Mathew G. Angelos
Entering Class: 2011
Chemistry and Biomedical Engineering majors
University of Minnesota
Microbiology, Immunology and Cancer Biology Graduate Program
Honor and Awards:
- J. Thomas Livermore Award, University of Minnesota Medical School, 2017
- Veneziale-Steer Award, University of Minnesota Medical School, 2017
- Ruth L. Kirschstein National Research Service Award for Predoctoral MD/PhD Fellows, National Institute of Diabetes and Digestive and Kidney Diseases, 2015-2018
- Medical School Year 2 Honors
MSTP Student Governance:
- Student Admissions Committee, 2014-2015
- Student Advisory Committee, 2016-2018
Thesis Advisor: Dan Kaufman, M.D., Ph.D.
Hemogenic endothelial cells (HE) represent a rare cell population that gives rise to hematopoietic stem cells (HSCs) through a process referred to as endothelial-to-hematopoietic transition (EHT). EHT is a key developmental stage required to produce the mature, adult hematopoietic system. The underlying genetic and molecular mechanisms that regulate EHT remain poorly elucidated. Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), provide a well-defined cellular platform that can be used to study these mechanisms and to improve the in vitro production of HSCs potentially suitable for clinical applications. The Kaufman lab has previously been successful in generating erythroid cells, myeloid cells, and natural killer cells from hPSCs using a variety of differentiation methods. Despite this unique potential, HSCs derived from hPSCs that are capable of robust lymphocyte differentiation and permanent engraftment into an immunodeficient mouse model has not yet been achieved. We hypothesize that hPSCs are intrinsically biased to recapitulate primitive hematopoiesis, defined by the early production of primitive erythrocytes with the distinct absence of B- and T-lymphocytes, rather than definitive hematopoiesis, where fully engraftable HSCs with full lymphoid potential are generated. My thesis research specifically aims to understand the regulatory networks that underlie human hemogenic endothelial cell development from hPSCs and their subsequent transformation into definitive HSCs. The results of my studies will further the field’s understanding of how early human hematoendothelial occurs and will be broadly applicable in improving the production of patient-specific HSCs suitable for transplantation in individuals with hematological disease.
Angelos MG, Abrahante JE, Blum RH, Kaufman DS. Single cell resolution of human hemato-endothelial cells defines transcriptional signatures of hemogenic endothelium. Stem Cells. Stem Cells. 2018 Feb;36(2):206-217.
Angelos MG, Ruh PN, Webber BR, Blum RH, Ryan CD, Bendzick L, Shim S, Yingst AM, Tufa DM, Verneris MR, and Kaufman DS. Aryl hydrocarbon receptor antagonism promotes early hemato-lymphoid development from human pluripotent stem cells. Blood. 2017 Jun 29;129(26):3428-3439.
Richards MM, Maxwell JS, Weng L, Angelos MG, Golzarian J. Intra-articular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine. Phys Sportsmed. 2016 May;44(2):101-8. PMCID: PMC4932822
Angelos MG, Kaufman DS. Pluripotent stem cell applications for regenerative medicine. Curr Opin Organ Transplant. 2015 Dec;20(6):663-70. PMCID: PMC4635470
Angelos MG, Kidwai F, Kaufman DS. Pluripotent Stem Cells and Gene Therapy. In Translating Gene Therapy to the Clinic. 2014. In Press. (Book chapter).
For work prior to entering the Program:
Angelos MG, Brown MA, Satterwhite LL, Levering VW, Shaked NT, Truskey GA. Dynamic adhesion of umbilical cord blood endothelial progenitor cells under laminar shear stress. Biophys J. 2010 Dec 1;99(11):3545-54. PMCID: PMC2998604
Brown MA, Wallace CS, Angelos M, Truskey GA. Characterization of umbilical cord blood-derived late outgrowth endothelial progenitor cells exposed to laminar shear stress. Tissue Eng Part A. 2009 Nov;15(11):3575-87. doi: 10.1089/ten.TEA.2008.0444.