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Maike Krenz, M.D.

Assistant Professor, Department of Medical Pharmacology and Physiology
 Office Location: 355 Dalton Cardiovascular Research Center
Office Phone: 884-8761
krenzm@missouri.edu

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 valve malformation may 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 the downstream signaling pathways through which mutant Shp2 mediates its effects in vivo. For example, we were recently able to show that the ERK pathway is both necessary and sufficient for the development of valve defects in a Noonan Syndrome mouse model. Furthermore, we use tissue culture approaches to investigate the effects of Shp2 mutations on the cellular and biochemical level to complement the in vivo mouse studies.

Professional Background

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

Selected Publications

  • Krenz M, Gulick J, Osinska HE, Colbert MC, Molkentin JD, and Robbins J. Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome. Proc Natl Acad Sci U S A (2008) 105:18930-5
  • Nakamura T, Colbert M, Krenz M, Molkentin JD, Hahn HS, Dorn GW 2nd, and Robbins J. Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome. J Clin Invest (2007) 117:2123-32
  • Krenz M, Sadayappan S, Osinska HE, Henry JA, Beck S, Warshaw DM, and Robbins J. Distribution and structure-function relationship of myosin heavy chain isoforms in the adult mouse heart. J Biol Chem (2007) 282:24057-64
  • Krenz M, Yutzey KE, and Robbins J. 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: dalton@missouri.edu
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