Karen Kemper Hirschi

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Primary Appointment

Professor, Cell Biology

Education

  • BS, Nutritional Biochemistry, Penn State University
  • PhD, Nutritional Biochemistry, University of Arizona
  • Postdoc Fellow, Cell Biology, University of Arizona
  • Postdoc Fellow, Vascular Biology, Harvard Medical School

Research Disciplines

Cell and Developmental Biology, Development, Stem Cells & Regeneration

Research Interests

Understanding Cellular and Molecular Mechanisms Leading to Blood Vessel Formation

Research Description

Our laboratory is 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.

Personal Statement

Our laboratory is 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.

Training

  • Basic Cardiovascular Research Training Grant
  • Biotechnology Training Grant

Selected Publications

2024

Dunaway, L. S., Luse, M. A., Nyshadham, S., Bulut, G., Alencar, G. F., Chavkin, N. W., . . . Isakson, B. E. (2024). Obesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium.. Physiological genomics, 56(2), 113-127. doi:10.1152/physiolgenomics.00109.2023

Horitani, K., Chavkin, N. W., Arai, Y., Wang, Y., Ogawa, H., Yura, Y., . . . Walsh, K. (2024). Disruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the profibrotic attributes of Y chromosome loss in heart failure. NATURE CARDIOVASCULAR RESEARCH. doi:10.1038/s44161-024-00441-z

2023

Genet, G., Genet, N., Paila, U., Cain, S. R., Cwiek, A., Chavkin, N. W., . . . Hirschi, K. K. (2024). Induced Endothelial Cell Cycle Arrest Prevents Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia.. Circulation, 149(12), 944-962. doi:10.1161/circulationaha.122.062952

Cochran, J. D., Yura, Y., Thel, M. C., Doviak, H., Polizio, A. H., Arai, Y., . . . Walsh, K. (2023). Clonal Hematopoiesis in Clinical and Experimental Heart Failure With Preserved Ejection Fraction. CIRCULATION, 148(15), 1165-1178. doi:10.1161/CIRCULATIONAHA.123.064170

Wilcox, N. S., Yarovinsky, T. O., Pandya, P., Ramgolam, V. S., Moro, A., Wu, Y., . . . Bender, J. R. (2023). Distinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages. ISCIENCE, 26(12). doi:10.1016/j.isci.2023.107985

Chavkin, N. W., Vippa, T., Jung, C., McDonnell, S., Hirschi, K. K., Gokce, N., & Walsh, K. (2023). Obesity accelerates endothelial-to-mesenchymal transition in adipose tissues of mice and humans. FRONTIERS IN CARDIOVASCULAR MEDICINE, 10. doi:10.3389/fcvm.2023.1264479

Wu, Y., Paila, U., Genet, G., & Hirschi, K. K. (2023). MicroRNA-223 limits murine hemogenic endothelial cell specification and myelopoiesis. DEVELOPMENTAL CELL, 58(14), 1237-+. doi:10.1016/j.devcel.2023.05.007

Kam, C. Y., Singh, I. D., Gonzalez, D. G., Matte-Martone, C., Sola, P., Solanas, G., . . . Greco, V. (2023). Mechanisms of skin vascular maturation and maintenance captured by longitudinal imaging of live mice. CELL, 186(11), 2345-+. doi:10.1016/j.cell.2023.04.017

Acharya, B. R., Fang, J. S., Jeffery, E., Chavkin, N. W., Genet, G., Vasavada, H., . . . Hirschi, K. K. (2023). Connexin 37 sequestering of activated-ERK in the cytoplasm promotes p27-mediated endothelial cell cycle arrest. LIFE SCIENCE ALLIANCE, 6(8). doi:10.26508/lsa.202201685

Leiby, K. L., Yuan, Y., Ng, R., Raredon, M. S. B., Adams, T. S., Baevova, P., . . . Niklason, L. E. (2023). Rational engineering of lung alveolar epithelium. NPJ REGENERATIVE MEDICINE, 8(1). doi:10.1038/s41536-023-00295-2

de Souza, V. B. C., Jordan, B. T. T., Tseng, E., Nelson, E. A. A., Hirschi, K. K. K., Sheynkman, G., & Robinson, M. D. D. (2023). Transformation of alignment files improves performance of variant callers for long-read RNA sequencing data. GENOME BIOLOGY, 24(1). doi:10.1186/s13059-023-02923-y

Genet, N., Genet, G., Chavkin, N. W., Paila, U., Fang, J. S., Vasavada, H. H., . . . Hirschi, K. K. (2023). Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone. CELL REPORTS, 42(4). doi:10.1016/j.celrep.2023.112371

2022

Chavkin, N. W., Genet, G., Poulet, M., Jeffery, E. D., Marziano, C., Genet, N., . . . Hirschi, K. K. (2022). Endothelial cell cycle state determines propensity for arterial-venous fate. NATURE COMMUNICATIONS, 13(1). doi:10.1038/s41467-022-33324-7

Sano, S., Horitani, K., Ogawa, H., Halvardson, J., Chavkin, N. W., Wang, Y., . . . Walsh, K. (2022). Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality. SCIENCE, 377(6603), 292-297. doi:10.1126/science.abn3100

Ronaldson-Bouchard, K., Teles, D., Yeager, K., Tavakol, D. N., Zhao, Y., Chramiec, A., . . . Vunjak-Novakovic, G. (2022). A multi-organ chip with matured tissue niches linked by vascular flow. NATURE BIOMEDICAL ENGINEERING, 6(4), 351-+. doi:10.1038/s41551-022-00882-6

Mehlferber, M. M., Jeffery, E. D., Saquing, J., Jordan, B. T., Sheynkman, L., Murali, M., . . . Sheynkman, G. M. (2022). Characterization of protein isoform diversity in human umbilical vein endothelial cells via long-read proteogenomics. RNA BIOLOGY, 19(1), 1228-1243. doi:10.1080/15476286.2022.2141938

Aragon, J. W. W., & Hirschi, K. K. K. (2022). Endothelial Cell Differentiation and Hemogenic Specification. COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 12(7). doi:10.1101/cshperspect.a041164

Hong, L., Li, N., Gasque, V., Mehta, S., Ye, L., Wu, Y., . . . Mani, A. (2022). Prdm6 controls heart development by regulating neural crest cell differentiation and. JCI INSIGHT, 7(4). doi:10.1172/jci.insight.156046

2021

Marziano, C., Genet, G., & Hirschi, K. K. (2021). Vascular endothelial cell specification in health and disease. ANGIOGENESIS, 24(2), 213-236. doi:10.1007/s10456-021-09785-7

Chavkin, N. W., Cain, S., Walsh, K., & Hirschi, K. K. (2021). Isolation of Murine Retinal Endothelial Cells for Next-Generation Sequencing. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (176). doi:10.3791/63133

Genet, N., & Hirschi, K. K. (2021). Understanding neural stem cell regulation in vivo and applying the insights to cell therapy for strokes. REGENERATIVE MEDICINE, 16(09), 861-870. doi:10.2217/rme-2021-0022

Tavakol, D. N., Chen, J., Chavkin, N. W., Tavakol, T. N., Hirschi, K. K., & Vunjak-Novakovic, G. (2021). Lessons from Biology: Engineering Design Considerations for Modeling Human Hematopoiesis. CURRENT STEM CELL REPORTS, 7(4), 174-184. doi:10.1007/s40778-021-00195-5

Chavkin, N. W., Sano, S., Wang, Y., Oshima, K., Ogawa, H., Horitani, K., . . . Walsh, K. (2021). The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation. JOURNAL OF THE AMERICAN HEART ASSOCIATION, 10(13). doi:10.1161/JAHA.120.019904

Nelson, E. A., Qiu, J., Chavkin, N. W., & Hirschi, K. K. (2021). Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (169). doi:10.3791/62391

Chavkin, N. W., Walsh, K., & Hirschi, K. K. (2021). Isolation of Highly Purified and Viable Retinal Endothelial Cells. JOURNAL OF VASCULAR RESEARCH, 58(1), 49-57. doi:10.1159/000510533

2020

Wu, Y., & Hirschi, K. K. (2021). Regulation of Hemogenic Endothelial Cell Development and Function. ANNUAL REVIEW OF PHYSIOLOGY, VOL 83, 83, 17-37. doi:10.1146/annurev-physiol-021119-034352

Matta, R., Lee, S., Genet, N., Hirschi, K. K., Thomas, J. -L., & Gonzalez, A. L. (2020). Minimally Invasive Delivery of Microbeads with Encapsulated, Viable and Quiescent Neural Stem Cells to the Adult Subventricular Zone (vol 9, 17798, 2019). SCIENTIFIC REPORTS, 10(1). doi:10.1038/s41598-020-57577-8

Wu, Y., & Hirschi, K. K. (2021). Tissue-Resident Macrophage Development and Function. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 8. doi:10.3389/fcell.2020.617879

Kasper, D. M., Hintzen, J., Wu, Y., Ghersi, J. J., Mandl, H. K., Salinas, K. E., . . . Nicoli, S. (2020). The N-glycome regulates the endothelial-to-hematopoietic transition. SCIENCE, 370(6521), 1186-+. doi:10.1126/science.aaz2121

Qiu, J., Nordling, S., Vasavada, H. H., Butcher, E. C., & Hirschi, K. K. (2020). Retinoic Acid Promotes Endothelial Cell Cycle Early G1 State to Enable Human Hemogenic Endothelial Cell Specification. CELL REPORTS, 33(9). doi:10.1016/j.celrep.2020.108465

Chavkin, N. W., & Hirschi, K. K. (2020). Single Cell Analysis in Vascular Biology. FRONTIERS IN CARDIOVASCULAR MEDICINE, 7. doi:10.3389/fcvm.2020.00042

Wang, Y., Sano, S., Yura, Y., Ke, Z., Sano, M., Oshima, K., . . . Walsh, K. (2020). Tet2-mediated clonal hematopoiesis in nonconditioned mice accelerates age-associated cardiac dysfunction. JCI INSIGHT, 5(6). doi:10.1172/jci.insight.135204

2019

Qiu, J., & Hirschi, K. K. (2019). Endothelial Cell Development and Its Application to Regenerative Medicine. CIRCULATION RESEARCH, 125(4), 489-501. doi:10.1161/CIRCRESAHA.119.311405

Fang, J., & Hirschi, K. (2019). Molecular regulation of arteriovenous endothelial cell specification.. F1000Research, 8, F1000 Faculty Rev-1208. doi:10.12688/f1000research.16701.1

Matta, R., Lee, S., Genet, N., Hirschi, K. K., Thomas, J. -L., & Gonzalez, A. L. (2019). Minimally Invasive Delivery of Microbeads with Encapsulated, Viable and Quiescent Neural Stem Cells to the Adult Subventricular Zone. SCIENTIFIC REPORTS, 9. doi:10.1038/s41598-019-54167-1

2018

Fang, J. S., Coon, B. G., Gillis, N., Chen, Z., Qiu, J., Chittenden, T. W., . . . Hirschi, K. K. (2018). Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification (vol 8, 2017). NATURE COMMUNICATIONS, 9. doi:10.1038/s41467-018-03076-4

Genet, N., Bhatt, N., Bourdieu, A., & Hirschi, K. K. (2018). Multifaceted Roles of Connexin 43 in Stem Cell Niches. CURRENT STEM CELL REPORTS, 4(1), 1-12. doi:10.1007/s40778-018-0110-3

Hirschi, K. K., & Dejana, E. (2018). Resident Endothelial Progenitors Make Themselves at Home. CELL STEM CELL, 23(2), 153-155. doi:10.1016/j.stem.2018.07.014

2017

Polacheck, W. J., Kutys, M. L., Yang, J., Eyckmans, J., Wu, Y., Vasavada, H., . . . Chen, C. S. (2017). A non-canonical Notch complex regulates adherens junctions and vascular barrier function. NATURE, 552(7684), 258-+. doi:10.1038/nature24998

Yu, P., Wilhelm, K., Dubrac, A., Tung, J. K., Alves, T. C., Fang, J. S., . . . Simons, M. (2017). FGF-dependent metabolic control of vascular development. NATURE, 545(7653), 224-+. doi:10.1038/nature22322

Dejana, E., Hirschi, K. K., & Simons, M. (2017). The molecular basis of endothelial cell plasticity. NATURE COMMUNICATIONS, 8. doi:10.1038/ncomms14361

Fuster, J. J., MacLauchlan, S., Zuriaga, M. A., Polackal, M. N., Ostriker, A. C., Chakraborty, R., . . . Walsh, K. (2017). Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. SCIENCE, 355(6327), 842-847. doi:10.1126/science.aag1381

Ceneri, N., Zhao, L., Young, B. D., Healy, A., Coskun, S., Vasavada, H., . . . Morrison, A. R. (2017). Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1β Production. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 37(2), 328-+. doi:10.1161/ATVBAHA.116.308507

Sivarapatna, A., Ghaedi, M., Xiao, Y., Han, E., Aryal, B., Zhou, J., . . . Niklason, L. E. (2017). Engineered Microvasculature in PDMS Networks Using Endothelial Cells Derived from Human Induced Pluripotent Stem Cells. CELL TRANSPLANTATION, 26(8), 1365-1379. doi:10.1177/0963689717720282

Fang, J. S., Coon, B. G., Gillis, N., Chen, Z., Qiu, J., Chittenden, T. W., . . . Hirschi, K. K. (2017). Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification. NATURE COMMUNICATIONS, 8. doi:10.1038/s41467-017-01742-7

Hirschi, K. K., Nicoli, S., & Walsh, K. (2017). Hematopoiesis Lineage Tree Uprooted: Every HSPC Is a Rainbow. DEVELOPMENTAL CELL, 41(1), 7-9. doi:10.1016/j.devcel.2017.03.020

2016

Gritz, E., & Hirschi, K. K. (2016). Specification and function of hemogenic endothelium during embryogenesis. CELLULAR AND MOLECULAR LIFE SCIENCES, 73(8), 1547-1567. doi:10.1007/s00018-016-2134-0

Goligorsky, M. S., & Hirschi, K. (2016). Stress-Induced Premature Senescence of Endothelial and Endothelial Progenitor Cells.. Advances in pharmacology (San Diego, Calif.), 77, 281-306. doi:10.1016/bs.apha.2016.04.007

Cuchiara, M. L., Coskun, S., Banda, O. A., Horter, K. L., Hirschi, K. K., & West, J. L. (2016). Bioactive poly(ethylene glycol) hydrogels to recapitulate the HSC niche and facilitate HSC expansion in culture. BIOTECHNOLOGY AND BIOENGINEERING, 113(4), 870-881. doi:10.1002/bit.25848

Fang, J. S., Gritz, E. C., Marcelo, K. L., & Hirschi, K. K. (2016). Isolation of Murine Embryonic Hemogenic Endothelial Cells. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (112). doi:10.3791/54150

Wang, Y., Baeyens, N., Corti, F., Tanaka, K., Fang, J. S., Zhang, J., . . . Simons, M. (2016). Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. DEVELOPMENT, 143(23), 4441-4451. doi:10.1242/dev.140129

Ola, R., Dubrac, A., Han, J., Zhang, F., Fang, J. S., Larrivee, B., . . . Eichmann, A. (2016). PI3 kinase inhibition improves vascular malformations in mouse models of hereditary haemorrhagic telangiectasia. NATURE COMMUNICATIONS, 7. doi:10.1038/ncomms13650

2015

Muralidharan, S., Sasi, S. P., Zuriaga, M. A., Hirschi, K. K., Porada, C. D., Coleman, M. A., . . . Goukassian, D. A. (2015). Ionizing particle radiation as a modulator of endogenous bone marrow cell reprogramming: implications for hematological cancers. FRONTIERS IN ONCOLOGY, 5. doi:10.3389/fonc.2015.00231

Muralidharan, S., Sasi, S. P., Zuriaga, M. A., Hirschi, K. K., Porada, C. D., Coleman, M. A., . . . Goukassian, D. A. (2015). Ionizing Particle Radiation as a Modulator of Endogenous Bone Marrow Cell Reprogramming: Implications for Hematological Cancers (vol 5, pg 231, 2015). FRONTIERS IN ONCOLOGY, 5. doi:10.3389/fonc.2015.00255

2014

Martin, K. A., & Hirschi, K. K. (2014). The Magic Touch Endothelial Cells Muscle-Up Adipose. CIRCULATION RESEARCH, 115(9), 752-754. doi:10.1161/CIRCRESAHA.114.305030

Coskun, S., Chao, H., Vasavada, H., Heydari, K., Gonzales, N., Zhou, X., . . . Hirschi, K. K. (2014). Development of the Fetal Bone Marrow Niche and Regulation of HSC Quiescence and Homing Ability by Emerging Osteolineage Cells. CELL REPORTS, 9(2), 581-590. doi:10.1016/j.celrep.2014.09.013

2013

Vunjak-Novakovic, G., Bhatia, S., Chen, C., & Hirschi, K. (2013). HeLiVa platform: integrated heart-liver-vascular systems for drug testing in human health and disease. STEM CELL RESEARCH & THERAPY, 4. doi:10.1186/scrt369

Fang, J. S., Dai, C., Kurjiaka, D. T., Burt, J. M., & Hirschi, K. K. (2013). Connexin45 Regulates Endothelial-Induced Mesenchymal Cell Differentiation Toward a Mural Cell Phenotype. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 33(2), 362-+. doi:10.1161/ATVBAHA.112.255950

Goldberg, J. S., Vadakkan, T. J., Hirschi, K. K., & Dickinson, M. E. (2013). A Computational Approach to Detect Gap Junction Plaques and Associate Them with Cells in Fluorescent Images. JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 61(4), 283-293. doi:10.1369/0022155413477114

Marcelo, K. L., Goldie, L. C., & Hirschi, K. K. (2013). Regulation of Endothelial Cell Differentiation and Specification. CIRCULATION RESEARCH, 112(9), 1272-1287. doi:10.1161/CIRCRESAHA.113.300506

Marcelo, K. L., Sills, T. M., Coskun, S., Vasavada, H., Sanglikar, S., Goldie, L. C., & Hirschi, K. K. (2013). Hemogenic Endothelial Cell Specification Requires c-Kit, Notch Signaling, and p27-Mediated Cell-Cycle Control. DEVELOPMENTAL CELL, 27(5), 504-515. doi:10.1016/j.devcel.2013.11.004

2012

Agrawal, V., Siu, B. F., Chao, H., Hirschi, K. K., Raborn, E., Johnson, S. A., . . . Badylak, S. F. (2012). Partial Characterization of the Sox2+Cell Population in an Adult Murine Model of Digit Amputation. TISSUE ENGINEERING PART A, 18(13-14), 1454-1463. doi:10.1089/ten.tea.2011.0550

Hirschi, K. K. (2012). Hemogenic endothelium during development and beyond. BLOOD, 119(21), 4823-4827. doi:10.1182/blood-2011-12-353466