Michael Simons

Bio Profile

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.


Ricard N, Scott RP, Booth CJ, Velazquez H, Cilfone NA, Baylon JL, Gulcher JR, Quaggin SE, Chittenden TW, Simons M: Endothelial ERK1/2 signaling maintains integrity of the quiescent endothelium. J Exp Med. 2019 Jun 13; 2019 Jun 13. PMID: 31196980

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: Publisher Correction: N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization. Nat Commun. 2019 May 7; 2019 May 7. PMID: 31064993

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: N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization. Nat Commun. 2019 Apr 5; 2019 Apr 5. PMID: 30952866

Chen PY, Simons M: Fibroblast growth factor-transforming growth factor beta dialogues, endothelial cell to mesenchymal transition, and atherosclerosis. Curr Opin Lipidol. 2018 Oct. PMID: 30080704

Zhou HJ, Xu Z, Wang Z, Zhang H, Simons M, Min W: SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis. Nat Commun. 2018 Aug 17; 2018 Aug 17. PMID: 30120232

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: Lacteal junction zippering protects against diet-induced obesity. Science. 2018 Aug 10. PMID: 30093598

Lee HW, Yu P, Simons M: Recent advances in understanding lymphangiogenesis and metabolism. F1000Res. 2018; 2018 Jul 20. PMID: 30079231

Yu P, Wu G, Lee HW, Simons M: Endothelial Metabolic Control of Lymphangiogenesis. Bioessays. 2018 Jun; 2018 May 11. PMID: 29750374

Schwartz MA, Vestweber D, Simons M: A unifying concept in vascular health and disease. Science. 2018 Apr 20. PMID: 29674582

Lee MY, Gamez-Mendez A, Zhang J, Zhuang Z, Vinyard DJ, Kraehling J, Velazquez H, Brudvig GW, Kyriakides TR, Simons M, Sessa WC: Endothelial Cell Autonomous Role of Akt1: Regulation of Vascular Tone and Ischemia-Induced Arteriogenesis. Arterioscler Thromb Vasc Biol. 2018 Apr; 2018 Feb 15. PMID: 29449333

Chen D, Simons M: Reprogramming the Endocardium: Trials and Tribulations. Circ Res. 2018 Mar 30. PMID: 29599272

Kofler N, Corti F, Rivera-Molina F, Deng Y, Toomre D, Simons M: The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling. J Biol Chem. 2018 Mar 30; 2018 Feb 7. PMID: 29425100

Yu P, Alves TC, Kibbey RG, Simons M: Metabolic Analysis of Lymphatic Endothelial Cells. Methods Mol Biol. 2018. PMID: 30242770

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: Synectin promotes fibrogenesis by regulating PDGFR isoforms through distinct mechanisms. JCI Insight. 2017 Dec 21; 2017 Dec 21. PMID: 29263300

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: SUMOylation Negatively Regulates Angiogenesis by Targeting Endothelial NOTCH Signaling. Circ Res. 2017 Sep 1; 2017 Jul 31. PMID: 28760777

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: FGF-dependent metabolic control of vascular development. Nature. 2017 May 11; 2017 May 3. PMID: 28467822

Burk K, Mire E, Bellon A, Hocine M, Guillot J, Moraes F, Yoshida Y, Simons M, Chauvet S, Mann F: Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits. Nat Commun. 2017 Feb 22; 2017 Feb 22. PMID: 28224988

Dejana E, Hirschi KK, Simons M: The molecular basis of endothelial cell plasticity. Nat Commun. 2017 Feb 9; 2017 Feb 9. PMID: 28181491

Corti F, Simons M: Modulation of VEGF receptor 2 signaling by protein phosphatases. Pharmacol Res. 2017 Jan; 2016 Nov 23. PMID: 27888154

Wang Y, Baeyens N, Corti F, Tanaka K, Fang JS, Zhang J, Jin Y, Coon B, Hirschi KK, Schwartz MA, Simons M: Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. Development. 2016 Dec 1; 2016 Oct 27. PMID: 27789626

Simons M, Gordon E, Claesson-Welsh L: Mechanisms and regulation of endothelial VEGF receptor signalling. Nat Rev Mol Cell Biol. 2016 Oct; 2016 Jul 27. PMID: 27461391

Chen PY, Qin L, Li G, Tellides G, Simons M: Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation. Sci Rep. 2016 Sep 16; 2016 Sep 16. PMID: 27634335

Pardanaud L, Pibouin-Fragner L, Dubrac A, Mathivet T, English I, Brunet I, Simons M, Eichmann A: Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity. Circ Res. 2016 Aug 19; 2016 Jun 27. PMID: 27354211

Chen PY, Qin L, Li G, Tellides G, Simons M: Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression. EMBO Mol Med. 2016 Jul; 2016 Jul 1. PMID: 27189169

Kofler N, Simons M: The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature. Curr Opin Hematol. 2016 May. PMID: 26849476

Chen PY, Simons M: Future Targets in Endothelial Biology: Endothelial Cell to Mesenchymal Transition. Curr Drug Targets. 2016. PMID: 27138761

Chen PY, Simons M: When endothelial cells go rogue. EMBO Mol Med. 2016 Jan 1. PMID: 26613939

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: Endothelial miR-17∼92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling. Proc Natl Acad Sci U S A. 2015 Oct 13; 2015 Sep 28. PMID: 26417068

Hegan PS, Lanahan AA, Simons M, Mooseker MS: Myosin VI and cardiomyopathy: Left ventricular hypertrophy, fibrosis, and both cardiac and pulmonary vascular endothelial cell defects in the Snell's waltzer mouse. Cytoskeleton (Hoboken). 2015 Aug. PMID: 26265212

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: Cardiomyopathy and Worsened Ischemic Heart Failure in SM22-α Cre-Mediated Neuropilin-1 Null Mice: Dysregulation of PGC1α and Mitochondrial Homeostasis. Arterioscler Thromb Vasc Biol. 2015 Jun; 2015 Apr 16. PMID: 25882068

Ricard N, Simons M: When it is better to regress: dynamics of vascular pruning. PLoS Biol. 2015 May; 2015 May 15. PMID: 25978860

Simons M, Eichmann A: Molecular controls of arterial morphogenesis. Circ Res. 2015 May 8. PMID: 25953926

Eelen G, de Zeeuw P, Simons M, Carmeliet P: Endothelial cell metabolism in normal and diseased vasculature. Circ Res. 2015 Mar 27. PMID: 25814684

Kofler NM, Simons M: Angiogenesis versus arteriogenesis: neuropilin 1 modulation of VEGF signaling. F1000Prime Rep. 2015; 2015 Mar 3. PMID: 25926977

Deng Y, Zhang X, Simons M: Molecular controls of lymphatic VEGFR3 signaling. Arterioscler Thromb Vasc Biol. 2015 Feb; 2014 Dec 18. PMID: 25524775

Bancroft T, Bouaouina M, Roberts S, Lee M, Calderwood DA, Schwartz M, Simons M, Sessa WC, Kyriakides TR: Up-regulation of thrombospondin-2 in Akt1-null mice contributes to compromised tissue repair due to abnormalities in fibroblast function. J Biol Chem. 2015 Jan 2; 2014 Nov 11. PMID: 25389299

Chang SH, Elemento O, Zhang J, Zhuang ZW, Simons M, Hla T: ELAVL1 regulates alternative splicing of eIF4E transporter to promote postnatal angiogenesis. Proc Natl Acad Sci U S A. 2014 Dec 23; 2014 Nov 24. PMID: 25422430

Baeyens N, Mulligan-Kehoe MJ, Corti F, Simon DD, Ross TD, Rhodes JM, Wang TZ, Mejean CO, Simons M, Humphrey J, Schwartz MA: Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling. Proc Natl Acad Sci U S A. 2014 Dec 2; 2014 Nov 17. PMID: 25404299

Yu P, Tung JK, Simons M: Lymphatic fate specification: an ERK-controlled transcriptional program. Microvasc Res. 2014 Nov; 2014 Aug 15. PMID: 25132472

Ricard N, Simons M: Fox(y) regulators of VEGF receptors. Circ Res. 2014 Sep 26. PMID: 25258399

Chen PY, Qin L, Tellides G, Simons M: Fibroblast growth factor receptor 1 is a key inhibitor of TGFβ signaling in the endothelium. Sci Signal. 2014 Sep 23; 2014 Sep 23. PMID: 25249657

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: Chemokine-coupled β2 integrin-induced macrophage Rac2-Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis. J Exp Med. 2014 Sep 22; 2014 Sep 1. PMID: 25180062

Lanahan AA, Lech D, Dubrac A, Zhang J, Zhuang ZW, Eichmann A, Simons M: PTP1b is a physiologic regulator of vascular endothelial growth factor signaling in endothelial cells. Circulation. 2014 Sep 9; 2014 Jun 30. PMID: 24982127

Lee MY, Luciano AK, Ackah E, Rodriguez-Vita J, Bancroft TA, Eichmann A, Simons M, Kyriakides TR, Morales-Ruiz M, Sessa WC: Endothelial Akt1 mediates angiogenesis by phosphorylating multiple angiogenic substrates. Proc Natl Acad Sci U S A. 2014 Sep 2; 2014 Aug 18. PMID: 25136137

Faber JE, Chilian WM, Deindl E, van Royen N, Simons M: A brief etymology of the collateral circulation. Arterioscler Thromb Vasc Biol. 2014 Sep; 2014 Jul 10. PMID: 25012127

Zhang X, Simons M: Receptor tyrosine kinases endocytosis in endothelium: biology and signaling. Arterioscler Thromb Vasc Biol. 2014 Sep; 2014 Jun 12. PMID: 24925972

Wang Y, Simons M: Flow-regulated lymphatic vasculature development and signaling. Vasc Cell. 2014; 2014 Jul 9. PMID: 25053993

Mulligan-Kehoe MJ, Simons M: Vasa vasorum in normal and diseased arteries. Circulation. 2014 Jun 17. PMID: 24934463

Chen PY, Qin L, Zhuang ZW, Tellides G, Lax I, Schlessinger J, Simons M: The docking protein FRS2α is a critical regulator of VEGF receptors signaling. Proc Natl Acad Sci U S A. 2014 Apr 15; 2014 Apr 2. PMID: 24706887

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: Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance. Cancer Cell. 2014 Mar 17. PMID: 24651014

Sakurai T, Woolls MJ, Jin SW, Murakami M, Simons M: Inter-cellular exchange of cellular components via VE-cadherin-dependent trans-endocytosis. PLoS One. 2014; 2014 Mar 6. PMID: 24603875

Ju R, Zhuang ZW, Zhang J, Lanahan AA, Kyriakides T, Sessa WC, Simons M: 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. J Biol Chem. 2014 Jan 3; 2013 Nov 14. PMID: 24235146

Ding BS, Cao Z, Lis R, Nolan DJ, Guo P, Simons M, Penfold ME, Shido K, Rabbany SY, Rafii S: Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis. Nature. 2014 Jan 2; 2013 Nov 20. PMID: 24256728

Moraes F, Paye J, Mac Gabhann F, Zhuang ZW, Zhang J, Lanahan AA, Simons M: Endothelial cell-dependent regulation of arteriogenesis. Circ Res. 2013 Oct 12; 2013 Jul 29. PMID: 23897694

Eichmann A, Simons M: Need glucose to sprout: local metabolic control of angiogenesis. EMBO Mol Med. 2013 Oct; 2013 Aug 27. PMID: 23982994

Atri D, Larrivée B, Eichmann A, Simons M: Endothelial signaling and the molecular basis of arteriovenous malformation. Cell Mol Life Sci. 2013 Sep 28; 2013 Sep 28. PMID: 24077895

Elfenbein A, Simons M: Syndecan-4 signaling at a glance. J Cell Sci. 2013 Sep 1; 2013 Aug 22. PMID: 23970415

Simons M, Eichmann A: Physiology. Lymphatics are in my veins. Science. 2013 Aug 9. PMID: 23929973

Deng Y, Larrivée B, Zhuang ZW, Atri D, Moraes F, Prahst C, Eichmann A, Simons M: Endothelial RAF1/ERK activation regulates arterial morphogenesis. Blood. 2013 May 9; 2013 Mar 25. PMID: 23529931

Corti F, Finetti F, Ziche M, Simons M: The syndecan-4/protein kinase Cα pathway mediates prostaglandin E2-induced extracellular regulated kinase (ERK) activation in endothelial cells and angiogenesis in vivo. J Biol Chem. 2013 May 3; 2013 Mar 22. PMID: 23525101

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: The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis. Dev Cell. 2013 Apr 29. PMID: 23639442

Jaba IM, Zhuang ZW, Li N, Jiang Y, Martin KA, Sinusas AJ, Papademetris X, Simons M, Sessa WC, Young LH, Tirziu D: NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth. J Clin Invest. 2013 Apr. PMID: 23454748

Deng Y, Atri D, Eichmann A, Simons M: Endothelial ERK signaling controls lymphatic fate specification. J Clin Invest. 2013 Mar; 2013 Feb 8. PMID: 23391722

Ju R, Simons M: Syndecan 4 regulation of PDK1-dependent Akt activation. Cell Signal. 2013 Jan; 2012 Sep 10. PMID: 22975683

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: FGF regulates TGF-β signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression. Cell Rep. 2012 Dec 27; 2012 Nov 29. PMID: 23200853

Tirziu D, Jaba IM, Yu P, Larrivée B, Coon BG, Cristofaro B, Zhuang ZW, Lanahan AA, Schwartz MA, Eichmann A, Simons M: Endothelial nuclear factor-κB-dependent regulation of arteriogenesis and branching. Circulation. 2012 Nov 27; 2012 Oct 22. PMID: 23091063

Mollmark JI, Park AJ, Kim J, Wang TZ, Katzenell S, Shipman SL, Zagorchev LG, Simons M, Mulligan-Kehoe MJ: Fibroblast growth factor-2 is required for vasa vasorum plexus stability in hypercholesterolemic mice. Arterioscler Thromb Vasc Biol. 2012 Nov; 2012 Sep 13. PMID: 22982464

Simons M: An inside view: VEGF receptor trafficking and signaling. Physiology (Bethesda). 2012 Aug. PMID: 22875452

Eichmann A, Simons M: VEGF signaling inside vascular endothelial cells and beyond. Curr Opin Cell Biol. 2012 Apr; 2012 Feb 25. PMID: 22366328

Larrivée B, Prahst C, Gordon E, del Toro R, Mathivet T, Duarte A, Simons M, Eichmann A: ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway. Dev Cell. 2012 Mar 13. PMID: 22421041

Schwartz MA, Simons M: Lymphatics thrive on stress: mechanical force in lymphatic development. EMBO J. 2012 Feb 15; 2012 Feb 15. PMID: 22334045

Hatanaka K, Lanahan AA, Murakami M, Simons M: Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2. PLoS One. 2012; 2012 May 22. PMID: 22629427

Zhuang ZW, Shi J, Rhodes JM, Tsapakos MJ, Simons M: Challenging the surgical rodent hindlimb ischemia model with the miniinterventional technique. J Vasc Interv Radiol. 2011 Oct; 2011 Apr 3. PMID: 21459613

Criscione JM, Dobrucki LW, Zhuang ZW, Papademetris X, Simons M, Sinusas AJ, Fahmy TM: Development and application of a multimodal contrast agent for SPECT/CT hybrid imaging. Bioconjug Chem. 2011 Sep 21; 2011 Sep 6. PMID: 21851119

Murakami M, Nguyen LT, Hatanaka K, Schachterle W, Chen PY, Zhuang ZW, Black BL, Simons M: FGF-dependent regulation of VEGF receptor 2 expression in mice. J Clin Invest. 2011 Jul. PMID: 21633168

Hatanaka K, Simons M, Murakami M: Phosphorylation of VE-cadherin controls endothelial phenotypes via p120-catenin coupling and Rac1 activation. Am J Physiol Heart Circ Physiol. 2011 Jan; 2010 Oct 29. PMID: 21037229

Tirziu D, Giordano FJ, Simons M: Cell communications in the heart. Circulation. 2010 Aug 31. PMID: 20805439

Lanahan AA, Hermans K, Claes F, Kerley-Hamilton JS, Zhuang ZW, Giordano FJ, Carmeliet P, Simons M: VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis. Dev Cell. 2010 May 18; 2010 May 6. PMID: 20434959

Simons M: Diabetic monocyte and vascular endothelial growth factor signaling impairment. Circulation. 2009 Jul 14; 2009 Jun 29. PMID: 19564554

Murakami M, Simons M: Regulation of vascular integrity. J Mol Med (Berl). 2009 Jun; 2009 Apr 1. PMID: 19337719

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: Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell. 2009 Mar 6; 2009 Feb 12. PMID: 19217150

Tirziu D, Simons M: Endothelium as master regulator of organ development and growth. Vascul Pharmacol. 2009 Jan-Feb; 2008 Sep 5. PMID: 18804188

Tirziu D, Simons M: Endothelium-driven myocardial growth or nitric oxide at the crossroads. Trends Cardiovasc Med. 2008 Nov. PMID: 19345317