Karen K. Hirschi, Ph.D.

Professor, Departments of Medicine, Genetics and Biomedical Engineering
Co-Director, Yale Cardiovascular Research Center (YCVRC)
Yale University School of Medicine

Primary Research:
The Hirschi laboratory predominantly studies vascular development and we are specifically interested in elucidating regulators of endothelial cell commitment, differentiation and specialization, as well as modulators of endothelial cell proliferation during blood vessel formation. We use the mouse model system to study vascular development in vivo (transgenesis), in situ (embryo culture) and in vitro (primary cell and co-culture systems). Information derived from the murine embryo model system is used to modulate the commitment of pluripotent human stem cells toward vascular cell fates, and to understand the mechanisms that govern human endothelial cell development. Insights gained from our cell and developmental studies are applied to clinically relevant strategies to promote endogenous vascular regeneration in vivo and to produce vascular and blood cells ex vivo, as part of multi-disciplinary projects that translate mechanisms of tissue morphogenesis into strategies to repair damaged and diseased tissues.

Some ongoing areas of investigation in the lab:
• Regulation of mouse and human hemogenic endothelial cell specification and function
• Role of endothelial cell cycle control in phenotypic specialization
• Role of vascular endothelial cells in the regulation of adult NSC
• Fetal bone marrow niche development, and vascular regulation of HSC
• Vascular tissue engineering and regeneration

Lab Web Site: https://medicine.yale.edu/intmed/cardio/ycvrc/facultylabs/k-hirschi.aspx

Members of the laboratory:
Antonin Bourdieu  - Postdoctoral Associate
Nicholas Chavkin  - Postdoctoral Associate
Jennifer Fang  - Associate Research Scientist
Zhiheng (Alan) He  - Associate Research Scientist
Nafiisha Khoyrattee  - Postdoctoral Associate
Jingyao Qiu  - Graduate Student
Yinyu Wu  - Graduate Student
Hema Vasavada  - Lab Manager
Laura Miller  - Administrative Assistant

Recent Publications:

• Hirschi KK, Nicoli S, Walsh K. Hematopoiesis lineage tree uprooted: Every HSPC is a rainbow. Developmental Cell 41:7-9, 2017.
• 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 355:842-847, 2017.
• Dejana E, Hirschi KK, Simons M: The molecular basis of endothelial cell plasticity. Nature Communications doi:10.1038/ncomms14361, 2017.
• 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 March, 2017.
• 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 doi: 10.1242/dev.140129, 2016
• 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. Nature Communications (7) doi:10.1038/ncomms13650, 2016.
• Fang JS, Gritz EC, Marcelo KL, Hirschi KK. Isolation of Murine Embryonic Hemogenic Endothelial Cells. J Visual Experimentation (112) e54150, doi:10.3791/54150, 2016.
• Gritz E, Hirschi KK. Specification and function of hemogenic endothelium during embryogenesis. Cell Molecular Life Sciences doi :0.1007/s00018-016-2134-0, 2016.
• Coskun S, Chao H, Vasavada H, Gonzales N, Zhou X, de Crombrugghe B Hirschi KK. Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability therein by emerging osteolineage cells. Cell Reports 9:1-10, 2014.
• Hirschi KK, Li S, Roy K. Induced pluripotent stem cells for regenerative medicine. Annual Review of Biomedical Engineering 16:277-294, 2014.
• Marcelo KL, Sills T, 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. Developmental Cell 27:504-515, 2013.
• Vunjak-Novakovic G, Bhatia S, Chen C, Hirschi KK. HeLiVa platform: integrated heart-liver-vascular systems for drug testing in human health and disease. Stem Cell Research & Therapy 4(1):S8 doi:10.1186/scrt369, 2013.
• Marcelo KL, Goldie LC, Hirschi KK. Endothelial cell differentiation and specification. Circulation Research 12:1272-1287, 2013.