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Maike Krenz, M.D.

Associate Professor, Department of Medical Pharmacology and Physiology
Office Location: 355 DCRC
Office Phone: 573-884-8761

Research Interests

Congenital heart disease; valve malformation; hypertrophic cardiomyopathy; heart failure; protein structure-function relationships

Research Description

Congenital heart defects remain the most common birth defect, occurring in about 1% of live births and constituting the leading cause of infant deaths in the US. Over the past decade, genetic analyses of families with congenital heart disease have directed us to the molecular causes of certain defects. In particular, gain-of-function mutations in the protein tyrosine phosphatase Shp2 have recently been discovered in families with Noonan syndrome. In the majority of cases, NS follows autosomal dominant inheritance and is characterized by short stature, facial dysmorphia, skeletal anomalies, and congenital heart disease. Among the heart defects, pulmonary valve stenosis and hypertrophic cardiomyopathy are most prominent. Understanding the exact cellular mechanism(s) by which dysfunction of Shp2 causes cardiomyopathy and valve malformations will provide the basis for future development of novel therapeutic approaches in congenital heart disease.

To study the pathomechanisms of heart malformations, we have been creating genetically altered mouse models that recapitulate human congenital heart disease. In particular, our mouse models are designed to express the mutant proteins in a time- and tissue-specific manner. These models can then be used to study in detail which developmental steps in the heart play a role in the disease process. Subsequently, we can dissect which downstream pathways (such as for example MAPK and Akt signaling) mediate Shp2's effects in vivo. Furthermore, we use tissue culture approaches to investigate the effects of Shp2 mutations on the cellular and biochemical level to complement the mouse models.

Recently, we found that Shp2 plays an essential role in the normal heart after birth as well. This has opened up very exciting new directions and led to novel hypotheses that will drive future studies regarding cardiac stress adaptation. The ability of the heart to adapt to hemodynamic challenges is critical for all of us, not just patients with congenital heart disease. Therefore, deepening our understanding of Shp2’s complex functions as a master regulator of critical signaling pathways in the heart is likely to significantly advance cardiovascular research.

Professional Background

  • MD, Heinrich-Heine-University, Düsseldorf, Germany
  • Residency, Department of Cardiology, Westfälische Wilhelms-University, Münster, Germany
  • Postdoctoral Fellowship, German Research Foundation, Department of Physiology, University of South Alabama
  • Postdoctoral Fellowship, American Heart Association, Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center

Selected Publications

Proteomic Mapping of Proteins Released During Cardiac Myocyte Necrosis K Marshall, MA Edwards, M Krenz, CP Baines AJP – Cell Physiology (2013) in press

KS McCommis, DL Douglas, M Krenz, CP Baines. Cardiac-specific hexokinase 2 overexpression attenuates hypertrophy by increasing pentose phosphate pathway flux. J Am Heart Assoc (2013) in press

C Schramm, MA Edwards, M Krenz. New approaches to prevent LEOPARD-Syndrome associated cardiac hypertrophy by specifically targeting Shp2-dependent signaling. J Biol Chem (2013) 288: 18335-18344

K Marshall, B Muller, M Krenz, L Hanft, KS McDonald, K Dellsperger, C Emter. Heart Failure with Preserved Ejection Fraction: Chronic Low-Intensity Interval Exercise Training Preserves Myocardial O2 Balance and Diastolic Function. J Appl Physiol (2013) 114: 131-147

C Schramm, DM Fine, MA Edwards, AN Reeb, M Krenz. The PTPN11 loss-of-function mutation Q510E-Shp2 causes hypertrophic cardiomyopathy by dysregulating mTOR signaling. Am J Physiol Heart Circ Physiol (2012) 302: H231 – H243

R Rice, P Guinto, C Dowell-Martino, H He, K Hoyer, M Krenz, J Robbins, JS Ingwall, JC Tardiff. Cardiac myosin heavy chain isoform exchange alters the phenotype of cTnT-related cardiomyopathies in mouse hearts., J Mol Cell Cardiol. 2010 May;48(5):979-88.

RW Tsika, L Ma, C Schramm, G Simmer, B Morgan, DM Fine, LM Hanft, KS McDonald, JD Molkentin, M Krenz, S Yang, J Li. TEAD-1 overexpression in the mouse heart promotes an age-dependent heart dysfunction., J Biol Chem. 2010 Apr 30;285(18):13721-35.

M Krenz, J Gulick, HE Osinska, MC Colbert, JD Molkentin, J Robbins. Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome. Proc Natl Acad Sci U S A (2008) 105:18930-5

T Nakamura, M Colbert, M Krenz, J Molkentin, J Robbins. Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome. J Clin Invest (2007) 117:2123-32

M Krenz, S Sakthivel, HE Osinska, JA Henry, S Beck, DM Warshaw, J Robbins. Distribution and structure-function relationship of myosin heavy chain isoforms in the adult mouse heart.J Biol Chem(2007) 282:24057-64

M Krenz, KE Yutzey, J Robbins. Noonan syndrome mutation Q79R in Shp2 increases proliferation of valve primordia mesenchymal cells via extracellular signal-regulated kinase 1/2 signaling.Circ Res(2005) 97:813-20

Published by Dalton Cardiovascular Research Center, 134 Research Park Dr., Columbia, MO 65211
Phone: 573-882-7588 | Fax: 573-884-4232 | Email: