Magdalena Chrzanowska, PhD, FAHA

Associate Professor, Pharmacology and Toxicology; Program Leader, Transfusion Medicine, Vascular Biology and Cell Therapy and Senior Investigator; Versiti Blood Research Institute

Locations

Versiti Blood Center of Wisconsin

Contact Information

Education

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

Research Interests

At the Vascular Signaling Lab, we are dedicated to understanding the multifaceted role of endothelial cells in health and disease. Led by Dr. Magdalena Chrzanowska, our work is anchored in elucidating the function of a small GTPase Rap1 in the endothelium.

We have uncovered pivotal roles of Rap1 isoforms—Rap1A and Rap1B—in the endothelium, influencing critical aspects of endothelial function, including nitric oxide release, VEGFR2 signaling, angiogenesis and dynamic regulation of vascular permeability. Specifically, Rap1B plays a key role in mitigating inflammatory responses and influencing tumor progression.

Our current endeavors are directed at unraveling the physiological and pathological consequences of endothelial cell (EC) Rap1 activity and unraveling the cellular mechanisms of Rap1.

Ongoing projects:

Endothelial control of heart function R01HL157893
Understanding how ECs communicate with cardiac myocytes is critical for the regulation of cardiac contractile function. We are investigating how Rap1 isoforms in coronary (vascular) and heart microcapillary (cardiac) endothelial compartments control endothelial-smooth muscle cells and endothelial-cardiac myocyte communication to maintain coronary vessel function and cardiac contractility.
Endothelial Rap1 in ischemic retinopathy R01EY036588 start 7/1/24
With diabetic retinopathy the most common microvascular complication and the leading cause of acquired vision loss worldwide, our focus is the Rap1-driven mechanisms that control endothelial-leukocyte interactions, aiming to alleviate the inflammatory responses that contribute to retinal damage.
EC mechanisms controlling hematopoiesis
The bone marrow's vascular niche is essential for hematopoietic stem cell regulation and its disruption is linked with blood disorders. We are examining the mechanisms through which Rap1 in bone marrow ECs impacts hematopoiesis and erythropoiesis.
EC Rap1 in tumor microenvironment
Our research addresses the critical challenge of immunosuppression within tumor vasculature, crucial for advancing cancer immunotherapy. We've identified that endothelial Rap1B inhibits T-cell activity, promoting tumor growth. Currently, we are probing the mechanisms through which endothelial Rap1 modulates VEGF-driven immunosuppression and the interactions between tumor endothelial cells and leukocytes.
Cell biology of Rap1A and Rap1B
Our research is focused on dissecting the distinct and shared roles of Rap1A and Rap1B in endothelial functions. We investigate how Rap1A contributes to lung permeability and how Rap1B regulates the balance between endothelial homeostasis and inflammatory response, crucial for vascular health.

Our lab is committed to advancing understanding in these areas, striving for breakthroughs that can lead to innovative treatments for cardiovascular, ocular, hematopoietic, and cancer-related conditions.

Funding:
Current: R01HL157893 | Endothelial Rap1 in the control of heart function
Pending: R01EY036588 | Endothelial Rap1 restricts inflammation in the retina

(Singh B, Kosuru R, Lakshmikanthan S, Sorci-Thomas MG, Zhang DX, Sparapani R, Vasquez-Vivar J, Chrzanowska M.) Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):638-650 PMID: 33267664 PMCID: PMC8105264 SCOPUS ID: 2-s2.0-85104181830 12/04/2020
(Ga艁膭zka P, Chrzanowska M, Styczy艃ski J.) In Vivo. 2021;35(1):585-591 PMID: 33402513 PMCID: PMC7880741 01/07/2021
(Kosuru R, Chrzanowska M.) Int J Mol Sci. 2020 Feb 27;21(5) PMID: 32120817 PMCID: PMC7084553 SCOPUS ID: 2-s2.0-85081026400 03/04/2020
(Balaji Ragunathrao VA, Anwar M, Akhter MZ, Chavez A, Mao Y, Natarajan V, Lakshmikanthan S, Chrzanowska-Wodnicka M, Dudek AZ, Claesson-Welsh L, Kitajewski JK, Wary KK, Malik AB, Mehta D.) Cell Rep. 2019 Dec 10;29(11):3472-3487.e4 PMID: 31825830 PMCID: PMC6927555 SCOPUS ID: 2-s2.0-85075997214 12/12/2019
(Lakshmikanthan S, Sobczak M, Li Calzi S, Shaw L, Grant MB, Chrzanowska-Wodnicka M.) J Cell Sci. 2018 Jan 10;131(1) PMID: 29222111 PMCID: PMC5818062 SCOPUS ID: 2-s2.0-85045634293 12/10/2017
(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 PMID: 28520221 PMCID: PMC5555789 SCOPUS ID: 2-s2.0-85021369017 05/19/2017
(Chrzanowska-Wodnicka M.) Curr Opin Hematol. 2017 May;24(3):248-255 PMID: 28178039 PMCID: PMC5920548 SCOPUS ID: 2-s2.0-85011903603 02/09/2017
(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 PMID: 26746789 PMCID: PMC4767500 SCOPUS ID: 2-s2.0-84957847497 01/10/2016
(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 PMID: 27606349 PMCID: PMC4996131 09/09/2016
(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 PMID: 25807985 PMCID: PMC4428051 SCOPUS ID: 2-s2.0-84928885238 03/27/2015
(Chrzanowska-Wodnicka M, White GC 2nd, Quilliam LA, Whitehead KJ.) PLoS One. 2015;10(12):e0145689 PMID: 26714318 PMCID: PMC4694701 SCOPUS ID: 2-s2.0-84958225316 12/30/2015
(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 PMID: 25092872 PMCID: PMC4144729 SCOPUS ID: 2-s2.0-84906544640 08/06/2014

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