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
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.
2. Cancer biology:
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.