subramanian.isbscience.org/research/Research Overview
The Subramanian Lab works in the fields of innate immunity and systems immunology. We employ experimental and computational approaches to tackle basic questions in innate immunity, its role in host defense against pathogens and the development of complex diseases. In particular, we are interested in exploring the functions and regulation of a class of cytosolic immune sensors called the NOD-like receptors (or NLRs) and how their dysregulation manifests disease. We apply the insights gleaned from this research to broadly address how the immune system goes awry in human immune disorders, and we develop strategies for therapeutic benefit.
Research Foci
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Host-Pathogen Crosstalk
Pathogens and hosts are engaged in a constant evolutionary arms race. Macrophages are one of the earliest cell types that detect pathogens through cell surface-associated Toll-like receptors (TLRs) and mount an innate immune response. Inside macrophages invading pathogens are detected by different classes of cytosolic sensors. Read more…
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The NLRP3 Inflammasome
We are investigating how the NLRP3 inflammasome is activated in response to diverse stimuli. NLRP3 is implicated in the pathophysiology of many autoinflammatory, autoimmune, metabolic and infectious diseases. NLRP3 is activated by a wide-range of molecules including crystals formed in gout and atherosclerosis, viruses and bacterial toxins, but the mechanisms by which NLRP3 senses and elicits a response to these chemically and structurally dissimilar stimuli remain elusive. Read more…
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Systems Biology of NLRs
In humans, 23 NLRs have been identified. These have been hypothesized to have distinct biological functions based on sequence and structure modeling analysis. To date, however, only a few NLRs have been studied intensively and the activating stimuli, physiologic functions, and relevant signaling pathways of most members of the NLR family are unknown or poorly defined. Read more…
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Lyme Disease
We are investigating heterogeneity of the immune response during Lyme Disease caused by the spirochaete Borrelia. An outstanding question in the field is why some patients resolve disease with antibiotic therapy while others progress to post-treatment disease. Using systems biology approaches we are dissecting the mechanisms of pathogen clearance and deriving immune correlates of disease.
