Muriel C. Maurer, Ph. D.
Professor of Chemistry
Phone Number: (502) 852-7008 (Office)
Fax Number: (502) 852-8149
Department of Chemistry
University of Louisville
Louisville, KY 40292
Ph. D. 1993, University of Virginia
Vice-Chair of Chemistry (2012-2015)
Laboratory Team Members:
Kelly Mouapi, Graduate Student (2012 - )
Ramya Billur, Graduate Student (2012 -)
Boris Anokhin, Graduate Student (2013 -)
Blake Lynch, Undergraduate Student (2013, 2014)
Sara Zink, Undergraduate Student (2013, 2014)
Kelsey Lamb, Undergraduate Summer Visitor (2013)
Deidre Dillon, Undergraduate Summer Visitor (2014)
Carmela Riposo, Undergraduate Student (2014, 2015, 2016)
Chad Stephens, Undergraduate Student (2015, 2016)
Biochemistry: protein-structure function relationships, enzyme-ligand interactions
Blood Coagulation: Factor XIII, Thrombin, Fibrinogen, Protease Activated Receptors
Methods: site-directed mutagenesis, protein expression, enzyme kinetics, Nuclear Magnetic Resonance, MALDI-TOF mass spectrometry, amide proton hydrogen/deuterium exchange, chemical modifications
Proteins in the blood coagulation cascade have far reaching effects on wound healing, heart disease, and stroke. Our research group in the Chemistry Department is focused on characterizing the serine protease thrombin, the transglutaminase Factor XIII, and the structural protein fibrinogen. Thrombin is responsible for cleaving fibrinopeptides A and B from fibrinogen. The resultant fibrin polymerizes into a fibrin blood clot. Thrombin-activated Factor XIII then introduces covalent crosslinks into this clot network. Intermolecular crosslinks involving reactive glutamines and lysines in the fibrinogen αC region lead to a clot with enhanced stiffness and hindered fibrinolysis ability. Current research projects involve 1) understanding how to control FXIII activation and conformation, 2) characterizing how Factor XIII interacts with fibrinogen αC (233-425), and 3) probing how (pro)thrombin accommodates peptide-based ligands at anion binding exosites. The studies employ a combination of mass spectrometry, nuclear magnetic resonance (NMR), and other biophysical methods to examine wild-type and mutant versions of the clotting proteins. Greater knowledge on the biochemical and structural features of thrombin, Factor XIII, and fibrinogen may lead to novel strategies to control the actions of these vital proteins and the resultant blood clot architecture.
- Mouapi KN, Bell JD, Smith KA, Ariëns RA, Philippou H, Maurer MC. Ranking reactive glutamines in the fibrinogen αC region that are targeted by blood coagulant factor XIII. Blood. 2016 May 5;127(18):2241-8. PubMed PMID: 26951791; PubMed Central PMCID: PMC4859198.
- Doiphode PG, Malovichko MV, Mouapi KN, Maurer MC. Evaluating factor XIII specificity for glutamine-containing substrates using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay. Anal Biochem. 2014 Jul 15;457:74-84. PubMed PMID: 24751466; NIHMSID: NIHMS588109; PubMed Central PMCID: PMC4512654.
- Malovichko MV, Sabo TM, Maurer MC. Ligand binding to anion-binding exosites regulates conformational properties of thrombin. J Biol Chem. 2013 Mar 22;288(12):8667-78. PubMed PMID: 23378535; PubMed Central PMCID: PMC3605685.
- Maurer MC. Liberating R169 promotes anticoagulant protein C. Blood. 2012 Jul 19;120(3):501-2. PubMed PMID: 22822000.
- Jadhav MA, Lucas RC, Goldsberry WN, Maurer MC. Design of Factor XIII V34X activation peptides to control ability to interact with thrombin mutants. Biochim Biophys Acta. 2011 Dec;1814(12):1955-63. PubMed PMID: 21798378; NIHMSID: NIHMS312369; PubMed Central PMCID: PMC3645320.
- Woofter RT, Maurer MC. Role of calcium in the conformational dynamics of factor XIII activation examined by hydrogen-deuterium exchange coupled with MALDI-TOF MS. Arch Biochem Biophys. 2011 Aug 1;512(1):87-95. PubMed PMID: 21640701; NIHMSID: NIHMS299589; PubMed Central PMCID: PMC3645313.
- Maurer MC. Switching cation-binding loops paves the way for redesigning allosteric activation. Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5145-6. PubMed PMID: 21415371; PubMed Central PMCID: PMC3069213.
- Jadhav MA, Isetti G, Trumbo TA, Maurer MC. Effects of introducing fibrinogen Aalpha character into the factor XIII activation peptide segment. Biochemistry. 2010 Apr 6;49(13):2918-24. PubMed PMID: 20218626; NIHMSID: NIHMS187023; PubMed Central PMCID: PMC2966857.
- Cleary DB, Doiphode PG, Sabo TM, Maurer MC. A non-reactive glutamine residue of alpha2-antiplasmin promotes interactions with the factor XIII active site region. J Thromb Haemost. 2009 Nov;7(11):1947-9. PubMed PMID: 19691486; NIHMSID: NIHMS730213; PubMed Central PMCID: PMC4685669.
- Sabo TM, Maurer MC. Biophysical investigation of GpIbalpha binding to thrombin anion binding exosite II. Biochemistry. 2009 Aug 4;48(30):7110-22. PubMed PMID: 19591434; NIHMSID: NIHMS131739; PubMed Central PMCID: PMC2842903.
- Sabo TM, Brasher PB, Maurer MC. Perturbations in factor XIII resulting from activation and inhibition examined by solution based methods and detected by MALDI-TOF MS. Biochemistry. 2007 Sep 4;46(35):10089-101. PubMed PMID: 17691819.
- Isetti G, Maurer MC. Employing mutants to study thrombin residues responsible for factor XIII activation peptide recognition: a kinetic study. Biochemistry. 2007 Mar 6;46(9):2444-52. PubMed PMID: 17286389.
Recent Awards & Honors:
- IMD3 Travel Awards: Kelly Mouapi, Ramya Billur, and Boris Anokhin
- Kelly Mouapi: XXIII International Fibrinogen Workshop (Young Investigator Award, 2014), International Society of Thrombosis and Hemostasis 2015 Congress (Factor XIII Session Co-Moderator, 2015), 60th Annual Biophysical Society Meeting (Education Committee Travel Award, 2016)
- Chad Stephens: American Chemical Society Outstanding Graduate in Chemistry 2016, American Institute of Chemists Award in Biochemistry 2016, University of Louisville Senior Honors Thesis 2016.