Abstract:
Defects in vascular cells can contribute to peripheral vascular disease, stroke, atherosclerosis/thrombosis, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, dementia, and some severe viral infectious diseases. However, the recognition of ECs as distinct subphenotypes exhibiting distinct functions has been somewhat controversial. The dominant paradigm previously viewed tip-specific ECs as ECs that temporarily took up their unique behavior while leading migration of a sprouting blood vessel. Newer studies show that tip ECs, as well as ECs subpopulations from different tissue/organs, exhibit phenotypic stability with distinct functional and gene expression profiles, suggesting that these are unique subpopulations of ECs. Our laboratory uses mouse and human embryonic stem cells (ESC) and human induced pluripotent stem (iPS) cells and human umbilical vein endothelial cells (HUVECs) to study endothelial cell functions and vascular development. We have identified soluble signals and unique surface markers that direct and purify tip-specific ECs from stem cells and primary endothelial cells, characterized these cells using a variety of cell markers, and conducted functional assays. Here, we will report on our induction strategies and highlight the differences that we found between mouse and human tip-specific induction and identification. The generation and identification of these specific angiogenic cells are critical in studies aimed at controlling or directing angiogenesis or anti-angiogenesis.
Biography:
Dr. Kara E. McCloskey, PhD, is a Founding Full Professor at the University of California, Merced in the Chemical and Materials Engineering (CME) Department. Dr. McCloskey is the current Program Director for a Training Program in Undergraduate Stem Cell Engineering and Biology (TUSCEB) as well as Program Director for a UC Merced facility developing Resources for Expanding Stem cell-derived Tissues and Organs for Regenerative Engineering (RESTORE), both funded by the California Institute of Regenerative Medicine. She has been Founder and Chair of the Graduates Program in Biological Engineering and Small-scale Technologies (BEST) and Materials and Biomaterials Science and Engineering (MBSE), as well as the program lead developer for a new B.S. degree in Chemical Engineering. She is well-known for her work in directing endothelial cell (EC) fate from both human and mouse ESCs and induced-pluripotent stem (iPS) cells, including a pioneering publication to identify and characterize the derivation of stable angiogenic and non-angiogenic ECs from stem cells. She has 14 publications in this specific area and has authored or co-authored over 50 peer-reviewed journal articles in areas from magnetic cell separation, stem cell differentiation, and tissue assembly. She is currently focusing her efforts examining cell-material interactions for developing functional tissues.
Dr. McCloskey earned a highly competitive $1.7 million New Faculty Award from the California Institute for Regenerative Medicine (CIRM) for studies on fabricating cardiac tissue models from stem cells; this was followed by a Basic Biology Award from CIRM on directing endothelial subphenotypes from embryonic stem cells (ESCs). Dr. McCloskey’s experience as a leader in the NSF-funded Science and Technology Center (STC) on Emergent Behavior in Integrated in Cellular Systems (EBICS, MIT, UIUC, and GT) for 10 years helped develop the appropriate expertise to successfully apply for the CREST Center for Cellular and Biomolecular Machines (CCBM), the first NSF-funded research center at UC Merced – a Hispanic serving institution. She now participates in another NSF-funded STC on Cellular Engineering in MechanoBiology (CEMB, UPenn) and an NSF-funded Engineering Research Center (ERC) on the Transformation of American Rubber through Domestic Innovation for Supply Security (TARDISS).
