Areas of Expertise (7)
Nuclear Magnetic Resonance Spectroscopy
Chunyu Wang, professor of Biological Sciences, and Chemistry and Chemical Biology at Rensselaer, is an expert in nuclear magnetic resonance (NMR) structural biology and in structural mechanisms of Alzheimer’s disease and cancer. In the field of Alzheimer’s research, his lab is studying the structural mechanisms of the generation of amyloid-β peptide (Aβ), as well as the interaction between glycan and tau, which facilitates the spread of tau pathology, neurofibrillary tangle (NFT, the other pathological hallmark of AD). In cancer, his lab is studying the structural mechanism of Hedgehog signaling and p53 interactions.
After establishing his own research group at Rensselaer in 2005, he developed a strong research program in structural mechanisms in protein autoprocessing and Alzheimer’s disease. Recently, his group is venturing into new and exciting areas such as drug discovery and biological sulfation. He has been awarded multiple grants from NIH and several grants for Alzheimer’s research, from Alzheimer’s Association, Warren Alpert Foundation, New York State and American Health Assistance Foundation (Now BrightFocus foundation).
Peking Union Medical College: Doctor of Medicine
Cornell University: Doctorate, Biochemistry and Molecular Genetics
Media Appearances (1)
RPI Researchers Working on Potentially Groundbreaking Alzheimer's Drug
Spectrum News tv
For the 5.8 million Americans living with Alzheimer’s presently, decades of research have provided little hope. “Drug discovery for Alzheimer’s has been very, very hard,” said Dr. Chunyu Wang, a biological sciences professor at RPI. “In the past 17 years, no new drug has been approved for Alzheimer’s.”
Substrate interaction inhibits intramembrane proteolysis and amyloid productionChemical Communications
Jackie Jing Zhao, Yuanyuan Xiao, Xinyue Liu, Marilia Barros, Yueming Li, Xuben Hou, Feng Xiong, Nikolaos Robakis, Jon Dordick, Yingkai Zhang, Iban Ubarretxena-Belandia and Chunyu Wang
Combining NMR, mass spectrometry, AlphaLISA and cell assays, we discovered a compound C1 that binds C-terminal juxtamembrane lysines at the transmembrane domain of the amyloid precursor protein (APPTM) and inhibits γ-secretase production of amyloid-β with μM IC50. Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery.
Rare 3‐O‐sulfation of Heparan Sulfate Enhances Tau Interaction and Cellular Uptake.Angewandte Chemie
Jing Zhao, Yanan Zhu, Xuehong Song, Yuanyuan Xiao, Guowei Su, Xinyue Liu, Zhangjie Wang, Yongmei Xu, Jian Liu, David Eliezer, Trudy F. Ramlall, Guy Lippens, James Gibson, Fuming Zhang, Robert J. Linhardt, Lianchun Wang, Chunyu Wang
Prion‐like transcellular spreading of tau in Alzheimer's Disease (AD) is mediated by tau binding to cell surface heparan sulfate (HS). However, the structural determinants for tau–HS interaction are not well understood. Microarray and SPR assays of structurally defined HS oligosaccharides show that a rare 3‐O‐sulfation (3‐O‐S) of HS significantly enhances tau binding. In Hs3st1−/− (HS 3‐O‐sulfotransferase‐1 knockout) cells, reduced 3‐O‐S levels of HS diminished both cell surface binding and internalization of tau. In a cell culture, the addition of a 3‐O‐S HS 12‐mer reduced both tau cell surface binding and cellular uptake. NMR titrations mapped 3‐O‐S binding sites to the microtubule binding repeat 2 (R2) and proline‐rich region 2 (PRR2) of tau. Tau is only the seventh protein currently known to recognize HS 3‐O‐sulfation. Our work demonstrates that this rare 3‐O‐sulfation enhances tau–HS binding and likely the transcellular spread of tau, providing a novel target for disease‐modifying treatment of AD and other tauopathies.