strain A3. Antimicrob Agents Chemother. 2015 Nov 16;60(1):580-91. doi: 10.1128/AAC.01813-15.

4.   Gupta AK, Parasar D, Sagar A, Choudhary V, Chopra BS, Garg R, Ashish, Khatri N. Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice. PLoS One. 2015 Aug 14;10(9):e0135558. doi: 10.1371/journal.pone.0135558. eCollection 2015.

5.   Mahajan S, Saini A, Chandra V, Nanduri R, Kalra R, Bhagyaraj E, Khatri N, Gupta P. Nuclear receptor Nr4a2 promotes alternative polarization of macrophages and confer protection in sepsis. J Biol Chem. 2015 Jul 24;290(30):18304-14. doi: 10.1074/jbc.M115.638064. Epub 2015 May 7.

6.   Khatri N, Sagar A, Peddada N, Choudhary V, Chopra BS, Garg V, Garg R, Ashish. Plasma gelsolin levels decrease in diabetic state and increase upon treatment with F-actin depolymerizing versions of gelsolin. J Diabetes Res. 2014;2014:152075. doi: 10.1155/2014/152075. Epub 2014 Nov 12.

7.  Singla AK, Gurram RK, Chauhan A, Khatri N, Vohra RM, Jolly RS, Agrewala JN. Caerulomycin A suppresses immunity by inhibiting T cell activity. PLoS One. 2014 Oct 6;9(10):e107051. doi: 10.1371/journal.pone.0107051. eCollection 2014.

8.  Singla AK, Gurram RK, Chauhan A, Khatri N, Vohra RM, Jolly RS, Agrewala JN. Cerulomycin Caerulomycin [corrected] A: a potent novel immunosuppressive agent.  Transplantation. 2014 May 15;97(9):e57-9. No abstract available. Erratum in: Transplantation. 2014 Nov 27;98(10):e88.

9.  Khatri N, Peddada N, Chopra BS, Gupta AK, Garg R, Ashish and Garg V. Plasma gelsolin levels in healthy mice as a function of age and gender. Journal of Scientific and Innovative Research. 2014; 3(5): 475-477.

10. Khatri N, Ashish and Garg V. Reviewing biomedical role of gelsolin. The Pharma Innovation – Journal. 2014; 3(10): 16-20.

11. Peddada N, Sagar A, Rathore YS, Choudhary V, Pattnaik UB, Khatri N, Garg R, Ashish. Global shapes of F-actin depolymerization-competent minimal gelsolins: insight into the role of g2-g3 linker in pH/Ca2+ insensitivity of the first half. J Biol Chem. 2013 Sep 27;288(39):28266-82. doi: 10.1074/jbc.M113.463224. Epub 2013 Aug 12.

12. Khatri N, Nichani AK, Sharma RD, Khatri M and Malhotra DV.Effect of vaccination in the field with the Theileria annulata (Hisar) cell culture vaccine on young calves born during the winter season. Veterinary Research Communications. 2001; 25 (3):179-88.

13. Singh S, Nichani AK, Khatri N, Manuja A, Sharma RD and Malhotra DV. (2001). Impact of field vaccination with a Theileria annulata schizont cell culture vaccine on the epidemiology of tropical theileriosis. Veterinary Parasitology.2001;101(2):91-100.

14. Khatri N, Nichani AK, Sharma RD and Khatri M (2000). Suitability of gelatin for preservation of in vitro propagated Theileria annulata schizonts. Indian Veterinary Journal. 2000; 77:479-482.

   
 ·Extension Articles:

 

  • Khatri N, Nichani AK, Khatri M and Sharma RD (1998). Bovine tropical theileriosis and its control in India. Livestock International 2(1): 4-6.

  • Khatri N, Khatri M, Nichani AK and Sharma RD (1998). Bovine babesiosis and its control in India. Livestock International 3(5): 4-7.

  • Khatri N, Khatri M and Nichani AK (1997). Common diseases of new born calves and their prevention. Haryana Farming. XXVII (December, 1997): 21-22.

Present group members:

  • Dr. Sachin S Raut, Scientist
  • Sh. S. S. Bawa, Senior Technical Officer
  • Sh. Bhupinder Singh Chopra, Technical Assistant
  • Sh. Vinod Kumar, Lab Attendant
  • Sh. Ashok Kumar Gupta, Project Assistant
  • Sh. Surendra Kumar Prajapat, PhD student

Past group members:

  • Sh. Devraj Prashar, Project Assistant
  • Ms. Garima Mittal, Project Assistant
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