Genetics, Vol. 175, 463-464, February 2007, Copyright © 2007
doi:10.1534/genetics.104.017522

The 2007 Genetics Society of America Medal

Steve Buratowski

THE recipient of the 2007 Genetics Society of America Medal is Shirley Tilghman. Shirley has made major scientific contributions to our understanding of gene expression and the epigenetic phenomenon of imprinting, but she has also been a national leader on matters of science policy and education. She has been a tireless advocate for improving the career prospects of all scientists, but particularly for women and minorities. Her own career serves as an example of how to combine family life with top-notch science and service to the academic community.

Shirley Tilghman was born in Toronto and received her undergraduate degree in chemistry and biochemistry from Queen's University. Foreshadowing her lifetime commitment to education, she spent 2 years teaching secondary school in Sierra Leone before working toward a Ph.D. degree at Temple University in Philadelphia. In 1975, she joined Phil Leder's lab at the NIH where she began her work on mammalian gene expression. She led the team in the cloning and characterization of the mouse ß-globin gene, one of the first eukaryotic genes to be isolated (TILGHMAN et al. 1977, 1978). In these early days of molecular biology, each new sequence was a heroic effort that revealed exciting new insights into gene structure. Details about promoters, introns, and 3' ends emerged from the pioneering work on globins and other genes.

With her expertise in gene cloning, Shirley started her own lab at the Institute for Cancer Research at the Fox Chase Cancer Center. The lab began by focusing on the mouse albumin and {alpha}-fetoprotein (AFP) genes. AFP turned out to be particularly interesting with respect to its developmental regulation, and Shirley's pioneering work on its enhancer and trans-acting factors made it a paradigm for eukaryotic transcriptional regulation. The attention this work garnered led to her recruitment by Princeton University in 1986. In 1988, she became an Investigator of the Howard Hughes Medical Institute.

It was the mouse H19 gene, isolated in 1988 solely because its expression pattern was similar to AFP (PACHNIS et al. 1988), that produced some of the most startling discoveries from Shirley's lab. H19 is adjacent to the gene for insulin-like growth factor 2 (Igf2), which was the first mammalian gene demonstrated to exhibit parental imprinting (the phenomenon by which a particular gene allele contributes differently depending upon whether it is transmitted through the paternal or the maternal germline). Shirley's team, led by Marisa Bartolomei, showed that H19 was also imprinted, but in the opposite manner to Igf2 (BARTOLOMEI et al. 1991). The interplay between these two loci and the molecular mechanisms underlying their imprinting have been the subject of many interesting and important articles from the Tilghman lab. Describing a series of elegant but technically difficult experiments, these articles document the lab's efforts to reconcile surprising data with evolving models. The linkage between the "epigenetic" phenomenon of imprinting and DNA methylation remains a very fertile area of research, with implications for studies of X chromosome inactivation, transcription insulators, and epigenetic silencing of tumor suppressor genes.

A second remarkable discovery about H19 was that it does not encode a protein; instead, it is the RNA that is functional (BRANNAN et al. 1990; PFEIFER et al. 1996). Although we take the existence of noncoding RNAs for granted today, this finding was a major shock in the early 1990s. Like other large noncoding transcripts produced by RNA polymerase II, the best known being the XIST RNA encoded by the X-inactivation center, the molecular function of the H19 RNA remains mysterious. Given enough time, it is likely that Shirley's lab would have solved that mystery, but that task will now fall to her successors as she underwent a major career change at the turn of the century.

In the 1990s, Shirley's opinion and leadership skills were clearly gaining national recognition, as she served on the National Advisory Council for the National Center for Human Genome Research and on the Advisory Council to the NIH director. She has been a member of multiple trustee and scientific advisory boards for academic institutions such as Cold Spring Harbor Lab, the Whitehead Institute at MIT, Rockefeller University, and Jackson Labs. In 1998, Shirley was appointed the founding director of the Lewis-Sigler Institute for Integrative Genomics at Princeton University. This initiative by Princeton mirrored efforts at universities around the country to capitalize on emerging technologies in genomics and systems biology. Most notable was the Lewis-Sigler Institute's emphasis not just on research, but also on the integration of this work with undergraduate and graduate education. Shirley's time as director was relatively short lived, as the trustees of Princeton appointed her president of the university in 2001. One of her first acts was to recruit David Botstein (the 1988 GSA Medalist) to succeed her as director, and together they have undertaken a bold experiment in undergraduate education in which biology, chemistry, physics, and math are taught as an integrated whole.

Well before becoming a university president, Shirley was renowned as an outstanding teacher and mentor. Indeed, she still participates in classroom teaching. Although she stopped accepting new students and postdocs, her lab remained open until the current members finished their work. Her publication list includes articles up through 2006. Shirley has been an outspoken advocate for making academic science a more attractive career path, particularly for young scientists trying to raise children. She raised two children as a single mother while advancing her career, so she is well aware of the factors that lead to the current gender imbalance at the higher levels of biological science. Her leadership on these issues, reinforced by her visibility as the head of a major university, will no doubt continue in years to come.

In recognition of her outstanding accomplishments in molecular genetics and her continuing efforts to promote biological science, the Genetics Society of America is very pleased to award the 2007 GSA Medal to Shirley Tilghman.
Figure 1
Shirley Tilghman

LITERATURE CITED

BARTOLOMEI, M. S., S. ZEMEL and S. M. TILGHMAN, 1991 Parental imprinting of the mouse H19 gene. Nature 351: 153–155.[CrossRef][Medline]

BRANNAN, C. I., E. C. DEES, R. S. INGRAM and S. M. TILGHMAN, 1990 The product of the H19 gene may function as an RNA. Mol. Cell. Biol. 10: 28–36.[Abstract/Free Full Text]

PACHNIS, V., C. I. BRANNAN and S. M. TILGHMAN, 1988 The structure and expression of a novel gene activated in early mouse embryogenesis. EMBO J. 7: 673–681.[Medline]

PFEIFER, K., P. A. LEIGHTON and S. M. TILGHMAN, 1996 The structural H19 gene is required for transgene imprinting. Proc. Natl. Acad. Sci. USA 93: 13876–13883.[Abstract/Free Full Text]

TILGHMAN, S. M., D. C. TIEMEIER, F. POLSKY, M. H. EDGELL, J. G. SEIDMAN et al., 1977 Cloning specific segments of the mammalian genome: bacteriophage lambda containing mouse globin and surrounding gene sequences. Proc. Natl. Acad. Sci. USA 74: 4406–4410.[Abstract/Free Full Text]

TILGHMAN, S. M., D. C. TIEMEIER, J. G. SEIDMAN, B. M. PETERLIN, M. SULLIVAN et al., 1978 Intervening sequence of DNA identified in the structural portion of a mouse beta-globin gene. Proc. Natl. Acad. Sci. USA 75: 725–729.[Abstract/Free Full Text]