Welcome to the ENGIN Lab
at the
University of Wisconsin-Madison
Our laboratory is dedicated to understanding the pathogenesis of type 1 diabetes (T1D) with the ultimate goal of identifying therapeutic targets for this disease. We take a multidisciplinary approach and utilize various experimental systems and state-of-the-art technologies. These include transgenic preclinical models, mouse and human pancreatic islets, super-resolution imaging, single cell multiomics, and machine learning.
Beta cell ER stress and the UPR in T1D pathogenesis
Perturbations to endoplasmic reticulum (ER) homeostasis and unmitigated stress lead to β-cell dysfunction and death. Evidence suggests an important role of β-cell ER stress and aberrant unfolded protein response (UPR) in T1D initiation and progression. By using β-cell-specific deletion models of the key UPR pathway genes in T1D preclinical model, NOD mice, we have begun to understand the specific functions of the each UPR sensors in β-cells during different stages of T1D development.
Beta cell senescence in T1D
A subset of insulin producing β-cells in T1D undergo a stress-response termed “senescence” that we recently found to exhibit substantial heterogeneity, comprising of distinct programs that either promote or protect against immune-mediated β-cell demise. The unique molecular features of these distinct responses remain unknown.
Beta cell-immune cell crosstalk in T1D
Stressed β-cells can become highly immunogenic due to the generation of neoantigens and abnormal antigen presentation, triggering an autoimmune response against the β-cells. Uncovering the dialogue between stressed β-cells and immune cells during T1D progression would provide a better understanding of the molecular mechanisms of disease process, and may reveal novel targets for development of effective therapies for T1D.