|1. Molecular events of inflammatory diseases and possible therapeutic approaches:
Studies on Asthma
Asthma is a growing concern in this country. Asthma is a chronic lung disease characterized by episodes of airflow obstruction. Symptoms of an asthma attack include coughing, wheezing, shortness of breath, and chest tightness. Asthma occurs in people who are predisposed to develop asthma because of genetic and environmental factors that determine susceptibility. A variety of "triggers" may initiate or worsen an asthma attack, including viral respiratory infections, exercise, and exposure to allergens or to airway irritants such as tobacco smoke and certain environmental pollutants.
To explore the genetic basis of asthma -
the study is enrolling asthmatic patients and their families in order to identify genes for asthma and for responsiveness to allergens. This study has identified several candidate genes for asthma, some of which may be more common in Indian populations. Reports are available for a genetic changes in interleukin-4 (IL-4), an immune-signaling molecule involved in asthma and allergic responses, which correlates with asthma severity. Besides that IL-8 is also involves in disease severity. Studies of such genes should facilitate development of new and more potent and selective therapies, and may help to identify patient populations who might respond best to a particular drug.
To explore the basic and clinical research - the mechanisms of disease specially involved cytokines and activation of signaling molecules (kinases and transcription factors) and ways to prevent asthma, allergic, and immunologic diseases basic and clinical research it is necessary to seeks to improve the diagnosis, treatment, and management of asthma, particularly in Indian populations disproportionately affected by this disease.
Studies on Arthritis
2. Cancer Biology:
Articular inflammation and enzymatic degradation of cartilage components characterize arthritic disease. Enzymatic destruction of proteoglycan found in articular cartilage, is one of the early signs of arthritis. Matrix metalloproteinases (MMPs) specifically cleave a lot of matrix proteins and cleaved products are found within synovial fluid of arthritic joints. MMPs are regulated by transcription factors like NF-kB and AP-1. So, our interest to regulate these transcription factors and to improve the therapy for articular diseases.
Apoptosis is a programmed cell death mechanism to control cell number in tissues and to eliminate individual cells that may lead to disease states. The term chemotherapy refers to the elimination of unwanted cells either by inhibiting their growth or by killing them. To regulate the abnormal growth of cells in lung cancerous tissue several chemotherapeutic drugs have been reported. Most of them become useless as the cells develop resistance to them by adopting mutation in the molecules involved in the signaling cascade related to cell growth. It is very useful to check the sensitivity of different chemotherapeutic agents by different lung cancer cells. In the event of only some cells showing resistance combination therapy may be suggested. It is necessary to detect signaling pathway(s) specially involving receptor associated molecules, kinases and transcription factors which differ in chemotherapeutically resistant and sensitive cells. Detection of cross-talk in these molecules is also important to understand the mechanism of signaling. Detection of such key molecule(s) for resistance helps in the design of suitable drug(s) which act as their inhibitors.
Current paradigms in cancer therapy suggest that up-regulated nuclear factor-kappa B (NF-kB) by a variety of stimuli acts as anti-apoptotic. Thus, inhibiting NF-kB activation may sensitize cells to anticancer therapy, thereby providing a more effective treatment for certain types of cancers. It is useful to understand the mechanism of constitutive expression of NF-kB shown by some cancer cells. This can be done by searching for such cells from breast cancer, colon cancer or prostate cancer to detect the differences in the activated kinases and transcription factors between normal and cancerous cells and to detect different anti-inflammatory agents implicated to inhibit NF-kB activation in such constitutively expressed cells.
3. Receptor Biology:
In case of inflammatory diseases or apoptosis signaling molecules including pro-inflammatory cytokines including TNF, IL-1, IL-6 and IL-8 exert their action through specific cell surface receptors. So receptor regulation is important to regulate these diseases.