Biochemistry and Molecular Biology
Division: Reproductive Biology
615 N. Wolfe Street, W8508
Baltimore , Maryland 21205
PhD, University of North Carolina, 1991
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 actin, myosin-II, and a protein family known as ERMs (an acronym that refers to the individual family members) play key roles in regulating cortical tension in eggs; disruption of function of any of these proteins 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 has studied the molecular basis of gamete membrane interactions (adhesion and fusion) with studies of gamete interaction molecules on the sperm and on the egg. 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.
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. Delta Omega Honorary Society in Public Health – induction spring 2013 Selected 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; co-chair of the Program Committee for the 2013 Annual Meeting in Montreal, Quebec. American Society of Andrology, Executive Council, 2001-4; Treasurer, 2005-8; co-chair of the Program Committee for the 2012 Annual Meeting in Tucson, Arizona. Selected 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 Awards for research presentations at the American Society of Andrology annual meeting (2007, 2008, 2010); Thomas S.K. Chang Trainee Travel Award, (2008); Lonnie D. Russell Travel Award, American Society of Andrology (2010).
Biochemistry and molecular biology, reproductive biology, fertilization, cell adhesion, cytoskeleton, egg, sperm, oocyte maturation, meiosis, contraception, infertility