Ph.D. Purdue University 1989
BS Nanjing University, China 1983
Dr. Xu came to USA in 1984 through CUSBEA program (Class 84) and received his Ph.D. from Purdue University in Biochemistry in 1989. After post-doctoral training in the Physics Department at University of California, San Diego, he joined the University of Chicago in 1992 as an assistant professor in the department of Medicine to develop atomic force microscopy (AFM) for biomedical applications. There, he applied AFM to many areas of biomedical research and made a number of original contributions to lipoprotein, amyloid fiber research as well as to the development of AFM technique. In 2002 he joined the Pathology Department, University of Pennsylvania as a senior research investigator and, using AFM and TEM, identified most of the important intermediates in tau protein aggregation involved in Alzheimer's disease. He came to the Florida Space Research Institute at Kennedy Space Center and Florida Institute of Technology in 2004 to continue his work in applying molecular imaging tools to important biological and biomedical problems. Dr. Xu reviews grant proposals for numerous funding agencies, including NASA, NSF and National Alzheimer's Association. He is also a reviewer for American Chemical Society, Biophysical Society and Microscopy Society journals.
Wade Dauberman, Samuel Breit, Shaohua Xu (2017) Protein Gelation around Axons Inhibits Action Potential Propagation in Nerve Fibers. 7(4):1000349.
Wade Dauberman, Shaohua Xu (2017) Alzheimer’s Disease Pathogenesis: The Denied Access Model. J. Alzheimer’s Disease & Parkinsonism. 7(4):1000359.
Wang, H Wang, Hongjie; Wang, Ruizhi; Xu, Shaohua; Lakshmana, Madepalli K. Transcription Factor EB Is Selectively Reduced in the Nuclear Fractions of Alzheimer's and Amyotrophic Lateral Sclerosis Brains. Neuroscience journal 2016 47328-37 2016
Wang, R Wang, R., Wang, H, Carrera, I, Xu, S., Lakshmana, M COPS5 Protein Overexpression Increases Amyloid Plaque Burden, Decreases Spinophilin-immunoreactive Puncta, and Exacerbates Learning and Memory Deficits in the Mouse Brain J. Biol. Chem. 290(14) 9299-9309 2015
Woodard D, Bell D, Tipton D, Durrance S, Cole L, Bin Li, Shaohua Xu. Gel Formation in Protein Amyloid Aggregation: A Physical Mechanism for Cytotoxicity. PLoS ONE 9(4): e94789, 2014.
Lisa C. Burnett, Benjamin J. Burnett, Bin Li, Samuel T. Durrance, Shaohua Xu. A Lysozyme Concentration, pH, and Time-Dependent Isothermal Transformation Diagram Reveals Fibrous Amyloid and Non-Fibrous, Amorphous Aggregate Species *Open Journal of Biophysics, 4, 39-50, 2014.
Palavicini, Juan Pablo; Wang, Hongjie; Minond, Dmitriy; Bianchi, Elisabetta; Xu, Shaohua; Lakshmana, Madepalli K. RanBP9 overexpression down-regulates phospho-cofilin, causes early synaptic deficits and impaired learning, and accelerates accumulation of amyloid plaques in the mouse brain. Journal of Alzheimer's disease, 39(4), 727-40, 2014
Wang, Hongjie; Wang, Ruizhi; Xu, Shaohua; Lakshmana, Madepalli K. RanBP9 overexpression accelerates loss of pre and postsynaptic proteins in the APDeltaE9 transgenic mouse brain. PloS one, 9(1), e85484, 2014.
Anson JR, Lu CH, Cui L, Yang X, Xu S. 2013. Techniques to quantify the size of protein colloids in amyloid fiber formation. Open Journal of Biophysics, 3, 22-32, 2013.
Wang, Hongjie; Dey, Debleena; Carrera, Ivan; Minond, Dmitriy; Bianchi, Elisabetta; Xu, Shaohua; Lakshmana, Madepalli K. COPS5 (Jab1) Protein Increases beta Site Processing of Amyloid Precursor Protein and Amyloid beta Peptide Generation by Stabilizing RanBP9 Protein Levels. The Journal of biological chemistry, 288 (37), 26668-77, 2013.
Palavicini, J P; Wang, H; Bianchi, E; Xu, S; Rao, J S; Kang, D E; Lakshmana, M K. RanBP9 aggravates synaptic damage in the mouse brain and is inversely correlated to spinophilin levels in Alzheimer's brain synaptosomes. Cell Death and Disease, 4, e667, 2013.
Lin Y, Xu S 2011. Atomic force microscopy of lacuna and canaliculi channals in bovine tibia. J. Microscopy, Vol. 241, Pt 3, pp. 291–302.
Xu S, Brunden KR, Trojanowski JQ, and Lee LMY. 2010. Characterization of tau fibrillization in vitro. Alzheimer's & Dementia, 6:110117
Xu S. 2009. The Cross-β-sheet
structure in amyloid fiber formation. J. Phys. Chem. B. 113:12447-12455.
Tansel B, Sager J, Garland J, Xu S. 2009. Effect of transmembrane pressure on overall membrane resistance during cross-flow filtration of solutions with high-ionic content.
J Memb Sci 328:205-210.
Tansel B, Sager J, Garland J, Xu S, Levine L, Bisbee P. 2008. Biofouling affinity of membrane surfaces under quiescent conditions J Memb Sci 227:264-273
Xu, S. 2007.
Aggregation drives "Misfolding"in Amyloid Fiber Formation. Amyloid-the Journal of Protein Folding Disorders. 14(2):119-131.
Xu, S., Yu, J. J. 2006. Benneath the Minerals, a Layer of Round Lipid Particles Was Identified to Mediate Collagen Calcification in Compact Bone Formation. Biophys. J. 91:4221-4229.
Tansel, B., J. Sager, J. Garland, S. Xu, L. Levine, P. Bisbee, 2006. Deposition of extracellular polymeric substances (EPS) and microtopographical changes on membrane surfaces during intermittent filtration conditions. J. Memb. Sci. 285:225-231.
Xu, S., D. Wu, M. F. Arnsdorf, R. Johnson, G. S. Getz, V. G. Cabana. 2005. Serum amyloid A fiber formation resembles the linear aggregation of colloidal gold particles. Biochem., 44 (14): 5381-5389.
Norris, E. H., B. I. Giasson, R. Hodara, S. Xu, J. Trojanowski, H. Ischiropoulos, V. V-M Lee. 2005. Implications of dopoamine-synuclein interactions on the pathogenesis of Parkinsons disease. J. Biol. Chem. 280 (22): 21212-21219.
Xu, S., B. Bevis, M. F. Arnsdorf. 2001. The assembly of amyloidogenic yeast Sup35 as assessed by scanning (atomic) force microscopy: an analogy to linear colloidal aggregation? Biophys. J. 81: 446-454.
Xu, S., B. Lin. 2001. The mechanism of oxidation-induced low-density lipoprotein aggregation: an analogy to colloidal aggregation and beyond? Biophys. J. 81: 2403-2413.
Kurutz, J., S. Xu. 2001. Hofmeister solute effects on hydrophobic adhesion forces in SFM experiments. Langmuir. 17 (23) : 7323-7326. http://my.fit.edu/~xshaohua/Langmuir%202001
Xu, S., 1998. Apolipoprotein (a) binds to low density lipoprotein at two distant sites in lipoprotein (a). Biochem. 37: 9284-9294.
Xu, S., M. F. Arnsdorf. 1995. Electrostatic force microscope for probing surface charges in aqueous solution. Proc. Natl. Acad. Sci. USA, 92(22) : 10384-10388. Communicated by Dr. Stuart Rice.
Xu S, Arnsdorf MF. 1994. Calibration of the scanning (atomic) force microscope with gold particles.
J Micros 173:199-210
Alzheimer’s disease Disease affects millions and costs the nation hundreds of billions of dollars annually , and soon will become the single most expensive disease-with direct care costs exceeding that of cancer and heart disease. Currently there is no cure for AD for the disease. Recent discovery that the root cause of Alzheimer’s disease involves a gelation process revises our hope to tackleof tackling this important medical issue.
Currently we are interested in the role of amyloid plaques found in Alzheimer's brain in synapse and neuornal loss, and the mechanism of protein self assembly and formation of amyloid fiber plaques or biogels and how various amyloid protein aggregates affect neuron's action potential propagation. We apply iWork, AFM, TEM, confocal microscopy, MALDI mass spectrometry, microplate reader for high-throughput screening, and traditional biochemical and molecular biology approaches to understand the effect of protein aggregates on the action potential of axons, and, at the molecular level, pathway and the energy driving protein fiber formation. Protein amyloid fiber formation is an early event in dozens of human diseases including Alzheimer's disease, Parkingon's disease, prion disease, and type 2 diabetes. A key observation in our understanding the mechanism of protein self-assembly and the formation of amyloid fibers was the identification by AFM and later TEM of spherical particles of colloidal size which form early in the process. These spheres assemble into linear chains, which evolve structurally into protofilaments, ribbons, and other forms of mature fibers. The size of the spheres assembled into a fiber is comparable to the size of the free spheres, and the density of the free spheres rises initially and then falls as they are consumed in fiber formation. Kinetic analysis indicates that fiber formation can be promoted by either seeding or physical agitation, factors well-known to accelerate colloidal aggregation. Although conditions that induce aggregation vary among different proteins, as do the kinetics and thermodynamics, fiber formation appears to be a generic property of peptides and proteins. Based on these observations, we introduced a linear colloidal aggregation model to elucidate the mechanism of amyloid fiber formation. A high interfacial energy drives amyloidogenic protein molecules to form a spherical aggregate, which minimizes both area of contact with the media and surface energy.
Although individual protein monomers are not considered colloids, the spherical aggregates observed as intermediates in amyloid fiber formation are colloidal particles. Formation of chemical colloids is dependent primarily on molecular properties such as charge and hydrophobicity, which are indirectly related to structure, but does not depend directly on structure-specific interaction between molecular groups; this paradigm may apply to protein amyloid aggregation as well. Dr. Xu is the original author who introduced the colloidal model for amyloid fiber formation.
Research & Project Interests
We are interested in applying theories and methods developed in physics and chemistry to the understanding of biomedical problems at the molecular level. We focus on the structural analysis of single molecules, the process of molecular assembly and aggregation, and the surface and interface phenomenon in biology. We are also interested in developing methods for imaging animal tissues with the highest structural resolution and molecular recognition. Such information is often found to be critical in the elucidation of a protein’s biological function and role in the pathogenesis of a medical disease.