Alex Holehouse, PhD

Alex Holehouse, PhD

Primary Academic Title

Assistant Professor, Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine

Research Interest

My lab works on understanding the molecular basis for how intrinsically disordered regions (IDRs) carry out cellular functions, and how this goes wrong in disease. Given almost every cancer-associated protein contains larger IDRs, this is a rich area for us in terms of relating molecular biophysics to human disease. Our goal is to enable the mechanistic interpretation of mutations in IDRs in the context of cancer - i.e. how and why do mutations cause disordered regions to misfunction.

Education

  • 2017: PhD, Computational Biophysics , Washington University, St. Louis, MO

Training

  • 2017 - 2019: Postdoctoral Fellow Department of Biomedical Engineering , Washington University, St. Louis, MO

Selected Research Publications

Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.
  • Lambourne L, Mattioli K, Santoso C, [...] Holehouse AS, [...] Fuxman Bass JI
  • Mol Cell 2025
Molecular determinants of condensate composition.
  • Holehouse AS, Alberti S
  • Mol Cell 2025
Rational Protein Engineering to Enhance MHC-Independent T-cell Receptors.
  • Chang JF, Landmann JH, Chang TC, [...] Holehouse AS, Singh N
  • Cancer Discov 2024
Partial wrapping of single-stranded DNA by replication protein A and modulation through phosphorylation.
  • Chadda R, Kaushik V, Ahmad IM, [...] Holehouse AS, [...] Antony E
  • Nucleic Acids Res 2024
Identification of plant transcriptional activation domains.
  • Morffy N, Van den Broeck L, Miller C, [...] Holehouse AS, [...] Strader LC
  • Nature 2024
Direct prediction of intermolecular interactions driven by disordered regions.
  • Ginell GM, Emenecker RJ, Lotthammer JM, Usher ET, Holehouse AS
  • bioRxiv 2024
Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator.
  • Jankowski MS, Griffith D, Shastry DG, [...] Holehouse AS, Hurley JM
  • Nat Commun 2024
Phase transition of GvpU regulates gas vesicle clustering in bacteria.
  • Li Z, Shen Q, Usher ET, [...] Holehouse AS, [...] Lu GJ
  • Nat Microbiol 2024
Direct prediction of intrinsically disordered protein conformational properties from sequence.
  • Lotthammer JM, Ginell GM, Griffith D, Emenecker RJ, Holehouse AS
  • Nat Methods 2024
Structural biases in disordered proteins are prevalent in the cell.
  • Moses D, Guadalupe K, Yu F, [...] Holehouse AS, Sukenik S
  • Nat Struct Mol Biol 2024
Dissecting the biophysics and biology of intrinsically disordered proteins.
  • Banerjee PR, Holehouse AS, Kriwacki R, [...] Mendell JT
  • Trends Biochem Sci 2024

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