Carmen Williams

Carmen Williams joined the NIEHS in September, where she heads the Reproductive Medicine Group in the Laboratory of Reproductive and Developmental Toxicology.

Her lab has two major interests. One is the regulation of endometrial function, which is relevant to infertility as well as endometriosis and endometrial cancer. The other is the study of gametes and preimplantation embryos to better understand infertility and to provide information relevant to contraceptive development.

Her past research on these topics—while holding various titles at the University of Pennsylvania in Philadelphia, from infertility fellow to assistant professor—mainly used mouse models. Her lab now also uses human sperm and endometrium samples. As a self-described fertility doc with a doctorate in cell biology, Williams said she hopes to serve as an information resource on women’s reproductive health for the NIH intramural staff.

A key protein involved in implantation in the mouse is epithelial membrane protein–2 (EMP2), a molecular facilitator thought to organize other proteins into cell surface signaling complexes, altering the adhesiveness of the endo-metrium.

EMP2 localizes on the surface of the uterine epithelium at the time of implantation, and reduced amounts hinder implantation. Conversely, a higher expression of EMP2 is seen in poor-prognosis endometrial cancer, the most common gynecologic cancer in the United States. Williams is collecting endometrial biopsies from women with and without fertility problems to futher examine the role of EMP2 in infertility and endometriosis.

As for male infertility, Williams said that surprisingly little was known before 2002 about how a sperm fertilizes an egg. Then a British group identified a key sperm molecule, phospholipase C-z (PLCz), which initiates calcium oscillations required for fertilization when sperm enters egg.

Williams’ group demonstrated how this molecule is biologically significant in mice. Because a repetitive pattern of calcium oscillations is required for successful pre- and postimplantation development, suboptimal PLCz function could explain some cases of infertility, Williams said.

If this hypothesis is correct, she envisions a test to identify couples who would benefit from treatment of this defect. "There is a huge gap in our understanding of male infertility," Williams said.

—Christopher Wanjek

Wei Li

Wei Li joined the Unit on Retinal Neurophysiology, NEI, in August 2007. He began his study of the physiology and circuitry of the mammalian retina as a postdoctoral fellow in Chicago in the Northwestern University laboratory of Steven DeVries, where he focused on the cone photoreceptors in the retina and their associated neurons.

Mammalian vision begins with two types of light-sensing neurons—rods, which function predominantly in low-light conditions, and cones, which function in daylight and are responsible for color vision. Both receive visual signals and send them on to the retinal neurons and ultimately to the brain. One research avenue Li is pursuing at NEI is determining how retinal neurons are wired and how they function.

Using direct synaptic stimulation or natural-light stimulation to take recordings from neurons, and combining these with anatomical connections, Li hopes to determine how these visual cues are processed in the retina and passed to the higher visual centers of the brain.

Most mammals, including humans, have rod-dominated retinas; but the ground squirrel—Li’s model organism—is unique in that its retina is composed predominantly of cone photoreceptors, allowing him to address more specific questions of mammalian color vision.

Humans and some primates have a trichromatic (blue-green-red) system of cones; most other mammals have only a blue-green cone system. Li is especially interested in elucidating the neural connections and and signaling process of the blue cones, which are the most evolutionarily conserved but least well understood.

Li is also using his ground squirrel model to examine degeneration and photoreceptor-protection mechanisms. During a squirrel’s hibernation, retinal neurons undergo degenerative-like changes, including detachment of the photoreceptor synaptic component from the membrane and retraction of neuronal structures. Once the squirrel comes out of hibernation, however, the retina completely recovers within five days.

This hibernation scenario, Li says, provides a unique window into natural photoreceptor-protection mechanisms in adverse environments. In addition, these studies offer a system in which to study synaptic regeneration and prevention of further degeneration after retinal damage.

—Yvonne Evrard

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