In the world of genetics and molecular research, scientists are exploring a phenomenon of gene functions they call the double-edged sword. On the one hand, a particular gene is shown to have a destructive effect, leading to disease in the human body. On the other, that same gene protects the body from other illnesses.
For much of the past 10 years, Shui Qing Ye, M.D., Ph.D., has honed much of his attention as a research scientist on one such double-edged sword, a gene known as Nicotinamide Phosphoribosyltransferase (NAMPT).
“A higher expression of the NAMPT gene is effective in reducing heart ischemic injury, ischemic stroke, drug induced liver toxicity, but individuals expressing high levels of NAMPT are more likely to suffer cancer, arthritis or inflammatory lung disease,” says Ye, professor and William R. Brown/Missouri Endowed Chair in Medical Genetics and Molecular Medicine. “A lower expression of the gene reduces the chances of cancer, arthritis, or inflammatory lung disease, but you’re more likely to suffer coronary artery disease, stroke, drug induced liver toxicity.”
Ye began looking at the effects of the NAMPT gene more than a decade ago while serving as director of the gene expression profiling core at the Center of Translational Respiratory Medicine at John’s Hopkins University School of Medicine. Working on a National Institutes of Health-funded project exploring large volumes of data, Ye was able to identify genetic markers, or a “signature,” to accurately predict patients with higher susceptibility to acute lung injury. That led to the development of the first commercial antibody for the product of the NAMPT gene, which is now widely used in disease diagnosis.
Now working across the street from the UMKC School of Medicine in his genetics laboratory at Children’s Mercy Kansas City, one of the school’s partner teaching hospitals, Ye and his team are collaborating with researchers throughout Kansas City and beyond. They are incorporating a variety of state-of-the-art tools, including high-speed DNA sequencing and methods from next-generation DNA sequencing and translational bioinformatics (gene sequence data analytics) to gather and explore big data to pinpoint new diagnostic biomarkers and therapeutic targets for human diseases.
Ye’s work has led him to write two acclaimed books. The first, Bioinformatics — A Practical Approach, published in 2007, looks at the practical applications of bioinformatics in biological and biomedical data analysis. His most recent book, “Big Data Analysis for Bioinformatics and Biomedical Discoveries,” published in 2016, covers topics surrounding big data analysis in biomedicine.
Ye has also developed a gene expression research core, a collection of cutting-edge technologies to explore the roles and relationships of gene expression and gene mutations in human diseases. In turn, he has been able to share information and collaborate with researchers at institutions including UMKC, the University of Kansas Medical Center, Kansas City University of Medicine and Biosciences and others to study and develop therapies for a number of ailments from arthritis to coronary disease.
“We’re not doing hypothesis-driven research alone,” Ye says. “We’re doing data-driven research in combination with hypothesis-driven research. Data-driven research gives you a global insight. You need to find out if a particular gene really is the target of a specific therapy. You don’t randomly pick one and say it looks like this gene is the key regulator. You look at the whole picture, and we have that luxury now because big data is available. Now you can look and see that this is the gene that is upper-regulated or down-regulated. And the data is not coming from one lab but from a national repository with similar reports from many labs.”
By applying translational bioinformatics to big data at his disposal, Ye is at work on several projects that may lead to biological discoveries and ultimately the creation of new diagnostic and therapeutic targets for a wide variety of diseases. Recently, he and collaborator, Dr. Mark Lee at the University of Missouri-Columbia, have developed a modified inhibitor of the NAMPT gene that has the potential to become a novel treatment for osteoporosis.
Also, while working with a Brad Warady, M.D., a well-known pediatric nephrologist at Children’s Mercy, to study 450 DNA samples of children with chronic kidney disease, he has been able to identify a number of new and novel genetic markers that indicate severity of the disease. Then, in collaboration with John Spertus, M.D., a leading cardiovascular outcomes researcher at Saint Luke’s Mid America Heart Institute, Ye uncovered NAMPT-related genetic variations that serve as predictors of coronary artery disease susceptibility, severity (the number of diseased vessels) and outcome (24-month mortality).
“I enjoy the interdisciplinary collaboration,” Ye said. “When you’re collaborating with other scientists, you not only relish a collective wisdom but also get a bigger patient sample. The bigger the sample, the better the data.”