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Faculty
Janice Evans
Associate Professor
Academic Degrees
PhD
Departmental Affiliation
Biochemistry and Molecular Biology
Division of Reproductive Biology
Departmental Address
615 N. Wolfe Street, W3112 BSPH
Baltimore, MD 21205
Phone: 410-614-5557
Fax: 410-614-2356
Research and Professional Experience

The goal of sexual reproduction is to combine the genomes of two individuals, passing DNA on to the next generation and creating a new, genetically distinct individual. We study fundamental cell biological processes in the sperm and egg, with research in two general areas.

(1) A crucial component of reproductive success is ensuring that cells inherit the correct amount of DNA. Our investigations in this area focus on how the egg membrane and cortical cytoskeleton regulate the fidelity of the female gamete's handling of DNA.

One project examines how the egg membrane prevents fertilization by more than one sperm. This is known as the membrane block to polyspermy, which works in conjunction with other mechanisms to prevent polyspermic fertilization. Polyspermic fertilization is thought to be the cause of at least 5% of spontaneous pregnancy losses in humans. However, very little is known about the membrane block to polyspermy in mammalian eggs, despite data dating back up 90 years that provide evidence for its existence. Our work has characterized the role of post-fertilization calcium signaling in the establishment of the membrane block (including collaborative studies with Carmen Williams [now at NIEHS] and Rafael Fissore [University of Massachusetts]), and we also have been examining the role of the egg cytoskeleton in regulating membrane receptivity to sperm. Read more about this work here.

A second project in this area is focused on the egg cortex (i.e., the cortical region of the cell, just underlying the plasma membrane). The egg cortex plays roles in multiple critical functions, such as progression through meiosis, responses to sperm, and regulation of activation and developmental potential. In all cells, one of most fundamental functions of the cortex is the regulation of the cell's shape and mechanical properties. With Doug Robinson in the Department of Cell Biology in the School of Medicine, we have been examining the mechanical properties of oocytes and eggs and have found that cortical tension changes dramatically as the egg progresses through meiosis and fertilization. Our work has also revealed that a protein family known as ERMs (an acronym that refers to the individual family members) play a key role in regulating cortical tension in eggs, as disruption of ERM function results in a decrease in cortical tension. Interestingly, this also leads to abnormalities during meiotic cytokinesis occurring in response to fertilization, suggesting that cortical mechanics are critical for the egg's completion of meiosis.

(2) Fertilization is the process by which the gametes, the carriers of individual's genetic contributions to the next generation, merge to create the zygote. This union involves a series of carefully orchestrated cellular interactions, mediated by multiple molecules on the surfaces of the sperm and egg. Our lab studies the molecular basis of gamete membrane interactions (adhesion and fusion) with studies of candidate gamete interaction molecules on both the sperm and on the egg. This work considers a broad range of molecular families know to play roles in cell-cell interactions, including integrins, tetraspanins, Immunoglobulin Superfamily (IgSF) members, and ADAMs. This research are also complements the studies of the membrane block to polyspermy noted above, as both lines of work are providing insights into the mechanisms underlying egg receptivity to sperm. A bit about our work in this area is covered here.

Keywords

Biochemistry and molecular biology, reproductive biology, fertilization, cell adhesion, cytoskeleton, egg, sperm, oocyte maturation, meiosis, contraception, infertility

Honors and Awards

American Cancer Society Post-doctoral Research Fellowship Award (1992-1994) N.I.H. National Research Service Award post-doctoral fellowship (1996-1997) American Society for Reproductive Medicine ASRM/Organon Inc. Research Grant in Reproductive Medicine (1998-1999) Faculty Innovation Award, Johns Hopkins University School of Public Health (2000-2001) Young Andrologist Award, 2006; given by the American Society of Andrology for significant contributions to the field of andrology by an individual less than 45 years of age.

Leadership activities: Gordon Conference on Fertilization and Activation of Development - vice chair for 2009, chair for 2011. Society for the Study of Reproduction, Board of Directors, 2007-9. American Society of Andrology, Executive Council, 2001-4; Treasurer, 2005-8.

Research honors to my trainees: Xiaoling Zhu - Recipient of a Lalor Foundation Merit Award for Trainees, Society for the Study of Reproduction (2003)

Genevieve Wortzman - Recipient of a Lalor Foundation Merit Award for Trainees, Study of Reproduction (2004); second place in poster presentation competition at the annual meeting of the Society for the Study of Reproduction. (2004).

Allison Gardner - Anna Steinberger Award for Excellence in Research by a Female Trainee at the American Society of Andrology annual meeting (2006)

Matthew Marcello - Trainee Merit Award and runner-up for Outstanding Trainee Investigator for poster presentation at the American Society of Andrology annual meeting (2007)

Matthew Marcello - Trainee Merit Award and Thomas S.K. Chang Trainee Travel Award.,American Society of Andrology annual meeting (2008)

Selected Publications

Evans, J.P. (2009) Egg integrins: Back in the game of mammalian fertilization. ACS Chem. Biol. 4, 321-323.

Vjugina, U., Zhu, X., Oh., E., Bracero, N., and Evans, J.P. (2009) Reduction of mouse egg surface integrin alpha9 subunit (ITGA9) reduces the egg's ability to support sperm-egg binding and fusion. Biol. Reprod. 80, 833-841.

Glazar, A.I. and Evans, J.P. (2009) IgSF8 (EWI-2) and CD9 in fertilization: Evidence of distinct functions for CD9 and a CD9-associated protein in mammalian sperm-egg interaction. Reprod. Fertil. Dev. 21, 293-303.

Dalo, D.T., McCaffery, J.M., and Evans, J.P. (2008) Ultrastructural analysis of egg membrane abnormalities in post-ovulatory aged eggs. Int. J. Dev. Biol. 52, 535 – 544.

Vjugina, U. and Evans, J.P. (2008) New insights into the molecular basis of mammalian sperm-egg membrane interactions. Front. Biosci. 13, 462-476.

Wortzman-Show, G.B., Kurokawa, M., Fissore, R.A., and Evans, J.P. (2007) Calcium and sperm components in the establishment of the membrane block to polyspermy: studies of intracytoplasmic sperm injection (ICSI) and activation with sperm factor. Mol. Human Reprod. 13, 557-565.

Gardner, A.J., Knott, J.G., Jones, K.T., Evans, J.P. (2007) CaMKII can participate in but is not sufficient for the establishment of the membrane block to polyspermy in mouse eggs. J. Cell. Physiol. 212, 275-280.

Gardner, A.J., Williams, C.J., and Evans, J.P. (2007) Establishment of the mammalian membrane block to polyspermy: Evidence for calcium-dependent and -independent regulation. Reproduction. 133, 383-393.

Gardner, A.J. and Evans, J.P. (2006) The mammalian membrane block to polyspermy: New insights into how mammalian eggs prevent fertilization by multiple sperm. Reprod. Fert. Dev. 18, 53-61.

Borghei, A., Ouyang, Y.-B., Marcello, M.R., Landel, C.P., Evans, J.P., and Moore, K.L. (2006) Targeted disruption of tyrosylprotein sulfotransferase-2, an enzyme that catalyzes post-translational protein tyrosine O-sulfation, causes male infertility. J. Biol. Chem. 281, 9423-9431.

Wortzman, G.B., Gardner, A.J. and Evans, J.P. (2006) Analysis of sperm-egg interactions during in vitro fertilization. In "Cell-cell Interactions in Health and Disease," Methods in Molecular Biology series. ed. S.P. Colgan. Totowa, NJ: Humana Press Inc.

Wortzman, G.B. and Evans, J.P. (2005) Membrane and cortical abnormalities in post-ovulatory aged eggs: analysis of fertilizability and establishment of the membrane block to polyspermy. Mol. Human Reprod. 11, 1-9.

Sharan, S.K., Pyle, A., Coppola, V., Babus, J., Swaminathan, S., Benedict, J., Swing, D., Martin, B., Tessarollo, L., Evans, J.P., Flaws, J.A., and Handel, M.A. (2004) BRCA2 deficiency in mice leads to meiotic impairment and infertility. Development 131, 131-142

Oh, E., Wortzman, G.B., Zhu, X., and Evans, J.P. (2003) Getting sperm and egg together: The molecules of mammalian gamete membrane interactions. ChemTracts. 16, 142-157.

Evans, J.P. and Florman, H.M. (2002) The state of the union: The cell biology of fertilization. Nature Cell Biol. 4 (S1), S57-S63, Nature Med. 8 (S1) S57-S63.

McAvey, B.A., Wortzman, G.B., Williams, C.J., and Evans, J.P. (2002) Involvement of calcium signaling and the actin cytoskeleton in the membrane block to polyspermy in mouse eggs. Biol. Reprod. 67, 1342-1352.

Evans, J.P. (2002) The molecular basis of sperm-oocyte membrane interactions during mammalian fertilization. Human Reprod. Update. 8, 297-311.

Zhu, X., and Evans, J.P. (2002) Analysis of the roles of RGD-binding integrins, alpha-4/alpha 9 integrins, alpha-6 integrins, and CD9 in the interaction of the fertilin beta (ADAM2) disintegrin domain with the mouse egg membrane. Biol. Reprod. 66, 1193-1202.

Hellsten, E., Evans, J.P., Bernard, D.J., Nussbaum, R. (2001) Disrupted sperm functions and fertilin beta processing in inositol polyphosphate 5-phosphatase deficient mice. Dev. Biol. 240, 641-653

Evans, J.P. (2001) Fertilin beta and other ADAMs as integrin ligands: Insights into cell adhesion and fertilization. BioEssays 23, 628-639.

Wong, G.E., Zhu, X., Prater, C.E., Oh, E., and Evans, J.P. (2001) Analysis of fertilin alpha (ADAM1)-mediated gamete cell adhesion during fertilization and identification of an adhesion-mediating sequence in the disintegrin-like domain. J. Biol. Chem. 276, 24937-24945.

Zhu, X., Bansal, N.P., and Evans, J.P. (2000) Identification of key functional amino acids of the mouse fertilin beta (ADAM2) disintegrin loop involved in cell-cell adhesion during fertilization. J. Biol. Chem. 275, 7677-7683.

Evans, J.P., Foster, J.A., McAvey, B.A., Gerton, G.L., Kopf,G.S., and Schultz, R.M. (2000) The effects of perturbation of cell polarity on molecular markers of sperm-egg binding sites on mouse eggs. Biol. Reprod. 62, 76-84.

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