Welcome to the ENGIN Lab
at the
University of Wisconsin-Madison
Our laboratory is committed to uncovering the mechanisms that drive the pathogenesis of Type 1 Diabetes (T1D), with the long-term goal of identifying new therapeutic targets for disease prevention and treatment. To achieve this, we employ a multidisciplinary research strategy and integrate a wide array of cutting-edge technologies including:
Transgenic preclinical models
Mouse and human pancreatic islets
Advanced super-resolution imaging
Single-cell multiomics and spatial transcriptomics approaches
Machine learning and computational analysis
Through this integrative approach, we aim to accelerate discovery and drive meaningful progress toward improving the lives of individuals affected by T1D.
Beta cell ER stress and the UPR in T1D pathogenesis
Perturbations in endoplasmic reticulum (ER) homeostasis and unresolved ER stress are known to drive β-cell dysfunction and death. Growing evidence highlights the critical role of β-cell ER stress and a dysregulated unfolded protein response (UPR) in both the initiation and progression of Type 1 Diabetes (T1D).
Using β-cell–specific deletion models targeting key UPR pathway components in the T1D preclinical model, NOD mice, our laboratory is dissecting the distinct contributions of each UPR sensor to β-cell health and survival across different stages of disease development. These studies are beginning to reveal how individual UPR branches shape β-cell fate, immune susceptibility, and the trajectory of T1D progression.
Beta cell senescence in T1D
A subset of insulin-producing β-cells in T1D undergoes a stress-induced state known as senescence. Our recent work has revealed that this senescent β-cell population is markedly heterogeneous, consisting of distinct cellular programs—some that promote immune-mediated β-cell destruction and others that appear to protect β-cells from immune attack. Despite this emerging understanding, the unique molecular signatures that define these divergent senescence responses remain unknown and represent a critical area of investigation.
Beta cell-immune cell crosstalk in T1D
Stressed β-cells can become highly immunogenic, generating neoantigens and displaying abnormal antigen presentation that, together, can trigger or amplify the autoimmune attack characteristic of T1D. Understanding the cross-talk between stressed β-cells and immune cells throughout disease progression is essential for revealing the molecular drivers of autoimmunity. Uncovering this dialogue may not only deepen our insight into T1D pathogenesis but also identify novel therapeutic targets for the development of effective interventions.