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Monday, March 3, 2008 - 4:30 PM
Convention Center Korbel Ballroom
Frank McKeon, Ph.D.
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Frank McKeon is Professor of Cell Biology at Harvard Medical School. He has a long standing interest
in regulators of stem cell activity. His laboratory discovered the p53 homolog p63 in 1998, leading to a
series of discoveries that have revealed the role of this gene in the regulation of epithelial stem cell
maintenance and ovarian germ cell survival.
Dr. McKeon was born in Connecticut and received his undergraduate degree from Pomona College. He
 received his Ph.D. in 1984 from the University of California, San Francisco under the direction of Marc
Kirschner, with whom he remained for his postdoctoral research. Dr. McKeon arrived at Harvard Medical
School in 1986 as an Assistant Professor, was appointed Associate Professor in 1991 and Professor in
1998.
For the past 10 years, McKeon and his colleagues have concentrated their attentions on close relatives
of the tumor suppressor gene p53, specifically p73 and p63. In 1998, the McKeon laboratory discovered
p63, which they showed to be critical to the
maintenance of the basal squamous epithelium in mice and consequently a marker for reserve and basal
cells of the breast, prostate, and genitourinary tract. Targeted mutations of this gene in mice from his
laboratory resulted in the loss of all stratified epithelia and major defects in limb development,
effects that foreshadowed the linking of p63 mutations in humans to the Ectrodactyly-Ectodermal
Dysplasia-Cleft Lip/Palate (EEC) Syndrome.
Practicing pathologists have had the opportunity to benefit from these discoveries by the McKeon
laboratory. Their antibody to p63, which is used by many pathologists, has become a staple of
immunohistochemistry laboratories, where it is both a potent marker for basal cells of the breast and
prostate a well as for the squamous phenotype. It thus has utility in distinguishing benign and
malignant proliferations in the breast and prostate and determining squamous epithelial differentiation
in tumors.
While pathologists were learning of the practical uses of the p63 antibody, the McKeon laboratory
sought to unravel the mysteries of p63 function, specifically why it was so critical to the perpetuation
of epithelial stem cells and yet so highly expressed in ovarian germ cells. In two recent publications
in Cell and Nature, McKeon and his group teased apart two different functions of this gene that have
disparate but enormous impacts on cell survival. In the first, they discovered that in the absence of
one form of p63, ovarian germ cells do not die when subjected to otherwise lethal amounts of irradiation,
a discovery that has identified p63 as an inducer of cell death in female germ cells following radiation
or chemotherapy. This function is similar to that attributed to its relative p53 in the somatic cells,
and has marked p63 as a guardian of the female germ cell genome.
In the second publication, the McKeon laboratory showed for the first time that epithelial cells of
the thymus and epidermis of the mouse embryo progressively diminish in number in the absence of p63,
firmly linking p63 to epithelial cell replenishment through the maintenance of "stemness". Both of these
recent discoveries, superimposed on nearly a decade of research in this gene, have important implications
for our current and future understanding of the regulation of genome integrity and epithelial stem cell
properties.
In addition to directing a highly innovative research enterprise in his laboratory at Harvard Medical
School, Dr. McKeon has developed a unique model for community outreach designed to pay dividends for
future scientists. Each summer, Dr. McKeon conducts a program for high school students that immerses
them in the laboratory and exposes them to translational research in both pathology and cell biology.
This program is emblematic of his belief that mentoring young scientists can make a critical and positive
difference in their eventual selection of a career path.
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