About

Jeff Holt is a Professor, General Faculty, and Director of Graduate Studies in the Department of Statistics at the University of Virginia. He holds a Ph.D. in Mathematics from the University of Texas at Austin and a B.A. in Mathematics from Humboldt State University. His role involves overseeing graduate programs and contributing to the academic leadership of the department. The information provided does not specify his research focus or key contributions.

Research topics

• Biology
• Biochemistry
• Biophysics
• Cell biology
• Genetics
• Neuroscience
• Medicine
• Chemistry
• Organic chemistry
• Anatomy

Selected publications

• Structural and functional basis of mechanosensitive TMEM63 channelopathies

  Neuron · 2025-06-05 · 10 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• A contemporary view of mechanosensory transduction in auditory hair cells

  Biophysical Journal · 2025-06-16 · 3 citations

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Mammalian TMC1 or 2 are necessary for scramblase activity in auditory hair cells

  Hearing Research · 2025-03-06 · 10 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Endocochlear potential contributes to hair cell death in TMPRSS3 hearing loss

  Journal of Clinical Investigation · 2025-07-17 · 5 citations

  articleOpen access

  Pathogenic variants in the gene TMPRSS3 are a common cause of hearing loss in humans, although the causal mechanisms remain unknown. Previous work has shown that Tmprss3Y260X/Y260X mice exhibit normal hair cell development, mechanosensory transduction, and spiral ganglion patterning, but experience rapid hair cell death from P12 to P14 at the onset of hearing. Here, we demonstrate that Tmprss3Y260X/Y260X mice display an early and temporary spike in endocochlear potential (EP) prior to the onset of hair cell death. In vitro experiments with cochlear explants from Tmprss3Y260X/Y260X mice and in vivo studies with Tmprss3Y260X/Y260X mice crossed with 2 different mutant models that lacked EP generation promoted hair cell survival. Furthermore, systemic administration of furosemide, a drug that reduces EP in vivo, reduced hair cell death in Tmprss3Y260X/Y260X mice. These findings suggest that extracellular factors, including EP, play a role in TMPRSS3-related hair cell survival and hearing loss, and suggest that modulating EP could be a therapeutic strategy.

  PublisherDOI

• Author response: Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels

  2025-01-08 · 1 citations

  peer-reviewOpen access
  PublisherDOI

• Evaluation and validation of a vacuum-compatible, spectrally tunable, flat panel uniform source for testing large aperture earth observation systems

  2025-09-17

  article

  NASA GSFC, in conjunction with Labsphere Inc. and Genesis Engineering Solutions Inc., has performed tests and characterizations of the Flat Panel Illuminator 2 (FPI-2) system in both ambient and thermal vacuum environments to validate and verify its performance prior to use with the Joint Polar Satellite System-3 (JPSS-3) Visible Infrared Imaging Radiometer Suite (VIIRS) and JPSS-4 VIIRS instruments during spacecraft level testing. The system is an innovative, vacuum compatible, calibrated spectroradiometric illumination source and successor to the FPI-1. Designed to provide a large, uniform, active output area, the FPI-2 maintains a small form factor allowing it to serve as an in-vacuum calibration target for the VIIRS instrument’s optical bands during pre-launch testing. The system utilizes an in-vacuum light head with liquid-cooled hybrid quartz-tungsten (QT) and light emitting diode (LED) sources and an optimized integration chamber. Temperature control, radiometric control, and radiometric monitoring are provided by non-vacuum compatible hardware: a chiller unit, fiber coupled spectroradiometers, custom power supplies and software. The test campaign at GSFC builds on evaluations performed at Labsphere, Inc to validate key performance requirements passed down from the VIIRS and JPSS programs including radiometric output and spatial uniformity in both ambient and vacuum environments. The demonstrated performance and adaptability of the system make it capable of meeting the needs of many other instruments/missions requiring this type of test/calibration. The system will soon be compared side-by-side with the FPI-1 system and serve as the radiometric target for performance tests of the JPSS-3 and JPSS-4 VIIRS instruments.

  PublisherDOI

• AAV-mediated exon skipping therapy for Usher syndrome, type 2A

  Molecular Therapy · 2025-09-24 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels

  eLife · 2025-01-08

  articleOpen access

  Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechano-electrical transduction (MET) apparatus. These interactions have been proposed to be functionally relevant across mechanosensory organs and vertebrate species. Here, we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line. Our AlphaFold 2 models suggest that vertebrate CIB proteins can simultaneously interact with at least two cytoplasmic domains of TMC1 and TMC2 as validated using nuclear magnetic resonance spectroscopy of TMC1 fragments interacting with CIB2 and CIB3. Molecular dynamics simulations of TMC1/2 complexes with CIB2/3 predict that TMCs are structurally stabilized by CIB proteins to form cation channels. Overall, our work demonstrates that intact CIB2/3 and TMC1/2 complexes are integral to hair-cell MET function in vertebrate mechanosensory epithelia.

  PublisherDOI

• AAV gene therapy rescues hearing and balance in a model of CLIC5 deafness

  EMBO Molecular Medicine · 2025-08-26 · 2 citations

  articleOpen access

  Adeno-associated virus-based gene therapy offers a promising treatment paradigm for inner ear diseases; however, the genetic heterogeneity of hereditary deafness requires gene-specific strategies and optimization of current approaches to identify the range of treatable conditions and improve therapeutic outcomes. To consider the therapeutic potential for a hearing loss gene not previously explored, we investigated the gene encoding the chloride intracellular channel protein CLIC5, mutations in which lead to DFNB103 in humans and deafness and circling behavior in a Clic5-deficient mouse model. In this study, we utilized two constructs to deliver the wild-type Clic5 coding sequence into Clic5-deficient mice: single-stranded and self-complementary adeno-associated virus, the latter known for rapid onset of transgene expression. We report a robust restoration of CLIC5 expression using either construct, including prevention of morphological degeneration and preserving auditory and vestibular function. Interestingly, the self-complementary construct achieved comparable functional recovery to single-stranded construct but at a lower titer. These findings highlight the potential of self-complementary adeno-associated virus to reduce dose requirements, minimize toxicity and broaden clinical utility for inner ear therapies.

  PublisherOA PDFDOI

• TMEM145 is a Principal Component of Outer Hair Cell Stereocilia

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

Recent grants

• TMC gene function in sensory hair cells

  NIH · $4.8M · 2013–2030

• Ion Channel Function in Auditory and Vestibular Hair Cells

  NIH · $5.5M · 2001–2021

• NIH Grant R56DC005439

  NIH · $379k · 2009

• NIH Grant R21DC011720

  NIH · $478k · 2014

• TMC gene function in sensory hair cells

  NIH · $372k · 2013–2016

Frequent coauthors

• Bifeng Pan

  Harvard University

  69 shared

• John W. Wilcut

  64 shared

• Laval M. Verhalen

  Oklahoma State University

  64 shared

• Wondi Mersie

  64 shared

• T. B. Moorman

  United States Department of Agriculture

  64 shared

• Lawrence Bozsa

  University of Wisconsin–Madison

  64 shared

• Glenn Wehtje

  Auburn University

  64 shared

• Meena Upadhyaya

  Cardiff University

  64 shared

Education

• Ph.D., Physiology

  University of Rochester

  1995