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Cardiovascular Sciences

Houston, Texas

BCM faculty, staff and trainees are the heart of the organization.
Section of Cardiovascular Sciences
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Sandra B. Haudek, Ph.D.

Assistant Professor
shaudek@bcm.edu

Education and Training

B.S. - Vienna University of Technology, Vienna, Austria, 1991
M.S. - Vienna University of Technology, Vienna, Austria, 1994
Ph.D. - Vienna University of Technology, Vienna, Austria, 1997

Postdoctoral Fellow, UT Southwestern Medical Center, Dallas, TX, 2000
Postdoctoral Associate, Baylor College of Medicine, Houston, TX, 2003

Research Interests

Dr. Haudek is interested in the identification, characterization and differentiation mechanisms of circulating, monocytic fibroblast precursors that mediate non-adaptive fibrosis in the heart. This cell population mainly consists of spindle-shaped, fast proliferating, CD34 (primitive cell marker) and CD45 (hematopoietic marker) expressing cells. We have first identified this population in a murine ischemia/reperfusion cardiomyopathy model (I/RC), in which, in the absence of cardiomyocyte death, the uptake of these cells was preceded by an upregulation of monocyte-macrophage chemoattractant protein 1 (MCP-1). The I/RC-mediated fibrotic cardiomyopathy as well as the appearance of these cells in the heart was prevented by genetic deletion of MCP-1 and by daily administration of serum amyloid P (SAP). Further studies revealed that SAP acted via Fcγ receptors expressed on monocytes. In vitro studies using endothelial transmigration assays in response to MCP-1 demonstrated that human CD14+ monocytes were required to migrate through endothelial cells to mature into fibroblasts, and that SAP had to be present before endothelial transmigration to inhibit this maturation. We also found that Rho-A associated kinase 1 (ROCK-1) was necessary for monocyte-to-fibroblast differentiation, since deletion of ROCK-1 in vivo (knockout mice undergoing I/RC) and in vitro (siRNA knockdown in monocytes before transendothelial migration) prevented the appearance of this fibroblast population. Thus, our research describes a potential link of non-adaptive fibrosis to inflammation. We are currently investigating the appearance and functional significance of these fibroblast precursor cells in other models of non-adaptive fibrosis such as in angiotensin-mediated and pressure overloaded hypertrophy.

Selected Publications

Haudek SB, Gupta D, Dewald O, Schwarz RJ, Wei L, Trial J, Entman ML. (2009). Rho Kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell differentiation. Cardiovascular Research, 83:511-518.

Haudek SB, Trial J, Xia Y, Gupta D, Pilling D and Entman ML. (2008). Fc Receptor Engagement Mediates Differentiation of Cardiac Fibroblast Precursor Cells. PNAS, 105:10179-10184.

Haudek SB, Taffet GE, Schneider MD and Mann DL. (2007). TNF provokes cardiac myocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways. Journal of Clinical Investigation, 117:2692-2701.

Frangogiannis NG, Dewald O, Xia Y, Ren G, Haudek SB, Leucker T, Kraemer D, Taffet G, Rollins BJ and Entman ML. (2007). Critical role of monocyte chemoattractant protein-1/CC chemokine ligand 2 in the pathogenesis of ischemic cardiomyopathy. Circulation, 115:584-92.

Haudek SB, Xie Y, Huebner P, Lee JM, Carlson S, Crawford JR, Pilling D, Gomer RH, Trial J, Frangogiannis NG and Entman ML. (2006). Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice. PNAS, 103:18284-9.

Misra A, Haudek SB, Knuefermann P, Vallejo JG, Chen ZJ, Michael LH, Sivasubramanian N, Olson EN, Entman ML and Mann DL. (2003). NF-κB protects the adult cardiac myocyte against ischemia-induced apoptosis in a murine model of acute myocardial infarction. Circulation, 108:3075-8.

Thomas JA, Haudek SB, Koroglu T, Tsen MF, Bryant DD, White DJ, Kusewitt DF, Horton JW and Giroir BP (2003). IRAK1 deletion disrupts cardiac Toll/IL-1 signaling and protects against contractile dysfunction. American Journal of Physiology, 285:H597-606, 2003.

Haudek SB, Bryant DD and Giroir BP. (2001). Differential regulation of myocardial NFκB following acute or chronic TNFα exposure. Journal of Molecular and Cellular Cardiology, 33:1263-7.

Haudek SB, Spencer E, Bryant DD, White JD, Maass D, Horton JW, Chen ZJ and Giroir BP. (2001). Overexpression of cardiac IκBα prevents endotoxin-induced myocardial dysfunction. American Journal of Physiology, 180:H962-968.

Haudek SB, Natmeßnig BE, Redl H, Schlag G, Hatlen LE and Tobias PS. (2000). Isolation, partial characterization, and concentration in experimental sepsis of baboon lipopolysaccharide-binding protein. Journal of Laboratory and Clinical Medicine, 136:363-70.

Publications

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