Faculty Profile

Paul Knoepfler
ASSISTANT PROFESSOR
Cell Biology and Human Anatomy (School of Medicine)
Stem Cell Program
Shriners Hospital Room 633A
Office 916-453-2289
Lab 916-453-2229
knoepfler@ucdavis.edu
http://www.stem.ws
[Picture of Paul Knoepfler]
WHAT CONTROLS STEM CELL BIOLOGICAL BEHAVIOR? We are interested in answering this question about stem cells both during normal embryonic development but also during healing and regeneration. Further, we are analyzing how this control system goes awry during diseases such as developmental disorders and cancer. Our lab studies the molecular programming of embryonic and neural stem cells as well as cancer stem cells. MYC IN STEM CELLS. We have found that a particular group of proteins called the Myc family appear to be master regulators of stem cell function. These Myc proteins are not only of critical importance for the ability of stem cells to do their normal "job" but also when the Myc genes are present at too high a concentration in stem cells they cause many human cancers. However we don't have a clear understanding of how Myc genes control the normal function of stem cells in development and regeneration nor how an excess of Myc leads to cancer. Therefore studying Myc's function in stem cells may provide critical clues as to how stem cells can be used in regenerative medicine as well as how to do our best to avoid cancer as a side effect from stem cell based regenerative medicine. Finally, these studies of Myc function should also help us to better understand human cancer in a more general sense, hopefully moving us one step closer to novel cures and prevention methods. STEM CELL EPIGENETICS. We are also interested in a key Myc cofactor called GCN5, a histone acetyltransferase, as well as epigenetics more generally in terms of their roles in gene transcription, stem cell biology and cancer. IPS CELLS. A final area of interest are induced pluripotent stem (iPS) cells. iPS cells are a major advance in regenerative medicine, but many questions remain about these cells in terms of their properties, both positive and negative such as tumorigenicity. We also do not know how Myc stimulates iPS production.

Degrees:
1998 - PhD - UC San Diego School of Medicine - Molecular Pathology

Awards:
Lucille P. Markey Graduate Fellowship, 1993-1998
Jane Coffin Childs Memorial Fund for Medical Research, Post-Doctoral Fellowship 1998-2001
Leukemia & 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 2008-2013

Department and Center Affiliations:
Institute for Pediatric Regenerative Medicine/Shriners Hospital
UC Davis Cancer Center
UC Davis Genome Center

Grad Group Affiliations and Specialties:
Biochemistry and Molecular Biology
Cell and Developmental Biology
Genetics
Neuroscience

Publications:
2009

Cotterman R and Knoepfler PS. N-Myc regulates expression of pluripotency genes in neuroblastoma including lif, klf2, klf4, and lin28b. PLoS One 2009 In press.

Knoepfler PS. Journal Club. A cell biologist looks at the risk and promise of a new insight into stem cells and cancer. Nature 2009. 457(228):361.

Knoepfler PS. Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells 2009. 27(5): 1050-1056.

2008

Knoepfler PS. Stem cells on the brain. Arch Neurology. 2008. 65(3): 311-315.

Cotterman R, Jin VX, Krig SR, Lemen JM, Wey A, Farnham PJ, and Knoepfler PS. N-Myc regulates a widespread euchromatic program in the human genome partially independent of its role as a classical transcription factor. Cancer Research 2008. 68(23): 9654-9662.

Laurenti E, Varnum-Finney B, Wilson A, Ferrero I, Blanco-Bose WE, Ehninger A, Knoepfler PS, Cheng PF, MacDonald R, Eisenman RN, Irwin D Bernstein ID, Trumpp A. Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity. Cell Stem Cell 2008. 3(6): 611-624.

Martins RA, Zindy F, Donovan S, Zhang J, Pounds S, Wey A, Knoepfler PS, Eisenman RN, Roussel MF, and Dyer, MA. N-Myc coordinates retinal growth with eye size during mouse development. Genes and Development 2008. 22(2): 179-93.

Knoepfler PS. Why Myc? An unexpected ingredient in the stem cell cocktail. Cell Stem Cell. 2008. 2(1):18-21

2007

Knoepfler PS. Myc goes global: new tricks for an old oncogene. Cancer Res 2007. 67(11):5061-3..

Ota S, Zhou ZQ, Knoepfler PS, and Hurlin PJ. Activities of N-Myc in the developing limb link control of skeletal size with digit separation. Development 2007. 134(8):1583-92.

Habib T, Tsang M, Moreno de Alboran I, Nicks A, Park H, Wilson L, Knoepfler PS, Andrews S, Rawlings D, Eisenman RN, and Iritani BM. Myc Stimulates Lymphocyte Differentiation and Amplifies Calcium Signaling. Journal of Cell Biology. 2007, 179(4):717-31.

2006

Hatton BA*, Knoepfler PS*, Kenney AM, Rowitch DH, de Alboran IM, Olson JM, and Eisenman RN. N-myc is an essential downstream effector of Shh signaling during both normal and neoplastic cerebellar growth. Cancer Res. 2006, 66 (17): 1-7. (*co-first authors).

Zindy F*, Knoepfler PS*, Xie S, Sherr CJ, Eisenman RN, Roussel MF. N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development. Proc Natl Acad Sci U S A. 2006, 103(31):11579-11583 (*co-first authors).

Knoepfler PS, Zhang XY, Cheng PF, Gafken P, McMahon SB, and Eisenman RN. Myc regulates global chromatin structure. Embo J 2006. 25(12): 2723-34.

Knoepfler PS, Kenney AM. Neural precursor cycling at Sonic speed: N-Myc pedals, GSK-3 brakes. Cell cycle. 2006, 5(1): 47-52.

Select earlier

Orian A, Grewall SS, Knoepfler PS, Edgar BA, Parkhurst SM, and Eisenman RN. Genomic Binding and Transcriptional Regulation by the Drosophila Myc and Mnt Transcription Factors. Cold Spring Harb Symp Quant Biol. 2005, 70:1-10.

Okubo, T, Knoepfler PS, Eisenman RN, and Hogan, BLM. Nmyc plays an essential role during lung development as a dosage sensitive regulator of progenitor cell proliferation and differentiation. Development. 2005, Mar; 132(6):1363-74.

Swanson KA*, Knoepfler PS*, Huang, K, Kang RS, Cowley SM, Eisenman RN and Ishwar Radhakrishnan. The HBP1 and Mad1 repressors Recruit Sin3 by Binding to the PAH2 Domain with Opposite Helical Orientations. Nat. Struc. and Mol. Bio. 2004, 11(8):738-46. (*co-first authors).

Knoepfler PS, Cheng PF, and Eisenman RN. N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation Genes & Dev 2002, 16(20): 2699-2712.

Knoepfler PS, and Eisenman, RN. Sin meets NuRD and other tails of repression. Cell. 1999, 99(5):447-50.

Laboratory Personnel:
Agnieszka Laskowski, Graduate Student Researcher, CDB

Jaime Connolly Rohrbach, Post-Doc Fellow

John Riggs, SRA I

Kelly Bush, SRA I

Marnie Morales, Graduate Student Researcher, Neuro

Natasha Varlakhanova, Post Doc Fellow

Rebecca Cotterman, Lab Manager

Vanessa Chan, Lab Assistant IV