Dr. Reena A. Rajput
Department of Human Health and Diseases



Assistant Professor
School of Biological Sciences and Biotechnology


Indian Institute of Advanced Research
Koba, Gandhinagar, 382 007
Gujarat, India
Ph: +91-79-30514252
Fax: +91-79-30514110
Email:
reena@iiar.res.in

 

Research Interest:

Reprogramming Immune Cells to Neurons

Neurodegenerative disorders account for a major toll to human health hence regeneration of neurons is palliative. We are trying to exploit the homologies of immune cells and neurons especially with respect to expression and function of CD40 and Toll- like Receptors (TLRs). These receptors might be crucial in maintaining self renewal or in differentiation of cells to desired cell lineage. We are aiming to regulate CD40 and TLR mediated maturation phases of the immune cells and reprogramme them to functional neurons.

Potential Roles of Toll like Receptors in Neuroimmunology

The concept of immune privilege is not a new one and in the rapidly changing world of biomedical science is a factum that is undergoing conceptual change but like all historical dogma has a large basis in fact. The brain is regarded as immunologically privileged, and, as such, has been thought of as an organ where the immune response to antigens is not destructive to tissue or is suppressed. The discovery that neurons express major histocompatibility complex class 1 molecules and, recently, the toll-like receptors (TLRs) is changing the way the field of neuroscience views the role that the immune system, both adaptive and innate, plays in the brain and contribute to neural homeostasis. So the question exists that if the brain is to be considered an immune-privileged organ why does it express a large majority of the already discovered 10 TLRs and of what use is the activation of these receptors if they are to be only thought about as useful in an immune response?

In our lab we are examining the role of TLRs in the central nervous system (CNS), these receptors are not only involved in peripheral innate immunity but may also play a role in the development and regulation of CNS inflammation, neurodegeneration and brain trauma. In addition the research group is exploring novel neuroprotective strategies that will reverse the extent and severity of injury.

Vaccine Reactogenicity

Reactogenicity of Vibrio cholera vaccine limits its use. There has been continuous research going on to generate better suited vaccine candidate. Whole cell based vaccine accompany reactogenicity but offer better protection compared to non-reactogenic component of cholera toxin (CTX). The preeminence of Cholera toxin made it a prime target in the development of cholera vaccine. While many of the V. cholerae vaccine strains do not cause cholera, they cause significant reactogenicity in the form of mild to moderate diarrhea. Reactogenicity has been attributed to leucocyte infiltration, presence of lactoferrin and inflammation. Inflammatory conditions have been attributed to TLR5 mediated IL-8 production. T regulatory (Treg) cells are one of the important components of suppressors of inflammation and there are no reports on regulation of Treg to abrogate reactogenicity. We are trying to check the interactions between GM1 receptor and TLR5 since both of these are activated by components of CTX. We plan to regulate the Treg number and function by varying the dose of TLR5 Ligand and to utilize immunosuppressive potential of Treg population to evaluate the abrogation of CTX mediated inflammation. Elucidating the mechanisms of TLR5 mediated mucosal inflammation; manipulation of its signaling strength to generate a state of immunosupression mediated by Treg offers many advantages to protect vaccine reactogenicity. The findings would be useful to develop alternate strategies to downregulate/inhibit TLR5 signal to produce a state of protection. The findings from the proposed study would also potentiate cholera toxin mediated immunomodulation and adjuvancy and can be exploited to other models of inflammation.

 

Team member:

 Sagar Gaikwad -SRF

 Naveen C. -JRF

 

Publications: 

  1. Sunil Martin, Reena Agrawal, G. Murugaiyan, and Bhaskar Saha. CD40 expression levels modulate regulatory T cells in L. donovani infection.(J. Immunol., 2010; 185: 551-9)
  2. G. Murugaiyan, Reena Agrawal, Gyan C Mishra, Debashis Mitra, Bhaskar Saha. Differential CD40/CD40L expression results in counteracting antitumor immune responses. (J. Immunol., 2007; 178: 2047-2055).
  3. G. Murugaiyan, Reena Agrawal, Gyan C Mishra, Bhaskar Saha.  Functional dichotomy in CD40 reciprocally regulates effector T cell functions. (J. Immunol. 2006; 177: 6642-9).
  4. Pallavi Wadhone, Moitrayee Maiti, Reena Agrawal, Vanita Kamat and Bhaskar Saha. Miltefosine Promotes IFN--Dominated Anti-Leishmanial Immune Response. (J. Immunol., 2009; 182: 7146 - 7154).
  5. Rathee D., Thanki M., Bhuva S., Anandjiwala S., Agrawal R. Irridoid glycosides-Kutkin, Picroside I and Kutkoside from Picrorrhiza kurroa Benth inhibits the invasion and migration of MCF-7 Breast cancer cells through the down regulation of Matrix Metalloprotienases. Arabian Journal of Chemistry 2012, (6), 49–58.
  6. Sagar Gaikwad, Divyesh Patel, Naveen C. R. and Reena Agrawal-Rajput. The critical role of JNK and p38 MAPKs for TLR4 induced microgliamediated neurotoxicity. European Journal of Experimental Biology, 2015, 5(8):34-42.
  7. Gaikwad S, Agrawal-Rajput R. Lipopolysaccharide from Rhodobacter sphaeroides Attenuates Microglia-Mediated Inflammation and Phagocytosis and Directs Regulatory T Cell Response. International Journal of Inflammation 04/2015; 2015(7). doi:10.1155/2015/361326.
  8. Sagar Gaikwad, Divyesh Patel and Reena Agrawal-Rajput. CD40 Negatively Regulates ATP-TLR4-Activated Inflammasome in Microglia. Cellular and Molecular Neurobiology 03/2016. doi: 10.1007/s10571-016-0358-z.
  9. Sagar Gaikwad, Naveen CR and Reena Agrawal-Rajput. (2016) Toll-like receptor-4 antagonism mediates benefits during neuroinflammation. Neural Regeneration Research 2016 Apr;11(4):552-3. doi: 10.4103/1673-5374.180732 Pubmed
  10. Sagar Gaikwad, Naveen CR and Reena Agrawal-Rajput. (2016)
    Berberine Induces Neuronal Differentiation through Inhibition of Cancer
    Stemness and Epithelial-Mesenchymal Transition in Neuroblastoma Cells. Phytomedicine  2016 Jun 15;23(7):736-44. doi: 10.1016/j.phymed.2016.03.013. Epub 2016 Apr 13. Pubmed
  11. Nitin Lunagariya, Anita Mahapatra and Reena Agrawal-Rajput. Induction of apoptosis by zerumbone and its derivatives on human lung cancer cells. Natural Product Communications (In Press).
  12.  

Abstracts in conference and symposia

  1. Naveen C. R and Reena Agrawal-Rajput. (2016). A Novel Approach to Direct Somatic Reprogramming of Macrophages to Neurons. CiRA/ ISSCR 2016 International Symposium on “Pluripotency: From Basic Science to Therapeutic Applications” at Kyoto, Japan, 22-24th March 2016.
  2. Naveen C. R, Manthan Patel and Reena Agrawal-Rajput. (2015). Reprogramming of immune cells to neurons: A lineage shift. 6th International Conference on Stem Cells and Cancer. October, 2015.
  3. Reena Agrawal-Rajput. (2015). Mucosal Immunity. One day Seminar Series On Translational Research In Immunology at B.V. Patel PERD Centre, Ahmedabad, 29th April 2015 (Invited Lecture)
  4. Sagar Gaikwad and Reena A Rajput. (2015). Antagonism of Innate Immune Receptor Confers Neuroprotection during Microglia Mediated Neuroinflammation and Neurodegeneration. National symposium, Innovative Research and Development in Science and Humanities (IRDSH), February, 2015 (Platform presentation).
  5. Sagar Gaikwad and Reena A. Rajput. (2014). “TLR4  Inhibition  Confers Neuroprotection  during  LPS and Amyloid β  Induced  Microglia  Mediated  Neuro-inflammation and Toxicity”, at Annual conference of Indian Immunology Society, December, 2014 (Immunocon-2014), at Madurai Kamraj University, India.
  6. Divyesh Patel, Omkar Naik and Reena Agrawal-Rajput. (2014). Syk Inhibition in Fine Tuning the Cytokine Orchestra during Antifungal Immunity. Immunocon 2014 (41st Annual Conference of Indian Immunology Society) held at Madurai Kamraj University (Invited Platform presentation).
  7. Divyesh Patel, Dipeeka Mandaliya, Manthan Patel and Reena Agrawal-Rajput. (2014).Cytoplasmic Signaling Inhibition in Dendritic Cells Fine Tune T-Cells Outcome during Antifungal Immunity. Emerging Trends in Biochemistry, MSU, Vadodara.
  8. Manthan Patel, Divyesh Patel, Dipeeka Mandaliya and Reena Agrawal-Rajput. (2014). Berberine inhibits cancer cell stemness and induces neuronal differentiation. Emerging Trends in Biochemistry, MSU, Vadodara.
  9. Sagar Gaikwad, Manthan Patel and Reena A Rajput. (2014). Cellular Alchemy: Unblocking the Molecular Roadblocks. CME- Immunology by Indian Immunology Society and Nirma University, Ahmedabad; August 2014.
  10. Dipeeka Patel, Divyesh Patel and Reena A Rajput. (2014). Intrepreting Mixed signal: The T cell conundrum in mucosal immunity. CME- Immunology by Indian Immunology Society and Nirma University, Ahmedabad; August 2014.
  11. Sagar Gaikwad, Reena A Rajput. (2014). TLR4 antagonism attenuates neuroinflammation and microglia mediated neurotoxicity. International conference on Current Perspectives in Drug Discovery, Development and Therapy, Ramanbhai  Patel College  of  Pharmacy,  Changa, Anand.; February 2014
  12. Dipeeka Mandaliya, Divyesh Patel and Reena A. Rajput. (2013) Rhein induces cell death through cell cycle arrest and caspase-dependent pathways along with inhibition of invasion and migration in PC3 cells. “Recent advances in Cancer Prevention and Therapeutics” at Central University of Gujarat, Gandhinagar.
  13. Patel M., Jain K. and Reena Agrawal-Rajput. (2013). Berberine induces apoptosis and inhibits cancer cell stemness and metastasis in neuroblastoma. International Conference on “Recent advances in Cancer Prevention and Therapeutics” at Central University of Gujarat, Gandhinagar. (Best Oral presentation).
  14. Charudatt  Samant,  Prashant  Kshirsagar,  Sagar  Gaikwad  and  Reena Agrawal-Rajput. (2012). Role of TLR9 agonist (CpG) and TLR9 siRNA as potent anti-cancer immunotherapeutics. International Symposium on Recent Advances in Cancer Research Therapeutics to Chemoprevention, Central University of Gujarat (Best Poster Award).
  15. Mahapatra A., Lunagariya N. and Reena Agrawal-Rajput. (2012). Induction Of p53 Independent Apoptosis via Mitochondrial Pathway by Zerumbone Analogues on Human Lung and Colon Cancer Cells. International Symposium on “Recent Advances in Cancer Research: Therapeutics to Chemoprevention: at Central University of Gujarat, Gandhinagar, India; 8-9 Feb 2012. (Best Oral presentation).
  16. Kshirsagar P., Samant C. and Reena Agrawal-Rajput. (2011). Paradoxial role of TLR9 agonist in cancer immunotherapy. Recent advances in Pharmacological Research held at Pravaranagar, Maharashtra. (Best Oral presentation).
  17. Vidhya Saini, Madhavi Thanki, Sheetal Anandjiwala and Reena Agrawal Rajput Evaluation of apoptotic and anti-invasive potential of Rhein on MCF-7 cells at AROMED, 2010, held at Jaipur
  18. Charudatt Samant, Prashant Kshirsagar and Reena Agrawal Rajput. Evaluating mechanism of action of TLR9 agonist for its anticancer potential at Cancercon 2010 held at IIT Chennai. 
  19. Reena Agrawal and Bhaskar Saha. Role of dendritic cells in anti-leishmanial T cell response at 31st Annual Conference of Indian Immunology Society held at Anna University, 2004, Chennai. (Best Poster presentation).