The Speicher Laboratory
Using state-of-the-art proteomics and associated computational methods, the Speicher laboratory 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.
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.
Amruta Ronghe, Ph.D.
The Speicher laboratory uses proteomics, metabolomics, computational methods, and biophysical approaches to characterize the roles of normal and mutant proteins in cancers and other human diseases. One approach uses systems biology strategies to better understand tumor progression and resistance to cancer therapeutics as well as to identify clinically useful biomarkers. Other major projects include systematic identification of biomarkers to improve clinical management of cardiotoxicity induced by cancer therapies, identification of ectopic pregnancy biomarkers, and use of chemical crosslinking coupled with high resolution mass spectrometry and molecular modeling to determine structures and dynamics of large protein complexes.
Rebecca, V.W., Nicastri, M.C., McLaughlin, N., Fennelly, C., McAfee, Q., Ronghe, A., Nofal, M., Lim, C.Y., Witze, E., Chude, C.I., Zhang, G., Alicea, G.M., Piao, S., Murugan, S., Ojha, R., Levi, S.M., Wei, Z., Barber-Rotenberg, J.S., Murphy, M.E., Mills, G.B., Lu, Y., Rabinowitz, J., Marmorstein, R., Liu, Q., Liu, S., Xu, X., Herlyn, M., Zoncu, R., Brady, D.C., Speicher, D.W., Winkler, J.D., Amaravadi, R.K. "A Unified Approach to Targeting the Lysosome's Degradative and Growth Signaling Roles." Cancer Discov. 2017 Nov;7(11):1266-1283. doi: 10.1158/2159-8290.CD-17-0741. Epub 2017 Sep 12.
Rivera-Santiago, R., Harper, S.L., Speicher, D.W., et al. "Full-Length Anion Exchanger 1 Structure and Interactions with Ankyrin-1 Determined by Zero Length Crosslinking of Erythrocyte Membranes." Structure. 2017 Jan 3;25(1):132-145. doi: 10.1016/j.str.2016.11.017. Epub 2016 Dec 15.
Goldman, A.R., Bitler, B.G., Speicher, D.W., et al. "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 Nov;15(11):3348-3360. Epub 2016 Sep 21.
Beer, L.A., Kossenkov, A.V., Liu, Q., Luning Prak, E., Domchek, S., Speicher, D.W., Ky, B. "Baseline Immunoglobulin E Levels as a Marker of Doxorubicin- and Trastuzumab-Associated Cardiac Dysfunction." Circ Res. 2016 Oct 28;119(10):1135-1144. Epub 2016 Aug 31.
Kraya, A.A., Piao, S., Speicher, D.W., et al. "Identification of secreted proteins that reflect autophagy dynamics within tumor cells." Autophagy. 2015;11(1):60-74. doi: 10.4161/15548627.2014.984273.