Rensselaer Polytechnic Institute | About RPI | Academics | Research | Student Life | Admissions | News & Information
Department of Chemistry and Chemical Biology at Rensselaer Chemistry and Chemical Biology
Wilfredo Colón
* *
Home Undergraduate Graduate Research Faculty Facilities Students News
* * *
Wilfredo Colón

Professor and Department Head
Department of Chemistry and Chemical Biology
Rensselaer Polytechnic Institute

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

Career Highlights:
After serving as a postdoctoral associate and then as a National Science Foundation (NSF) Fellow at the Fox Chase Cancer Center in Philadelphia, Colón joined the Rensselaer faculty in 1997. He was promoted to associate professor in 2004.

Colón’s many honors and awards include the 2010 American Chemical Society Award for Encouraging Disadvantaged Students into Careers in the Chemical Sciences, election as a fellow of the AAAS in 2007, the Rensselaer Early Career Award in 2002, a NSF Presidential Early Career Award for Scientists and Engineers (PECASE) in 2001, a NSF faculty Early Career Development (CAREER) Award in 2000, a Research Corporation Innovation Award in 1999. a American Heart Association Scientist Development Award in 1998, and a New Faculty Award from the Camille And Henry Dreyfus Foundation in 1997.

Research Areas:
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.

Selected Publications:

Broom, A., Ma, S.M., Xia, K., Rafalia, H., Trainor, K., Colón, W., Gosavi, S and Meiering, E.M. (2015) Designed protein reveals topological complexity as a central determinant of extreme kinetic stability. Proc. Natl. Acad. Sci., “in press”.

Colón W., Aguilera J.J., Srinivasan S. (2015) Intrinsic Stability, Oligomerization, and Amyloidogenicity of HDL-Free Serum Amyloid A. Adv Exp Med Biol. 855, 117-134.

Aguilera, J., Zhang, F., Beaudet, J.M., Linhardt, R.J. and Colón, W. (2014) Divergent effect of glycosaminoglycans on the in vitro aggregation of Serum Amyloid A. Biochimie 104, 70-80.

Patke, S., Srinivasan, S., Maheshwari, R., Srivastava, S.K., Aguilera, J. J., Colón, W.* and Kane, R.S.* (2013) Characterization of the oligomerization and aggregation of human Serum Amyloid A. PLoS One 8:e64974. doi: 10.1371.

Srinivasan, S., Patke, S., Wang, Y., Ye, Z., Litt, J., Lopez, M.M., Kane, R.S. and Colón, W. (2013) Pathogenic SAA1.1 shows a longer oligomer-rich fibrillation lag phase contrary to the non-pathogenic SAA2.2. J. Biol. Chem. 288, 2744-2755.

Ramakrishnan V., Srinivasan, S., Salem, S.M., Matthews, S. J., Colón, W, Zaki M.J. and Bystroff, C. (2012) GeoFold: Topology-based protein unfolding pathways capture the effects of engineered disulfides on kinetic stability. Proteins 80, 920-934.

Xia, K, Zhang, S., Bathrick, B., Liu, S., Garcia, Y. and Colon, W. (2012) Quantifying the kinetic stability of hyperstable proteins via time-dependent SDS-trapping. Biochemistry 51, 100-107.

Xia, K., Manning, M., Zhang, S. and Colón, W. (2012) Proteomics Analysis of kinetically stable proteins, Integrative Proteomics, Hon-Chiu Eastwood Leung, Subject editors: Tsz-Kwong Man and Ricardo J. Flores (Ed.), ISBN: 978-953-51-0070-6, InTech.

Ye, Z, Bayron, D., Aguilera, J.J., Srinivasan, S., Wang, Y., Serpell, L.C. and Colón, W. (2011) Inflammation protein SAA2.2 spontaneously forms marginally stable amyloid fibrils at physiological temperature. Biochemistry 50, 9184-9191.

Wang, Y., Srinivasan, S., Ye, Z., Aguilera, J.J., Lopez, M. and Colón, W. (2011) Serum amyloid A 2.2 refolds into a octameric oligomer that slowly converts to a more stable hexamer. Biochem. Biophys. Res. Commun. 407, 725-729.

Vassall, K.A, Stubbs, H.A., Primmer, H.A., Tong, M.S., Sullivan, S.M,, Sobering, R., Srinivasan, S., Briere, L.K., Dunn, S.D., Colòn, W. and Meiering, E.M. (2011) Decreased stability and increased formation of soluble aggregates by immature SOD1 do not account for disease severity in ALS. Proc. Natl. Acad. Sci. 108, 2210-2215.

Xia, K., Zhang, S, Solina, B., Barquera, B. and Colón, W. (2010) Do prokaryotes have more hyperstable proteins than eukaryotic organisms? Biochemistry 49, 7239-7241.

Zhang, S., Xia, K., Chung, W., Cramer, S.M., and Colón, W. (2010) Identifying kinetically stable proteins with capillary zone electrophoresis. Prot. Science 19, 888-892.

Shang, W., Nuffer, J.H., Muñiz-Papandrea, V.A., Colón, W., Siegel, R.W., and Dordick, J.S. (2009) Cytochrome c on silica nanoparticles: Influence of nanoparticle size on protein structure, stability, and activity. Small 4, 470-476.

Xia, K, Manning, M., Hesham, H., Bystroff, C., Lin, Q. and Colón, W. (2007) Identifying the subproteome of kinetically stable proteins via diagonal 2D SDS-PAGE. Proc. Natl. Acad. Sci. 104, 17329-17334.

Lynch, S. M. and Colón, W. (2006) Dominant role of copper in the kinetic stability of Cu/Zn superoxide dismutase. Biochem. Biophys. Res. Commun. 340, 457-461.

Meinhold, D., Boswell, S. and Colón, W. (2005) P61A mutation in the factor for inversion stimulation results in a thermostable dimeric intermediate. Biochemistry 44, 14715-14724.

Lynch, S.M., Boswell, S.A. and Colón, W. (2004) Kinetic stability of SOD is dependent on its metal ligands: Implications for ALS. Biochemistry 43, 16525-16531.

Manning, M. and Colón, W. (2004) Structural basis of protein kinetic stability: Resistance to sodium dodecyl sulfate suggests a central role for rigidity and a bias towards beta-sheet structure. Biochemistry 43, 11248-11254.


RPI Home > Academics > School of Science > Chemistry & Chemical Biology:
Home Undergraduate Graduate Research Faculty Facilities Students News

 Copyright ©2005 Rensselaer Polytechnic Institute. All rights reserved.