When a pathogen enters the body, the immune system responds by mounting an attack against it.<\/p>\n
Seems simple. But this description doesn\u2019t account for why some people get much sicker than others from the same exposure.<\/p>\n
Jianbin Ruan, assistant professor of immunology at UConn School of Medicine, leads a lab focused on discovering the molecular mechanisms at work in immune signaling to provide answers to this question and pathways for more effective treatments and vaccines.<\/p>\n
Ruan\u2019s Ph.D. work at the University of Science and Technology of China focused on epigenetics \u2013 not immunology.<\/p>\n
Humans share 99.9% of their DNA. Yet, people have vastly different health outcomes. Epigenetics, the study of gene expression changes that occur without changes to the underlying DNA, helps us understand why this happens.<\/p>\n
As Ruan was preparing to graduate, he was seeing more and more scientific literature about unexpected engagement of proteins in immune signaling. Ruan pivoted during his postdoctoral fellowship at Harvard Medical School where he studied how immune signaling mediated responses to infection.<\/p>\n
\u201cIn the big picture, epigenetics and immunology are quite similar,\u201d Ruan says. \u201cEverybody has the same genes, but they can have different shapes, different looks, and different behaviors. A lot of that is influenced by epigenetics. The immune system works in a similar way \u2014 people may share the same immune genes, yet respond to infections differently.\u201d<\/p>\n
Ruan\u2019s lab at UConn Health focuses on three areas of research: non-canonical inflammasome signaling, gasdermin-mediated programmed cell death, and pore-forming proteins\/toxins.<\/p>\n
\u201cIn my lab, the most exciting part, although it\u2019s very basic, it\u2019s also the most fundamental part \u2013understanding how our immune system works at the molecular level, especially immune signaling,\u201d Ruan says. \u201cThe ultimate goal of all the projects is to try to understand the basic mechanisms of how the immune system works and how bacteria manipulate our signaling and to try to provide some ideas for clinical translation of those studies.\u201d<\/p>\n
Canonical inflammasomes, a type of protein complex that has been studied extensively, rely on sensor proteins to detect infection or cellular damage. This signals the cells to release cytokines (signaling proteins that help coordinate immune responses) and induces inflammatory cell death to eliminate infected cells.<\/p>\n
Non-canonical inflammasomes, by contrast, are not well studied. These proteins sense lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, in the cytosol (the liquid inside cells). Recognition of cytosolic LPS triggers inflammatory cell death, a key driver of sepsis.<\/p>\n
Previous studies found that LPS with six lipid chains trigger non-canonical inflammasomes. But different bacteria have different LPS with more or fewer lipid chains. LPS with only five lipid chains, for example, do not activate the inflammasomes.<\/p>\n
A recent study Ruan published in Science Advances<\/a> demonstrated that the number of lipid chains in LPS dictates activation of the non-canonical inflammasome.<\/p>\n \u201cWe study how, in response to upstream secondary activation of what\u2019s called the \u2018executioner protein\u2019, it causes immediate cell death and how this kind of cell death can affect our immune system,\u201d Ruan says. \u201cGasdermin is responsible for this process.\u201d<\/p>\n
![\"Cryo-Em](\"https:\/\/today.uconn.edu\/wp-content\/uploads\/2026\/06\/Cyro-em-Ruan-lab-series-of-views-1500x1000-8.png\")