Magdalena Chrzanowska-Wodnicka, PhD

Magdalena Chrzanowska-Wodnicka, PhD, FAHA

Associate Professor; Pharmacology and Toxicology; Investigator, The Blood Research Institute

Locations

BloodCenter of Wisconsin

Contact Information

Biography

Education

PhD, Cell and Cardiovascular Biology, University of North Carolina at chapel Hill, 1997

Research Interests

Our laboratory is interested in the function of small G proteins in the cardiovascular system. We use transgenic mouse and zebrafish models for in vivo studies and a variety of biochemical, molecular and microscopy approaches to interrogate signaling by small GTPases in vascular cells ex vivo.

Small G protein Rap1 has been the main focus of our research over the past few years. Rap1, evolutionarily conserved and ubiquitously expressed, is activated downstream from multiple cell surface receptors and regulates several basic cellular functions: adhesion, migration, polarity, differentiation and growth. Well studied in vitro, Rap1 functions in mammalian systems in vivo are still not very well understood.

Angiogenesis

Using Rap1b-knockout mice we have recently revealed a novel role of Rap1bin vivo: regulation of angiogenesis. In an in vivo neonatal retinal model and a Matrigel plug model we demonstrated that Rap1b-deficiency leads to a defect in angiogenesis, and through ex vivo and in vitro studies, we localized the defect to endothelial cells and shown that endothelial proliferation and migration are affected by Rap1b-deficiency. At the molecular level, the underlying mechanism involves defective activation and signaling downstream from Vascular Endothelial Growth Factor (VEGF) Receptor 2. Current research in the laboratory is focused on elucidating molecular mechanisms through which Rap1 regulates endothelial cell responses to VEGF promoting angiogenesis.

Cardiac hypertrophy and hypertension

In addition to promoting angiogenesis, our studies indicate that Rap1b is required for maintenance of normal blood pressure as Rap1b-knockout mice are hypertensive and develop cardiac hypertrophy. This is a novel function of Rap1 and we are currently utilizing tissue-specific knockout mice to understand which physiological processes involved in regulation of blood pressure and normal cardiac function are regulated by Rap1.

Rap1B promotes VEGF-induced endothelial permeability and is required for dynamic regulation of the endothelial barrier.

(Lakshmikanthan S, Sobczak M, Li Calzi S, Shaw L, Grant MB, Chrzanowska-Wodnicka M.) J Cell Sci. 2018 Jan 10;131(1).
Rap1b Is an Effector of Axin2 Regulating Crosstalk of Signaling Pathways During Skeletal Development.

(Maruyama T, Jiang M, Abbott A, Yu HI, Huang Q, Chrzanowska-Wodnicka M, Chen EI, Hsu W.) J Bone Miner Res. 2017 Sep;32(9):1816-1828.
Rap1 in endothelial biology.

(Chrzanowska-Wodnicka M.) Curr Opin Hematol. 2017 May;24(3):248-255.
Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization.

(Wang H, Han X, Bretz CA, Becker S, Gambhir D, Smith GW, Samulski RJ, Wittchen ES, Quilliam LA, Chrzanowska-Wodnicka M, Hartnett ME.) Mol Ther Methods Clin Dev. 2016;3:16056.
Nogo-B receptor deficiency causes cerebral vasculature defects during embryonic development in mice.

(Rana U, Liu Z, Kumar SN, Zhao B, Hu W, Bordas M, Cossette S, Szabo S, Foeckler J, Weiler H, Chrzanowska-Wodnicka M, Holtz ML, Misra RP, Salato V, North PE, Ramchandran R, Miao QR.) Dev Biol. 2016 Feb 15;410(2):190-201.
Small GTPase Rap1 Is Essential for Mouse Development and Formation of Functional Vasculature.

(Chrzanowska-Wodnicka M, White GC 2nd, Quilliam LA, Whitehead KJ.) PLoS One. 2015;10(12):e0145689.
Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function.

(Lakshmikanthan S, Zheng X, Nishijima Y, Sobczak M, Szabo A, Vasquez-Vivar J, Zhang DX, Chrzanowska-Wodnicka M.) EMBO Rep. 2015 May;16(5):628-37.
The small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation.

(Kumar S, Xu J, Kumar RS, Lakshmikanthan S, Kapur R, Kofron M, Chrzanowska-Wodnicka M, Filippi MD.) J Exp Med. 2014 Aug 25;211(9):1741-58.
Rap1b in smooth muscle and endothelium is required for maintenance of vascular tone and normal blood pressure.

(Lakshmikanthan S, Zieba BJ, Ge ZD, Momotani K, Zheng X, Lund H, Artamonov MV, Maas JE, Szabo A, Zhang DX, Auchampach JA, Mattson DL, Somlyo AV, Chrzanowska-Wodnicka M.) Arterioscler Thromb Vasc Biol. 2014 Jul;34(7):1486-94.
Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization.

(Wang H, Jiang Y, Shi D, Quilliam LA, Chrzanowska-Wodnicka M, Wittchen ES, Li DY, Hartnett ME.) FASEB J. 2014 Jan;28(1):265-74.
Rap1 GTPase activation and barrier enhancement in rpe inhibits choroidal neovascularization in vivo.

(Wittchen ES, Nishimura E, McCloskey M, Wang H, Quilliam LA, Chrzanowska-Wodnicka M, Hartnett ME.) PLoS One. 2013;8(9):e73070.
Distinct functions for Rap1 signaling in vascular morphogenesis and dysfunction.

(Chrzanowska-Wodnicka M.) Exp Cell Res. 2013 Sep 10;319(15):2350-9.