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Cell signaling

fibroblast and T cells.PNG

T cells (green) attaching to antigen presenting cells (red) resulting in formation of cytosolic protein clusters (yellow) that induce T cell activation. 

We study the cell signaling mechanisms that allow proliferation of cancer cells and the signaling pathways that activate lymphocytes to counter the cancer cells. By studying these cell signaling pathways, we aim to understand how cancers grow and how the immune system combats cancer. These insights help us develop better cancer-targeting therapies.

Lymphocytes such as T cells are key component of the immune system and play a pivotal role in recognizing and killing cancer cells. T cells express the T cell receptor (TCR) on the cell surface. TCR binding to an antigen presented by antigen presenting cells (APCs) leads to a signaling cascade that ends of activation of transcription factor NF-kB. We use imaging and biochemical tools to discover the mechanism of TCR signaling to NF-kB.

TCR signaling triggers the activation of various intracellular kinases, leading to the recruitment and activation signaling proteins such as PKC, CARMA1, BCL10, MALT1. The BCL10-MALT1 signaling complex activates another set of kinases called IKK which ultimately signals to NF-kB. NF-kB. NF-kB is a transcription factor that, which translocates to the cell nucleus and induce the expression of genes involved in T cell proliferation, cytokine production, and effector function. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The TCR to NF-kB pathway is a complex and tightly regulated process, ensuring that T cell activation occurs only when warranted and that the immune response is appropriately tailored to the specific antigen encountered. Dysregulation of this pathway can lead to immune-related disorders, autoimmune diseases, or impaired immune responses to infections and cancers. Understanding the intricacies of this pathway has significant implications for the development of immunotherapies and treatments aimed at modulating T cell responses in various disease contexts.

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Read about our work on cell signaling:

A transient, HDAC6-independent aggresome-like structure sustains T cell receptor-dependent Malt1 signal transduction

manuscript in review

Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape

manuscript in review

NEDD4L intramolecular Interactions regulate its auto- and substrate NaV1.5 ubiquitination

Journal of Biological Chemistry, 2024

CARD19, the protein formerly known as BinCARD, is a mitochondrial protein that does not regulate Bcl10-dependent NF-κB activation after TCR engagement

Cellular Immunology, 2020

T Cell Receptor Activation of NF-κB in Effector T Cells: Visualizing Signaling Events Within and Beyond the Cytoplasmic Domain of the Immunological Synapse

Methods in Molecular Biology, 2017

Visualizing TCR-induced POLKADOTS formation and NF-κB activation in the D10 T-cell clone and mouse primary effector T cells

Methods in Molecular Biology, 2015

T cell receptor signals to NF-κB are transmitted by a cytosolic p62-Bcl10-Malt1-IKK signalosome

Science Signaling, 2014

A new look at T cell receptor signaling to nuclear factor-κB

Trends in Immunology, 2013

Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-κB

Immunity, 2012

Selective autophagy regulates T cell activation

Autophagy, 2012

Cutting edge: TCR ligation triggers digital activation of NF-κB

The Journal of Immunology, 2010

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