Farooq Syed Lab

The Syed Lab studies how inflammation alters the epigenome, including DNA and RNA modifications, and how these changes affect gene expression and protein translation in pancreatic islet and immune cells.

Our team develops innovative in vitro systems and preclinical models that closely mirror human diabetes, enabling us to uncover the molecular events that drive beta cell failure. Through this work, we aim to identify novel mechanisms and therapeutic targets that preserve beta cell health and improve outcomes for people living with diabetes.

Research Highlights

Beta Cell Stress and Autoimmune Activation

Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of insulin-producing beta cells, leading to insulin deficiency and chronic hyperglycemia. Although the precise molecular drivers of T1D remain incompletely understood, clinical and preclinical studies consistently implicate inflammatory cytokines in accelerating beta cell dysfunction and death. Our recent work demonstrates that inflammation activates specific beta cell-intrinsic signaling pathways, creating a feed-forward loop of cellular stress and immune activation that increases beta cell visibility to the immune system.

This project investigates how the integrated stress response disrupts messenger RNA (mRNA) translation and contributes to beta cell failure. We use state-of-the-art multi-omics approaches, including epigenomics, transcriptomics and translatomics, to define how inflammation reshapes RNA and protein landscapes in human beta cells. We also employ targeted small-molecule inhibitors to dissect stress-response pathways and determine their roles in T1D pathogenesis.

Age-Related Beta Cell Diversity in T1D

Evidence from human clinical studies suggests that age at onset influences disease heterogeneity in T1D, with children often experiencing more rapid beta cell loss than adults. The goal of this project is to identify the factors that contribute to beta cell stress resilience and heterogeneity and help explain age-dependent differences in metabolic outcomes.

In collaboration with Carmella Evans-Molina, M.D., Ph.D., at Indiana University in Indianapolis and Mark Atkinson, Ph.D., at the University of Florida in Gainesville, we apply leading-edge multi-omics approaches, including single-cell and spatial omics, to intact pancreatic tissue sections. These analyses aim to uncover the molecular mechanisms that drive accelerated beta cell dysfunction in younger individuals and reveal age-specific therapeutic opportunities.

Non-Coding RNAs in Beta Cell Function and Survival

Non-coding RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and transfer RNAs (tRNAs), are essential regulators of gene expression and cellular homeostasis. In pancreatic beta cells, these molecules play critical roles in maintaining normal cellular function and coordinating stress responses.

This project examines how non-coding RNAs modulate beta cell responses to immune-mediated inflammation, a defining feature of T1D. By influencing pathways involved in insulin production, cellular stress adaptation, and inflammatory signaling, lncRNAs and miRNAs can alter beta cell fate and susceptibility to autoimmune attack. Using targeted genetic and molecular approaches, we aim to identify non-coding RNA-based mechanisms and therapeutic targets that preserve beta cell function and delay or prevent T1D onset.

Early Biomarkers of Beta Cell Dysfunction and Death

Early detection is essential for developing personalized prevention and intervention strategies for T1D. This project focuses on identifying cell-specific biomarkers of early disease by analyzing circulating nucleic acids and protein signatures derived from beta cells and immune cells.

Using in vitro systems, in vivo models, and liquid biopsy samples from individuals with and without T1D, we investigate disease-associated molecular signatures carried by extracellular vesicles (EVs) and non-EV fractions. These studies aim to identify reliable biomarkers that signal early beta cell injury or immune activation before clinical onset, enabling more precise disease monitoring and informed therapeutic decision-making.