Randall Johnson's Group
Our laboratory uses genetic models to study the effects of hypoxia in physiological and pathological contexts, specifically dissecting the roles of different isoforms of Hypoxia Inducible Factors (HIF) as regulators of the hypoxia response in different cell types.
One of the functions of the mammalian hypoxic response in development and cancer is the generation of nascent vascular networks through angiogenesis. Through transcriptional regulation of the vascular endothelial growth factor A (VEGF-A) and other angiogenic factors, the Hypoxia-Inducible Factors can increase angiogenesis in an oxygen dependent fashion, and gives a survival and growth advantage to HIF wild type tumors. However, their role in other cell types is not always redundant. We are starting to understand that each cell type within the tumor microenvironment has specific hypoxia response strategies that independently affect tumor growth and tumor dispersion. We use genetic techniques to identify the role of hypoxia-triggered and HIF-dependent responses in different cell types, with a particular focus on cancer.
Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging.
Ho YH, Del Toro R, Rivera-Torres J, Rak J, Korn C, García-García A, et al
Cell Stem Cell 2019 Sep;25(3):407-418.e6
The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.
Sim J, Cowburn AS, Palazon A, Madhu B, Tyrakis PA, Macías D, et al
Cell Metab. 2018 04;27(4):898-913.e7
An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression.
Palazon A, Tyrakis PA, Macias D, Veliça P, Rundqvist H, Fitzpatrick S, et al
Cancer Cell 2017 11;32(5):669-683.e5
S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate.
Tyrakis PA, Palazon A, Macias D, Lee KL, Phan AT, Veliça P, et al
Nature 2016 12;540(7632):236-241
Constitutive Glycolytic Metabolism Supports CD8+ T Cell Effector Memory Differentiation during Viral Infection.
Phan AT, Doedens AL, Palazon A, Tyrakis PA, Cheung KP, Johnson RS, et al
Immunity 2016 11;45(5):1024-1037