Name: Sunil Kumar Manna

My Area of Interest: Cell signaling

My Favourite Quote: Success will come if you have wish

I am a: Senior Scientist at Govt institute

Short Profile:

Question and Answers :

What are your future goals? Where do you see your research going?:
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 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 a nd 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-B and AP-1. So, to regulate these transcription factors and to improve the therapy for articular diseases are important strategy.
Study on allergic responses:
Mast cells play a major role in the initiation of allergic reaction. Mast cell numbers need to be tightly controlled by cell proliferation, development and death. As NF-B is important transcription factor and a downstream signaling molecule for cell proliferation and differentiation, the regulation of NF-B in mouse mast cell line (MC-9) by overexpressing dominant negative IB (inhibitory subunit of NF-B) or mutant NF-B will be important to understand its role in cell proliferation, allergic responses, and apoptosis. Mast cell apoptosis is another aspect to regulate asthma. Mast cell activation requires FcR aggregation on binding with IgE. So, targeting mast cells using this receptor for apoptosis will be a viable strategy to control allergy. Preliminary data show that melanocyte stimulating hormone (MSH) downregulates NF-B and different cell types but induces apoptosis in mast cells. The crosslinked MSH and IgE (MSH-IgE) specifically induces cytotoxicity of mast cells. In this proposed project we want establish mast cell apoptosis by detecting different caspases, death domain containing molecules, pro- and anti-apoptotic factors and to test this in mouse model by developing allergic response and then challenge with the MSH-IgE complex and understand the disease severity. Cytokines especially IL-8 induces mast cells through interaction of cell surface receptors. So, receptor regulation is another important aspect to control allergic responses. Chemotaxis of mast cells will be regulated by down-modulating chemokine receptors such as IL-8Rs which will be detected by western blot, receptor crosslinking, fluorescence microscopy and Scatchard analysis. Preliminary data suggest that -MSH downregulates IL-8Rs. So, the possible mechanism of downregulation of IL-8R or other receptors (if any) will be studied by detecting the membrane fluidity and microviscosity and the involvement of mast cell proteases will be carried out. It is also important that all sorts of inflammations are preceded through the upregulation of a wide array of inflammatory proteins including cytokines, growth factors, proteases and adhesion molecules. Most of these proteins depend on activation of nuclear transcription factor kappa B (NF-B). Thus, regulation of NF-B and its upstream (kinases and receptor-associated molecules) and downstream (mostly inflammatory proteins) molecules will be carried out in this project. Cytokine secreted from T helper 2 (TH2) cells are central to do the development of allergic diseases - what role do SOCS (suppressor of cytokine signaling) proteins have in this setting? Recently, SOCS proteins are targeted for anti-allergy drugs. It is important to understand the regulation of these proteins in mast cells by downregulating NF-B. This study would be helpful to regulate the mast cell mediated inflammatory and allergic responses, which may be useful for designing a novel anti-allergic and anti-inflammatory drug against mast cell mediated allergic and inflammatory diseases.
The main objectives are -

• elucidati on of cell signaling pathway(s) involving allergic responses in mast cells,
• the role of NF-B in mast cell proliferation, differentiation, and allergic responses,
• regulation of cell surface receptor(s) which activate mast cells,
• detection of mast cell target specific modulator(s) to regulate NF-B and to induce apoptosis,
• testing in an animal model.

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) especially 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-B) by a variety of stimuli acts as anti-apoptotic. Thus, inhibiting NF-B 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-B 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-B 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.

Technologies seem to changing faster than ever, how do you adapt to that? What are the current technologies you are using?:
A lot of back-dated expreiments should be change with the modern-day technology to prove the same. Adaptation with the new technology and grabbing the techniques are the main ‘Mantra’ of research. Those - who have the good hands to grab these techniques are the real successor in this field. Now a days, modern art of technology by various companies really helping us to go really fast and neat research.

In the broader picture, where do you see the application for your cutting-edge research?:
Systemic biology would be good approach for me to define various diseases and for better therapy against those.
Fast forward to 2020. What’s your vision of Genomics in 2020?:
Genomics should translate into prognosis and solution for diseases