Department of Cell Biology and Human Anatomy, School of Medicine
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 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. 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.
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
Specialties / Focus
- Animal Genomics
- Cancer Biology
- Cell Biology
- Chromosome Biology
- Chromosome Dynamics and Nuclear Function
- Developmental Biology
- Genomics, Proteomics and Metabolomics
- Human Genetics and Genomics
- Integrated Genetics and Genomics
- Molecular Medicine
- Stem Cell Biology
- Histology CHA402
- Kelly Bush, Lab Manager
- Vanessa Cervantes, Graduate Student Researcher, BMCDB
- Kuang-Yui Michael Chen, Post-Doc Fellow
- Nichole Lewis
- 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
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.
Tung PY, Varlakhanova NV, and Knoepfler PS. (2013). Identification of DPPA4 and DPPA2 as a novel family of pluripotency-related oncogenes. Stem Cells, Aug 20. doi: 10.1002/stem.1526. [Epub ahead of print]. NIHMS525053
Bush KM, Yuen BT, Barrilleaux BL, Riggs JW, O Geen H, Cotterman R, Knoepfler PS. (2013). Endogenous mammalian histone H3.3 exhibits chromatin-related functions during development. Epigenetics Chromatin, Apr 9;6(1):7. PMC36359032013 Apr 9;6(1):7.
Riggs JW, Barrilleaux B, Varlakhanova N, Bush K, Chan V, and Knoepfler PS. Induced pluripotency and oncogenic transformation are related processes. Stem Cells & Dev. 2013 Jan 1;22(1):37-50.
Laskowski AI and Knoepfler PS. (2013). Myc binds the pluripotency factor Utf1 through the basic-helix-loop-helix leucine zipper domain. BBRC, Jun 14;435(4):551-6. PMC3694802
Automation of Library Preparation for High-resolution ChIP-seq Profiling. IM Henry, R Cotterman, P Knoepfler, L Comai, RW Kim, H O'Geen. Journal of Biomolecular Techniques. 2013. JBT 24 (Suppl), S45.
Chromatin immunoprecipitation assays for myc and N-myc. Barrilleaux BL, Cotterman R, Knoepfler PS. The Myc Gene, 117-133.
Scientists: you really need to get out of the lab more. Knoepfler PS. Nat Med. 2013 Sep 6;19(9):1086. doi: 10.1038/nm0913-1086.
Key Action Items for the Stem Cell Field: Looking Ahead to 2014. PS Knoepfler. Stem cells and development.
Stem Cells: An Insider's Guide. Book. 2013. World Scientific Publishing Company. Paul S. Knoepfler. http://www.amazon.com/Stem-Cells-An-Insiders-Guide/dp/9814508802
Meissen JK , Yuen BTK, Kind T, Riggs JW, Barupala DK, Knoepfler PS*, and Fiehn O*. (2012). Induced pluripotent stem cells show metabolomic differences to embryonic stem cells in polyunsaturated phosphatidylcholines and primary metabolism. PLoS One, 7(10): e46770. *co-corresponding authors. PMC3471894.