Cell Biologist Seeks Greater Understanding of Nerve Cell Signaling

            Over time, small errors can add up to cause major difficulties. That is especially true in the formation of neural circuits, a complex process in which mistakes can lead to significant problems of brain function.

            David M. Sherry, Ph.D., associate professor in the Department of Cell Biology, has several areas of focus in his laboratory, including his long-term interest in the signals that allow nerve cells to properly identify one another. The signals permitting that identification allow the cells to build the right contacts so information can be processed correctly.

            “We’re very interested in those signals because they tell the nerve cells who they’re supposed to ‘talk’ to and who they’re not supposed to talk to,” Sherry said. “In addition, what are the details of that contact necessary in order for it to work properly? If there are mistakes in this process, you end up with problems in brain function of varying severity. Those include migration problems, where cells don’t migrate during development, which is devastating and often lethal, as well as intellectual disabilities and problems like seizures. Other conditions like schizophrenia and bipolar disorder also are associated with the formation of the contacts that we’re studying.”

            Investigating the intricacies of such cell signaling is critical because in order to repair damage in the nervous system, there must be an understanding of how it works. The nervous system has a low capacity to regenerate cells, Sherry said, and the research community has had limited success introducing new cells to restore function. Sherry is driven to add to the body of knowledge of how the process works.

            “If nerve cells are lost because of an injury or a progressive disease state, then in order to restore the lost function, you have to be able to put new cells in, in the form of progenitor cells or stem cells, for example,” he said. “But you have to actually put those cells into the damaged area, get them to move to where they need to be, find their proper partners and re-form all those connections. The cells have to do that properly in order to completely restore function.”

            Sherry’s model system is the retina – accessible because it is external yet highly suitable because, developmentally, it is a piece of brain nervous tissue. His laboratory uses a variety of approaches, working with both individual cells and the tissues as a whole.

            Working with the retina led Sherry’s lab to a new project studying a process associated with age-related macular degeneration, a progressive disease that affects a large number of people. The leading cause of blindness in the United States is the loss of photoreceptors during age-related macular degeneration. During the disease process, people lose photoreceptors in the central part of the retina, which houses the cones necessary for seeing colors and reading. To repair that damage, lost cells must be replaced and correctly rewired.

            “Our project works on synaptic adhesion proteins, which allow cells to recognize one another and build a contact so they can ‘talk,’” he said. The synapse is the contact through which the information is exchanged and processed. Our hypothesis is that there is a code that allows the cells to identify who they should be talking to, and how they know which type of synapse to build.”