Quantcast

Department of Cell Biology and Human Anatomy

Paul Knoepfler, Ph.D.

Paul Knoepfler

Assistant Professor
633A Shriners Hospital, Sacramento Campus
(916) 453-2289
e-mail


Recent/Current
Research Funding

National Cancer Institute Howard Temin Award Grant

Shriners Hospital for Children Grant

Brain Tumor Society Grant

Graduate Group Affiliations

Genetics

Cell and Developmental Biology

Neuroscience

Research Interests

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 stiumlates iPS production.

For more information please visit the Knoepfler lab homepage at: http://www.stem.ws

Representative Publications

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

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

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 both during normal and neoplastic cerebellar growth. Cancer Res. 2006, 66 (17): 1-7. (*co-first authors).

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

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

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

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.

Cotterman R, Jin VX, Krig SR, Lemen JM, Wey A, Farnham PJ and Knoepfer 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. In press.

Laurenti E, Varnum-Finney B, Wilson A, Ferrero i, Blanco-Bose WE, Ehninger A, Knoepfler PS, Cheng PF, MacDonald R, Eisenmann RN, Irwin D Berstein ID, Trumpp A. Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity. Cell Stem Cell 2008. In press.

Recent/Current Teaching

CHA 402, Cell and Tissue Biology

CHA 199, Undergraduate Research

NSC 290C, Research Conference in Neuroscience

NSC 299, Graduate Research

Teaching and Research Awards

  • Leukemia & Lymphoma Society Special Fellowship, 2002-2005
  • Howard Temin Award, NCI, 2005-2010
  • Brain Tumor Society Award: 2007-8 Steven C. Higgins Leadership Chair of Research
  • March of Dimes Basil O'Conner Starter Scholar Award, 2008-9.
  • CIRM New Faculty Award: 2008-2013