Karen Kemper Hirschi, PhD

Undergraduate Education:

Honors B.S. with Highest Distinction, Nutritional Biochemistry

Schreyer Honors College, Pennsylvania State University, University Park, PA

1980-1984, University Scholar

Graduate Education:

Ph.D., Nutritional Biochemistry

University of Arizona, Tucson, AZ

1985-1990, Cowden Predoctoral Fellow

Postgraduate Training:

Postdoctoral Fellow, University of Arizona, Tucson, AZ

1991-1992, AHA Grant-in-Aid for Junior Investigators

Postdoctoral Fellow, Harvard Medical School, Boston, MA

1993-1996, NIH NRSA Postdoctoral Fellowship

Academic Appointments:

1996-1997, Instructor, Dept. Surgery, Harvard Medical School

1997-2002, Assistant Professor, Dept. Pediatrics, Baylor College of Medicine (BCM), Houston, TX 1998-2002, Adjunct Assistant Professor, Dept. of Molecular & Cellular Biology, BCM

2000-2002, Adjunct Assistant Professor, Dept. Bioengineering, Rice University

2003-2007, Associate Professor w/ tenure, Dept. Pediatrics; Adjunct in Depts. Molecular & Cellular Biol. and Molecular Phys. & Biophysics, BCM, and Dept. of Bioengineering, Rice

2005-2011, Co-Founder and Deputy Director, Stem Cell Regenerative Medicine Center, BCM

2006-2011, Co-Director, Medical Scientist Training (MD/PhD) Program, BCM

2007-2011, Professor w/ tenure, Dept. Pediatrics; Adjunct in Depts. Molecular & Cellular Biol. and Molecular Phys. & Biophysics, BCM, and Dept. of Bioengineering, Rice University

2011-present, Adjunct Professor, Department of Pediatrics, Department of Molecular & Cellular Biology and Department of Molecular Physiology & Biophysics, BCM

2011-present, Professor w/ tenure, Departments of Medicine, Genetics and Biomedical Engineering, Yale University School of Medicine

2016-present, Co-Director, Yale Cardiovascular Research Center, Yale University

1997-present, Faculty, Children’s Nutrition Research Center, BCM

2000-present, Faculty, Center for Cell and Gene Therapy, BCM

2000-2013, Faculty, Graduate Program in Molecular & Cellular Biology, BCM

2000-2011, Faculty, Center for Cardiovascular Development, BCM

2000-2011, Faculty, Graduate Program in Cardiovascular Sciences, BCM

2002-2011, Faculty, Graduate Program in Developmental Biology, BCM

2002-2011, Faculty, Graduate Program in Cell and Molecular Biology, BCM

2002-2011, Faculty, Center for Nanoscale Science & Technology, Rice University

2005-2011, Faculty, Graduate Program in Translational Biology, BCM

2006-2011, Faculty, Dan Duncan Cancer Center, BCM

2007-2011, Faculty, University of Texas Graduate School of Biomedical Sciences

2011-present, Faculty, Yale Cardiovascular Research Center

2011-present, Faculty, Yale Vascular Biology and Therapeutics Program

2011-present, Faculty, Yale Stem Cell Center

2015-present, Faculty, Yale Combined Graduate Program in the Biological and Biomedical Sciences

Honors and Awards:

1982-1984 University Scholar (top 2%), Pennsylvania State University

1987-1990  Cowden Predoctoral Fellowship, University of Arizona

1991-1992  Grant-in-Aid for Junior Investigators, American Heart Association

1993-1996 NRSA Postdoctoral Fellowship, National Institutes of Health

1998-1999 Davenport/Fleming Award, Texas Medical Center

1999-2003 Scientist Development Award, AHA National Foundation

2000-2002 Gillson Longenbaugh Foundation Award, Baylor College of Medicine

2004-2007 Member of Scientific Council, North American Vascular Biology Organization

2004-2009 Established Investigator Award, AHA National Foundation

2006 Center for Cell & Gene Therapy Basic Science Teaching Award

2009 Chair, North American Vascular Biology Organization Annual Meeting

2011-2013 Kingsley Award in Medical Research, Yale University School of Medicine

2012 Chair, Gordon Conference on Signal Transduction in Engineered Extracellular Matrices

2014-2015 President, North American Vascular Biology Organization

2014-2018 Advisory Council, UK Regenerative Medicine Program: A Hub for Engineering and Exploiting the Stem Cell Niche

2014-2018 Appointed Member, National Advisory Council, NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB)

2014-2015 Member, NIBIB National Advisory Council Task Force on Strategic Funding

2015-present Scientific Advisory Panel, Ted Rogers Centre for Heart Research. Toronto

2015-present Scientific Advisory Committee, Rutgers/Princeton Biomaterials Training Program

Publications:

Hirschi, K.K., J.E. Sabb and P.M. Brannon. (1991) Effects of diet and ketones on pancreatic lipase in cultured acinar cells. J. Nutrition 121:1129-1134.

Hirschi, K.K., S. Kenny, J.D. Justice and P.M. Brannon. (1991) Effects of secretin and cholecystokinin on enzymes of cultured pancreatic acinar cells. In Vitro Cell & Developmental Biology 27A:660-664.

Hirschi, K.K., B.N. Minnich, L.K. Moore and J.M. Burt. (1993) Differential effects of oleic acid on gap junction mediated coupling in vascular smooth muscle and neonatal heart cells. Am. J. Physiology 265:C1517-1526.

Hirschi, K.K., P. Vasiloudes and P.M. Brannon. (1994) Effects of secretin and caerulein on pancreatic digestive enzymes in cultured rat acinar cells. Pancreas 9(1):91-100.

Hirschi, K.K., C. Xu, T. Tsukamoto and R. Sager. (1996) Gap junction genes Cx43 and Cx26 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential. Cell Growth and Differentiation 7:861-870.

Hirschi, K.K. and P.A. D'Amore. (1996) Pericytes in the microvasculature. Cardiovascular Research 32:687-698.

Rohovsky, S.A., K.K. Hirschi and P.A. D’Amore (1996) Growth factor effects on vessel formation. Surgical Forum XLVII.

Hirschi, K.K., S.A. Rohovsky and P.A. D’Amore (1997) Cell-cell interactions in vessel assembly: a model for the fundamentals of neovascularization. Transplant Immunology 5:177-178.

Hirschi, K.K., S.A. Rohovsky and P.A. D'Amore. (1998) PDGF, TGF-b and heterotypic cell-cell interactions mediate the recruitment and differentiation of 10T1/2 cells to a smooth muscle fate. J. Cell Biology 141:805-814.

Hirschi, K.K., S.A. Rohovsky, L.H. Beck, S. Smith and P.A. D’Amore. (1999) Endothelial cells modulate the proliferation of mural cell precursors via PDGF-BB and heterotypic contact. Circulation Research 84:298-305.

Niklason, L., C. Gao, P. Abbott, K.K. Hirschi, M. Houser, D. Marini and R. Langer. (1999) Functional arterial grafts grown in vitro. Science 284:422-425.

Arbiser, J., G. Raab, R. Rohan, S. Paul, K.K. Hirschi, E. Flynn, E.R. Price, D. Fisher, C. Cohen and M. Klagsbrun. (1999) Isolation of mouse stromal cells associated with a human tumor using differential diphtheria toxin sensitivity. Am. J. Pathology 155:723-729.

Hirschi, K.K. and C.L. Keen. (2000) Nutrition in embryonic and fetal development. Nutrition 16:495-499.

Niklason, L.E., W. Abbott, J. Gao, B. Klagges, K.K. Hirschi, K. Ulubayram, N. Conroy, R. Jones, A. Vasanawala, S. Sanzgiri and R. Langer. (2001) Morphologic and mechanical characteristics of bovine engineered arteries. J. Vascular Surgery 33:628-638.

Hirschi, K.D., J.A. Kreps and K.K. Hirschi (2001) Molecular approaches to studying nutrient metabolism and function: an array of possibilities. J. Nutrition 131:1605S-1609S.

Jackson, K.A., S.M. Majka*, H. Wang, J. Pocius, C. Hartley, M.W. Majesky, L. Michael, M. Entman, K.K. Hirschi* and M.A. Goodell*. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clinical Investigation 107:1395-1402. *Co-senior authors.

Goodell, M.A., K.A. Jackson, S.M. Majka, T. Mi, H. Wang, J. Pocius, C.J. Hartley, M.W. Majesky, M.L. Entman, L.H. Michael and K.K. Hirschi (2001) Stem cell plasticity in muscle and bone marrow.

Ann. NY Acad. Science 938:208-218.

Hirschi, K.K. and M.A. Goodell (2001) Common origins of blood and blood vessels in adults? Differentiation 68:186-192.

Hirschi, K.K., L. Lai, N.S. Belaguli, D. Dean, R.J. Schwartz and W.E. Zimmer. (2001) TGF-b induction of a smooth muscle cell phenotype requires transcriptional and post-transcriptional control of serum response factor. J. Biological Chemistry 277:6287-95.

Noveroske, J.K., L. Lai, V. Gaussin, J. Northrop, K.K. Hirschi and M.J. Justice. (2002) Quaking is essential for embryonic blood vessel formation. Genesis 32:218-230

Hirschi, K.K. and M.A. Goodell (2002) Hematopoietic, vascular and cardiac fates of bone marrow-derived stem cells. Gene Therapy 9:648-652.

Hirschi, K.K., T.C. Skalak, S.M. Peirce and C.D. Little. (2002) Vascular assembly in natural and engineered tissues. Ann. NY Acad. Science 961:223-242.

Skalak, T.C., C.D. Little, L.V. McIntire, K.K. Hirschi, R.T. Tranquillo, M. Post, J. Ranieri (2002) Vascular assembly in natural and engineered tissues: breakout session summary. Ann. NY Acad. Sci. 961:255-257.

Majka, S.M., K.A. Jackson, K.A. Kienstra, M.W. Majesky, M.A. Goodell and K.K. Hirschi. (2003) Distinct populations of vascular progenitors in skeletal muscle are bone marrow-derived and exhibit different cell fates during vascular regeneration. J. Clinical Investigation 111:71-79. (Featured Article – with editortial)

Bohnsack, B.L. and K.K. Hirschi (2003) The FAKs about blood vessel assembly. Circulation Research 92:255-257.

Bohnsack, B.L. and K.K. Hirschi (2003) Molecular regulation of vascular development. ASNR 100:1-6.

Hirschi, K.K., J.M. Burt, K.D. Hirschi and C. Dai. (2003) Gap junction communication mediates TGF-b activation and endothelial-induced mural cell differentiation. Circulation Research 93:429-437.

Nadin, B.M., M.A. Goodell and K.K. Hirschi. (2003) Phenotype and hematopoietic potential of side population cells throughout embryonic development. Blood 102:2436-2443.

Lai, L., B.L. Bohnsack, K. Niederreither and K.K. Hirschi. (2003) Retinoic acid signaling regulates endothelial cell proliferation during vasculogenesis. Development 130:6465-6474.

McKinney-Freeman, S., S.M. Majka, K.A. Jackson, K.K. Hirschi and M.A. Goodell. (2003) Altered phenotype and reduced function of muscle-derived hematopoietic stem cells. Experimental Hematology 31:806-814.

Olmstead-Davis, E., Z. Gugala, F. Camargo, F.H. Gannon, K.A. Jackson, K.A. Kienstra, H.D. Shine, R.W. Lindsey, K.K. Hirschi, M.A. Goodell, M.K. Brenner and A.R. Davis. (2003) Primitive adult hematopoietic stem cells can function as osteoblast precursors. Proc. Natl. Acad. Sci. 100:15877-82.

Abramowitz, J., C. Dai, K.K. Hirschi, R.I. Dmitrieva, P.A. Doris, L. Liu and J.C. Allen. (2003) Oubain- and marinoburagenin-induced proliferation of human umbilical vein smooth muscle cells and a rat vascular smooth muscle cell line, A7r5. Circulation 108:3048-53.

Hirschi, K.K. and M.W. Majesky (2004) Smooth muscle stem and progenitor cells. Anat. Rec. 276A:22-33.

Huss, W.J., L. Lai, R.J. Barrios, K.K. Hirschi and N.M. Greenberg. (2004) Retinoic acid slows tumor progression and promotes apoptosis of spontaneous prostate cancer. Prostate 9999:1-11.

Bohnsack, B.L., L. Lai, P. Dolle and K.K. Hirschi. (2004) Signaling hierarchy downstream of retinoic acid that independently regulates endothelial cell proliferation and vascular remodeling. Genes & Development 18:1345-1358. (Highlighted by Faculty of 1000)

Bohnsack, B.L. and K.K. Hirschi. (2004) Nutrient regulation of cell cycle progression. Annual Reviews of Nutrition 24:433-453.

Bohnsack, B.L. and K.K. Hirschi. (2004) Red light, green light: signals that control endothelial cell proliferation during embryonic vascular development. Cell Cycle 3:1506-1511.

Enciso JM. and K.K. Hirschi. (2005) Understanding abnormalities in vascular specification and

remodeling. Pediatrics 116:228-30.

Bohnsack, B.L., L. Lai, J. Northrop, M.J. Justice and K.K. Hirschi. (2006) Visceral endoderm function is regulated by quaking and required for vascular development. Genesis 44:93-104.

Saunders, W.B., B.L. Bohnsack, J.B. Faske, N.J. Anthis, K.J. Bayless, K.K. Hirschi and G.E. Davis. (2006) Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3.

J. Cell Biology 175:179-191.

Falender, A.E. and K.K. Hirschi (2006) What is the role of the vasculature in the neural stem cell niche? Regenerative Medicine 1:481-484.

Adams, K.E., S. Ke, S. Kwon, F. Liang, Z. Fan, Y. Lu, M.A. Barry, K.K. Hirschi, M.E. Mawad and E.M. Sevick-Muraca. (2006) Comparison of visible and near-infrared wavelength excitable fluorescent dyes for molecular

imaging of cancer. J. Biomedical Optics 12:24017.

Enciso, J.M. and K.K. Hirschi (2007) Nutrient regulation of tumor and vascular endothelial cell proliferation. Current Cancer Drug Targets 7:432-437.

Kienstra, K.A., D. Freysdottir, N.M. Gonzales and K.K. Hirschi (2007) Murine neonatal intravascular injections: modeling newborn disease. J. Am. Assoc. Lab. An. Sci. 46:50-54.

Kienstra, K.A., K.A. Jackson and K.K. Hirschi. (2008) Injury mechanism dictates contribution of bone marrow-derived cells to neovascularization. Pediatric Research 63:131-136.

Hirschi, K.K. D.A. Ingram and M.C. Yoder. (2008) Assessing identity, phenotype, and fate of endothelial progenitor cells. Arteriosclerosis, Thrombosis and Vascular Biology 28:1584-95.

Goldie L.C., M.K. Nix and K.K. Hirschi. (2008) Embryonic vasculogenesis and hematopoietic specification. Organogenesis. 4:257-63.

Goldie, L.C., J. Lucitti, M.E. Dickinson and K.K. Hirschi. (2008) Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis. Blood 112:3194-3204.

Kelly, M.A. and K.K. Hirschi. (2009) Signaling hierarchy regulating human endothelial cell development. Arteriosclerosis, Thrombosis and Vascular Biology 29:718-24.

Boles, M.K., B.M. Wilkinson, A. Maxwell, L. Lai, A.A. Mills, I. Nishijima, A.P. Salinger, I. Moskowitz, K.K. Hirschi, B. Liu, A. Bradley and M.J. Justice. (2009) A mouse chromosome 4 balancer ENU

mutagenesis screen isolates eleven lethal lines. BMC Genetics 10:12.

Goldberg, J.S. and K.K. Hirschi (2009) Diverse roles of the vasculature within the neural stem cell niche. Regenerative Medicine 4:879-97.

Dilling, C.F., A.M. Wada, M. Merched-Savage, Z.W. Lazard, F.H. Gannon, T.J. Vadakkan, L. Gao , K.K. Hirschi, M.E. Dickinson, A.R. Davis, E.A., Olmsted-Davis (2009) Vessel formation is induced prior to the appearance of cartilage in BMP2-mediated heterotopic ossification. J. Bone & Min. Res. 25:1147-56.

Boles, M.K., B.M Wilkinson, L. Wilming, J. Harrow, D. Grafham, J.R. Lupski, K.E. Hentges, L.P. Woodward, Maxwell, B. Liu, K. Mitchell, M.D. Risley, R. Johnson, K.K. Hirschi, S. Humphray, C. Scott, C. Nicholson, S. Searle, T. Cox, C. Loyd, L. Matthews, A. Dunham, A.J. Coffey, A. Parker, J. Smith, T.J., Hubbard, J. Rogers, A. Bradley, M.J. Justice and D.J. Adams. (2009) Discovery of candidate

disease genes in ENU–induced mouse mutants by large-scale sequencing, including a splice-site mutation

in nucleoredoxin. PLoS Genetics 5(12):e1000759.

Agrawala, V., S.A. Johnsona, J. Reinga, L. Zhang, S. Tottey, G. Wange, K.K. Hirschi, S. Braunhut, L.J. Gudas and S.F. Badylak. (2010) An epimorphic regeneration approach to tissue replacement in adult mammals. Proc. Natl. Acad. Sci. 107:3351-5.

Chao, H. and K.K. Hirschi (2010) Hemato-vascular origins of endothelial progenitor cells? Microvascular

Research 79:169–173.

Kazanis, I., J.D. Lathia, T.J. Vadakkan, E.Raborn, R. Wan, M.R. Mughal, D.M. Eckley, T. Sasaki, B. Patton,

M.P. Mattson, K.K. Hirschi, M.E. Dickinson and C. ffrench-Constant. (2010) Quiescence and activation of stem and precursor cell populations in the subependymal zone neurogenic niche of the mammalian brain are associated with distinct cellular and extracellular matrix signals. J. Neuroscience 30:9771-9781.

Armstrong, J.J., I.V. Larina, M.E. Dickinson, W.E. Zimmer and K.K. Hirschi. (2010) Characterization of

transgenic mice expressing mCherry fluorescent protein substituted for the murine smooth muscle alpha-actin gene. Genesis 48:457-463.

Hirschi, K.K. (2010) Vascular precursors: origin, regulation and potential. Arteriosclerosis, Thrombosis and

Vascular Biology 30:1104-1109.

Iacobas, I., A. Vats and K.K. Hirschi. (2010) Vascular potential of human pluripotent stem cells. Arteriosclerosis,

Thrombosis and Vascular Biology 30:1110-1117.

Enciso, J.M., C.M. Konecny and K.K. Hirschi. (2010) Molecular regulation of cell migration during vascular remodeling. Developmental Dynamics 239:2570-2583.

Abbas, H.A., S. Coskun, T. Sills, M.J. You, K.K. Hirschi and G. Lozano. (2010) Mdm2 is required for

survival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity.

Cell Stem Cell 7:606-617.

Coskun, S. and K.K. Hirschi. (2010) Establishment and maintenance of the HSC niche: distinct roles of

osteoblastic and vascular compartments. Birth Defects Research: Reviews 90:229-242. (Cover Image)