About

Mario R. Capecchi, Ph.D., is a distinguished professor of human genetics and biology at the University of Utah's Eccles Institute of Human Genetics and a Howard Hughes Medical Institute investigator. He is renowned for his pioneering work on "knockout mice" technology, a gene-targeting technique that has revolutionized mammalian biology. This technology has enabled the creation of animal models for hundreds of human diseases, including cancer, by allowing precise genetic modifications in mice. In 2007, Capecchi was awarded the Nobel Prize in Physiology or Medicine in recognition of these groundbreaking contributions. Upon receiving the Nobel Prize, Capecchi expressed that the honor was significant not only for himself but also for the University, the Department of Human Genetics, and all members of his laboratory, past and present. His work has had a profound impact on biomedical research, providing essential tools for understanding gene function and disease mechanisms.

Research topics

• Genetics
• Medicine
• Cancer research
• Pathology
• Biology
• Computational biology

Selected publications

• Microglia respond to and induce anxiety and grooming in mice using calcium signaling

  Molecular Psychiatry · 2026-04-13

  articleOpen accessSenior author

  Disruption of the mouse Hoxb8 gene causes chronic anxiety and pathological over-grooming resulting from defective Hoxb8 microglia. Furthermore, optogenetic stimulation of Hoxb8 microglia in specific regions of the brain induces elevated anxiety and/or grooming. Herein we show that the molecular signals for inducing anxiety and/or grooming in response to optogenetic activation are calcium ions. Conversely, induction of grooming and anxiety in mice produces calcium transients within microglia. Unexpectedly, calcium transients are not produced in Hoxb8 mutant mice in response to the induction of these behaviors. The likely cause for this lack of response by Hoxb8 mutant mice to induced grooming is the presence of high constitutive levels of free calcium within Hoxb8 mutant microglia resulting from the gene disruption. These calcium ions, in turn, serve as relentless signals to increase anxiety and grooming leading to chronic anxiety and pathological overgrooming in Hoxb8 mutant mice. Thus, we have shown that calcium signaling is used by microglia: 1) to induce anxiety and/or grooming by optogenetic stimulation of Hoxb8 microglia in WT mice, 2) to respond by microglia to the induction of both behaviors in WT mice and 3) as the causative agent for producing chronic anxiety and pathological overgrooming in Hoxb8 mutant mice.

  PublisherDOI

• Basic enables selection-free efficient knockin of large DNA in primary human T cells

  Molecular Therapy · 2026-01-02

  articleOpen access
  PublisherOA PDFDOI

• Tic-related behaviors in Celsr3 mutant mice are contributed by alterations of striatal D3 dopamine receptors

  Molecular Psychiatry · 2025-03-28 · 7 citations

  article
  PublisherDOI

• Defective Hoxb8 microglia are causative for both chronic anxiety and pathological overgrooming in mice

  Molecular Psychiatry · 2025-09-02 · 4 citations

  articleOpen accessSenior author

  Disruption of the Hoxb8 gene results in chronic anxiety and pathological overgrooming in mice. Using bilateral intracerebral cell transplantation, we demonstrate that mutant Hoxb8 microglia are causative for both behaviors. Mice contain two microglia lineages, Hoxb8 and non-Hoxb8 microglia. We proposed that the two lineages work as a binary system, in opposition to each other with Hoxb8 microglia functioning to reduce anxiety and grooming (function as brakes), whereas non-Hoxb8 microglia increase the levels of both behaviors (function as accelerators). This model makes a strong, unexpected prediction: mice containing only wild-type canonical non-Hoxb8 microglia should exhibit pathological levels of grooming and anxiety. We demonstrate that this is the case, providing strong support for both microglia functioning as a binary system and for the 'Accelerator/Brake' model. Since mice containing only non-Hoxb8 microglia represent mice with a loss of Hoxb8 function due to the absence of Hoxb8 microglia, the more intensive pathology associated with Hoxb8 mutant mice must reflect that mutant mice have both gain and loss of function components. We identify and quantify the relative contribution of each component.

  PublisherOA PDFDOI

• Arid1a Loss Enhances Disease Progression in a Murine Model of Osteosarcoma

  Cancers · 2024-07-31 · 1 citations

  articleOpen access

  Osteosarcoma is an aggressive bone malignancy, molecularly characterized by acquired genome complexity and frequent loss of TP53 and RB1. Obtaining a molecular understanding of the initiating mutations of osteosarcomagenesis has been challenged by the difficulty of parsing between passenger and driver mutations in genes. Here, a forward genetic screen in a genetic mouse model of osteosarcomagenesis initiated by Trp53 and Rb1 conditional loss in pre-osteoblasts identified that Arid1a loss contributes to OS progression. Arid1a is a member of the canonical BAF (SWI/SNF) complex and a known tumor suppressor gene in other cancers. We hypothesized that the loss of Arid1a increases the rate of tumor progression and metastasis. Phenotypic evaluation upon in vitro and in vivo deletion of Arid1a validated this hypothesis. Gene expression and pathway analysis revealed a correlation between Arid1a loss and genomic instability, and the subsequent dysregulation of genes involved in DNA DSB or SSB repair pathways. The most significant of these transcriptional changes was a concomitant decrease in DCLRE1C. Our findings suggest that Arid1a plays a role in genomic instability in aggressive osteosarcoma and a better understanding of this correlation can help with clinical prognoses and personalized patient care.

  PublisherOA PDFDOI

• Supplementary Figure S8 from Targeting the Wnt Pathway in Synovial Sarcoma Models

  2023-04-03

  preprintOpen access

  <p>Supplementary Figure S8 - PDF file 1084K, Figure S8: Effects of SSTC-104 on Wnt-regulated tissues</p>

  PublisherOA PDFDOI

• Supplementary Figure S8 from Targeting the Wnt Pathway in Synovial Sarcoma Models

  2023-04-03

  preprintOpen access

  <p>Supplementary Figure S8 - PDF file 1084K, Figure S8: Effects of SSTC-104 on Wnt-regulated tissues</p>

  PublisherDOI

• Supplementary Figure S11 and Tables S1-S3 from Targeting the Wnt Pathway in Synovial Sarcoma Models

  2023-04-03

  preprintOpen access

  <p>Supplementary Figure S11 and Tables S1-S3 - PDF file 460K, Figure S11: Regulation of an embryonic Wnt-interactive network by SYT-SSX2 and in human synovial sarcomas Table S1: Differentially regulated Wnt components in mesenchymal precursor cells expressing SYT-SSX2 and in synovial sarcoma tumors Table S2: Differentially regulated Wnt targets in mesenchymal precursor cells expressing SYT-SSX2 and in synovial sarcoma tumors Table S3: The embryonic Wnt interactive network in mesenchymal precursor cells expressing SYTSSX2 and in synovial sarcoma tumors</p>

  PublisherOA PDFDOI

• Correction: Lrig1 expression identifies quiescent stem cells in the ventricular‑subventricular zone from postnatal development to adulthood and limits their persistent hyperproliferation

  Neural Development · 2023-05-23

  erratumOpen accessSenior author

  Correction: Lrig1 expression identifies quiescent stem cells

  PublisherOA PDFDOI

• Supplementary Figures S2 and S3 from Targeting the Wnt Pathway in Synovial Sarcoma Models

  2023-04-03

  preprintOpen access

  <p>Supplementary Figures S2 and S3 - PDF file 2332K, Figure S2:SG3 tumors are positive for beta-catenin and Myf5 Figure S3:Normal development of Myf5 myoblasts in beta-catenin knockout mice</p>

  PublisherDOI

Recent grants

• NIH Grant R01HD030701

  NIH · $2.5M · 2003

• NIH Grant R37GM021168

  NIH · $3.2M · 2002

• Developmental Biology Training Program

  NIH · $8.3M · 1995–2028

• NIH Grant R37HD030701

  NIH · $3.9M · 2014

• Targeting of Genes in the Mammalian Genome

  NIH · $6.4M · 1976–2016

Frequent coauthors

• Kenneth E. Bernstein

  New York University

  107 shared

• Pierre Corvol

  Académie de Paris

  90 shared

• Jonathan W. Adams

  University of Cambridge

  63 shared

• Josiane E. Eid

  University of Miami

  56 shared

• Taylor P. Sherrill

  Vanderbilt University Medical Center

  54 shared

• Andrea L. Frump

  Indiana University – Purdue University Indianapolis

  54 shared

• Christina B. Garcia

  Centre College

  54 shared

• Whitney Barham

  54 shared

Education

• B.S.

  Antioch College

• Ph.D.

  Harvard University

Awards & honors

• 2007 Nobel Prize Winner for Physiology or Medicine