Title of project

Investigating early glycemic deviations through generative AI and integrative glycoprofiling technologies

Abstract

Type 2 diabetes (T2D) develops gradually, with early deviations in glucose homeostasis long preceding clinical diagnosis. These early deviations are often undetected by conventional clinical assessment tools, leaving a critical gap in our ability to intervene before irreversible metabolic dysfunction occurs. At the molecular level, the drivers of these early changes remain largely unknown. Protein glycosylation, a posttranslational modification regulating protein stability, signaling, and cell–cell communication, represents a promising but unexplored axis for understanding these earliest stages of the disease.

My overarching hypothesis is that glycans act as dynamic modulators of glucose sensing and metabolic adaptation. To test this, Aim 1 will integrate AI-derived features from continuous glucose monitoring (CGM) in individuals without T2D with high-resolution glycomics across two well-characterized human cohorts to identify glycosylation patterns associated with early glycemic deviations. Aim 2 will use human adipocyte models to examine how metabolic stressors perturb glycan pathways and identify candidate glycogenes. Aim 3 will validate these pathways in immuno-vascularized 3D adipose tissue models, integrating CRISPR-based perturbations with single-cell transcriptomics, secretome profiling, and highcontent image phenotyping.

The project is embedded in a collaborative and interdisciplinary environment, leveraging algorithms and deep-phenotype and molecular data from the EIC-funded GLUCOTYPES consortium and state-of-the-art adipose tissue models developed in the Wandall laboratory. A planned research stay in the Claussnitzer Lab at the Broad Institute of MIT and Harvard will provide international training in advanced cellular imaging and mechanistic insight of initial drivers in obesity and dysglycemia.

By bridging population studies, molecular biology, tissue engineering, and cellular imaging tools, this systems-biology project will illuminate early mechanisms of T2D and uncover glycosylation pathways as potential precision-prevention targets. At the same time, it will provide a uniquely interdisciplinary training platform, preparing me to foster my professional development and contribute to the future of precision medicine in diabetes research.