Biosciences Graduate Program

Maria Spies, PhD

Portrait

Associate Professor of Biochemistry

Contact Information

Office: 4-532 Bowen Science Building
Iowa City, IA 52242
Phone: 319-335-3221

Email: maria-spies@uiowa.edu
Web: Maria Spies Laboratory

Education

BS, Physics/Biophysics, St. Petersburg State Polytechnic University
MS, Physics/Biophysics, St. Petersburg State Polytechnic University/ Petersburg Nuclear Physics Institute
PhD, Biological Sciences, Graduate School of Science, Osaka University

Fellowship, Dept. of Microbiology, University of California at Davis

Education/Training Program Affiliations

Department of Biochemistry PhD
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program

Research Summary

Work in my lab focuses on genome caretakers at the intersection of the 3Rs of DNA maintenance, Replication, Recombination and DNA Repair. Understanding the molecular bases and regulation of these processes is fundamentally important because accumulation or incomplete repair of DNA lesions can lead to genetic instability and chromosomal rearrangements causing cancer and cell senescence, while erroneous attempts to reestablish stalled or collapsed replication forks may result in diseases associated with progressive expansion of repeated sequences (such as myotonic dystrophy and Fragile X, syndrome among many others). We study DNA repair at the most fundamental level by first deconstructing the macromolecular ensembles orchestrating distinct DNA repair events down to the level of individual proteins. By combining physical and single-molecule biochemistry, we then investigate molecular mechanisms of the key players in these DNA repair pathways and how other protein partners and posttranslational modifications affect their action. We are also developing novel experimental approaches allowing us to sort and interrogate individual macromolecular complexes extracted from human cells and tissue samples. The resulting integrated in vivo – in vitro – in singulo approach is aimed at identifying features of genome caretaker proteins that can be exploited in designing the new therapeutics. Current projects in our lab focus on regulation of RAD51 protein, which orchestrates the central step of homologous genetic recombination, on deciphering the molecular mechanisms and regulation of several motor proteins (FBH1, FANCJ, RTEL, CHLR1 and XPD) involved in control of RAD51-mediated recombination, replication fork progression and chromosome segregation, as well as on interplay between recombination and mismatch repair.

Selected Publications

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Spies M, Fishel R.  Mismatch repair during homologous and homeologous recombination..  Cold Spring Harbor perspectives in biology.  2015 March 2. 7(3):a022657.
[PubMed]

Honda M, Okuno Y, Hengel S, Martin-Lopez J, Cook C, Amunugama R, Soukup R, Subramanyam S, Fishel R, Spies M.  Mismatch repair protein hMSH2-hMSH6 recognizes mismatches and forms sliding clamps within a D-loop recombination intermediate.  Proc Natl Acad Sci USA.  2014 January 21. 11(3):E316-25.
[PubMed]

Ghoneim M, Spies M.  Direct correlation of DNA binding and single protein domain motion via dual illumination fluorescence microscopy.  Nano Lett.  2014. 14(10):5920-31.
[PubMed]

Spies M.  Fulfilling the dream of a perfect genome editing tool.  Proc Natl Acad Sci U S A.  2014. 11(28):10029-30.
[PubMed]

Spies M.  Two steps forward, one step back: determining XPD helicase mechanism by single-molecule fluorescence and high-resolution optical tweezers.  DNA Repair (Amst).  2014. 20:58-70.
[PubMed]

Haghighat Jahromi A, Honda M, Zimmerman S, Spies M.  Single-molecule study of the CUG repeat-MBNL1 interaction and its inhibition by small molecules.  Nucleic acids research.  2013 May. 
[PubMed]

Spies M.  There and back again: new single-molecule insights in the motion of DNA repair proteins.  Current opinion in structural biology.  2013 February. 23(1):154-60.
[PubMed]

Subramanyam S, Jones W, Spies M, Spies M.  Contributions of the RAD51 N-terminal domain to BRCA2-RAD51 interaction.  NAR.  2013. 
[PubMed]

Spies M.  DNA repair: trust but verify.  Curr Biol.  2013. 
[PubMed]

Wu C, Spies M.  Overview: what are helicases?.  Advances in experimental medicine and biology.  2013. 767:16-Jan.
[PubMed]

Date Last Modified: 04/12/2016 - 14:29:46