Biosciences Graduate Program

Maria Spies, PhD


Associate Professor of Biochemistry

Contact Information

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

Web: Maria Spies Laboratory


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. computational chemistry often plays a central role in addressing research questions centering on the discovery and design of novel ligands to validated drug targets. Computational insights are bolstered by in vitro and in vivo assays. Ongoing projects include: i) development of parallelized in silico docking using high performance computing (HPC) on the University of Iowa's Helium cluster, ii) use of steered molecular dynamics to perform highly accurate and precise free energy calculations to accurately rank order drug leads to a number of antimicrobial and antineoplastic targets, iii) use of hybrid QM/MM electronic structure methods to understand remote allosteric modulation of enzyme catalytic power and iv) development of cheminformatics tools for parsing attractive regions of chemical space in screening libraries.

Selected Publications

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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.

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. 

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.

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

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

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

Qi Z, Pugh R, Spies M, Chemla Y.  Sequence-dependent base pair stepping dynamics in XPD helicase unwinding.  eLife.  2013. 2:e00334.

Masuda-Ozawa T, Hoang T, Seo Y, Chen L, Spies M.  Single-molecule sorting reveals how ubiquitylation affects substrate recognition and activities of FBH1 helicase.  NAR.  2013. 41(6):3579-3587.

Beyer D, Ghoneim M, Spies M.  Structure and Mechanisms of SF2 DNA Helicases.  Advances in experimental medicine and biology.  2013. 767:47-73.

Murfuni I, Basile G, Subramanyam S, Malacaria E, Bignami M, Spies M, Franchitto A, Pichierri P.  Survival of the replication checkpoint deficient cells requires MUS81-RAD52 function.  PLOS Genetics.  2013. 

Date Last Modified: 10/09/2015 - 15:23:31