|
||||||||||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Our research group primarily focuses on proteomics of human diseases and structure-function of protein-protein interactions. We are currently pursuing proteomics projects in four major areas using technologies recently developed and/or optimized by us. One project uses comprehensive gel-based protein profiling methods to identify key protein changes associated with development of metastatic potential in human breast cancer. A second group of projects uses a mass spectrometry/bioinformatics strategy to discover human biomarkers of several different types of cancers in a mouse model system. A third group of projects involves the direct analysis of patients' serum samples using high throughput methods to discover protein patterns that correlate with cancers and other human diseases. This project also involves development of superior high throughput serum protein profiling methods, including new analytical separation strategies and new computational tools for data analysis and biomarker pattern recognition. The fourth proteomics project investigates the role of oxidative stress in development of acute lung injury utilizing mouse models and human plasma samples. We are also currently pursuing three structure-function projects that primarily utilize biophysical methods including isothermal titration calorimetry, sedimentation equilibrium analysis and mass spectrometry analysis of recombinant proteins and protein domains. One project involves the membrane skeletal protein spectrin, a human red cell actin crosslinking protein involved in numerous human hereditary hemolytic anemias. Another project involves structure-function analysis of the GA733 antigen (EP-CAM), a cell adhesion protein expressed at high levels in most colorectal and pancreatic cancers that is a promising cancer therapeutic target. The final structure-function project involves analysis of macromolecular assembly and active site oxidation of peroxiredoxin 6, an antioxidant enzyme with glutathione peroxidase activity, which plays a critical role in protecting lung tissue from damage due to oxidative stress. Selected Publications: Tang, H.-Y., Speicher, D.W. (2004) In vivo phosphorylation of human erythrocyte spectrin occurs in a sequential manner. Biochemistry 43:4251-4262. Zuo, X. and Speicher, D.W. (2002) Comprehensive analysis of complex proteomes using microscale solution isoelectrofocusing and slightly overlapping narrow range two-dimensional gels. Proteomics 2:58-68. Zuo, X., Hembach, P., Echan, L., and Speicher D.W. (2002) Enhanced analysis of human breast cancer proteomes using micro-scale solution isoelectrofocusing combined with high resolution 1-D and 2-D gels. Journal of Chromatography B 782:253-265. Harper, S.L., Begg, G.E., and Speicher, D.W. (2001) Role of terminal non-homologous domains in initiation of human red cell spectrin dimerization. Biochemistry 40:9935-9943. Chong, J.M. and Speicher, D.W. (2001) Determination of disulfide bond assignments and N-glycosylation sites of the human gastrointestinal carcinoma antigen GA733-2 (CO17-1A, EGP, KS1-4, KSA, Ep-CAM). J. Biol. Chem. 276:5804-5813. |
