Biology subjects

Katz, D. H.

Publications and source records attributed to Katz, D. H..

7 recordsLinked to original sources

bioRxiv2026

The Common Fund Data Ecosystem (CFDE)

The NIH Common Fund Data Ecosystem (CFDE) integrates data resources from 18 NIH Common Fund programs for discovery and integrative analysis. These programs generate valuable but heterogeneous datasets that can be difficult to discover, access, and reuse. CFDE aims to provide a collaborative, community-built infrastructure that links and enriches Common Fund programs. We describe the evolution, structure, and core technologies of CFDE, including practical approaches that support submission, integration, visualization, and public release of multimodal data. Training programs and workforce initiatives lower barriers to adoption. CFDE has devised solutions to critical issues facing cross-program initiatives, including data scale and heterogeneity, dataset integration, and long-term sustainability. We demonstrate the utility of linking Common Fund resources through integrative tools and cross-dataset queries to yield insights that would otherwise be infeasible. Collectively, CFDE shows that a standards-driven, federated approach enhances and unifies cross-disciplinary resources, fostering collaboration and data-driven discovery.

scientific communication and education↗

bioRxiv2026

Multi-omic responses to acute exercise in abdominal subcutaneous adipose tissue of sedentary adults: findings from MoTrPAC

Exercise induces widespread health benefits across multiple tissues, yet the acute molecular responses in human adipose tissue remain poorly defined. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) profiled temporal molecular changes in abdominal subcutaneous adipose tissue (ASAT) following a single bout of exercise. Healthy sedentary adults were randomized to endurance (EE), resistance (RE), or control (CON) groups. ASAT biopsies were collected pre-exercise and at 45min, 4hr, and 24hr post-exercise, followed by transcriptomic, proteomic, phosphoproteomic, and metabolomic analyses. EE and RE elicited distinct, time-resolved molecular programs involving angiogenesis, extracellular matrix remodeling, mitochondrial metabolism, substrate utilization, and circadian regulation. Phosphoproteomics revealed acute changes in cytoskeletal and branched-chain amino acid metabolism proteins associated with glycemic control. Temporal metabolomic shifts were cell-type-specific. Finally, we identified candidate adipose-derived exerkines with predicted endocrine actions. This multi-omic map of acute ASAT responses offers insight into adipose-specific mechanisms by which exercise promotes metabolic health.

systems biology↗

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

Blood Biochemical Responses to Acute Exercise: Findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

Exercise benefits numerous organ systems and tissues, however limited knowledge exists about its underlying molecular pathways. Identifying the exercise-induced biochemical changes that occur in the circulation may provide further insights into how exercise confers systemic health changes. Here, we perform large-scale plasma proteomic, metabolomic, and whole blood transcriptional profiling in sedentary human participants undergoing acute endurance exercise (EE), resistance exercise (RE), or a non-exercise control (CON) in up to 7 timepoints over a 24 hour period. We observe 7066 transcript, 189 protein, and 448 metabolite changes in response to EE or RE compared to CON. Our analyses reveal numerous shared biochemical responses between EE and RE modes, but also differences in immune cell responses, lipid metabolism, and pathways reflective of tissue repair and angiogenesis. Taken together, our findings highlight novel temporal and exercise mode-specific blood-based molecular responses to acute exercise, and provide a new resource for the scientific community.

systems biology↗

bioRxiv2026

Exercise modulation of the alternative splicing landscape in human tissues

The diverse health benefits of exercise are associated with multi-organ molecular responses. Alternative RNA splicing (AS) is an important determinant of transcriptome and proteome diversity. We profiled the temporal effects of acute endurance and resistance exercise on the AS landscape of human skeletal muscle, adipose tissue, and blood, and studied regulatory mechanisms through integrated multi-omic analyses. We identified 5102 distinct differential AS (DAS) events, with the majority modifying protein-coding sequence (89%) and being independent of altered RNA expression (67%). Endurance and resistance exercise induced differing patterns of AS alterations with divergent temporal trajectories. We inferred the DAS-associated RNA-binding and DNA-binding proteins. In skeletal muscle, where DAS events were the most abundant, DAS genes were enriched for muscle structure- and RNA splicing-related processes, and splicing machinery components were regulated at the protein phosphorylation, RNA, and AS levels. These findings implicate AS regulation as a major mediator of the responses to exercise.

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↗

bioRxiv2023

Human Plasma Proteomic Profile of Clonal Hematopoiesis

Plasma proteomic profiles associated with subclinical somatic mutations in blood cells may offer novel insights into downstream clinical consequences. Here, we explore such patterns in clonal hematopoiesis of indeterminate potential (CHIP), which is linked to several cancer and non-cancer outcomes, including coronary artery disease (CAD). Among 61,833 ancestrally diverse participants (3,881 with CHIP) from NHLBI TOPMed and UK Biobank with blood-based DNA sequencing and proteomic measurements (1,148 proteins by SomaScan in TOPMed and 2,917 proteins by Olink in UK Biobank), we identified 32 and 345 unique proteins from TOPMed and UK Biobank, respectively, associated with the most prevalent driver genes (DNMT3A, TET2, and ASXL1). These associations showed substantial heterogeneity by driver genes, sex, and race, and were enriched for immune response and inflammation pathways. Mendelian randomization in humans, coupled with ELISA in hematopoietic Tet2-/- vs wild-type mice validation, disentangled causal proteomic perturbations from TET2 CHIP. Lastly, we identified plasma proteins shared between CHIP and CAD.

genetics↗