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  UB oral biologist Chunhao (Chris) Li has spent his career studying spirochetes, a family of bacteria whose species cause a variety of human diseases. Photo: DOUGLAS LEVERE

By JUDSON MEAD

Published: February 25, 2009

When Chunhao (Chris) Li joined the faculty in the Department of Oral Biology, School of Dental Medicine, in 2005, he put UB on the map of research hotspots in the effort to better understand spirochetes, a family of bacteria whose different species cause a variety of human diseases, including syphilis and Lyme disease.

More than 60 species of spirochetes have been identified among human oral flora and one, Treponema denticola, is strongly associated with periodontal disease.

Spirochetes have highly specialized features that play roles in their virulence. The coil-shaped microbes can move rapidly, practically sprinting compared with their less-mobile bacterial cousins; more remarkably, they travel easily through viscous media, such as cartilage or dental plaque, that other bacteria can’t transit; and they can adapt to radically different host environments in one lifetime. And for such medically important bacteria, spirochetes are poorly understood.

Before coming to UB, Li spent seven years at the University of West Virginia as a postdoctoral researcher and then a faculty member working with Nyles Charon, one of the world’s leading experts on spirochetes.

Now he directs his own lab on the third floor of Foster Hall, South Campus. This summer, Li’s lab was awarded three grants totaling more than $2 million from the National Institute of Dental and Craniofacial Research and the National Institute of Allergy and Infectious Diseases, and a smaller grant from the American Heart Association to pursue research on three fronts.

Li is studying the ability to move in particular directions (motility) and the ability to select destination (chemotaxis) of the Lyme disease-causing spirochete Borrelia burgdorferi, and the roles of both motility and chemotaxis in the disease it causes. He also is looking at how Borrelia burgdorferi regulates its host-adaptation, thriving in both ticks and humans. And he is studying the role of a particular toxin produced by Treponema denticola in periodontal disease.

Li’s lab currently employs a single postdoctoral researcher; the research funds will allow him to recruit three more postdocs and a full-time technician.

In earlier research, Li demonstrated that removing a particular gene interferes with Borrelia burgdorferi’s motility. Spirochetes are shaped like long coils and travel with a wave-like motion. Reversing course requires the coordination of their flagella from each end. The gene Li removed coded a protein that is essential for that coordination. Li showed in a mouse model that interfering with the spirochete’s motility in this way prevented it from causing disease. This suggests an avenue for attack on the spirochete.

A second potentially exploitable vulnerability is the internal signaling that allows Borrelia burgdorferi to switch genes on and off to adapt to the host environments of mammal and tick, with their different temperatures and immune responses. Li has described a two-stage signal sequence. If the sequence could be interrupted, the spirochete’s ability to infect humans through ticks would presumably be stopped.

The lab’s work on Treponema denticola currently is focused on a toxin it secretes that appears to cut up human immunoglobulin. Treponema denticola is particularly interesting in dental medicine because it is always found at the frontier in dental plaque, suggesting that it plays a role in periodontal infection. Li hopes to discover whether this protein is a virulence factor.

Although it is only now, using 21st-century tools, that researchers are discovering how it may cause disease, Treponema denticola was one of the first bacteria ever described, in 1683 by Antonio van Leeuwenhoek, who is known as the Father of Microbiology.

One of Li’s recent research successes is the development of a reliable method for producing genetic mutants of Treponema denticola in large enough quantity to study.

Li started research on spirochetes after graduating from medical school in China and working in a hospital for two years. He was interested in infectious diseases and went to graduate school for more study; his mentor and Ph.D. director was an expert on spirochetes, and that set Li on a career path that led through West Virginia to Buffalo.

As it happens, Nyles Charon, Li’s mentor at West Virginia, whom he credits with his success as an independent researcher, has a daughter in medical school at UB, so he visits Buffalo occasionally, much to Li’s delight.