Developmental Biology Program

Address

1311 Biomedical Rsch Bldg II/III (office)
1320 Biomedical Rsch Bldg II/III (lab)
421 Curie Boulevard
Philadelphia, PA 19104-6080

Office tel.: 215 573-4781
Lab tel.: 215 573-4786
Fax: 215 573-7627
E-mail: gerton@mail.med.upenn.edu

Link(s)

George Gerton at the CRRWH

Education

University of California, Santa Barbara, B.A (Biochemistry/ Molecular Biology), 1975

University of California, Davis, Ph.D. (Biochemistry), 1980

Research Interests

• Spermatogenesis
• Fertilization
• Pre-implantation Mammalian Embryo Development

Key words: Spermatogenesis, Acrosome, Spermatid, Flagellum, Acrosomal matrix, Preimplantation, Embryo, Trophoblast..

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Description of Research

The Gerton laboratory uses a multidisciplinary approach to examine issues pertaining to mammalian spermatogenesis, sperm function, and preimplantation embryo development. In addition, we are carrying out clinical studies directed toward improving the diagnosis of ectopic pregnancies.

Several of the major components of the acrosome and sperm tail have been purified and their corresponding cDNAs cloned for studies of protein structure and expression. The deduced amino acid sequences of these proteins have provided new clues concerning the functions of acrosomal and flagellar proteins. One major direction of the laboratory is to study acrosomal and flagellar protein targeting and function in spermatogenic cells and transfected somatic cells using tools of molecular biology and cell biology and to extend these studies to cases of infertility in humans and other species.

Other projects in the laboratory focus upon the functions of proteins identified as components of the sperm acrosome. Acrosomal matrix protein sp56 is involved in sperm-zona pellucida interactions. These studies are leading to a re-evaluation of acrosomal exocytosis. A revised paradigm has been developed that describes acrosomal exocytosis as a continuously variable process with functional intermediates rather a two-step, acrosome-intact/acrosome-reacted, process.

We are continuing our analysis of the roles of proteins associated with the accessory structures of sperm flagellum. Our results suggest that these non-axonemal proteins perform novel functions in regulating sperm motility.

Regarding preimplantation embryo development in mammals, we are studying the function of progranulin (acrogranin), the precursor of the granulin and epithelin peptides, on mouse embryos. Our results show that acrogranin is an essential growth factor for the development of embryos to the blastocyst stage.

Finally, we are taking proteomic and genomic approaches to identify biomarkers that can be used for the early diagnosis of ectopic pregnancy. This is a translational research project that involves applying basic science approaches to address a clinical need.

Recent Publications

Qin, J., Diaz-Cueto, L., Schwarze, J. E., Takahashi, Y., Imai, M.,
Isuzugawa, K., Yamamoto, S., Chang, K. T., Gerton, G. L., and
Imakawa, K. (2005). Effects of progranulin on blastocyst hatching and subsequent adhesion and outgrowth in the mouse. Biol Reprod 73, 434-42.

Cao, W., Gerton, G.L., and Moss S.B. (2006). Proteomic profiling of accessory structures from the mouse sperm flagellum. Mol Cell Proteomics. 5:801-810.

Nipper, R. W., Jones, B.H., Gerton, G. L., and Moss, S. B. (2006). Protein domains govern the intracellular distribution of mouse sperm AKAP4. Biol. Reprod. 75, 189-96.

Cao, W., Ladewig-Haig, L., Gerton, G.L., and Moss S.B. (2006). Adenylate kinases 1 and 2 are part of the accessory structures in the mouse sperm flagellum. Biol Reprod. 75, 492-500.

Edwards, S.E., Buffone, M.G., Knee, G.R., Rossato, M., Bonanni, G., Masiero, S., Ferasin, S., Gerton, G.L., Moss, S.B., Williams, C.J. Effects of extracellular adenosine 5’-triphosphate on human sperm motility. Reprod. Sci. in press.

Lab

Rotation Projects

1. Identification of ligands bound by acrosomal matrix proteins.
2. Effect of recombinant progranulin on cultured somatic and embryonic cells
3. Role of sp56 as a zona-binding protein (in vitro fertilization experiments).
4. Characterization of the human homologue of mouse sp56.
5. Use proteomic or genomic approaches to assess biomarkers for diagnosing ectopic pregnancy.

Lab personnel:

Mariano G. Buffone, Ph.D., Postdoctoral Researcher
Ling Hui, Ph.D., Postdoctoral Researcher
Tanya Merdiushev, Research Specialist
Wenlei Cao, M.D. Research Associate
Takashi Ijiri, Ph.D., Postdoctoral Researcher
Lisa Haig-Ladewig, Research Specialist