Rajeev K. Tyagi

CSIR-Institute of Microbial Technology (IMTECH)

Dr. Rajeev K. Tyagi earned Ph.D. degree at Biomedical Parasitology Unit, Institute Pasteur, Paris, France in June 2011 on a very challenging and interesting topic of malaria immunology/parasitology. He developed a long lasting, stable and straightforward laboratory animal model (humanized mouse model: a versatile mouse model). The developed humanized mouse model was deployed to study asexual blood stage infection of P. falciparum and understand biology, physiology and immunology of this human parasite during his doctoral thesis at Pasteur (Tyagi et al, Malaria J 2010, PloS One 2011). As P. falciparum has the potential to evolve extreme artemisinin resistance and more complex patterns of multidrug resistance than anticipated, therefore Dr. Tyagi explored the developed mouse to study the artemisinin resistance (Tyagi et al, BMC Medicine 2018). Dr. Tyagi worked as postdoc fellow in the laboratory of Dr. John Adams, University of South Florida, USA and received training to explore the potential of the developed “humanized mouse” to characterize attenuated asexual blood stage falciparum parasite to understand the innate immune response of the attenuated parasite (growth mutant). Additionally, he developed small laboratory human liver chimeric mice by transplanting the human hepatocytes in transgenic/immunodeficient mice (TK/NOG) at USF, USA to study the least known liver stage infection of P. falciparum (Tyagi et al, 2018 Frontiers in Immunology). Further, discovery of novel dendritic like cell population called “pathogen differentiated dendritic cells (PDDCs)” when incubated with P. gingivalis and tracking of monocyte derived dendritic cells (MoDcs) in a reconstituted immunodeficient NOD.PrkdcscidIl2rg-/- (NSG) mice gave Dr. Tyagi a platform to make the excellent use of his post-Ph.D. training at Augusta University, USA to gain expertise in advanced translational biomedical research aimed at understanding the host-pathogen interaction (Tyagi et al, 2017 Scientific Reports). Dr. Tyagi at the Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition Vanderbilt University Medical Centre (VUMC), USA deployed his efforts to understand the role of IL-23R in the modulation of functioning of regulatory T cells and its role in the pathogenesis of colitis in an experimental humanized mouse (reconstituted with stem cells) as well as IL-23R deficient and sufficient mice (Tyagi et al, 2020, Biochem. Pharmacology). Also, he looked at the role of low-dose IL-2 in expanding Foxp3 regulatory T cells in CD34+ cells reconstituted NSG (NOD-scid IL2Rgammanull) mice and its therapeutic role on the treatment of experimental colitis in these mice. Dr. Tyagi has been leading group at CSIR-Institute of Microbial Technology, Chandigarh and his lab is focused to:  1) develop human-liver chimeric mice for huHep transplantation. The huHep reconstituted TK/NOG transgenic mice by non-invasive Ultra Sound Guided Injection technique through intrasplenic route showing development of human liver “chimeric mouse” to study liver stage infection of P. falciparum and transition to asexual blood stage infection to test antimalarial drugs and vaccine candidates in one host.  2) select highly Artemisinin-resistant asexual blood stage Plasmodium falciparum (ART-R) with Quinine co-resistance under in vitro artesunate pressure. The experimentally selected resistant P. falciparum parasites are being used to find-out the underlying molecular mechanisms that parasite may have been employing to escape and/or cope-up the drug pressure. The engraftment of select ART-R parasites will be grafted in a blood stage humanized mice to complement the in vitro results.  3) Dendritic cells as "therapeutic vaccines" playing a crucial role in translational biomedical research.  4) formulation and characterization of nanoscale drug carriers to deliver methotrexate (MTX) and aceclofenac to address Rheumatoid Arthritis, cancer and other inflammatory diseases (Tygai et al, Nanomedicine, 2016, Int. J. Pharmaceutics, 2016, Acta Biomaterialia, 2015) as well as candidate vaccines (Tyagi et al, vaccine 2015, Human Vacc. Immunothear, 2016). His group is looking at anti-inflammatory effect of methotrexate in breast cancer therapeutics. GRANTS AND CONTRACTS: Dr. Tyagi’s group is funded by DST-SERB, DBT and ICMR, New Delhi. There are grants applications under review with DBT, Wellcome-DBT India Alliance, DST-SERB and BIRAC, New Delhi. Selected Publications: 1. Tyagi RK, Li J, Jacobse J, Snapper SB, Shouval DS, Goettel JA. Humanized mouse models of genetic immune disorders and hematological malignancies. Biochem Pharmacol. 2020 Apr;174:113671. doi: 10.1016/j.bcp.2019.113671. Epub 2019 Oct 18. 2. Tyagi RK, Gleeson PJ, Arnold L, Tahar R, Prieur E, Decosterd L, Pérignon JL, Olliaro P, Druilhe P. High-level artemisinin-resistance with quinine co-resistance emerges in P. falciparum malaria under in vivo artesunate pressure. BMC Med. 2018 Oct 1;16 (1):181. doi: 10.1186/s12916-018-1156-x. 3. Tyagi RK*, Tandel N, Deshpande R, Engelman RW, Patel SD, Tyagi P. Humanized Mice Are Instrumental to the Study of Plasmodium falciparum Infection. Front Immunol. 2018 Dec 13;9:2550. doi: 10.3389/fimmu.2018.02550. eCollection 2018 4. Tyagi RK*, Miles B, Parmar R, Garg NK, Dalai SK, Baban B, Cutler CW. Human IDO-competent, long-lived immunoregulatory dendritic cells induced by intracellular pathogen, and their fate in humanized mice. Nature Scientific Reports, (2017) 7: 41083; 1-18 doi: 10.1038/srep41083 5. Jain A, Jain A, Garg NK, Tyagi RK, Singh B, Katare OP, Webster TJ, Soni V. Surface engineered polymeric nanocarriers mediate the delivery of transferrin–methotrexate conjugates for an improved understanding of brain cancer. Acta Biomaterialia, (2015) 24: 140-151 6. Garg NK, Singh B, Kushwah V, Tyagi RK*, Sharma R, Jain S, Katare OP. The ligand (s) anchored lipobrid nanoconstruct mediated delivery of methotrexate: an effective approach in breast cancer therapeutics. Nanomedicine. 2016 Oct;12 (7):2043-2060. doi: 10.1016/j.nano.2016.05.008. 7. Tyagi RK*, Garg NK*, Singh B, Sharma G, Nirbhavane P, Kushwah V, Jain S, Katare OP. Nanostructured lipid carrier mediates effective delivery of methotrexate to induce apoptosis of rheumatoid arthritis via NF-κB and FOXO1. International Journal of Pharmaceutics. (2016) 499 (1-2): 301-320 8. Tyagi RK*, Garg NK, Dalai SK, Awasthi A. Transdermal immunization of P. falciparum surface antigen (MSP-119) via elastic liposomes confers robust immunogenicity. Hum Vaccin Immunother. 2016 Apr 2;12 (4):990-2. doi: 10.1080/21645515.2015.1116656. Epub 2016 Jan 25 9. Tyagi RK*, Garg NK, Jadon R, Sahu T, Katare OP, Dalai SK, Awasthi A, Marepally SK. Elastic liposome-mediated transdermal immunization enhanced the immunogenicity of P. falciparum surface antigen, MSP-119. Vaccine. 2015 Aug 26;33 (36):4630-8. doi: 10.1016/j.vaccine.2015.06.054. Epub 2015 Jun 30 10. Tyagi RK, Arnold L, Meija P, Swetman C, Gleeson J, Pérignon JL, Druilhe P. Further improvements of the P. falciparum humanized mouse model. PLoS One. 2011 Mar 31;6(3):e18045. doi: 10.1371/journal.pone.0018045. 11. Tyagi RK, Arnold L, Mejia P, Van Rooijen N, Pérignon JL, Druilhe P Analysis of innate defences against Plasmodium falciparum in immunodeficient mice. Malar J. 2010 Jul 9;9:197. doi: 10.1186/1475-2875-9-197. * Corresponding author

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Latest work with IntechOpen by Rajeev K. Tyagi

Medical Nanotechnology and Nanomedicine introduces non-experts to the world of nanomedicine and its evolving organizational infrastructure. Considering the fluid nature of nano breakthroughs and the delicate balance between benefits and consequences as they apply to medicine, readers at all levels will gain a practical, understandable base of information on these developments so that they may take the greatest advantage of them. This practical reference investigates the impact of nanotechnology on applications in medicine and biomedical sciences, and the broader societal and economic effects. Eschewing technological details, it focuses on enhancing awareness of the business, regulatory, and administrative aspects of medical applications. It gives readers a critical, balanced, and realistic evaluation of existing nanomedicine developments and future prospects and provides an ideal foundation upon which to plan and make decisions.

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