Paul Knoepfler

Paul Knoepfler

Position Title

  • Department of Cell Biology and Human Anatomy, School of Medicine
Shriners Hospital Room 633

Profile Introduction

The research in the Knoepfler lab focuses on defining the epigenetic and transcriptional control mechanisms that direct stem cell cell fate and tissue growth, including especially abnormal grown in cancer. We are also working to determine the relationship between stem cells and cancer at the epigenomic level. How are normal stem cells programmed and how does this programming go awry in cancer? Our cancer focus is predominantly on pediatric nervous system tumors. Our model systems include knockoout mice as well as pluripotent stem cells and cancer cells. We are particularly interested in complementing our mouse genetics studies with newer CRISPR-based gene editing studies of human stem and cancer cells, where we have provided new insights into childhood glioma. For many of our projects we use cutting edge genomics methods. Our two big picture goals are to develop innovative cancer treatments (particularly for pediatric tumors) and to make stem cell-based regenerative medicine therapies more effective as well as safer with lower risk of tumorigenesis.

Research Interests

Stem cell and cancer epigenomics


Our lab's main research interest is focused on epigenomic control of stem and cancer cell behavior. We are particularly interested in three types of regulatory factors: MYC proteins, DPPA4/2, and the histone variant H3.3. Althought these proteins are not related to each other at the amino acid level, they share the same pattern of having key roles in normal stem cells and, when deregulated, in cancer. To study these factors we use a variety of methods including genetics, cell and molecular biology, genomics, protein biochemistry, and emerging gene editing technologies.

Grad Group Affiliations

  • Biochemistry, Molecular, Cellular and Developmental Biology
  • Integrative Genetics and Genomics
  • Neuroscience

Specialties / Focus

  • Animal Genomics
  • Cancer Biology
  • Cell Biology
  • Chromosome Biology
  • Chromosome Dynamics and Nuclear Function
  • Developmental Biology
  • Epigenomics
  • Genomics, Proteomics and Metabolomics
  • Human Genetics and Genomics
  • Integrated Genetics and Genomics
  • Molecular Medicine
  • Stem Cell Biology


  • Histology CHA402


  • Jennifer Yee, Lab Manager
  • Vanessa Cervantes, Graduate Student Researcher, BMCDB
  • Shering Torres, Medical Student Researcher
  • Cailin Kelly, Graduate Student Researcher, BMCDB
  • Rachel Klein, Post-Doctoral Fellow

Honors and Awards

  • Lucille P. Markey Graduate Fellowship, 1993-1998
  • Jane Coffin Childs Memorial Fund for Medical Research, Post-Doctoral Fellowship 1998-2001
  • Leukemia and Lymphoma Society Special Fellowship, 2002-2005
  • Howard Temin Award, NCI, 2005-2010
  • Brain Tumor Society, Leadership Chair of Research, 2007-9
  • March of Dimes Basil O'Connor Starter Scholar Award, 2008-10
  • California Institute of Regenerative Medicine (CIRM) New Faculty Award 2009-2014
  • GPI National Advocacy Award 2013 (Top American Stem Cell Advocate of 2013)


    • 1998 PhD Molecular Pathology UC San Diego School of Medicine
    • 1989 BA English Literature Reed College


    Kim M, Knoepfler PSAnticipated impact of stem cell and other cellular medicine clinical trials for COVID-19Regen Med. 2021 Jun 11. doi: 10.2217/rme-2021-0025. Epub ahead of print. PMID: 34114493.

    Klein RH, Knoepfler PSStem cell models help crack regional oncohistone codes driving childhood gliomasCell Stem Cell. 2021 May 6;28(5):785-787. doi: 10.1016/j.stem.2021.04.013. PMID: 33961758.

    Gene editing: sloppy definitions misleadKnoepfler PNature. 2018 Dec;564(7736):345. doi: 10.1038/d41586-018-07802-2. No abstract available. PMID: 30568213

    Mapping and driving the stem cell ecosystemKnoepfler PSRegen Med. 2018 Oct;13(7):845-858. doi: 10.2217/rme-2018-0056. Epub 2018 Oct 5. PMID: 30289055

    Genomic functions of developmental pluripotency associated factor 4 (Dppa4) in pluripotent stem cells and cancer. Klein RH, Tung PY, Somanath P, Fehling HJ, Knoepfler PSStem Cell Res. 2018 Jul 19;31:83-94. doi: 10.1016/j.scr.2018.07.009. [Epub ahead of print]

    Too Much Carrot and Not Enough Stick in New Stem Cell Oversight Trends. Knoepfler PSCell Stem Cell. 2018 Jul 5;23(1):18-20. doi: 10.1016/j.stem.2018.06.004. Epub 2018 Jun 21.

    The FDA and the US direct-to-consumer marketplace for stem cell interventions: a temporal analysis. Knoepfler PS, Turner LG., Regen Med. 2018 Jan 12. doi: 10.2217/rme-2017-0115. [Epub ahead of print]

    ERBB3-Binding Protein (EBP1) is a novel DPPA4 cofactor in human pluripotent cells. Somanath P, Bush KM, Knoepfler PS.Stem Cells. 2018 Jan 12. doi: 10.1002/stem.2776. [Epub ahead of print]

    Chen, KY., Bush, K., Klein, R.H. et al. Reciprocal H3.3 gene editing identifies K27M and G34R mechanisms in pediatric glioma including NOTCH signalingCommun Biol 3, 363 (2020).

    Yuen BTK, Bush KM, Barrilleaux BL, Cotterman R, and Knoepfler, PS. Histone H3.3 regulates dynamic chromatin states during spermatogenesis. (2014) Development. Sep;141(18):3483-94.

    BTK Yuen, PS Knoepfler. (2014) Histone H3. 3 Mutations: A Variant Path to Cancer. Cancer Cell 24 (5), 567-574.