Undergraduate education: I have completed my under-graduation (B Sc) in Microbiology from Madras University, India. Following which, I have completed my masters in Immunology and Microbiology from The American College, Madurai, India (Autonomous and affiliated to Madurai Kamaraj University, India).
Statement of research interests: I have had the opportunity of working on the regulation of transcription factors Activator Protein-1 (AP-1) and Nuclear Factor-?B (NF-?B) in breast cancer cell lines, which has formed the basis of my thirst to gain a deep insight into their influence on inflammation & cancer. Chronic inflammation is intimately associated with tumor progression due to the reciprocal interactions between neoplastically-initiated cells & immune cells. This is a stimulating research field for me wherein one could develop immuno-therapeutic strategies.
NF-?B & AP-1 is one of the most fascinating areas of exploration to me, due to my inherent interest in its multiple signaling cascades. NF- ?B & AP-1 are a “hub” in the plethora of intricate signaling pathways deciding the fate of an individual cell by arbitrating between life & death. It has dramatic implications in homeostasis as well as in inflammation, disease & cancer. Their importance in oncogenesis owes to their
constitutive activation & regulation of multiple paradigms such as cellular proliferation, control of apoptosis & metastasis. One of the quintessential conundra is whether there is an existence of a specific combination of dimers of NF-?B in context of differential ?B
sites, different genes & unrelated/related activating stimuli & how it ultimately results in a sequence specific-critical shaping of the NF-?B response?
Having completed my masters in Immunology, I am truly enthralled by the complex architecture of the immune system, with specific reference to the physiological & pathophysiological role of Nitric oxide (NO). NO is a diatomic radical which acts as a multifunctional, ubiquitous & pleiotropic modulator of cellular function. It is produced in copious amounts in phagocytes during inflammatory responses. NO has multifaceted
roles & is a double-edged sword in carcinogenesis. NO further is known for its ability to activate NF-?B & AP-1 responses.
In this regard, Cisplastin, a broad-spectrum anti-cancer drug is said to up regulate NO production in macrophages, which is critical for its anti-tumor activity. In contrast,
macrophages are themselves targets for NO induced apoptosis & are susceptible to premature death when activated to express iNOS.
Furthermore, Cyclooxygenases (COX), the eicosanoids which are the key physiological mediators of inflammation, play a prime role in development & progression of inflammation associated cancer (IAC) since they afford protection from apoptosis. Besides, COX-2 induction depends on NF-?B &AP-1 signaling cascades since the presence of defined consensus sequences within the COX-2 promoter has been reported.
Yet another appealing perspective is the negative regulation of JNK pathway by NF-?B. This has been observed to occur either via Gadd45? (Myd118) or XIAP induction both of which inhibit JNK signaling. Nevertheless, what would be the nature of crosstalk between partner transcription factors under conditions of stimulation by cisplastin-
induced NO & consequently how would it modulate COX-2 expression?
Alternatively, NO is known to cause the disintegration of the zinc finger structure by nitrosation of thiols & ejection of Zn. Since AP-1 contains a Zn finger in its DNA-binding domain, would this be one of the mechanisms by which cisplastin-generated NO could abrogate AP-1 signaling in cancer cells?
Keeping in mind the above aspects I would like to investigate on the following future directions: 1) Determining influence of sequence-specific dimer composition of NF-?B on regulation of transcription program of COX in different stages of IAC 2) Deducing significance of cisplastin induced-NO in signal transmission & target interaction by understanding its redox & additive chemistry.3) Dissection of pathways involved in cross talk between NF-?B & AP-1 within intratumoral macrophages 4) Defining synergism/ antagonism between NF-?B & AP-1 in COX induction with reference to the possibility of a transrepression mechanism.
Expectations from Integramm: At the outset, INTEGRAMM is a wonderful opportunity to me and it has opened the portals of my research career. What I expect out of INTEGRAMM is constant support, encouragement and motivation during the course of my Ph D. Mutual interaction and co-operation between all participants and the institutional body would be a boon to budding young scientists like us. However, what expect I out of INTEGRAMM is rather, what I expect out of myself-since what I want INTEGRAMM to do for me is ultimately what I make of it. I hope that when I step out with a doctorate in hand I will be enriched in terms of professional and personal experiences and would have attained growth in multidimensional aspects. I hope that INTEGRAMM would be my route to acquiring a drop in the ocean of knowledge and further strengthen my yearning to search and research for something that is yet to be discovered!