Welcome to the Vascular Signaling Lab at the Versiti Blood Research Institute. Our mission is to decipher the complex roles of endothelial cells in maintaining health and their involvement in disease processes. Under the leadership of Dr. Magdalena Chrzanowska, a distinguished cell and vascular biologist, we explore the 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

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.

• R01EY036588 “Endothelial Rap1 restricts inflammation in the retina” Chrzanowska, M. PD/PI (MPI, co-PI: M. Grant, UAB) 9/30/2024 – 8/31/2029
• HL157893-01 “Endothelial Rap1 in the control of heart function” Chrzanowska, M. PD/PI (MPI, co-PI: P. Goldspink, UIC) 1/18/22 – 12/31/25

Ramoji Kosuru
Research Scientist I

Behshid Ghadrdoost Nakhchi
Postdoctoral Fellow

Click Here for a full list of publications from Dr. Magdalena Chrzanowska

Selected Publications

• Ghadrdoost Nakhchi B, Kosuru R and Chrzanowska M. “Towards targeting endothelial Rap1B to overcome vascular immunosuppression in cancer.” Int J Mol Sci. 2024 Sep 12;25(18):9853. doi: 10.3390/ijms25189853. 
• Kosuru R, Ghadrdoost Nakhchi B, Sharma GP, Ferraresso F, Mammoto T, Mammoto A, Kastrup C, Zheng DX, Goldspink P, Trebak M and Chrzanowska M. “Rap1A modulates Store-Operated Calcium Entry in Lung Endothelium: Novel Mechanism Controlling NFAT-Mediated Vascular Inflammation and Permeability” Arterioscler Thromb Vasc Biol. 2024 Nov;44(11):2271-2287. This article is accompanied by an editorial: Martín-Aragón Baudel M, Nieves-Cintrón M, Navedo MF. “Rap1 Brings the A Game to Control Lung Endothelium”. Arterioscler Thromb Vasc Biol. 2024 Nov;44(11):2288-2290.
• Sharma, G.P., Kosuru, R., Lakshmikanthan, S., Zheng, S., Chen, Y., Burns, R., Xin, G., Cui, W., Chrzanowska M. Endothelial Rap1B mediates T-cell exclusion to promote tumor growth - a novel mechanism underlying vascular immunosuppression. Angiogenesis, 2023; 26 (2), 265-278. PMCID: PMC36403190.
• Kosuru, R. and Chrzanowska, M. “Integration of Rap1 and calcium signaling”. Int. J. Mol Sci., 2020, 21, 1616; doi:10.3390/ijms21051616. PMCID: PMC7084553
• Singh, B., Kosuru, R., Lakshmikanthan, S., Sorci -Thomas, M., Sparapani, R., Vasquez-Vivar, J., Zhang, D.X. and Chrzanowska, M. Endothelial Rap1 restricts inflammatory signaling to protect from the progression of atherosclerosis. ATVB, 2021; 41: 638-650. PMCID: PMC8105264.
• Kosuru, R., Lakshmikanthan, R., Nishijima, Y., Vasquez-Vivar, J., Zhang, D.X. and Chrzanowska M. “Distinct signaling functions of Rap1 isoforms in NO release from endothelium” Frontiers in Cell Dev. Biology, special topic “Molecular Mechanisms and Signaling in Endothelial Biology and Vascular Heterogeneity, 2021. doi: 10.3389/fcell.2021.687598 PMCID: PMC8247587.
• Lakshmikanthan, S., Sobczak, M., Li Calzi, S., Shaw, L., Grant, M.B., Chrzanowska-Wodnicka, M. Rap1b promotes VEGF-induced endothelial permeability and is required for the dynamic regulation of endothelial barrier. J. Cell Sci., 2018; 131 (1), doi:10.1242/jcs.207605. PMCID: PMC5818062.
• Chrzanowska-Wodnicka, M. “Rap1 in endothelial biology”. Curr. Opin. Hematol., 2017; 24:248-55. PMCID: PMC5920548
• Lakshmikanthan, S., Zhong, X., Nishijima, Y., Szabo, A., Vasquez-Vivar, J., Zhang, D., Chrzanowska-Wodnicka, M. Rap1 promotes signals from endothelial mechanosensing complex, NO release and normal endothelial function. EMBO Reports, 2015; 16:628-37. PMCID: PMC4428051.
• Chrzanowska-Wodnicka, M., White, G.C., Quilliam, L. and Whitehead, K.J. “Small GTPase Rap1 is essential for mouse development and formation of functional vasculature” – PLoS One, 2015 Dec 29;10(12):e0145689. doi:10.1371/journal.pone.0145689. PMCID: PMC4694701.
• Lakshmikanthan, S., Sobczak, M., Chun, C.Z., Dargatz, J., Ramchandran, R., Chrzanowska-Wodnicka, M. Rap1 regulates angiogenesis by a mechanism involving integrin αvβ3-dependent VEGFR2 activation. Blood, 2011; 118:2015-2026, with “Inside Blood” commentary. PMCID: PMC3158727;
• Sobczak, M., Dargatz, J., Chrzanowska-Wodnicka, M. Isolation and culture of murine microvascular endothelial cells. J Vis Exp, 2010; 46:pii.2316; http://www.jove.com/index/details.stp?id=2316, PMCID: PMC3278331.
• Chrzanowska-Wodnicka, M., Kraus, A.E., Gale, D., White, G.C., VanSluys, J. Defective angiogenesis, endothelial migration and MAPK signaling in Rap1b-/- mice. Blood, 2008; 111: 2647-56, with “Inside Blood“ commentary. PMCID: PMC2254536.

Funding