Mirza Saqib Baig
Indian Institute of Technology, India
Postdoctoral Research at Mayo Clinic, Rochester, USA (2014-2015), University of Illinois at Chicago, USA (2010-2014), Indian Institute of Toxicology Research, Lucknow, India (2009-2010). His research interests focus on the role of macrophages in the initiation, progression and resolution of inflammatory processes. The long term research interest is to elucidate the inflammatory signaling in macrophages during chronic and acute inflammation. Macrophage recruitment and plasticity are key components of several inflammatory diseases including asthma, fibrosis/cirrhosis, rheumatoid arthritis and atherosclerosis. Understanding the mechanisms that regulate macrophage phenotypic plasticity in tissues is critical for the identification and validation of markers and therapeutic targets in inflammatory diseases.
Awards 2010: Ramanujan Fellowship Award
2014: Ramalinga Swami Fellowship Award
2013: Mirus Research Award, Mirus Bio LLC, USA
2009: Research Bursary Award, UK
2008: FEBS Pre Doctoral Award , Greece
e Cheminfo Award, USA
2007: EMBL International Ph.D Fellow Award
2007: Research Travel Grant Award, USA
Nitric oxide synthases are a family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule, having essential roles in many biological processes including the control of blood pressure, regulation of neuronal activity and immune responses. NOS3 (endothelial NOS or e NOS) and NOS2 (inducible NOS or I NOS) have been appreciated as mediators of inflammatory processes. However, considerably less is known about the role of NOS1 (neuronal NOS or n NOS) in inflammation. We have uncovered an important role for this enzyme in regulating TLR4 signaling. We demonstrate that in contrast to the enhanced susceptibility of NOS2-/- and NOS3-/- mice to LPS, NOS1-/- mice are, in fact, more resistant to LPS-induced lethality and tissue injury. We demonstrate that the loss of NOS1 attenuates TLR4-stimulated cytokine production and NF-κB activity in vivo and in vitro. Macrophages from NOS1-/- animals demonstrate an LPS-induced decrease in protein levels of the p65 subunit of NF-κB. This decrease in p65 protein correlates with an increase in protein levels of suppressor of cytokine signaling-1 (SOCS1) and increased physical association between SOCS1 and p65. On studying the mechanism of NOS1-regulation of inflammation we found that an early pulse of NOS1-derived NO was required to stabilize p65 in the nucleus of macrophages via the inhibitory S-nitrosation of suppressor of Cytokine Signaling-1 (SOCS1). NOS1-derived NO through nitrosation of Cys147 and Cys179 on SOCS1 permits p65-mediated pro-inflammatory gene transcription and is essential for the mechanism of inflammation. Taken together, our results demonstrate that NOS1 is a fundamental early regulator of gene transcription of the inflammatory response thereby heavily impacting the course, type and duration of the inflammatory process.
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