Our Science

David W. Speicher, Ph.D.

David W. Speicher, Ph.D.

  • Caspar Wistar Professor in Computational and Systems Biology
  • Director, Center for Systems and Computational Biology

  • Program Co-leader, Molecular and Cellular Oncogenesis Program

  • Scientific Director, Proteomics Facility
  • 215-898-3972, Office

Summary

The Speicher laboratory is a recognized leader in the 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, innate resistance to viral infection, red cell diseases, ectopic pregnancy and other clinical disorders. The laboratory is also using structural mass spectrometry techniques coupled with molecular modeling to determine medium resolution structures of large protein complexes and characterize conformational changes involved with physiological processes.

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 biochemistry 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 seven major projects.  Two projects use proteomics to study ovarian cancer and melanoma from a systems biology perspective and to identify biomarkers with clinical utility.  A third project uses proteomics to identify and characterize biomarkers for improved detection and clinical management of colon cancer. They are also using similar methods to identify biomarkers for improved diagnosis of cardiotoxicity caused by cancer therapies.  A fifth project involves discovery and validation of plasma biomarkers to help clinicians distinguish between ectopic pregnancy, normal intrauterine pregnancy, and non-viable intrauterine pregnancy. A sixth project uses proteomics to study the effects of pathogenic and acquired mutations red cell membrane integrity and structural mass spectrometry to develop comprehensive structural models of large red cell membrane complexes to understand function and dynamics.  A seventh project uses a proteomics based systems biology approach to study human natural killer  (NK) cells and their role in resistance to HIV. 

 
Selected Publications

1.  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.

2.  Beer, L.A., Tang, H.-Y., Sriswasdi, S., Barnhart, K.T., and Speicher, D.W. 2011. Systematic discovery of ectopic pregnancy serum biomarkers using 3-D protein profiling coupled with label-free quantitation. J Proteome Research. 10:1126-1138. PMID: 21142075. PMCID: PMC3048922.

3.  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.

4.  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. 10:4005-17. PMID: 21726088. PMCID: PMC3166403.

5.  Wang, H., Tang, H.-Y., Tan, G.C., and Speicher, D.W. 2011. A data analysis strategy for maximizing high-confidence protein identifications in complex proteomes such as human tumor secretomes and human sera. J. Proteome Res. 10:4993-5005.PMID: 21955121. PMCID: PMC3221390.

6.  Tang, H.-Y., Beer, L., Chang-Wong, T., Hammond, R., Gimotty, P., Coukos, G., and Speicher, D.W. 2012. A xenograft mouse model coupled with in-depth plasma proteome analysis facilitates identification of novel serum biomarkers for human ovarian cancer. J Proteome Res. 11:678-91. PMID: 22032327. PMCID: PMC3272104.

7.  Bhattacharjee, S., Stahelin, R.V., Speicher, K.D., Speicher, D.W., Haldar, K. 2012. Endoplasmic reticulum PI(3)P lipid binding targets malaria proteins to the host cell. Cell. 148:201-12. PMID:22265412. PMCID: PMC3268671.

8.  Pesciotta, E., Sriswasdi, S., Tang, H.-Y., Mason, P.J., Bessler, M., and Speicher, D.W. 2012. A label-free proteome analysis strategy for identifying quantitative changes in erythrocyte membranes induced by red cell disorders. J. Proteomics. doi: 10.1016/j.jprot.2012.08.010. PMID: 22954596. PMCID: PMC3508302.

9.  Roesch, A., Vultur, A., Speicher, D.W., Bogeski, I., Hoth, M., Laschke, M., Koerbel, C., Gimotty, P., Philipp, S.E., Villanueva, J., Fukunaga-Kalabis, M., Bastian, B., Vogt, T., and Herlyn, M. 2013. Overcoming intrinsic drug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B+ cells. Cancer Cell. 6:811-825. PMID: 23764003.PMC In process.

10. Tang, H.-Y., Beer, L.A., Tanyi, J.L., Zhang, R., Liu, Q., and Speicher, D.W. 2013.  Protein isoform-specific validation defines multiple specific chloride intracellular channel and tropomyosin isoforms as serological biomarkers of ovarian cancer. J. Proteomics 89:165-178. PMID: 23792823.  PMC In process.