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Research Interests

We study the cell biology of signal transduction, with a focus on tiny 'molecular switches', called monomeric and trimeric GTPases.

The problems we seek to tackle and the questions we are wresting to answer:

receptor-signaling.jpgAlthough we know a lot about how cells communicate between themselves, we still know awfully little about how cells communicate messages within itself. How does it integrate information that it perceives? How does it decide before it can act/react? And finally, how does it learn and adapt over time, in health and disease? These are the secrets that remain to be resolved before we can bigen to think of cells as they are meant to be, i.e., tiniest autonomous units of life!

Cells perceive their surroundings via a myriad of receptors on their surface which initiate a variety of signaling cascades to be transmitted to the nucleus. En route to the nucleus, these signals are selectively either amplified or attenuated in a spatio-temporally restricted fashion to efficiently drive one cellular process at any given time.

While timely amplification of signals is essential to tide over stress or injury in physiologic conditions (such as promote healing in any epithelial wounds/ulcers), sustained enhancement/amplification of signals (in response to growth factors/agonists) heralds oncogenesis and cancer metastasis.

cell-migration.jpgSimilarly, abnormal signal amplification is a key feature during an overzealous inflammatory response during wound healing and can be associated with yet another undesired outcome, i.e., fibrogenesis (cardiac fibrosis after myocardial infarction, all causes of liver cirrhosis, pulmonary and renal fibrosis) thereby distorting normal anatomy and impairing normal functions.

We seek to gain insights into how incoming signals initiated by a variety of cell surface receptors are amplified in an unrestricted fashion to drive key cellular processes (secretion, autophagy, growth, proliferation, migration) in health and disease, and identify novel 'signal-amplification switches/interfaces' within these signaling pathways which can also serve as therapeutic targets.

Ongoing Projects

Fundamental (basic) research projects currently ongoing in our laboratory include:

  • A comprehensive analysis of the phosphoproteome of G proteins by growth factors
  • Compartmentalization of G protein signaling by growth factors (a comprehensive assessment of impact on GPCRs and Ric8A/B).
  • Decoding the invariant allosteric path to bring about a nucleotide 'fumble' in the trimeric GTPase Gi.
  • Structural basis for modulation (inhibition as a GDI) of the oncoprotein GNAS by GEMs
  • Cell permeant peptides as surrogates to modulate G proteins in cells (Collaborative with Professor Diana Imhof, Germany).
  • Numerous Receptors/Receptor-downstream pathways are being studied (see Research-Main 'Landing' Page).

As a physician-scientist, we relentlessly pursue the translational relevance of our fundamental discoveries. Because we believe that "the patient is always right."

Diseases currently being studied in our laboratory include:

  • Bacterial Infections:
    • Sepsis
    • Colitis
    • Fundamental biology investigating pathogen sensors (NOD2, TLRs).
    • Multi-omic approach to decoding innate immune responses (Macrophage and Neutrophils)
    • The impact of gender on innate immune responses
  • Immunometabolism:
    • Obesity and Insulin resistance
    • Atherosclerosis
    • Circadian Rhythm
    • Non-alcoholic steato hepatitis
  • Cancer Biology [breast, lung, colon, gastric, esophageal, pancreas, biliary]
    • Tumor stroma niche (Bone marrow messenchymal stem cells)
    • Tumor associated macrophages (TAMs)
    • Reprogramming Cancer stem cells
    • Impact of Microbial Sensing in Cancer progression
    • Pre-cancer program (Barrett's, colorectal polyp, gastric metaplasia)
  • Neuronal disorders
    • Alzheimer's
    • Autism