The human innate immune system plays a vital role in defense against various maladies, such as pathogen invasion, dysfunctional organelles, and cancer formation.
Research in my laboratory focuses on understanding the mechanisms by which our innate immune system (1) senses molecular patterns that signify various assaults, (2) coordinates signal integration at each step of the cascade, and (3) becomes dysregulated and elicits auto-inflammatory responses.
We use multiple cutting-edge and classic biophysical approaches in our research: cryo-EM, steady and pre-steady state kinetics, Rosetta computational suites, mathematical modeling, X-ray crystallography, SAXS, and various imaging techniques.
Inflammasomes. Inflammasomes are supramolecular signaling platforms that play crucial roles in innate immune defense against various maladies, ranging from pathogen invasion to cancer. A unique aspect of the inflammasome cascade is that initially diverse signaling pathways progressively converge, culminating to the activation of the caspase-1 protease.
We will delineate the mechanisms by which inflammasome receptors, adaptors, and negative regulators recognize their specific signaling partners while avoiding crosstalk.
Most recent publication: Matyszewski et al., PNAS, 2018 (http://www.pnas.org/content/115/9/E1963.long)
Current support: American Cancer Society
Cytoplasmic DNA sensing pathways. The presence of double-stranded (ds)DNA in the cytoplasm signals serious problems in eukaryotic cells, ranging from dysfunctional mitochondria to pathogen invasion. In mammals, the innate immune system detects these rogue dsDNA and initiate inflammatory responses. Cytoplasmic dsDNA sensing pathways are integral to host defense against numerous pathogens, and their malfunctions are also implicated in various human maladies.
We will define the molecular mechanisms by which multiple cytoplasmic dsDNA sensors initiate host innate immune responses in a coordinated fashion.
Most recent publication: Hooy and Sohn, eLife, 2018 (https://elifesciences.org/articles/39984)
Current support: National Institute of Health
Translational Research. Dysregulation of the innate immune system is linked to various human maladies such as cancer (e.g. colon cancer, melanoma, and lung cancer) and auto-inflammatory disorders (e.g. lupus, psoriasis, and Sjögren’s syndrome). Over the years, we have developed multiple quantitative assays that can track various activities of a number of innate immune sensors. Using these tools, we have recently launched a high-throughput drug discovery program. This project is in collaboration with Division of Rheumatology and Division of Infectious Diseases at Johns Hopkins School of Medicine.
Most recent publication: Antiochos et al., JCI insight, 2018 (https://insight.jci.org/articles/view/120179)
Current support: Johns Hopkins School of Medicine