About

Paul Robbins, PhD, is a Professor of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota. He serves as the Associate Director of the Masonic Institute on the Biology of Aging and Metabolism (MiBAM) and is part of the Medical Discovery Team on the Biology of Aging. His research has significantly contributed to understanding gene regulation and autoimmune diseases. Robbins was among the first to identify enhancer elements that regulate transcription at a distance and to demonstrate that the retinoblastoma tumor suppressor regulates transcription. He also developed gene therapies for autoimmune diseases, including an ongoing clinical trial for osteoarthritis. His recent work involves identifying senotherapeutic compounds capable of reducing senescent cell burden and extending healthspan and lifespan in mouse models, with these compounds now in more than 15 clinical trials for age-related diseases and conditions. His research focuses on pathways that drive autoimmune, inflammatory, and age-related degenerative diseases, emphasizing the inhibition of transcription factors like NF-κB and IL-1ß signaling. Robbins' lab develops novel approaches to treat diseases such as type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease, and osteoarthritis using biologics, small molecules, gene transfer techniques, stem cells, microvesicles, and drugs that reverse cellular senescence, aiming to improve healthy aging.

Research topics

• Biology
• Genetics
• Medicine
• Cell biology
• Internal medicine
• Immunology
• Computational biology
• Virology
• Bioinformatics
• Gerontology

Selected publications

• RNAseq data from the brain of a C57Bl/6 female mouse

  Cellular Senescence Network (SenNet) · 2026-01-16

  datasetOpen access
  PublisherDOI

• Tomatidine is a senotherapeutic compound that improves cognitive function and reduces cellular senescence in aged mice

  EMBO Molecular Medicine · 2026-04-01 · 1 citations

  articleOpen access

  Abstract Cellular senescence drives aging and age-related dysfunction across multiple tissues, including the brain. Through a high-content, senescent cell-based phenotypic screen of a small panel of natural products, we identified tomatidine, an aglycone of tomatine found in tomatoes, as a previously unrecognized senotherapeutic agent. In senescent human brain microvascular endothelial cells and fibroblasts, tomatidine selectively suppressed SASP expression without affecting p16 Ink4a or p21 Cip1 levels consistent with a senomorphic effect. In aged mice, tomatidine reduced frailty and improved motor coordination and cognitive performance. These functional benefits were accompanied by reduced senescence markers (p16 Ink4a , p21 Cip1 , and telomere-associated DNA damage foci) in liver, skin, and hippocampal neurons, along with decreased neuroinflammation and microglial activation. Tomatidine also diminished brain endothelial cell senescence while enhancing tight junction protein expression, suggesting preserved blood–brain barrier integrity. Together, these findings identify tomatidine as a promising senescence-targeting compound with beneficial effects in aged mice and support its further evaluation in mechanistic and translational studies.

  PublisherOA PDFDOI

• Ensemble of Time-Evolving SASP Gene Sets Identifies IGFBP7 and CDKN1A as a Potential Marker Pair for Senescent Fibroblast Subpopulations Across Tissues

  International Journal of Molecular Sciences · 2026-03-26

  articleOpen access

  The senescence-associated secretory phenotype (SASP) is a hallmark of senescent cells and plays a critical role in the development and progression of various age-related diseases, including cancer, cardiovascular disorders, and neurodegenerative diseases. In this study, we characterize SASP heterogeneity using single-cell RNA sequencing (scRNA-seq) data, focusing on the transcriptional signatures associated with elevated expression of individual SASP genes in mature senescent cells, as well as time-dependent variation in SASP expression across the early and mature senescent states in the WI-38 human lung fibroblast cell line. We generated multiple gene sets, each representing the transcriptional landscape linked to high expression of a specific SASP gene, and integrated them into an ensemble that reflects the temporal dynamics of SASP gene expression. Applying SASP scores derived from this ensemble of gene sets (SASP scores/EGS) to publicly available scRNA-seq datasets from human lung, skin, and eye tissues enabled the identification of senescent fibroblasts and revealed IGFBP7 as a consistently upregulated marker in p21+ or p16+ fibroblasts across diverse human tissues. Our framework supports improved detection of both early and mature fibroblast replicative senescent cells, offering valuable insights into aging and age-related disease research.

  PublisherOA PDFDOI

• RNAseq data from the brain of a C57Bl/6 female mouse

  Cellular Senescence Network (SenNet) · 2026-01-16

  datasetOpen access
  PublisherDOI

• RNAseq data from the brain of a C57Bl/6 female mouse

  Cellular Senescence Network (SenNet) · 2026-01-16

  datasetOpen access
  PublisherDOI

• RNAseq data from the brain of a C57Bl/6 female mouse

  Cellular Senescence Network (SenNet) · 2026-01-16

  datasetOpen access
  PublisherDOI

• RNAseq data from the brain of a C57Bl/6 female mouse

  Cellular Senescence Network (SenNet) · 2026-01-16

  datasetOpen access
  PublisherDOI

• RNAseq data from the brain of a C57Bl/6 female mouse

  Cellular Senescence Network (SenNet) · 2026-01-16

  datasetOpen access
  PublisherDOI

• A transcriptomic analysis reveals shared and inducer-specific expression patterns of cellular senescence

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-23

  articleOpen access

  Abstract Cellular senescence is a heterogeneous cell state induced by diverse stressors, including telomere attrition, genotoxic agents, oxidative damage, and inflammation. Despite ongoing efforts to identify conserved senescence biomarkers, it remains unclear whether senescence-inducing stimuli converge at the level of individual genes or broader molecular processes. Here, we profiled transcriptomic changes in human primary lung fibroblasts (IMR-90) driven toward senescence by replicative exhaustion, bleomycin, H 2 O 2 , or ionizing radiation under matched, dose- or time-resolved conditions. Across all four senescent inducers, global transcriptomic variation aligned along a shared axis of senescence progression, consistent with established machine learning-based senescence classifiers. However, overlap at the level of individual genes was limited, with most responses being inducer-specific or only partially conserved. In contrast, pathway-level analysis revealed far more consistent enrichment across all conditions, including downregulation of proliferation-associated pathways and activation of stress-related and pro-inflammatory pathways, accompanied by distinct inducer-specific patterns. These results support a hierarchical organization of the senescent transcriptome, in which diverse senescence inducers converge on shared pathway-level features while maintaining gene-level heterogeneity. These results provide a foundational basis for interpreting senescence signatures and may facilitate the development of more robust transcriptome-based markers of cellular senescence in aging and disease.

  PublisherDOI

• RNAseq data from the brain of a C57Bl/6 female mouse

  Cellular Senescence Network (SenNet) · 2026-01-16

  datasetOpen access
  PublisherDOI

Recent grants

• Administrative Core

  NIH · $10.6M · 2021–2026

• Administrative Supplement to: Cell Autonomous and Non-Autonomous Mechanisms of Aging

  NIH · $17.7M · 2019–2020

• NIH Grant R56AG059675

  NIH · $385k · 2019

• NIH Grant N01AR062225

  NIH · $2.4M · 2001

• NIH Grant P01AG04337603

  NIH · $4.1M · 2016

Frequent coauthors

• Laura J. Niedernhofer

  University of Minnesota

  243 shared

• Christopher H. Evans

  214 shared

• Steven C. Ghivizzani

  138 shared

• Andrea Gambotto

  UPMC Hillman Cancer Center

  77 shared

• Michael T. Lotze

  55 shared

• Luise Angelini

  University of Minnesota System

  52 shared

• Matthew J. Yousefzadeh

  Institute on Aging

  51 shared

• Hideaki Tahara

  Osaka International Cancer Institute

  48 shared

Education

• Ph.D., Molecular Biology

  University of California Berkeley

  1985

• B.A., Biology

  Haverford College

  1980

Awards & honors

• Dr. James E. Rubin Medical Memorial Award
• Graduating Medical Student Research Award
• Veneziale-Steer Award
• Dr. Marvin and Hadassah Bacaner Research Awards
• Schmidt Steer Award