Understanding aging through chromatin, proteins, and single cells

Our laboratory studies how chromatin organization changes during aging and how these changes influence cellular identity, tissue function, and healthspan. A central idea in the lab is that aging is associated with a progressive loss of chromatin organization. As chromatin becomes less compact, normally silent regions of the genome may become accessible, gene regulation becomes less coordinated, and cells can begin to lose their functional identity. Our research asks three main questions:

1) What molecular events drive chromatin disorganization during aging?

2) How does chromatin instability affect gene regulation, cellular identity, and tissue function?

3) What protective mechanisms help some cells preserve chromatin stability and maintain function across the lifespan?

Research areas

Chromatin proteomics and histone modification biology

Histone modifications help determine how the genome is organized, accessed, and interpreted. We develop quantitative mass spectrometry methods to measure histone post-translational modifications with high specificity and depth, including individual marks, combinatorial histone codes, histone readers, and chromatin-associated proteins. Our goal is to understand which histone modification patterns are functional and how they regulate transcription, chromatin compaction, genome stability, and cellular identity.

Metabolism, histone acylation, and aging biology

Metabolism can regulate chromatin by controlling the availability of molecules used to modify histones, including acetyl-CoA, succinyl-CoA, and other acyl-CoAs. A major focus of the lab is histone succinylation and its possible role in chromatin stability, transcriptional fidelity, longevity, and healthspan. This work connects biochemical mechanism, metabolism, chromatin regulation, aging biology, and gerotherapeutic interventions.

Three-dimensional and tissue-like models

Standard two-dimensional cell culture often fails to reproduce key features of tissue biology. We use 3D spheroids and microphysiological systems to study chromatin regulation under more tissue-like conditions. These models allow us to study slow proliferation, hypoxia, metabolism, nuclear architecture, histone modification dynamics, and aging-associated chromatin changes in controlled experimental systems.

Proteomic technology development and translational applications

Many biological questions cannot be answered with existing methods. We develop mass spectrometry technologies to improve sensitivity, throughput, robustness, and biological interpretability. Current directions include single-cell proteomics, single-cell histone modification profiling, small-molecule analysis, protein-ligand interaction mapping, and proteome-wide approaches for drug target discovery.

Single-cell chromatin and proteomic heterogeneity

Cells that appear similar can behave very differently. These differences are often invisible when thousands or millions of cells are analyzed together. We develop single-cell mass spectrometry workflows to study proteomic and chromatin heterogeneity one cell at a time. These approaches allow us to identify rare cell states, distinct histone modification profiles, heterogeneous drug responses, aging-associated chromatin states, and infection-associated phenotypes that would be missed in bulk measurements.