Distinguished University Professor, Vice Chair of the Department of Biochemistry and Structural Biology, and Zachry Distinguished University Chair in Cancer Research Jean X. Jiang explores the mechanisms that regulate cell communication. Cells communicate via gap junctions—clusters of channels made of connexin (a protein) that connect the cytoplasm of adjacent cells. These connexin channels are necessary for cell survival and regulation of cellular functions. Un-apposed halves of gap junctions are called hemichannels.
Dr. Jiang is especially interested in these hemichannels, which mediate communication between the inside and outside of cells, especially under stress conditions. For example, mechanical stress on bones can stimulate the hemichannels on bone cells to transmit signals for bone formation and remodeling.
Dr. Jiang pioneered the modulation of hemichannel activation using targeting antibodies. Her team discovered two targeting antibodies: one to open the hemichannels and another to block. While other teams have been able to block hemichannels, Dr. Jiang’s team was the first to activate and open the hemichannel.
Hemichannels are very promising drug targets for treating multiple disease indications. Studies from Dr. Jiang’s lab and others have found that abnormal opening of these channels can result in neurological damage, such as secondary injuries after spinal cord trauma, which could be mitigated by closing the hemichannels. In another study, opening hemichannels on osteocytes allowed the bone cells to release factors that target cancer cells, potentially suppressing cancer-cell growth and metastasis.
“I am very, very grateful to The Welch Foundation because it has been supporting my research for years. It really motivates me to continue to explore new directions.”
While Dr. Jiang’s team has clarified the antibodies’ functions—the power to inhibit or activate hemichannels—further work is needed in structural biology, study of the antibodies, and microscopic approaches to identify the exact amino acids the antibodies are binding to on the connexin protein.
“This is both to further our basic understanding and also to help us design better drugs. For example, if we identify the specific binding site, then we can design reagents for use in therapeutics to specifically target that unique location and cause the channel to open or close to treat diseases.”
If Dr. Jiang’s team successfully illuminates the gating mechanism of connexin hemichannels—if they define the structure on the cell membrane and identify the key amino acid that regulates opening and closing of the hemichannels—they will claim another first.
Advances in technology and the Welch support have allowed Dr. Jiang to overcome challenges associated with studying cell structure and interactions on the cell membrane at high resolution.
“The Welch Foundation grant helps us tremendously because Welch is willing to invest in projects that could be high risk but also have the potential for very high impact, projects that would not be funded by traditional grants. One of the ways we mediate this risk is by switching approaches. Welch is terrific because they allow us to have this kind of flexibility.”