个人简介

Ph.D., Chemistry, Texas A&M University, 1993 B.S., Chemistry, Summa Cum Laude, the University of Puerto Rico at Mayagüez, 1988

研究领域

Biochemistry/Biophysical

The Colón laboratory is interested in understanding the role of protein stability in protein function, folding, misfolding, oligomerization, and aggregation. It is well known that many diseases, including Alzheimer’s disease, Type II diabetes, Parkinson’s disease, Cystic fibrosis, and prion diseases are pathologically linked to protein misfolding and abnormal aggregation. Furthermore, it is likely that many types of cancer and the aging process are related to the problem of protein misfolding. Two main ongoing projects in the Colón lab addresses protein stability and protein misfolding from different perspectives. Protein kinetic stability: From biology to pathology Most proteins in nature are in equilibrium with partially and globally unfolded conformations. However, some proteins appear to have been trapped in their native state by “mother nature” to allow them to remain active under harsh conditions and to safeguard the structure of those proteins that are intrinsically prone to misfolding and aggregation. These so called “kinetically stable proteins” (KSPs) are physically trapped by an energy barrier that virtually blocks their ability to transiently sample other conformations. The biological significance and structural basis of kinetic stability remain poorly understood. We are developing and applying methods to explore at the systems, cellular and organism level, the biological and pathological significance of this intriguing property of proteins. The biological and pathological roles of the inflammation-related protein serum amyloid A Serum amyloid A (SAA) belongs to a highly conserved family of lipid-binding proteins that appears to play very important roles in the inflammatory response. SAA is predominantly synthesized in the liver and then secreted to the plasma, where it binds to high-density lipoprotein (HDL). SAA has been linked to many biological functions and pathological processes, but these remain poorly understood. Most notably, SAA is the principal component of amyloid fibril deposits in the liver, kidney and spleen of individuals suffering from AA amyloidosis, a protein misfolding disease that occurs as a secondary effect of chronic inflammatory disease. One of the main goals of the Colón lab is to understand the mechanism by which SAA misfolds and aggregates, leading to AA amyloidosis. A longer term goal is to understand the many biological roles of SAA and how they might be related to immune defense and different diseases.

近期论文

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Wang, Y.; Srinivasan, S.; Ye, Z.; Aguilera, J. J.; Lopez, M. M.; Colon, W. "Serum Amyloid a 2.2 Refolds into a Octameric Oligomer That Slowly Converts to a More Stable Hexamer" Biochem. Biophys. Res. Commun. 2011, 407, 725-729. Vassall, K. A.; Stubbs, H. R.; Primmer, H. A.; Tong, M. S.; Sullivan, S. M.; Sobering, R.; Srinivasan, S.; Briere, L.-A. K.; Dunn, S. D.; Colon, W.; Meiering, E. M. "Decreased Stability and Increased Formation of Soluble Aggregates by Immature Superoxide Dismutase Do Not Account for Disease Severity in Als" PNAS 2011, 108, 2210-2215. Sroga, G. E.; Karim, L.; Colon, W.; Vashishth, D. "Biochemical Characterization of Major Bone-Matrix Proteins Using Nanoscale-Size Bone Samples and Proteomics Methodology" Molecular & Cellular Proteomics 2011, 10, 10.1074/mcp.M1110.006718 Muniz, V. A.; Srinivasan, S.; Boswell, S. A.; Meinhold, D. W.; Childs, T.; Osuna, R.; Colon, W. "The Role of the Local Environment of Engineered Tyr to Trp Substitutions for Probing the Denaturation Mechanism of Fis" Protein Sci. 2011, 20, 302-312. Zhang, S.; Xia, K.; Chung, W. K.; Cramer, S. M.; Colon, W. "Identifying Kinetically Stable Proteins with Capillary Electrophoresis" Protein Sci. 2010, 19, 888-892. Xia, K.; Zhang, S.; Solina, B. A.; Barquera, B.; Colon, W. "Do Prokaryotes Have More Kinetically Stable Proteins Than Eukaryotic Organisms?" Biochemistry 2010, 49, 7239-7241. Xia, K.; Zhang, S.; Colon, W. "Identifying Kinetically Stable Proteins Via Electrophoresis Methods" J. Biomol. Struct. Dyn. 2009, 26, 860-860. Shang, W.; Nuffer, J. H.; Muniz-Papandrea, V. A.; Colon, W.; Siegel, R. W.; Dordick, J. S. "Cytochrome C on Silica Nanoparticles: Influence of Nanoparticle Size on Protein Structure, Stability, and Activity" Small 2009, 5, 470-476. Xia, K.; Manning, M.; Hesham, H.; Lin, Q.; Bystroff, C.; Colon, W. "Identifying the Subproteome of Kinetically Stable Proteins Via Diagonal 2d Sds/Page" PNAS 2007, 104, 17329-17334. Wang, L.; Colon, W. "Effect of Zinc, Copper, and Calcium on the Structure and Stability of Serum Amyloid A" Biochemistry 2007, 46, 5562-5569. Muniz, V. A.; Boswell, S.; Meinhold, D. W.; Childs, T.; Osuna, R.; Colon, W. "The Importance of Location of Tryptophan Residues in Probing the Folding Pathway of Factor for Inversion Stimulation" J. Biomol. Struct. Dyn. 2007, 24, 766-767. Moriarty, D. F.; Fiorillo, C.; Miller, C.; Colon, W. "A Truncated Peptide Model of the Mutant P61a Fis Forms a Stable Dimer" Biochim. Biophys. Acta, Proteins Proteomics 2007, 1774, 78-85. Meinhold, D.; Beach, M.; Shao, Y.; Osuna, R.; Colon, W. "The Location of an Engineered Inter-Subunit Disulfide Bond in Factor for Inversion Stimulation (Fis) Affects the Denaturation Pathway and Cooperativity" Biochemistry 2006, 45, 9767-9777. Lynch, S. M.; Colon, W. "Dominant Role of Copper in the Kinetic Stability of Cu/Zn Superoxide Dismutase" Biochem. Biophys. Res. Commun. 2006, 340, 457-461. Feldman-Cohen, L. S.; Shao, Y. P.; Meinhold, D.; Miller, C.; Colon, W.; Osuna, R. "Common and Variable Contributions of Fis Residues to High-Affinity Binding at Different DNA Sequences" J. Bacteriol. 2006, 188, 2081-2095. Wang, L. M.; Lashuel, H. A.; Colon, W. "From Hexamer to Amyloid: Marginal Stability of Apolipoprotein Saa2.2 Leads to in Vitro Fibril Formation at Physiological Temperature" Amyloid-Journal of Protein Folding Disorders 2005, 12, 139-148. Wang, L. M.; Colon, W. "Urea-Induced Denaturation of Apolipoprotein Serum Amyloid a Reveals Marginal Stability of Hexamer" Protein Sci. 2005, 14, 1811-1817.