Vig, Monika

Ph.D.
Assistant Professor of Pathology and Immunology

Research Abstract:

We study signaling mechanisms in developing and mature lymphocytes. In particular, we are interested in understanding the origin and outcome of localized intracellular calcium fluxes. Calcium ions are important ‘second messengers’ that regulate nearly every cellular process such as gene expression, secretion, migration, cell death and metabolism.

In most cells, cross-linking of tyrosine kinase or G-protein coupled receptors initiates a signaling cascade that results in endoplasmic reticulum (ER) calcium store depletion. Calcium release from the ER in turn activates store-operated calcium entry (SOCE) across plasma membrane. In lymphocytes and many other cells, receptor induced calcium flux is mediated by calcium release activated calcium (CRAC) channels. A major goal of my lab is to understand the molecular steps involved in the activation of SOCE via CRAC channels.

Using genome-wide RNAi screens, we have identified two of the long sought molecular components involved in CRAC channel activation, CRACM1 (or Orai1) and alpha-SNAP. We use a combination of molecular, biochemical, genetic and imaging approaches to identify and characterize the role of proteins involved in SOCE. Recently we have found that assembly of CRAC channel pore subunit into multimeric functional channels is orchestrated on-site by alpha-SNAP upon stimulation. We are testing the hypothesis that this highly unusual process of CRAC channel assembly allows T lymphocytes to localize and regulate the strength of signal via cell surface receptors.

Point mutations in molecular components of CRAC channel complex have been associated with immune-deficiencies and cancers in human and mice. Using mouse models of CRAC channel deficiency, we are interested in characterizing novel physiological roles for SOCE and identify signaling nodes where SOCE intersects with other signaling networks to regulate pathological processes such as inflammation and cancer.