Robert K. Yu, Ph.D., Med.Sc.D.
Molecular and Cellular Neurobiology
Drawing on deep expertise in both neurochemistry and neurobiology, Robert Yu has made tremendous contributions to our knowledge of how the brain develops and matures. Now, Yu and his team are using these discoveries to develop new treatments for Alzheimer’s disease, Parkinson’s disease and an array of other neurological disorders.
Much of Yu’s research has to do with glycoconjugates, complex sugar molecules that facilitate many biological functions, including communication between cells. Glycoconjugates are just beginning to be widely studied, and Yu’s lab has identified almost a third of the known structures of brain gangliosides, a type of glyconjugate that is abundant in the brain and the rest of the nervous system. In fact, Yu’s peers credit him as a pioneer in the field of ganglioside research.
It’s known that both the overproduction or underproduction of gangliosides can lead to a range of neurodegenerative diseases and disorders. One ganglioside studied more intensively by Yu and his colleagues is called GD3, which is highly enriched in neural stem cells, the basic cell type that other brain cells are derived. One of GD3’s major functions is to interact with the epithelial growth factor (EGF), which is crucial in early brain development. Without GD3, the brain can’t form normally. Yu’s study has major implications in neuro-regeneration and neural repair in traumatic brain injury and neurodegenerative diseases.
Yu’s research on glycoconjugates has also helped him shed light on Guillain-Barre syndrome, a disease in which the body’s immune system attacks the nervous system. The cause for this unwelcome attack may be something called “molecular mimicry,” meaning the surface of the bacteria that caused the original illness has a similar structure to gangliosides and other glycoconjugates on the nerve tissues. Yu found, for instance, that Guillain-Barre patients had antibodies against the ganglioside GD3.
The standard clinical treatment for Guillain-Barre is to replace the patient’s plasma and remove all antibodies — not just the harmful ones. Such a procedure, however, puts the patient’s immune system at risk. Yu and his colleagues developed a new treatment strategy that eliminates the harmful antibodies only, leaving the rest of the patient’s immune defenses intact. They developed this treatment by creating a peptide chain about twelve amino acids long that binds only to the harmful, ganglioside-attacking antibodies and neutralizes them so they can be eliminated. Yu’s team patented the procedure and is now commercializing it for wider use.
Through his work with gangliosides, Yu also discovered and patented a treatment for cholera — and this invention is closest to his heart. Cholera infects 3 to 5 million people each year and kills 100,000, mostly children in the developing world. The cholera toxin does its lethal work by binding to a cell surface receptor in the gut, a ganglioside called GM1. When the toxin binds to GM1, the toxin is granted entrance into the cell, where the destruction begins.
Using the same approach as their treatment for Guillain-Barre, Yu and his colleagues created a chain of peptides that neutralizes the cholera toxin by binding to it — and blocking it from connecting to a cell. Yu is still searching to license the technology to a pharmaceutical company, and he is eager to bring this treatment available to the areas that need it most.
Just as he led the way in the field of ganglioside research, Yu and his team also have developed cutting-edge techniques to expand their capabilities in the lab. They pioneered the use of nuclear magnetic resonance to study glycolipids. They created a method to separate glycolipids using silica gel, so they could analyze a single glycolipid molecule and understand its properties. They also developed techniques for identifying and determining the unique structural configurations of each sugar molecule. These techniques, developed by Yu and his colleagues, are now taught in textbooks.
- The role of glycoconjugates in cellular proliferation & differentiation
- Mechanisms underlying neurodegenerative disorders
- Neuro-oncology and the mechanisms of how tumors form
- Cell transplantation and immunotherapy for neurodegenerative disorders and cancers
Straight from the Scholar
The state support in higher education through the Georgia Research Alliance as well as other initiatives is unsurpassed. There are ample opportunities for collaborative research among researchers in Georgia. Georgia is rapidly rising to the leading edge of biotechnological and biomedical development, and I am very happy to be part of this effort.