The general focus of our lab's research is on addressing the question "What controls stem cell 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. Although our lab is mostly focused on studying neural stem cells we are also beginning to examine other types such as embryonic stem cells. One important reason for studying a variety of types of stem cells is that it enables us to ask whether the same types of control system are at work in different stem cells. So far 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 should also help us to better understand human cancer in a more general sense, hopefully moving us one step closer to a cure.

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

For more information please visit the OTHER Knoepfler lab homepage at: http://www.chromatin.com

Publications:

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. In Press Cell Stem Cell 2008.

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. In Press Cancer Research 2008.

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

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.

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.

Myc goes global: new tricks for an old oncogene. Cancer Research 2007 June 1 issue.

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):8655-61. (*co-first authors).

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).

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.

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.