Sanjay Jain, M.D.

Sanjay Jain, M.D., Assistant Professor of Pediatrics

sjain5@jhmi.edu

Research interests: My research interests include pathogenesis of central nervous system (CNS) tuberculosis, comparing Mycobacterium tuberculosis genotypic requirements across animal models and in the development of imaging technology for real-time evaluation of M. tuberculosis infection in animal models and human beings.

Recent work: We have developed both in vitro and in vivo murine models to study CNS invasion by M. tuberculosis. Using genotypically defined M. tuberculosis transposon mutants, we have shown that certain M. tuberculosis genes are required for invasion into the CNS and that this phenotype is unique to the CNS and not seen in the lungs. We are currently studying the role of these genes in CNS invasion. Further, we are also studying the unique immune-privileged host environment in the CNS and its effect on M. tuberculosis infection.

Using pooled infections with genotypically defined M. tuberculosis transposon mutants, we have compared M. tuberculosis genotypic requirements across 2 different animal species – guinea pigs (which display caseous necrosis in response to tuberculosis) and the standard mouse model. By performing long term mouse infection, we found that both models identify the same M. tuberculosis genes for survival in the lung. However, the guinea pig model identified these M. tuberculosis genes much earlier. We believe that this difference is likely due to the caseous necrosis (and therefore more stringent immunological stressors) in the guinea pig model. Further studies are underway to identify the mechanisms involved with this differential phenotype displayed by some of the mutants identified in this study.

To simply pre-clinical evaluation of anti-tuberculosis regimens, we are developing existing and novel imaging technologies to evaluate M. tuberculosis infections in real-time. We anticipate that not only will these imaging technologies be used for experimental animal infections but could also be used for diagnosis and follow up of human tuberculosis disease in the future. In collaboration with Dr. Martin Pomper at Johns Hopkins, we have used CT and PET imaging to evaluate the anatomic and inflammatory state of lungs of animals experimentally infected with M. tuberculosis. Further, using novel radio-nucleotide imaging technology we have also been able to image live mycobacteria using SPECT imaging. We are currently involved with optimizing this imaging technology for evaluating the response to anti-tuberculosis therapy in animal models of tuberculosis.

Also see: http://in.news.yahoo.com/071206/32/6o4i7.html and

Peer-reviewed publications:

1.      Jain SK, Hernandez-Abanto S, Cheng Q, Singh P, Ly LH, Klinkenberg G, Morrison NE, Converse PJ, Nuermberger E, Grosset J, McMurray DN, Karakousis PC, Lamichhane G, Bishai WR. Accelerated detection of Mycobacterium tuberculosis genes essential for bacterial survival in guinea pigs compared with mice. J Infect Dis. 2007 Jun 1;195(11):1634-42.

2.      Jain SK, Paul-Satyaseela M, Lamichhane G, Kim KS, Bishai WR. Mycobacterium tuberculosis Invasion and Traversal across an In Vitro Human Blood-Brain Barrier as a Pathogenic Mechanism for Central Nervous System Tuberculosis. J Infect Dis. 2006 May 1;193(9):1287-95.

3.      Hernandez-Abanto S, Woolwine SC, Jain SK, Bishai WR. Tetracycline-inducible gene expression in mycobacteria within an animal host using Streptomyces-derived tetO and tetR regulatory elements. Arch Microbiol. 2006 Dec;186(6):459-64.

4.      Jain SK, Kwon P, Moss WJ. Management and outcomes of intracranial tuberculomas developing during antituberculous therapy: case report and review. Clin Pediatr (Phila). 2005 Jun;44(5):443-50.

5.      Jain SK, Bishai WR. Adherence, treatment success, and resistance. Infectious Diseases and Clinical Practice. 2006 Infect Dis Clin Pract. 2006 July 14(4) Supplement 4:S15-S18.

6.      Jain SK, Gupta A, Glanz B, Dick J, Siberry GK. Antimicrobial-resistant Shigella sonnei: Limited antimicrobial treatment options for children and challenges of interpreting in vitro azithromycin susceptibility. Pediatr Infect Dis J. 2005 Jun;24(6):494-497.

7.      Jain SK, Persaud D, Perl TM, Pass MA, Murphy KM, Pisciotta JM, Scholl PF, Casella JF, Sullivan DJ. Nosocomial Malaria and Saline Flush. Emerg Infect Dis. 2005 July;11(7):1097-99.

8.      Bhally HS, Jain S, Shields C, Halsey N, Cristofalo E, Merz WG. Infection in a neonate caused by Pichia fabianii: importance of molecular identification. Med Mycol. 2006 Mar;44(2):185-7.

9.      Jain SK, Tunkel DE, Bishai WR. Management of Acute Rhinosinusitis, Bronchitis Syndromes, and Acute Otitis Media. Adv Stud Med. 2005; 5(7):344-350.

10.  Jain SK. Index of suspicion. Case 3. Diagnosis: Jaundice. Pediatr Rev. 2001 Aug;22(8):271-6.

11.      Jain SK, Deepak KK. Cost Effective Computerized Analysis of Biological Signals. Indian J Physiol Pharmacol 1995; 39(4): 389-394.