Biology subjects

Xia, A. Y.

Publications and source records attributed to Xia, A. Y..

4 recordsLinked to original sources

bioRxiv2026

Integrative Multi-omics Analysis of the Human Skeletal Muscle Response to Endurance or Resistance Exercise: Findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to systematically characterize the molecular basis of the health benefits of exercise. Here, we present the integrative, multi-omics response of human skeletal muscle to acute endurance (EE) and resistance (RE) exercise. Distinct temporal responses were observed, with changes in ATAC-seq, phosphoproteome, and metabolome occurring before changes in the transcriptome and proteome. These distinct temporal multi-omic dynamics were used to identify transcriptional regulatory hubs converging around MEF2A and NFIC regulation of autophagy, angiogenesis and metabolism. Further, early RE-specific phosphoproteome signatures counteracted epigenetic modifications and downregulated transcripts involved in protein turnover. Additional findings include suppression of HIPK2/3 kinase signatures linked to the acute exercise regulation of sarcomeric proteins TTN, NEB, ANKRD2 and LMOD2. Our data demonstrate distinct temporal regulation across the multi-omic landscape of human skeletal muscle, with EE and RE eliciting common and unique molecular signatures.

systems biology↗

bioRxiv2026

Multi-Omic, Multi-Tissue Responses to Acute Exercise in Sedentary Adults: Findings from the Molecular Transducers of Physical Activity Consortium

Regular physical activity represents one of the greatest mechanisms for maintaining human health, yet the underlying molecular transducers of these benefits remain incompletely understood. Multi-omic assays now provide new opportunities to study the coordinated molecular responses of body tissues to different exercise modalities. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this need by creating a molecular map of the response to physical activity. Described here is the first human cohort of MoTrPAC: sedentary adults enrolled prior to study suspension during the COVID-19 pandemic (N=175) randomized to either endurance or resistance exercise, or non-exercise control. From these participants, we detail their global acute molecular response in skeletal muscle, adipose tissue, and blood, integrated at multiple levels: tissue, exercise modality, timepoint, and omic category. These analyses characterize key molecular pathways, identify central regulators, and implicate novel candidate exerkines in mediating multi-organ exercise effects.

systems biology↗

bioRxiv2025

Single-cell, Spatially-Resolved TCR Profiling Links T Cell Phenotype and Clonality in Human Tumors

Despite remarkable success in melanoma and other cancers, immune checkpoint blockade has shown limited efficacy in head and neck squamous cell carcinoma (HNSCC), with durable responses in only [~]10% of patients. This is paradoxical given the abundant infiltration of CD8 T cells in HNSCC, suggesting that current T cell profiling methods fail to fully capture functional anti-tumor immunity and that key immunosuppressive mechanisms remain poorly understood. To uncover mechanisms regulating T cell function in situ, we developed a multimodal profiling framework integrating high-dimensional flow cytometry, single-cell RNA- and TCR-sequencing, and spatial transcriptomics, including spatially-resolved TCR profiling at single-cell resolution. Applying this approach to paired blood and tumor samples from 27 HNSCC patients enabled single-cell resolution mapping of T cell clonality, transcriptional state, and spatial localization within intact tumors. Tumors with similar clinical features and immune profiles by flow cytometry and scRNA-seq exhibited markedly different spatial immune architectures. Within the T cell compartment, stem- and memory-like T cells localized within immune-rich niches, while exhausted cells were broadly dispersed in tumor-rich regions. Targeted spatial TCR mapping revealed that tumor-enriched TCR clones were distributed throughout the tumor yet adopted distinct, location-dependent phenotypes, indicating that both antigen specificity and spatial cues shape T cell differentiation and function in human tumors. These findings reveal fundamental principles of T cell organization in solid tumors and establish a versatile platform for spatially-resolved, antigen-specific T cell profiling.

immunology↗

bioRxiv2021

High-Throughput and High-Dimensional Single Cell Analysis of Antigen-Specific CD8+ T cells

Although critical to T cell function, antigen specificity is often omitted in high-throughput multi-omics based T cell profiling due to technical challenges. We describe a high-dimensional, tetramer-associated T cell receptor sequencing (TetTCR-SeqHD) method to simultaneously profile TCR sequences, cognate antigen specificities, targeted gene-expression, and surface-protein expression from tens of thousands of single cells. Using polyclonal CD8+ T cells with known antigen specificity and TCR sequences, we demonstrated over 98% precision for detecting the correct antigen specificity. We also evaluated gene-expression and phenotypic differences among antigen-specific CD8+ T cells and characterized phenotype signatures of influenza- and EBV-specific CD8+ T cells that are unique to their pathogen targets. Moreover, with the high-throughput capacity of profiling hundreds of antigens simultaneously, we applied TetTCR-SeqHD to identify antigens that preferentially enrich cognate CD8+ T cells in type 1 diabetes patients compared to healthy controls, and discovered a TCR that cross reacts between diabetic and microbiome antigens. TetTCR-SeqHD is a powerful approach for profiling T cell responses.

immunology↗