The Speicher laboratory is a recognized leader in the emerging field of proteomics, the systematic study of the full set of proteins produced by a given cell, tissue, or organism. Using state-of-the-art proteomics and associated computational methods, many of which were developed or optimized in the Speicher laboratory, this research group is investigating protein changes associated with a number of different cancers, resistance to viral infection and biomarkers for ectopic pregnancy. The laboratory is also studying specific proteins associated with certain forms of hereditary hemolytic anemia and proteins that protect against oxidative stress.

Dr. Speicher joined Wistar in 1986 from the Yale University School of Medicine. He was born and raised in Pennsylvania and attended Pennsylvania State University as both an undergraduate and graduate biology student.  He received his Ph.D. in 1977 and subsequently pursued postdoctoral training at the Yale University School of Medicine.  He then accepted a position on the Yale Medical School research faculty with a joint appointment as the Director of Yale’s Protein Chemistry Laboratory, prior to moving to Wistar.

The Speicher laboratory is currently pursuing eight major projects. Three projects use proteomics to identify and characterize cancer biomarkers associated with ovarian, colon, and prostate cancers. The goal is to identify specific biomarkers that will improve detection and clinical management of these major cancers. They are also using similar methods to identify biomarkers that distinguish ectopic pregnancy from normal intrauterine pregnancy and non-viable intrauterine pregnancy. A fifth project uses proteomics-based systems biology approaches to study the role of autophagy in melanoma progression and resistance to conventional therapies. A sixth project involves the use of proteomics to characterize innate immunity and its role in resistance to HIV infection. The seventh project involves a structure-function analysis of the role of spectrin in stabilizing red blood cell membranes and the mechanisms of membrane destabilization in hereditary hemolytic anemias. The eighth project involves a structure-function analysis of peroxiredoxin 6, a protein that plays a unique role in protecting lung tissue from damage due to excessive oxidative stress.

1 - Wang, H., Chang-Wong, T., Tang, H-Y., and Speicher, D.W. 2010. Comparison of extensive protein fractionation and repetitive LC-MS/MS analyses on depth of analysis for complex proteomes. J. Proteome Res. 9:1032-40. PMID: 20014860. PMCID: PMC2870931.

2 - Harper, S., Li, Donghai, Maksimova, Y., Gallagher, P.G., and Speicher, D.W. 2010. A fused alpha-beta “mini-spectrin” mimics the intact erythrocyte spectrin head-to-head tetramer binding site. J. Biol. Chem. 285:11003-11012. PMID: 20139081. PMCID: PMC2856305.

3 - Osborne, A.R., Speicher, K.D., Tamez, P.A., Bhattacharjee, S., Speicher, D.W., and Haldar, K. 2010. The host targeting motif in exported Plasmodium proteins is cleaved in the parasite endoplasmic reticulum. Mol. Biochem. Parasitol. 171:25-31. PMID: 20117149. PMCID: PMC2843544.

4 - Ipsaro, J.J., Harper, S., Messick, T.E., Marmorstein, R., Mondragón, A., and Speicher, D.W. 2010. Crystal structure and functional interpretation of the erythrocyte spectrin tetramerization domain complex. Blood. 115:4843-4852. PMID: 20197550. PMCID: PMC2890174.

5 - Li, D., Harper, S.L., Tang, H.Y., Maksimova, Y., Gallagher, P.G., and Speicher, D.W. 2010. A comprehensive model of the spectrin divalent tetramer binding region deduced using homology modeling and chemical cross-linking of a mini-spectrin. J. Biol. Chem. 285:29535-29545. PMID: 20610390. PMCID: PMC2937985.

6 - Han, M-J., Wang, H., Beer, L., Tang, H.-Y., Herlyn, M., and Speicher, D.W. 2010. A systems biology analysis of metastatic melanoma using in-depth three-dimensional protein profiling. Proteomics 10:4450-4462. PMID: 21136598. PMCID: PMC307844.

7 - Beer LA, Tang HY, Sriswasdi S, Barnhart KT, Speicher DW., Systematic discovery of ectopic pregnancy serum biomarkers using 3-D protein profiling coupled with label-free quantitation., Journal of proteome Research. 2011 Mar 4;10(3):1126-38. [Epub 2011 Jan 7.], 21142075

8 - Chatterjee, S., Feinstein, S.I., Dodia, C., Nguyen, S., Lien, Y.-C., Sorokina, E., Debolt, K., Speicher, D., and Fisher, A.B. 2011. Peroxiredoxin 6 phosphorylation and subsequent phospholipase A₂ activity are required for agonist-mediated activation of NADPH oxidase in mouse pulmonary microvascular endothelium. J Biol Chem. 286:11696-11706. PMID: 21262967. PMCID: PMC3064221.

9 - Krieger, C.C., An, X., Tang, H.-Y., Mohandas, N., Speicher, D.W., and Discher, D.E. 2011. Cysteine shotgun-mass spectrometry (CS-MS) reveals dynamic sequence of protein structure changes within mutant and stressed cells. Proc. Natl. Acad. Sci. USA. 108:8269-8274. PMID: 21527722. PMCID: PMC3100976.

10 - Tang, H.-Y., Beer, L.A., Barnhart, K.T., and Speicher, D.W. 2011. Rapid verification of candidate serological biomarkers using gel-based, label-free multiple reaction monitoring. J. Proteome Res. July 5, Epub ahead of print. PMID: 21726088. PMC Journal – In Process.