Honors & Awards
Outstanding research and creativity award, Indiana State University (2012)
Award for Academic Excellence, Indiana State University (2011)
Maaveran Sundalingan Fellowship Award, Madurai Kamaraj University (2007)
Gold Medal, Bangalore University (2006)
Doctor of Philosophy, Indiana State University, IN, Immunology (2013)
Master of Science, Madurai Kamaraj University, Madurai, India, Biochemistry (2008)
Bachelor of Science, Bangalore University, Bangalore, India, Microbiology (2006)
Yueh-Hsiu Chien, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
My research interest focuses on understanding how γδ T cells regulate and contribute to two fundamentally different immunological phenomena: immune competence and immune tolerance.
Synthetic adjuvants for vaccine formulations: phytol derivatives
EXPERT OPINION ON DRUG DELIVERY
2013; 10 (4): 437-450
The development of vaccines is considered a key milestone in preventive medicine. There is no comparable cost-effective means for controlling or eradicating infectious diseases. Yet, a persistent societal problem is the concern about vaccine's safety and long-term effects, and this caters to detractors of vaccination. Pathogen-derived antigen(s) as well as adjuvants/immunostimulants are essential for vaccine efficacy. Currently, adjuvant selection is largely empirical, but the mechanism underlying adjuvanticity is beginning to unravel. This should help develop more defined or targeted adjuvants.This review provides a brief account and analysis of the host immune parameters modulated by some commonly used as well as new adjuvants, including phytol-based diterpenoids. The major efforts are directed toward evaluating their relative safety and immunomodulatory efficiency, compared to known synthetic and natural adjuvants. Concerns for adverse pathological inflammation and autoimmunity are also addressed.The phytol-based adjuvants hold great promise for improving vaccine efficacy, as they cause little or no persistent inflammation, but are highly effective in stimulating a multifaceted immune response, characterized by proficient recruitment of immune cells, generation of antibody and immunological memory, and activation of both Th1 and Th2 responses. Future focus will be on developing cocktail adjuvants to activate the complement system, mobilize follicular T helper cells as well as NKT and γδ T cells and activate cross-presenting dendritic cells to stimulate CD8(+) effector T cells.
View details for DOI 10.1517/17425247.2013.757591
View details for Web of Science ID 000316128100003
View details for PubMedID 23293963
Efficacy of phytol-derived diterpenoid immunoadjuvants over alum in shaping the murine host's immune response to Staphylococcus aureus.
2013; 31 (8): 1178-1186
The ubiquitous gram-positive bacterium Staphylococcus aureus occupies a unique niche in humans for its ability to survive both as a commensal and a life-threatening pathogen. Its complex relationship with the host and its ability to engender a throng of virulence factors, have hindered the development of a successful vaccine against it. The use of immunoadjuvants to enhance host immunity and prevent the shift from commensalism to pathogenicity is a rational approach for containing infection. The objective of this study was to understand the mechanisms by which alum and two phytol-derived immunoadjuvants, phytanol (PHIS-01)(1) and phytanyl chloride (PCl)(2) shape the interaction between S. aureus and its murine host. We studied the effects of the phytol derivatives, relative to alum, on the induction of inflammatory cytokines and chemokines, recruitment of CD11b(+) cells, generation of specific anti-S. aureus antibodies and in vitro clearance of S. aureus. Our results showed that both PHIS-01 and PCl were stronger inducers of protective cytokines IL-17 and IL-1β than alum, and far exceeded alum in enhancing anti-S. aureus antibody response. However, both alum and the phytol derivatives (particularly PCl) promoted efficient recruitment of CD11b(+) cells. Furthermore, PHIS-01, alum and to a lesser extent, PCl were able to up-regulate the expression of key inflammation-related genes that were highly down-regulated by S. aureus alone. In vitro killing assays showed that both PHIS-01 and PCl were far more potent than alum in promoting S. aureus clearance; this indicated their efficiency in shaping an effective anti-S. aureus immune microenvironment. In summary, our study provides evidence for the better effectiveness of phytol-derived immunoadjuvants over alum in enhancing anti-S. aureus immunity.
View details for DOI 10.1016/j.vaccine.2012.12.069
View details for PubMedID 23313815
Effects of small intestinal submucosa (SIS) on the murine innate immune microenvironment induced by heat-killed Staphylococcus aureus.
2012; 7 (11)
The use of biological scaffold materials for wound healing and tissue remodeling has profoundly impacted regenerative medicine and tissue engineering. The porcine-derived small intestinal submucosa (SIS) is a licensed bioscaffold material regularly used in wound and tissue repair, often in contaminated surgical fields. Complications and failures due to infection of this biomaterial have therefore been a major concern and challenge. SIS can be colonized and infected by wound-associated bacteria, particularly Staphylococcus aureus. In order to address this concern and develop novel intervention strategies, the immune microenvironment orchestrated by the combined action of S. aureus and SIS should be critically evaluated. Since the outcome of tissue remodeling is largely controlled by the local immune microenvironment, we assessed the innate immune profile in terms of cytokine/chemokine microenvironment and inflammasome-responsive genes. BALB/c mice were injected intra-peritoneally with heat-killed S. aureus in the presence or absence of SIS. Analyses of cytokines, chemokines and microarray profiling of inflammasome-related genes were done using peritoneal lavages collected 24 hours after injection. Results showed that unlike SIS, the S. aureus-SIS interactome was characterized by a Th1-biased immune profile with increased expressions of IFN-γ, IL-12 and decreased expressions of IL-4, IL-13, IL-33 and IL-6. Such modulation of the Th1/Th2 axis can greatly facilitate graft rejections. The S. aureus-SIS exposure also augmented the expressions of pro-inflammatory cytokines like IL-1β, Tnf-α, CD30L, Eotaxin and Fractalkine. This heightened inflammatory response caused by S. aureus contamination could enormously affect the biocompatibility of SIS. However, the mRNA expressions of many inflammasome-related genes like Nlrp3, Aim2, Card6 and Pycard were down-regulated by heat-killed S. aureus with or without SIS. In summary, our study explored the innate immune microenvironment induced by the combined exposure of SIS and S. aureus. These results have practical implications in developing strategies to contain infection and promote successful tissue repair.
View details for DOI 10.1371/journal.pone.0048724
View details for PubMedID 23189134
Phytol-derived novel isoprenoid immunostimulants.
Frontiers in immunology
2012; 3: 49-?
This review describes the adjuvanticity of novel diterpenoids (synthetic phytol derivatives) compared to some commercially available adjuvants. The efficacy of the phytol-derived immunostimulants was evaluated in terms of their ability to activate innate immunity, amplify various antigen-specific immune responses, and engender immunological memory with no discernible adverse effects in both competent and immune-deficient mice. The profile that emerges out of these studies reveals that the phytol derivatives are excellent immunostimulants, superior to a number of commercial adjuvants in terms of long-term memory induction and activation of both innate and acquired immunity. Additionally, the phytol-derived compounds have no cumulative inflammatory or toxic effects even in immuno-compromised mice.
View details for DOI 10.3389/fimmu.2012.00049
View details for PubMedID 22566931
Molecular signatures of phytol-derived immunostimulants in the context of chemokine-cytokine microenvironment and enhanced immune response
2011; 271 (2): 227-238
In a previous report, we observed that the phytol-derived immunostimulant, PHIS-01 (phytanol), is a nontoxic oil-in-water adjuvant which is superior to most commercial adjuvants. In contrast, the parent diterpene alcohol phytol, though highly effective as an adjuvant, is relatively toxic. To assess the importance of the polar functional group in PHIS-01, we prepared two new compounds PHIS-02 (phytanyl amine) and PHIS-03 (phytanyl mannose). All three phytol derivatives proved to be excellent adjuvants, but differed in solubility and mode of action. To delineate their molecular signatures in the local microenvironment, we performed inflammasome and cytokine microarray analyses with the peritoneal fluid of mice treated with alum or the phytol compounds above, in the presence or absence of soluble protein antigens. We report here that the phytol derivatives had a significant time-dependent impact on the host chemokine-cytokine microenvironment and subsequently on specific humoral responses. Moreover, the inclusion of protein immunogens induced further changes in host microenvironments, including rapid (<2h) expression of cytokines and chemotactic factors (IL-6, MCP-1, KC, MIP-1, and LIX), implying mobilization and activation of neutrophils, and monocytes. PHIS-01 proved to be the most effective in this regard. Inflammatory cytokine cascades were dominant even after 24h possibly to facilitate involvement of the acquired immune system with the release of B-lymphocyte chemo-attractant BLC, T-cell activation-3 chemokines TCA, IL-4, IL-12, and TIMP-1. We also noted enhanced expression of NLRP genes including NLRP3 with both alum and phytol derivatives (particularly PHIS-01).
View details for DOI 10.1016/j.cellimm.2011.07.001
View details for Web of Science ID 000296219900005
View details for PubMedID 21813116