Medicinal Chemistry, Bioorganic Chemistry, Coordination Chemistry, Nanomaterials and Chemical Biology.
Research in our laboratory is focused on two major areas: chemistry (Organic / Inorganic / nanomaterial) and biology, at the interface of chemistry and biology. Research group aims to understand the roles of proteins that play in physiological and pathological process and to use this knowledge to identify novel therapeutic targets for the treatment of complex diseases. Goal is to develop the engineering solutions for those complex diseases and to achieve our goals we develop and apply new technologies that bridge the fields of chemistry and biology. A large variety of powerful tools are used to explore the chemistry–biology interface—a unique and exciting opportunity for students to engage in a number of existing multi-disciplinary research. Students will be exposed to a broad range of techniques in chemistry as well as biology research focused on organic, inorganic, nanomaterial and polymer synthesis, characterization tools, protein purification, gel electrophoresis, cell biology etc.
1) Detoxification of Organomercurials and other toxic heavy metals:
Organomercurials are highly poisonous and selectively neurotoxic environmental pollutant that preferentially accumulates in glia of the central nervous system. Thus, the detoxification of organomercurials is of critical importance and, in nature, this is achieved by the combined action of two mercury resistance bacterial enzymes, organomercurial lyase (MerB) which catalyzes the protolytic cleavage of the otherwise inert Hg-C bond and the mercuric ion reductase (MerA), which reduces Hg(II) to less toxic elemental mercury, Hg(0). Although MerB successfully converts toxic MeHg to Hg(II), the role of amino acids present at the active site of the enzyme in demethylation of methylmercury is not clear yet. Our goal in this project is to understand the mechanism of demethylation of organomercurials.
2) Autoimmune Diseases:
Autoimmune diseases (AD) result from a dysfunction of the immune system in which the body’s immune system mistakenly attacks and destroys its own organs, tissues, and cells. Physicians and scientists have identified so far more than 80 clinically distinct autoimmune diseases. Several are well known AD, including MS, T1D, rheumatoid arthritis, inflammatory bowel disease (IBD), and systemic lupus erythematosus; and some AD including autoimmune hepatitis, Sjögren’s syndrome, autoimmune ear disease, and pemphigus are less known. Recently, a novel class of helper CD4+ T cells is identified that secrete proinflammatory cytokines such as IL17A, IL-17F, IL-21, and IL-22 with characterized pathological roles in autoimmune diseases and have provided new insights into the mechanisms that are important in the development of AD and the immune responses that are essential for effective antimicrobial host defense. In general, proinﬂammatory activity of Th17 is critical for mucosal and epithelial host defense against extracellular bacteria and fungi. However, uncontrolled or inappropriate activation of Th17 cells associated with the pathogenesis of numerous autoimmune diseases. Proinﬂammatory cytokine IL-17 ampliﬁes ongoing inﬂammation by inducing expression of tumor necrosis factor-α (TNF-α), IL-1β, and IL-6 in epithelial and endothelial cells as well as other cell types such as keratinocytes, synoviocytes, ﬁbroblasts, and macrophages. Our laboratory is focused in designing and identifying small molecules which can selectively block the differentiation pathway of this pathogenic T cell and study the mechanisms associated with these molecules to understand more about this recently discovered T helper cells. Our ultimate goal in this project is to discover potential drug that could be used to control those inflammatory diseases.
2) Target specific hormone delivery (Nanomedicine):
Multiple sclerosis (MS) is an example of chronic inﬂammatory demyelinating disease of the central nervous system (CNS) where major thyroid hormone receptor alpha (TRa) is expressed in higher amount. Damage of the insulating and protective fatty substance around the nerve fibers, called myelin sheath, in brain, spinal cord and optic nerves is major concern in MS. The effects of thyroid hormone (TH) are mediated at a cellular level by two different nuclear thyroid hormone receptor (TR) subtypes, TRa and TRb. These two subtypes are not uniformly distributed across tissues and organs. TRa is enriched in the heart (70% of TRs), brain and bone whereas TRb is enriched in the liver (80% of TRs). Recently it has been shown that thyroid hormone treatment can improve remyelination in different MS experimental rodent models and suggested that TH treatment could be used as an effective therapeutic intervention in MS. On the other hand, THs have the potential as lipid lowering and antiobesity agents, but the lack of selectivity of naturally occurring agonists prohibits their use and arise safety concerns for clinical use. Therefore target-specific hormone delivery has an immense potential in the treatment of organ specific diseases including MS, obesity, and other orphan related diseases, without any or less side effect. Goal in this project is targeted delivery of natural agonist to the different tissues to cure tissue specific diseases.
4) Discovery of ‘intelligent' systems for tumor & cardiovascular diseases (Nanotechnology):
Cardiovascular disease (CVD) has now become the number one killer in India and the leading cause of death worldwide. CVD is caused in large part by atherosclerosis. Today, the average age of a person suffering with heart attack has come down drastically. In fact the rate of CVD in the Indian community – particularly in young men – is almost twice as high as their western counterparts. This high number of death associated with atherosclerosis has driven us to focus on the early diagnosis and more effective, yet less-expensive, treatment of atherosclerosis. During the progression of atherosclerotic lesion, macrophages undergo activation, migration, differentiation, proliferation, and death. Therefore, intervention of macrophage activities has potential therapeutic application for the diagnosis and treatment of this particular disease.
On the other hand, survival rates of cancer patients, particularly prostate, pancreatic and breast cancer might be dramatically improved if we could detect tumors in their early stages. As for example, pancreatic cancer usually goes undetected until it's advanced. Although diagnosing pancreatic cancer is usually relatively straightforward but by the time symptoms occurs, unfortunately, a cure is rarely possible at that point. Therefore, early diagnosis of cancers and its treatment are of great interest due to the widespread occurrence of these diseases, high death rate throughout the world, and recurrence after treatment. Our research is focusing on developing novel technologies for the detection and monitoring cancer, cardiovascular diseases in their early stage to offer improved sensitivity, specificity, and cost-effectiveness. Our philosophy is to discover new small molecules for a targeted function and apply novel chemistry to biological problems of broader interest.