Karen Hirschi

Bio Profile

Karen K. Hirschi, PhD

Professor of Medicine (Cardiology) and of Genetics

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Hirschi Lab


A primary interest of our laboratory is to understand, at the cellular and molecular level, the events leading to blood vessel formation. We are specifically interested in the regulation of vascular cell commitment, differentiation and cell cycle progression, and defining signaling pathways that modulate these processes. We also aim to understand how some vascular cells acquire specialized functions, such as the generation and/or maintenance of multi-lineage stem/progenitor cells.

Publications

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

Hirschi KK, Nicoli S, Walsh K: Hematopoiesis Lineage Tree Uprooted: Every Cell Is a Rainbow. Dev Cell. 2017 Apr 10. PMID: 28399402

Sivarapatna A, Ghaedi M, Xiao Y, Han E, Aryal B, Zhou J, Fernandez-Hernando C, Qyang Y, Hirschi KK, Niklason LE: Engineered microvasculature in PDMS networks using endothelial cells derived from human induced pluripotent stem cells. Cell Transplant. 2017 Mar 9; 2017 Mar 9. PMID: 28281438

Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, Chakraborty R, Wu CL, Sano S, Muralidharan S, Rius C, Vuong J, Jacob S, Muralidhar V, Robertson AA, Cooper MA, Andrés V, Hirschi KK, Martin KA, Walsh K: Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science. 2017 Feb 24; 2017 Jan 19. PMID: 28104796

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

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

Ola R, Dubrac A, Han J, Zhang F, Fang JS, Larrivée B, Lee M, Urarte AA, Kraehling JR, Genet G, Hirschi KK, Sessa WC, Canals FV, Graupera M, Yan M, Young LH, Oh PS, Eichmann A: PI3 kinase inhibition improves vascular malformations in mouse models of hereditary haemorrhagic telangiectasia. Nat Commun. 2016 Nov 29; 2016 Nov 29. PMID: 27897192

Fang JS, Gritz EC, Marcelo KL, Hirschi KK: Isolation of Murine Embryonic Hemogenic Endothelial Cells. J Vis Exp. 2016 Jun 17; 2016 Jun 17. PMID: 27341393

Cuchiara ML, Coşkun S, Banda OA, Horter KL, Hirschi KK, West JL: Bioactive poly(ethylene glycol) hydrogels to recapitulate the HSC niche and facilitate HSC expansion in culture. Biotechnol Bioeng. 2016 Apr; 2015 Oct 26. PMID: 26497172

Gritz E, Hirschi KK: Specification and function of hemogenic endothelium during embryogenesis. Cell Mol Life Sci. 2016 Apr; 2016 Feb 5. PMID: 26849156

Muralidharan S, Sasi SP, Zuriaga MA, Hirschi KK, Porada CD, Coleman MA, Walsh KX, Yan X, Goukassian DA: Corrigendum: Ionizing Particle Radiation as a Modulator of Endogenous Bone Marrow Cell Reprogramming: Implications for Hematological Cancers. Front Oncol. 2015; 2015 Nov 25. PMID: 26636037

Muralidharan S, Sasi SP, Zuriaga MA, Hirschi KK, Porada CD, Coleman MA, Walsh KX, Yan X, Goukassian DA: Ionizing Particle Radiation as a Modulator of Endogenous Bone Marrow Cell Reprogramming: Implications for Hematological Cancers. Front Oncol. 2015; 2015 Oct 14. PMID: 26528440

Coşkun S, Chao H, Vasavada H, Heydari K, Gonzales N, Zhou X, de Crombrugghe B, Hirschi KK: Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells. Cell Rep. 2014 Oct 23; 2014 Oct 9. PMID: 25310984

Martin KA, Hirschi KK: The magic touch: endothelial cells muscle-up adipose. Circ Res. 2014 Oct 10. PMID: 25301822

Hirschi KK, Li S, Roy K: Induced pluripotent stem cells for regenerative medicine. Annu Rev Biomed Eng. 2014 Jul 11; 2014 May 29. PMID: 24905879

Marcelo KL, Sills TM, Coskun S, Vasavada H, Sanglikar S, Goldie LC, Hirschi KK: Hemogenic endothelial cell specification requires c-Kit, Notch signaling, and p27-mediated cell-cycle control. Dev Cell. 2013 Dec 9. PMID: 24331925

Marcelo KL, Goldie LC, Hirschi KK: Regulation of endothelial cell differentiation and specification. Circ Res. 2013 Apr 26. PMID: 23620236

Goldberg JS, Vadakkan TJ, Hirschi KK, Dickinson ME: A computational approach to detect gap junction plaques and associate them with cells in fluorescent images. J Histochem Cytochem. 2013 Apr; 2013 Jan 15. PMID: 23324867

Fang JS, Dai C, Kurjiaka DT, Burt JM, Hirschi KK: Connexin45 regulates endothelial-induced mesenchymal cell differentiation toward a mural cell phenotype. Arterioscler Thromb Vasc Biol. 2013 Feb; 2012 Dec 6. PMID: 23220276

Agrawal V, Siu BF, Chao H, Hirschi KK, Raborn E, Johnson SA, Tottey S, Hurley KB, Medberry CJ, Badylak SF: Partial characterization of the Sox2+ cell population in an adult murine model of digit amputation. Tissue Eng Part A. 2012 Jul; 2012 Jun 5. PMID: 22530556

Hirschi KK: Hemogenic endothelium during development and beyond. Blood. 2012 May 24; 2012 Mar 13. PMID: 22415753

Badylak SF, Hirschi KK, Niklason LE: Cardiovascular regenerative biology. Cells Tissues Organs. 2012; 2011 Oct 12. PMID: 22179179

Chaudhury H, Raborn E, Goldie LC, Hirschi KK: Stem cell-derived vascular endothelial cells and their potential application in regenerative medicine. Cells Tissues Organs. 2012; 2011 Oct 14. PMID: 22005724

Kienstra KA, Hirschi KK: Studying vascular progenitor cells in a neonatal mouse model. Methods Mol Biol. 2012. PMID: 22890936

Kienstra KA, Hirschi KK: Vascular progenitor cell mobilization. Methods Mol Biol. 2012. PMID: 22890930

Chaudhury H, Goldie LC, Hirschi KK: Vascular precursor cells. Genes Cancer. 2011 Dec. PMID: 22866199

Coskun S, Hirschi KK: Establishment and regulation of the HSC niche: Roles of osteoblastic and vascular compartments. Birth Defects Res C Embryo Today. 2010 Dec. PMID: 21181885

Abbas HA, Maccio DR, Coskun S, Jackson JG, Hazen AL, Sills TM, You MJ, Hirschi KK, Lozano G: Mdm2 is required for survival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity. Cell Stem Cell. 2010 Nov 5. PMID: 21040902

Enciso JM, Konecny CM, Karpen HE, Hirschi KK: Endothelial cell migration during murine yolk sac vascular remodeling occurs by means of a Rac1 and FAK activation pathway in vivo. Dev Dyn. 2010 Oct. PMID: 20737513

Kazanis I, Lathia JD, Vadakkan TJ, Raborn E, Wan R, Mughal MR, Eckley DM, Sasaki T, Patton B, Mattson MP, Hirschi KK, Dickinson ME, ffrench-Constant C: Quiescence and activation of stem and precursor cell populations in the subependymal zone of the mammalian brain are associated with distinct cellular and extracellular matrix signals. J Neurosci. 2010 Jul 21. PMID: 20660259

Armstrong JJ, Larina IV, Dickinson ME, Zimmer WE, Hirschi KK: Characterization of bacterial artificial chromosome transgenic mice expressing mCherry fluorescent protein substituted for the murine smooth muscle alpha-actin gene. Genesis. 2010 Jul. PMID: 20506352

Iacobas I, Vats A, Hirschi KK: Vascular potential of human pluripotent stem cells. Arterioscler Thromb Vasc Biol. 2010 Jun; 2010 May 7. PMID: 20453170

Hirschi KK: Vascular precursors: origin, regulation and function. Arterioscler Thromb Vasc Biol. 2010 Jun; 2010 May 7. PMID: 20453165

Chao H, Hirschi KK: Hemato-vascular origins of endothelial progenitor cells? Microvasc Res. 2010 May; 2010 Feb 10. PMID: 20149806

Agrawal V, Johnson SA, Reing J, Zhang L, Tottey S, Wang G, Hirschi KK, Braunhut S, Gudas LJ, Badylak SF: Epimorphic regeneration approach to tissue replacement in adult mammals. Proc Natl Acad Sci U S A. 2010 Feb 23; 2009 Dec 4. PMID: 19966310

Justice MJ, Hirschi KK: The role of quaking in mammalian embryonic development. Adv Exp Med Biol. 2010. PMID: 21189687

Goldberg JS, Hirschi KK: Diverse roles of the vasculature within the neural stem cell niche. Regen Med. 2009 Nov. PMID: 19903006

Kelly MA, Hirschi KK: Signaling hierarchy regulating human endothelial cell development. Arterioscler Thromb Vasc Biol. 2009 May; 2009 Feb 12. PMID: 19213939

Boles MK, Wilkinson BM, Maxwell A, Lai L, Mills AA, Nishijima I, Salinger AP, Moskowitz I, Hirschi KK, Liu B, Bradley A, Justice MJ: A mouse chromosome 4 balancer ENU-mutagenesis screen isolates eleven lethal lines. BMC Genet. 2009 Mar 6; 2009 Mar 6. PMID: 19267930

Goldie LC, Lucitti JL, Dickinson ME, Hirschi KK: Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis. Blood. 2008 Oct 15; 2008 Aug 6. PMID: 18684862

Goldie LC, Nix MK, Hirschi KK: Embryonic vasculogenesis and hematopoietic specification. Organogenesis. 2008 Oct. PMID: 19337406

Hirschi KK, Ingram DA, Yoder MC: Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2008 Sep; 2008 Jul 31. PMID: 18669889

Kienstra KA, Jackson KA, Hirschi KK: Injury mechanism dictates contribution of bone marrow-derived cells to murine hepatic vascular regeneration. Pediatr Res. 2008 Feb. PMID: 18043513

Kienstra KA, Freysdottir D, Gonzales NM, Hirschi KK: Murine neonatal intravascular injections: modeling newborn disease. J Am Assoc Lab Anim Sci. 2007 Nov. PMID: 17994673

Enciso JM, Hirschi KK: Nutrient regulation of tumor and vascular endothelial cell proliferation. Curr Cancer Drug Targets. 2007 Aug. PMID: 17691902

Saunders WB, Bohnsack BL, Faske JB, Anthis NJ, Bayless KJ, Hirschi KK, Davis GE: Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J Cell Biol. 2006 Oct 9. PMID: 17030988

Bohnsack BL, Lai L, Northrop JL, Justice MJ, Hirschi KK: Visceral endoderm function is regulated by quaking and required for vascular development. Genesis. 2006 Feb. PMID: 16470614

Enciso JM, Hirschi KK: Understanding abnormalities in vascular specification and remodeling. Pediatrics. 2005 Jul. PMID: 15995057

Bohnsack BL, Hirschi KK: Red light, green light: signals that control endothelial cell proliferation during embryonic vascular development. Cell Cycle. 2004 Dec; 2004 Dec 29. PMID: 15611620

Huss WJ, Lai L, Barrios RJ, Hirschi KK, Greenberg NM: Retinoic acid slows progression and promotes apoptosis of spontaneous prostate cancer. Prostate. 2004 Oct 1. PMID: 15305337

Bohnsack BL, Lai L, Dolle P, Hirschi KK: Signaling hierarchy downstream of retinoic acid that independently regulates vascular remodeling and endothelial cell proliferation. Genes Dev. 2004 Jun 1. PMID: 15175265

Hirschi KK, Majesky MW: Smooth muscle stem cells. Anat Rec A Discov Mol Cell Evol Biol. 2004 Jan. PMID: 14699631

Bohnsack BL, Hirschi KK: Nutrient regulation of cell cycle progression. Annu Rev Nutr. 2004. PMID: 15189127

Olmsted-Davis EA, Gugala Z, Camargo F, Gannon FH, Jackson K, Kienstra KA, Shine HD, Lindsey RW, Hirschi KK, Goodell MA, Brenner MK, Davis AR: Primitive adult hematopoietic stem cells can function as osteoblast precursors. Proc Natl Acad Sci U S A. 2003 Dec 23; 2003 Dec 12. PMID: 14673088

Abramowitz J, Dai C, Hirschi KK, Dmitrieva RI, Doris PA, Liu L, Allen JC: Ouabain- and marinobufagenin-induced proliferation of human umbilical vein smooth muscle cells and a rat vascular smooth muscle cell line, A7r5. Circulation. 2003 Dec 16; 2003 Nov 24. PMID: 14638550

Lai L, Bohnsack BL, Niederreither K, Hirschi KK: Retinoic acid regulates endothelial cell proliferation during vasculogenesis. Development. 2003 Dec; 2003 Nov 19. PMID: 14627725

Nadin BM, Goodell MA, Hirschi KK: Phenotype and hematopoietic potential of side population cells throughout embryonic development. Blood. 2003 Oct 1; 2003 Jun 12. PMID: 12805065

Hirschi KK, Burt JM, Hirschi KD, Dai C: Gap junction communication mediates transforming growth factor-beta activation and endothelial-induced mural cell differentiation. Circ Res. 2003 Sep 5; 2003 Aug 14. PMID: 12919949

McKinney-Freeman SL, Majka SM, Jackson KA, Norwood K, Hirschi KK, Goodell MA: Altered phenotype and reduced function of muscle-derived hematopoietic stem cells. Exp Hematol. 2003 Sep. PMID: 12962727

Bohnsack BL, Hirschi KK: The FAKs about blood vessel assembly. Circ Res. 2003 Feb 21. PMID: 12595334

Majka SM, Jackson KA, Kienstra KA, Majesky MW, Goodell MA, Hirschi KK: Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. J Clin Invest. 2003 Jan. PMID: 12511590

Skalak TC, Little CD, McIntire LV, Hirschi KK, Tranquillo R, Post M, Ranieri J: Vascular assembly in engineered and natural tissues: breakout session summary. Ann N Y Acad Sci. 2002 Jun. PMID: 12081911

Hirschi KK, Skalak TC, Peirce SM, Little CD: Vascular assembly in natural and engineered tissues. Ann N Y Acad Sci. 2002 Jun. PMID: 12081906

Hirschi KK, Goodell MA: Hematopoietic, vascular and cardiac fates of bone marrow-derived stem cells. Gene Ther. 2002 May. PMID: 12032711

Noveroske JK, Lai L, Gaussin V, Northrop JL, Nakamura H, Hirschi KK, Justice MJ: Quaking is essential for blood vessel development. Genesis. 2002 Mar. PMID: 11892011

Hirschi KK, Lai L, Belaguli NS, Dean DA, Schwartz RJ, Zimmer WE: Transforming growth factor-beta induction of smooth muscle cell phenotpye requires transcriptional and post-transcriptional control of serum response factor. J Biol Chem. 2002 Feb 22; 2001 Dec 11. PMID: 11741973

Goodell MA, Jackson KA, Majka SM, Mi T, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK: Stem cell plasticity in muscle and bone marrow. Ann N Y Acad Sci. 2001 Jun. PMID: 11458510

Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, Goodell MA: Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 2001 Jun. PMID: 11390421

Hirschi KD, Kreps JA, Hirschi KK: Molecular approaches to studying nutrient metabolism and function: an array of possibilities. J Nutr. 2001 May. PMID: 11340125

Niklason LE, Abbott W, Gao J, Klagges B, Hirschi KK, Ulubayram K, Conroy N, Jones R, Vasanawala A, Sanzgiri S, Langer R: Morphologic and mechanical characteristics of engineered bovine arteries. J Vasc Surg. 2001 Mar. PMID: 11241137

Hirschi KK, Keen CL: Nutrition in embryonic and fetal development. Nutrition. 2000 Jul-Aug. PMID: 10906534

Niklason LE, Gao J, Abbott WM, Hirschi KK, Houser S, Marini R, Langer R: Functional arteries grown in vitro. Science. 1999 Apr 16. PMID: 10205057

Hirschi KK, Rohovsky SA, Beck LH, Smith SR, D'Amore PA: Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact. Circ Res. 1999 Feb 19. PMID: 10024303

Hirschi KK, Rohovsky SA, D'Amore PA: Cell-cell interactions in vessel assembly: a model for the fundamentals of vascular remodelling. Transpl Immunol. 1997 Sep. PMID: 9402682

Hirschi KK, D'Amore PA: Control of angiogenesis by the pericyte: molecular mechanisms and significance. EXS. 1997. PMID: 9002230

Hirschi KK, D'Amore PA: Pericytes in the microvasculature. Cardiovasc Res. 1996 Oct. PMID: 8915187

Hirschi KK, Xu CE, Tsukamoto T, Sager R: Gap junction genes Cx26 and Cx43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential. Cell Growth Differ. 1996 Jul. PMID: 8809403

Hirschi KK, Vasiloudes P, Brannon PM: Effects of secretin and caerulein on pancreatic digestive enzymes in cultured rat acinar cells. Pancreas. 1994 Jan. PMID: 7509067

Hirschi KK, Minnich BN, Moore LK, Burt JM: Oleic acid differentially affects gap junction-mediated communication in heart and vascular smooth muscle cells. Am J Physiol. 1993 Dec. PMID: 7506488

Hirschi KK, Kenny S, Justice JD, Brannon PM: Effects of secretin and caerulein on enzymes of cultured pancreatic acinar cells. In Vitro Cell Dev Biol. 1991 Aug. PMID: 1717428

Hirschi KK, Sabb JE, Brannon PM: Effects of diet and ketones on rat pancreatic lipase in cultured acinar cells. J Nutr. 1991 Jul. PMID: 2051233