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

  • Co-Program Leader, Molecular and Cellular Oncogenesis Program

  • Scientific Director, Proteomics and Metabolomics 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, some of which were developed or optimized in the Speicher laboratory, this research group is investigating protein changes associated with ovarian cancer, melanoma, cardiac injury resulting from breast cancer therapies, ectopic pregnancy, red cell diseases, and other clinical disorders. The laboratory is also using chemical crosslinking-based structural mass spectrometry techniques coupled with molecular modeling to determine structures of large protein complexes and characterize protein 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 five major projects.  Two projects use proteomics to study ovarian cancer and melanoma from a systems biology perspective and to identify new biomarkers with clinical utility.  A third project uses proteomics to identify and characterize biomarkers for improved diagnosis of cardiotoxicity caused by cancer therapies.  A fourth project involves discovery and validation of plasma biomarkers to help clinicians distinguish between ectopic pregnancy, normal intrauterine pregnancy, and non-viable intrauterine pregnancy. A fifth project uses structural mass spectrometry to develop comprehensive structural models of large protein complexes and to understand function-related dynamics.  This project is exploring the organization of red cell membrane complexes as well as chromatin remodeling complexes.  

 
Selected Publications

1.  Sriswasdi S, Harper SL, Tang HY, Gallagher PG, Speicher DW. Probing large conformational rearrangements in wild-type and mutant spectrin using structural mass spectrometry. Proc. Natl. Acad. Sci. USA. 2014; 111:1801-1806. PMID: 24453214. PMCID: PMC3918770.

2.  Kraya AA, Piao P, Xu X, Zhang G, Herlyn M, Gimotty P, Levine B, Amaravadi RK, Speicher DW. Identification of secreted proteins that reflect autophagy dynamics within tumor cells.  Autophagy. 2015; 11:60-74.  PMID: 25484078.  PMCID:  PMC4502670.

3. Bitler BG, Aird KM, Garipov A, Li H, Amatangelo M, Kossenkov AV, Schultz DC, Liu Q, Shih IM, Conejo-Garcia JR, Speicher DW, Zhang R. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers.  Nat Med. 2015; 21:231-238. PMID: 25686104. PMCID: PMC4352133.  

4.  Rivera-Santiago RF, Harper SL, Zhou S, Sriswasdi S, Feinstein SI, Fisher AB, Speicher DW. Solution Structure of the Reduced Form of Human Peroxiredoxin-6 Elucidated Using Zero-Length Chemical Cross-linking And Homology Modeling. Biochem J. 2015; 468:87-98.  PMID: 25748205.  PMCID:  PMC4420655.

5.  Rivera-Santiago RF, Sriswasdi S, Harper SL, Speicher DW. Probing structures of large protein complexes using zero-length cross-linking. Methods. 2015; 89:99-111. PMID: 25937394. PMCID: PMC4628899.

6.  Brown JW, Bullitt E, Sriswasdi S, Harper S, Speicher DW, McKnight CJ. The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap. PLoS Comput Biol. 2015; 11:e1004302. PMID: 26067675.  PMCID:  PMC4466138.

7.  Goldman, AR, Bitler BG, Schug Z, Conejo-Garcia JR, Zhang R, Speicher DW.  The Primary Effect on the Proteome of ARID1A-Mutated Ovarian Clear Cell Carcinoma is Downregulation of the Mevalonate Pathway at the Post-Transcriptional Level.  Mol Cell Proteomics. 2016; 15(11):3348-3360. PMID:  27654507. PMCID:    PMC5098034.

8.  Beer LA, Kossenkov AV, Liu Q, Luning Park E, Domchek S, Speicher DW, Ky B.  Baseline Immunoglobulin E Levels as a Marker of Doxorubicin and Trastuzumab-Associated Cardiac Dysfunction.  Circ Res. 2016; 119(10):1135-1144. PMID: 27582370.  PMCID: PMC5085891.

9.  Chae YC, Vaira V, Caino MC, Tang HY, Seo JH, Kossenkov AV, Ottobrini L, Martelli C, Lucignani G, Bertolini I, Locatelli M, Bryant KG, Ghosh JC, Lisanti S, Ku B, Bosari S, Languino LR, Speicher DW, Altieri DC.  Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming. Cancer Cell. 2016; 30:257-272.  PMID:  27505672.  PMCID: PMC5131882.

10. Rivera-Santiago R, Harper SL, Sriswasdi S, Hembach P, Speicher DW. Full-Length Anion Exchanger 1 Structure and Interactions with Ankyrin-1 Determined by Zero Length Crosslinking of Erythrocyte Membranes. Structure. 2017; 25(1):132-145. PMID: 27989623. PMCID: PMC5214978.