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Jyotika Sharma

Jyotika Sharma

Regular Member

Associate Professor

[email protected]
MDA JBF Y6.6024 (Unit 110)

The University of Texas MD Anderson Cancer Center
Department of Critical Care 

Using state of the art techniques and resources including unique transgenic mouse lines (many of which are not available commercially); and human patient samples, my laboratory is investigating neutrophil functions in acute and chronic inflammatory diseases. Specifically, we study the mechanisms of :

1) neutrophil turnover (granulopoiesis and efferocytosis); and

2) neutrophil extracellular trap (NET) formation.

Neutrophil homeostasis is key to successful resolution of infection without causing overt pathology.  Perturbations in the processes controlling the generation of functional and mature neutrophils in the bone marrow (granulopoiesis), their mobilization to the site of infection and their clearance  can lead to pathological conditions. During systemic bacterial infection, the extensive loss of neutrophils in the periphery is balanced by increased production and mobilization of these leukocytes by emergency granulopiesis. We have discovered novel function of a C-type lectin receptor in emergency granulopoiesis and modulation of neutrophil clearance mechanisms by a respiratory pathogen.  Two projects focusing on these aspects in the lab are:

  1. Mechanism of Efferocytosis and neutrophil homeostasis in pneumonic sepsis; and
  2. Role of galectins as alarmins
  3. Neutrophil functions in secondary pneumonia

NETs are DNA fibrils expelled by neutrophils that are decorated with granular contents such as various proteases. NETs have been reported to play protective roles in infectious diseases by trapping, neutralizing and killing extracellular microbes. On the flip side, an exuberant NET formation has been linked to immunopathology of sepsis, autoimmune diseases and even cancer metastasis. To harness the beneficial outcome of NETs while avoiding their potentially harmful effects, a clear understanding of the molecular mechanism of neutrophil NET formation is essential. In this regard we have identified critical functions of C-type lectin receptor Mincle, and  calcium channel protein TRPM2 in regulating NET formation via activation of autophagy. With these mechanistic discoveries, a major thrust of my lab research is therapeutic modulation of NET formation in disease specific manner, a yet unmet clinical need. As a result, we have identified FDA approved drugs which can be repurposed to modulate NET formation. We have also discovered novel anti-inflammatory biofactors (isolated from helminth parasites) and small-molecule inhibitors (we termed PIns) that can inhibit neutrophil NET formation and mitigate sepsis, without affecting antimicrobial function of neutrophils. Major projects covering these aspects in the lab are:

  1. Mechanism of Mincle-mediated NET formation: Implications in sepsis and metabolic disease conditions
  2. NET formation and its therapeutic modulation in breast cancer
  3. Epigenetic mechanisms of chromatin release in NET formation : Diagnostic implications
  4. Therapeutic modulation of NETs in neonatal sepsis
  5. Novel biofactors as NET modulators: implications in metabolic diseases and COPD


MDACC Faculty

Education & Training

PhD, Kanpur University, India, 2001