Professor, Director of Somatic Stem Cell Center, and CPRIT Established Investigator in Cancer Research
Department of Biology and Biochemistry
Research Division: Cell and Molecular Biology (Primary)
Office: Science & Engineering Research Center, 4023
Contact: email@example.com - (713) 743-0563
Education: Ph.D., University of California, San Francisco
Dr. Frank McKeon was extremely fortunate to receive his graduate and postdoctoral training in the Department of Biochemistry & Biophysics at the University of California, San Francisco under the guidance of Prof. Marc Kirschner, as well as to be recruited by Prof. Howard Green, the pioneer in somatic stem cell cloning, as an assistant professor at the Harvard Medical School.
McKeon’s laboratory has since studied aspects of cell cycle control, stem cell regulation, and developmental biology and has mentored a number of highly talented postdocs, graduate, undergraduate, and even high school students, many of whom have become leaders in their fields. Their discovery of the p53 homolog p63 and its role as a master regulator of stem cells of stratified epithelia has aided the understanding of regenerative processes in stratified epithelial organs such as the skin, prostate, and mammary gland. In addition, the monoclonal antibodies the lab generated to p63 turned out to be exceedingly useful for accurate diagnoses of prostate cancer and now is included in as an FDA- cleared test used on a large fraction of prostate and breast cancer workups worldwide.
More recently, McKeon’s lab has developed novel stem cell cloning strategies that have significantly advanced concepts of lung regeneration, understanding the origins of highly aggressive upper gastrointestinal tract diseases, and the stem cell biology of the gastrointestinal tract in general and how this information can be used to address the genetics and pathophysiology of inflammatory bowel disease. In particular, the lab’s work on acute respiratory distress syndrome (ARDS) due to H1N1 influenza virus infections was the first to demonstrate lung regeneration. This work also identified and cloned the lung stem cell responsible for this alveolar regeneration and demonstrated that these cloned p63/Krt5 stem cells have a remarkable capacity to new alveoli during autologous transplantations. The lab’s efforts on upper GI tract cancers, which have very poor prognosis, have focused on the cancers’ metaplastic precursors such as Barrett’s esophagus which arise 20 years before the lethal malignancies. The lab has cloned the stem cells of these precursors, demonstrated that they arise from a lineage of cells distinct from those of the local epithelia, and are developing means of targeting such cells in preemptive strategies. Finally, McKeon foresees that the lab’s cloning technologies are likely to transform the understanding of the epithelial contributions to chronic inflammatory diseases of the gastrointestinal tract such as Crohn’s, ulcerative colitis, and chronic or recurrent infections.
- Wang X, Yamamoto Y, Wilson LH, Zhang T, Howitt B, Farrow MA, Kern F, Ning G, Hong, Y, Khor CC, Chevalier B, Bertrand D, Nagarajan, N., Sylvester,,FA, Hyams, JS, Devers, T, Bronson, R, Lacy, DB, Ho, KY, Crum, CP,McKeon, F, and Xian, W. (2015). Cloning and variation of ground state intestinal stem cells. Nature. 522, 173-178.
- Zuo, W., Zhang, T.,Wu, D.Z-A, Guan, SP, Liew, AA, Yamamoto, Y., Wang, X., Lim, SW, Vincent, M., Lessard, M., Crum, CP, Xian, W., and McKeon, F. (2015). p63 /Krt5 Distal airway stem cells are essential for lung regeneration. Nature 517, 616-620.
- Wang X, Ouyang H, Yamamoto Y, Kumar PA, Wei TS, Dagher R, Vincent M, Lu X, Bellizzi AM, Ho KY, Crum CP, Xian W, McKeon F. (2011). Residual embryonic cells as precursors of a Barrett's-like metaplasia. Cell 145, 1023-1035.
- Kumar, P.A., Hu, Y., Yamamoto, Y. Neo, B.N., Wei, T.S., Mu, D., Sun, Y., Lim, S.J., Dagher, R., Zielonka, E.M., Wang, D.Y., Lim, B., Chow, V.T., Crum, C.P., Xian, W., and McKeon, F. (2011). Distal airway stem cells render alveoli in vitro and during lung regeneration following H1N1 influenza infection. Cell 147, 525-538.
- Senoo M, Pinto F, Crum CP, McKeon F. (2007). p63 Is essential for the proliferative potential of stem cells in stratified epithelia. Cell. 2007 May 4;129(3):523-36.
- Suh EK, Yang A, Kettenbach A, Bamberger C, Michaelis AH, Zhu Z, Elvin JA, Bronson RT, Crum CP, McKeon F. (2006). p63 Protects the female germ line during meiotic arrest. Nature. 2006 Nov 30;444(7119):624-8.
- Ryeom S, Greenwald RJ, Sharpe AH, McKeon F. (2003). The threshold pattern of calcineurin-dependent gene expression is altered by loss of the endogenous inhibitor calcipressin. Nat Immunol. 2003.
- Yang, A., Schweitzer, R., Sun, D., Kaghad, M., Walker, N., Bronson, R., Tabin, C., Sharpe, A., Caput, D., Crum, C., and McKeon, F. (1999). p63 Is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398, 714-718.
- Zhu, J., and McKeon, F. (1999). Regulation of NF-AT shuttling and transcriptional activity by mutually exclusive binding of calcineurin and CRM1. Nature 398, 256-260.
- Zhu, J., Shibasaki, F., Price, R., Guillemont, J.-C., Yano, T., Doetsch, V., Wagner, G., Ferrara, P., and McKeon, F. (1998). Intramolecular masking of nuclear import signal on NF-AT4 by casein kinase I and MEKK1. Cell 93, 851-861.
- Yang, A., Kaghad, M., Wang, Y., Gillett, E., Fleming, M.D., Dotsch, V., Andrews, N.C., Caput, D., McKeon, F. (1998). p63, A p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Molecular Cell 2, 305-316.
- Taylor SS, McKeon F. (1997). Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage. Cell. 1997 May 30;89(5):727-35.
- Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D. (1997). Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 1997 Aug 22;90(4):809-19.
- Shibasaki, F., Price, E. R., Milan, D., and McKeon, F. (1996). Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4. Nature 382, 370-373.
- Heald, R., McLoughlin, M., and McKeon, F. (1993). Human p50-Wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated cdc2 kinase. Cell 74, 463-474.
- Holtz D, Tanaka RA, Hartwig J, McKeon F. (1989). The CaaX motif of lamin A functions in conjunction with the nuclear localization signal to target assembly to the nuclear envelope. Cell. 1989 Dec 22;59(6):969-77.
- McKeon FD, Kirschner MW, Caput D. (1986). Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins. Nature. 1986 Feb 6-12;319(6053):4638.