Michael Simons

Michael Simons, MD, FACC, FAHA
Professor of Medicine (Cardiology)
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Simons Lab

The major areas of research in my laboratory include the regulation of arterial development and branching morphogenesis, the regulation of vascular maintenance, Syndecan-4 signaling, and endothelial signaling and metabolism. Emerging areas of research include the role of Raf1 and MAPK signaling in regulation of arterial specification and the activation of arteriogenesis in arteriogenesis-resistant states.

Publications

FRS2α-dependent cell fate transition during endocardial cushion morphogenesis.Chen D, Zhu X, Kofler N, Wang Y, Zhou B, Simons M. Dev Biol. 2019 Oct 25; 2019 Oct 25. PMID: 31669335.
Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis.Chen PY, Qin L, Li G, Wang Z, Dahlman JE, Malagon-Lopez J, Gujja S, Kauffman KJ, Sun L, Sun H, Zhang X, Aryal B, Canfran-Duque A, Liu R, Kusters P, Sehgal A, Jiao Y, Anderson DG, Gulcher J, Fernandez-Hernando C, Lutgens E, Schwartz MA, Pober JS, Chittenden TW, Tellides G, Simons M. Nat Metab. 2019 Sep; 2019 Aug 26. PMID: 31572976.
Author Correction: SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis.Zhou HJ, Xu Z, Wang Z, Zhang H, Zhuang ZW, Simons M, Min W. Nat Commun. 2019 Aug 15; 2019 Aug 15. PMID: 31417083.
Endothelial ERK1/2 signaling maintains integrity of the quiescent endothelium.Ricard N, Scott RP, Booth CJ, Velazquez H, Cilfone NA, Baylon JL, Gulcher JR, Quaggin SE, Chittenden TW, Simons M. J Exp Med. 2019 Aug 5; 2019 Jun 13. PMID: 31196980.
Publisher Correction: N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA₁₆₅-dependent neovascularization.Corti F, Wang Y, Rhodes JM, Atri D, Archer-Hartmann S, Zhang J, Zhuang ZW, Chen D, Wang T, Wang Z, Azadi P, Simons M. Nat Commun. 2019 May 7; 2019 May 7. PMID: 31064993.
N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA₁₆₅-dependent neovascularization.Corti F, Wang Y, Rhodes JM, Atri D, Archer-Hartmann S, Zhang J, Zhuang ZW, Chen D, Wang T, Wang Z, Azadi P, Simons M. Nat Commun. 2019 Apr 5; 2019 Apr 5. PMID: 30952866.
Fibroblast growth factor-transforming growth factor beta dialogues, endothelial cell to mesenchymal transition, and atherosclerosis.Chen PY, Simons M. Curr Opin Lipidol. 2018 Oct. PMID: 30080704.
SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis.Zhou HJ, Xu Z, Wang Z, Zhang H, Zhuang ZW, Simons M, Min W. Nat Commun. 2018 Aug 17; 2018 Aug 17. PMID: 30120232.
Lacteal junction zippering protects against diet-induced obesity.Zhang F, Zarkada G, Han J, Li J, Dubrac A, Ola R, Genet G, Boyé K, Michon P, Künzel SE, Camporez JP, Singh AK, Fong GH, Simons M, Tso P, Fernández-Hernando C, Shulman GI, Sessa WC, Eichmann A. Science. 2018 Aug 10. PMID: 30093598.
Recent advances in understanding lymphangiogenesis and metabolism.Lee HW, Yu P, Simons M. F1000Res. 2018; 2018 Jul 20. PMID: 30079231.
Endothelial Metabolic Control of Lymphangiogenesis.Yu P, Wu G, Lee HW, Simons M. Bioessays. 2018 Jun; 2018 May 11. PMID: 29750374.
A unifying concept in vascular health and disease.Schwartz MA, Vestweber D, Simons M. Science. 2018 Apr 20. PMID: 29674582.
Endothelial Cell Autonomous Role of Akt1: Regulation of Vascular Tone and Ischemia-Induced Arteriogenesis.Lee MY, Gamez-Mendez A, Zhang J, Zhuang Z, Vinyard DJ, Kraehling J, Velazquez H, Brudvig GW, Kyriakides TR, Simons M, Sessa WC. Arterioscler Thromb Vasc Biol. 2018 Apr; 2018 Feb 15. PMID: 29449333.
Reprogramming the Endocardium: Trials and Tribulations.Chen D, Simons M. Circ Res. 2018 Mar 30. PMID: 29599272.
The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling.Kofler N, Corti F, Rivera-Molina F, Deng Y, Toomre D, Simons M. J Biol Chem. 2018 Mar 30; 2018 Feb 7. PMID: 29425100.
Metabolic Analysis of Lymphatic Endothelial Cells.Yu P, Alves TC, Kibbey RG, Simons M. Methods Mol Biol. 2018. PMID: 30242770.
Synectin promotes fibrogenesis by regulating PDGFR isoforms through distinct mechanisms.Drinane MC, Yaqoob U, Yu H, Luo F, Greuter T, Arab JP, Kostallari E, Verma VK, Maiers J, De Assuncao TM, Simons M, Mukhopadhyay D, Kisseleva T, Brenner DA, Urrutia R, Lomberk G, Gao Y, Ligresti G, Tschumperlin DJ, Revzin A, Cao S, Shah VH. JCI Insight. 2017 Dec 21; 2017 Dec 21. PMID: 29263300.
SUMOylation Negatively Regulates Angiogenesis by Targeting Endothelial NOTCH Signaling.Zhu X, Ding S, Qiu C, Shi Y, Song L, Wang Y, Wang Y, Li J, Wang Y, Sun Y, Qin L, Chen J, Simons M, Min W, Yu L. Circ Res. 2017 Sep 1; 2017 Jul 31. PMID: 28760777.
FGF-dependent metabolic control of vascular development.Yu P, Wilhelm K, Dubrac A, Tung JK, Alves TC, Fang JS, Xie Y, Zhu J, Chen Z, De Smet F, Zhang J, Jin SW, Sun L, Sun H, Kibbey RG, Hirschi KK, Hay N, Carmeliet P, Chittenden TW, Eichmann A, Potente M, Simons M. Nature. 2017 May 11; 2017 May 3. PMID: 28467822.
Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits.Burk K, Mire E, Bellon A, Hocine M, Guillot J, Moraes F, Yoshida Y, Simons M, Chauvet S, Mann F. Nat Commun. 2017 Feb 22; 2017 Feb 22. PMID: 28224988.
The molecular basis of endothelial cell plasticity.Dejana E, Hirschi KK, Simons M. Nat Commun. 2017 Feb 9; 2017 Feb 9. PMID: 28181491.
Modulation of VEGF receptor 2 signaling by protein phosphatases.Corti F, Simons M. Pharmacol Res. 2017 Jan; 2016 Nov 23. PMID: 27888154.
Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development.Wang Y, Baeyens N, Corti F, Tanaka K, Fang JS, Zhang J, Jin Y, Coon B, Hirschi KK, Schwartz MA, Simons M. Development. 2016 Dec 1; 2016 Oct 27. PMID: 27789626.
Mechanisms and regulation of endothelial VEGF receptor signalling.Simons M, Gordon E, Claesson-Welsh L. Nat Rev Mol Cell Biol. 2016 Oct; 2016 Jul 27. PMID: 27461391.
Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation.Chen PY, Qin L, Li G, Tellides G, Simons M. Sci Rep. 2016 Sep 16; 2016 Sep 16. PMID: 27634335.
Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.Pardanaud L, Pibouin-Fragner L, Dubrac A, Mathivet T, English I, Brunet I, Simons M, Eichmann A. Circ Res. 2016 Aug 19; 2016 Jun 27. PMID: 27354211.
Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression.Chen PY, Qin L, Li G, Tellides G, Simons M. EMBO Mol Med. 2016 Jul; 2016 Jul 1. PMID: 27189169.
The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature.Kofler N, Simons M. Curr Opin Hematol. 2016 May. PMID: 26849476.
Future Targets in Endothelial Biology: Endothelial Cell to Mesenchymal Transition.Chen PY, Simons M. Curr Drug Targets. 2016. PMID: 27138761.
When endothelial cells go rogue.Chen PY, Simons M. EMBO Mol Med. 2016 Jan 1. PMID: 26613939.
Endothelial miR-17∼92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling.Landskroner-Eiger S, Qiu C, Perrotta P, Siragusa M, Lee MY, Ulrich V, Luciano AK, Zhuang ZW, Corti F, Simons M, Montgomery RL, Wu D, Yu J, Sessa WC. Proc Natl Acad Sci U S A. 2015 Oct 13; 2015 Sep 28. PMID: 26417068.
Myosin VI and cardiomyopathy: Left ventricular hypertrophy, fibrosis, and both cardiac and pulmonary vascular endothelial cell defects in the Snell's waltzer mouse.Hegan PS, Lanahan AA, Simons M, Mooseker MS. Cytoskeleton (Hoboken). 2015 Aug. PMID: 26265212.
Cardiomyopathy and Worsened Ischemic Heart Failure in SM22-α Cre-Mediated Neuropilin-1 Null Mice: Dysregulation of PGC1α and Mitochondrial Homeostasis.Wang Y, Cao Y, Yamada S, Thirunavukkarasu M, Nin V, Joshi M, Rishi MT, Bhattacharya S, Camacho-Pereira J, Sharma AK, Shameer K, Kocher JP, Sanchez JA, Wang E, Hoeppner LH, Dutta SK, Leof EB, Shah V, Claffey KP, Chini EN, Simons M, Terzic A, Maulik N, Mukhopadhyay D. Arterioscler Thromb Vasc Biol. 2015 Jun; 2015 Apr 16. PMID: 25882068.
When it is better to regress: dynamics of vascular pruning.Ricard N, Simons M. PLoS Biol. 2015 May; 2015 May 15. PMID: 25978860.
Molecular controls of arterial morphogenesis.Simons M, Eichmann A. Circ Res. 2015 May 8. PMID: 25953926.
Endothelial cell metabolism in normal and diseased vasculature.Eelen G, de Zeeuw P, Simons M, Carmeliet P. Circ Res. 2015 Mar 27. PMID: 25814684.
Angiogenesis versus arteriogenesis: neuropilin 1 modulation of VEGF signaling.Kofler NM, Simons M. F1000Prime Rep. 2015; 2015 Mar 3. PMID: 25926977.
Molecular controls of lymphatic VEGFR3 signaling.Deng Y, Zhang X, Simons M. Arterioscler Thromb Vasc Biol. 2015 Feb; 2014 Dec 18. PMID: 25524775.
Up-regulation of thrombospondin-2 in Akt1-null mice contributes to compromised tissue repair due to abnormalities in fibroblast function.Bancroft T, Bouaouina M, Roberts S, Lee M, Calderwood DA, Schwartz M, Simons M, Sessa WC, Kyriakides TR. J Biol Chem. 2015 Jan 2; 2014 Nov 11. PMID: 25389299.
ELAVL1 regulates alternative splicing of eIF4E transporter to promote postnatal angiogenesis.Chang SH, Elemento O, Zhang J, Zhuang ZW, Simons M, Hla T. Proc Natl Acad Sci U S A. 2014 Dec 23; 2014 Nov 24. PMID: 25422430.
Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling.Baeyens N, Mulligan-Kehoe MJ, Corti F, Simon DD, Ross TD, Rhodes JM, Wang TZ, Mejean CO, Simons M, Humphrey J, Schwartz MA. Proc Natl Acad Sci U S A. 2014 Dec 2; 2014 Nov 17. PMID: 25404299.
Lymphatic fate specification: an ERK-controlled transcriptional program.Yu P, Tung JK, Simons M. Microvasc Res. 2014 Nov; 2014 Aug 15. PMID: 25132472.
Fox(y) regulators of VEGF receptors.Ricard N, Simons M. Circ Res. 2014 Sep 26. PMID: 25258399.
Fibroblast growth factor receptor 1 is a key inhibitor of TGFβ signaling in the endothelium.Chen PY, Qin L, Tellides G, Simons M. Sci Signal. 2014 Sep 23; 2014 Sep 23. PMID: 25249657.
Chemokine-coupled β2 integrin-induced macrophage Rac2-Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis.Morrison AR, Yarovinsky TO, Young BD, Moraes F, Ross TD, Ceneri N, Zhang J, Zhuang ZW, Sinusas AJ, Pardi R, Schwartz MA, Simons M, Bender JR. J Exp Med. 2014 Sep 22; 2014 Sep 1. PMID: 25180062.
PTP1b is a physiologic regulator of vascular endothelial growth factor signaling in endothelial cells.Lanahan AA, Lech D, Dubrac A, Zhang J, Zhuang ZW, Eichmann A, Simons M. Circulation. 2014 Sep 9; 2014 Jun 30. PMID: 24982127.
Endothelial Akt1 mediates angiogenesis by phosphorylating multiple angiogenic substrates.Lee MY, Luciano AK, Ackah E, Rodriguez-Vita J, Bancroft TA, Eichmann A, Simons M, Kyriakides TR, Morales-Ruiz M, Sessa WC. Proc Natl Acad Sci U S A. 2014 Sep 2; 2014 Aug 18. PMID: 25136137.
A brief etymology of the collateral circulation.Faber JE, Chilian WM, Deindl E, van Royen N, Simons M. Arterioscler Thromb Vasc Biol. 2014 Sep; 2014 Jul 10. PMID: 25012127.
Receptor tyrosine kinases endocytosis in endothelium: biology and signaling.Zhang X, Simons M. Arterioscler Thromb Vasc Biol. 2014 Sep; 2014 Jun 12. PMID: 24925972.
Flow-regulated lymphatic vasculature development and signaling.Wang Y, Simons M. Vasc Cell. 2014; 2014 Jul 9. PMID: 25053993.
Vasa vasorum in normal and diseased arteries.Mulligan-Kehoe MJ, Simons M. Circulation. 2014 Jun 17. PMID: 24934463.
The docking protein FRS2α is a critical regulator of VEGF receptors signaling.Chen PY, Qin L, Zhuang ZW, Tellides G, Lax I, Schlessinger J, Simons M. Proc Natl Acad Sci U S A. 2014 Apr 15; 2014 Apr 2. PMID: 24706887.
Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance.Cao Z, Ding BS, Guo P, Lee SB, Butler JM, Casey SC, Simons M, Tam W, Felsher DW, Shido K, Rafii A, Scandura JM, Rafii S. Cancer Cell. 2014 Mar 17. PMID: 24651014.
Inter-cellular exchange of cellular components via VE-cadherin-dependent trans-endocytosis.Sakurai T, Woolls MJ, Jin SW, Murakami M, Simons M. PLoS One. 2014; 2014 Mar 6. PMID: 24603875.
Angiopoietin-2 secretion by endothelial cell exosomes: regulation by the phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) and syndecan-4/syntenin pathways.Ju R, Zhuang ZW, Zhang J, Lanahan AA, Kyriakides T, Sessa WC, Simons M. J Biol Chem. 2014 Jan 3; 2013 Nov 14. PMID: 24235146.
Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis.Ding BS, Cao Z, Lis R, Nolan DJ, Guo P, Simons M, Penfold ME, Shido K, Rabbany SY, Rafii S. Nature. 2014 Jan 2; 2013 Nov 20. PMID: 24256728.
Endothelial cell-dependent regulation of arteriogenesis.Moraes F, Paye J, Mac Gabhann F, Zhuang ZW, Zhang J, Lanahan AA, Simons M. Circ Res. 2013 Oct 12; 2013 Jul 29. PMID: 23897694.
Need glucose to sprout: local metabolic control of angiogenesis.Eichmann A, Simons M. EMBO Mol Med. 2013 Oct; 2013 Aug 27. PMID: 23982994.
Endothelial signaling and the molecular basis of arteriovenous malformation.Atri D, Larrivée B, Eichmann A, Simons M. Cell Mol Life Sci. 2013 Sep 28; 2013 Sep 28. PMID: 24077895.
Syndecan-4 signaling at a glance.Elfenbein A, Simons M. J Cell Sci. 2013 Sep 1; 2013 Aug 22. PMID: 23970415.
Physiology. Lymphatics are in my veins.Simons M, Eichmann A. Science. 2013 Aug 9. PMID: 23929973.
Endothelial RAF1/ERK activation regulates arterial morphogenesis.Deng Y, Larrivée B, Zhuang ZW, Atri D, Moraes F, Prahst C, Eichmann A, Simons M. Blood. 2013 May 9; 2013 Mar 25. PMID: 23529931.
The syndecan-4/protein kinase Cα pathway mediates prostaglandin E2-induced extracellular regulated kinase (ERK) activation in endothelial cells and angiogenesis in vivo.Corti F, Finetti F, Ziche M, Simons M. J Biol Chem. 2013 May 3; 2013 Mar 22. PMID: 23525101.
The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis.Lanahan A, Zhang X, Fantin A, Zhuang Z, Rivera-Molina F, Speichinger K, Prahst C, Zhang J, Wang Y, Davis G, Toomre D, Ruhrberg C, Simons M. Dev Cell. 2013 Apr 29. PMID: 23639442.
NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth.Jaba IM, Zhuang ZW, Li N, Jiang Y, Martin KA, Sinusas AJ, Papademetris X, Simons M, Sessa WC, Young LH, Tirziu D. J Clin Invest. 2013 Apr. PMID: 23454748.
Endothelial ERK signaling controls lymphatic fate specification.Deng Y, Atri D, Eichmann A, Simons M. J Clin Invest. 2013 Mar; 2013 Feb 8. PMID: 23391722.
Syndecan 4 regulation of PDK1-dependent Akt activation.Ju R, Simons M. Cell Signal. 2013 Jan; 2012 Sep 10. PMID: 22975683.
FGF regulates TGF-β signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression.Chen PY, Qin L, Barnes C, Charisse K, Yi T, Zhang X, Ali R, Medina PP, Yu J, Slack FJ, Anderson DG, Kotelianski V, Wang F, Tellides G, Simons M. Cell Rep. 2012 Dec 27; 2012 Nov 29. PMID: 23200853.
Endothelial nuclear factor-κB-dependent regulation of arteriogenesis and branching.Tirziu D, Jaba IM, Yu P, Larrivée B, Coon BG, Cristofaro B, Zhuang ZW, Lanahan AA, Schwartz MA, Eichmann A, Simons M. Circulation. 2012 Nov 27; 2012 Oct 22. PMID: 23091063.
Fibroblast growth factor-2 is required for vasa vasorum plexus stability in hypercholesterolemic mice.Mollmark JI, Park AJ, Kim J, Wang TZ, Katzenell S, Shipman SL, Zagorchev LG, Simons M, Mulligan-Kehoe MJ. Arterioscler Thromb Vasc Biol. 2012 Nov; 2012 Sep 13. PMID: 22982464.
An inside view: VEGF receptor trafficking and signaling.Simons M. Physiology (Bethesda). 2012 Aug. PMID: 22875452.
VEGF signaling inside vascular endothelial cells and beyond.Eichmann A, Simons M. Curr Opin Cell Biol. 2012 Apr; 2012 Feb 25. PMID: 22366328.
ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway.Larrivée B, Prahst C, Gordon E, del Toro R, Mathivet T, Duarte A, Simons M, Eichmann A. Dev Cell. 2012 Mar 13. PMID: 22421041.
Lymphatics thrive on stress: mechanical force in lymphatic development.Schwartz MA, Simons M. EMBO J. 2012 Feb 15; 2012 Feb 15. PMID: 22334045.
Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2.Hatanaka K, Lanahan AA, Murakami M, Simons M. PLoS One. 2012; 2012 May 22. PMID: 22629427.
Challenging the surgical rodent hindlimb ischemia model with the miniinterventional technique.Zhuang ZW, Shi J, Rhodes JM, Tsapakos MJ, Simons M. J Vasc Interv Radiol. 2011 Oct; 2011 Apr 3. PMID: 21459613.
Development and application of a multimodal contrast agent for SPECT/CT hybrid imaging.Criscione JM, Dobrucki LW, Zhuang ZW, Papademetris X, Simons M, Sinusas AJ, Fahmy TM. Bioconjug Chem. 2011 Sep 21; 2011 Sep 6. PMID: 21851119.
FGF-dependent regulation of VEGF receptor 2 expression in mice.Murakami M, Nguyen LT, Hatanaka K, Schachterle W, Chen PY, Zhuang ZW, Black BL, Simons M. J Clin Invest. 2011 Jul. PMID: 21633168.
Phosphorylation of VE-cadherin controls endothelial phenotypes via p120-catenin coupling and Rac1 activation.Hatanaka K, Simons M, Murakami M. Am J Physiol Heart Circ Physiol. 2011 Jan; 2010 Oct 29. PMID: 21037229.
Cell communications in the heart.Tirziu D, Giordano FJ, Simons M. Circulation. 2010 Aug 31. PMID: 20805439.
VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis.Lanahan AA, Hermans K, Claes F, Kerley-Hamilton JS, Zhuang ZW, Giordano FJ, Carmeliet P, Simons M. Dev Cell. 2010 May 18; 2010 May 6. PMID: 20434959.
Diabetic monocyte and vascular endothelial growth factor signaling impairment.Simons M. Circulation. 2009 Jul 14; 2009 Jun 29. PMID: 19564554.
Regulation of vascular integrity.Murakami M, Simons M. J Mol Med (Berl). 2009 Jun; 2009 Apr 1. PMID: 19337719.
Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization.Mazzone M, Dettori D, de Oliveira RL, Loges S, Schmidt T, Jonckx B, Tian YM, Lanahan AA, Pollard P, de Almodovar CR, De Smet F, Vinckier S, Aragonés J, Debackere K, Luttun A, Wyns S, Jordan B, Pisacane A, Gallez B, Lampugnani MG, Dejana E, Simons M, Ratcliffe P, Maxwell P, Carmeliet P. Cell. 2009 Mar 6; 2009 Feb 12. PMID: 19217150.
Endothelium as master regulator of organ development and growth.Tirziu D, Simons M. Vascul Pharmacol. 2009 Jan-Feb; 2008 Sep 5. PMID: 18804188.
Endothelium-driven myocardial growth or nitric oxide at the crossroads.Tirziu D, Simons M. Trends Cardiovasc Med. 2008 Nov. PMID: 19345317.

Michael Simons

Simons Lab

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Michael Simons

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