Mount Sinai Logo

Paul M. Wassarman

  • PROFESSOR Developmental and Regenerative Biology
Print ProfilePrint Profile

Education

  • Ph.D., Brandeis University, Graduate Dept. Biochemistry
    Biochemistry

  • Medical Research Council, Laboratory of Molecular Biology
    Structural Studies

  • Harvard Medical School, Dept. Biological Chemistry
    Developmental Biochemistry

Biography

    Our laboratory studies signaling pathways that have important roles in mouse embryonic development.

    For more information, please visit the Wassarman Laboratory website.


Awards

  • 1972 - 1974
    Rockefeller Foundation Special Research Fellow
    Harvard Medical School

  • 1967 - 1970
    Helen Hay Whitney Postdoctoral Fellow
    Medical Research Council, Laboratory of Molecular Biology

Research

Molecular Mechanisms of Mammalian Fertilization

For all animals, maintenance of life and speciation depend on the process of fertilization. Fusion of eggs and sperm to form a zygote is the culmination of a complex series of interactions between two highly specialized gametes. In mammals, interactions between gametes begin when free-swimming sperm reach the site of ovulated eggs in the oviduct and then bind to eggs.

Our research focuses on mammalian egg and sperm surface components that account for species-specific binding of sperm to eggs during fertilization. For example, one of these components is a glycoprotein, called ZP3, that is present in the ovulated egg extracellular coat, or zona pellucida (ZP). ZP3 serves as a receptor for sperm during fertilization. We discovered and characterized ZP3 biochemically and, subsequently, cloned and characterized the gene encoding ZP3. While much of our research has been carried out with mice, ZP3 is present in the ZP of all mammalian eggs, including human eggs, and a ZP3-like glycoprotein is present in the extracellular coat (vitelline envelope) of eggs from amphibians, birds, fish, and many invertebrates.

Our studies have revealed that ZP3 is synthesized, processed, and secreted by oocytes, the precursors of eggs, during the growth phase of oogenesis. During growth of the oocyte, ZP3 and two other glycoproteins, called ZP1 and ZP2, assemble into an extensive network of interconnected filaments that constitute the ZP. The filaments consist of ZP2 and ZP3, present every 150 Å, and are interconnected by ZP1. Free-swimming sperm recognize and bind to specific oligosaccharides present on ZP3 at its sperm combining-site. Binding to ZP3 activates the signal transduction pathway of sperm that culminates in exocytosis, the acrosome reaction, and enables bound sperm to penetrate the ZP. Therefore, ZP3 is a structural glycoprotein, a species-specific sperm receptor, and an activator of signal transduction when sperm bind to unfertilized eggs.

All ZP glycoproteins share a large region of polypeptide (approximately 260 amino acids), called the "ZP domain". A ZP domain is also present in a wide variety of other proteins of diverse origins and functions. For example, ZP domain containing proteins are components of the mammalian egg, inner ear, nose, and kidney, as well as the Drosophila cuticle, wing epithelium, and mechanosensory organ. Our research strongly suggests that the ZP domain is a conserved module used for polymerization of extracellular proteins. Since the domain is found in a number of proteins involved in human pathologies, we are also investigating relationships between mutations in the ZP domain and disease.

In our research, we use a wide variety of contemporary methodology, including transfection of mammalian cells, exon swapping, site-directed mutagenesis, transgenesis, and targeted gene disruption. Overall, the object of our research is to understand the molecular basis of the multiple functions of ZP glycoproteins during mammalian oogenesis, fertilization, and preimplantation development and to understand the role of the ZP domain in normal and diseased states.

For more information, please visit the Wassarman Laboratory website.

Publications

Wassarman PM. Mammalian fertilization: molecular aspects of gamete adhesion, exocytosis, and fusion. Cell 1999 Jan 22 96(2):175-83.

Williams Z, Wassarman PM. Secretion of mouse ZP3, the sperm receptor, requires cleavage of its polypeptide at a consensus furin cleavage-site. Biochemistry 2001 Jan 30; 40(4): 929-937.

Wassarman PM, Jovine L, Litscher E. A profile of fertilization in mammals. Nature Cell Biology 2001 Feb; 3(2): E59-E64.

Qi H, Williams Z, Wassarman PM. Secretion and assembly of zona pellucida glycoproteins by growing mouse oocytes microinjected with epitope-tagged cDNAs for mZP2 and mZP3. Moecularl Biology Cell 2002 Feb; 13: 530-541.

Jovine L, Qi H, Williams Z, Litscher E, Wassarman PM. The ZP domain is a conserved module for polymerization of extracellular proteins. Nature Cell Biology 2002 Jun; 4(6): 457-461.

Jovine L, Qi H, Williams Z, Litscher ES, Wassarman PM. A duplicated motif controls assembly of zona pellucida domain proteins. Proc Natl Acad Sci U S A 2004 Apr 20; 101(16): 5922-5927.

Darie CC, Miniossek M, Jovine L, Litscher ES, Wassarman PM. Structural characterization of fish egg vitelline envelope proteins by mass spectrometry. Biochemistry 2004 Jun 15; 43(23): 7459-7478.

Darie CC, Biniossek ML, Gawinowicz MA, Milgrom Y, Thumfart JO, Jovine L, Litscher ES, Wassarman PM. Mass spectrometric evidence that proteolytic processing of rainbow trout vitelline envelope proteins takes place on the egg. J Biological Chemistry 2005 Nov; 280(45): 37585-98.

Jovine L, Darie CC, Litscher ES, Wassarman PM. Zona pellucida domain proteins. Annual Review Biochemistry 2005; 74: 83-114.

Williams Z, Litscher ES, Jovine L, Wassarman PM. Polypeptide encoded by mouse ZP3 exon-7 Is Necessary and Sufficient for binding of mouse sperm in vitro. J Cellular Physiology 2006 Apr; 207(1): 30-39.

Wassarman PM. Zona pellucida glycoproteins. J Biological Chemistry 2008; 283: 24285-24289.

Wassarman PM. The strange case of sperm protein 56. BioEssays 2009; 31: 153-158.

Wassarman PM. Egg's ZP3 structure speaks volumes. Cell 2010; 143: 337-338.

Plaza S, Chanut-Delalande H, Fernandes I, Wassarman PM, Payre F. Apical structures and zona pellucida-domain proteins. Trends Cell Biology 2010; 20: 524-532.

Wassarman PM, Litscher ES. Egg's ZP3 structure speaks volumes. Cell 2010; 143: 337-338.

Wassarman PM. The sperm's sweet tooth. Science 2011; 233: 1708-1709.

Wassarman PM, Litscher ES. Influence of the zona pellucida of the mouse egg on folliculogenesis and fertility. Intl J Developmental Biology 2012; 56: 833-839.

Wassarman PM, Litscher ES. Biogenesis of the mouse egg's extracellular coat, the zona pellucida. Current Topics Developmental Biology 2013; 102: 243-266.

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Wassarman did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

Edit profile in Sinai Central

Address

Annenberg Building Floor 25th Floor Room 22
1468 Madison Avenue
New York, NY 10029

Tel: 212-241-8616
Fax: 212-860-9279