Professor Randall Johnson
Position: Professor
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PubMed journal articles - click here
Professor Randall Johnson is pleased to consider applications from prospective PhD students.
We work on how the body responds to hypoxia, or low levels of tissue oxygen. This is relevant to a number of diseases, including cancer, and the laboratory is interested in hypoxic response in disease as well as in normal physiology. The response to hypoxia acts in significant part through the Hypoxia Inducible Factor, or HIF. The actions of this transcription factor are evident in almost all forms of cancer, but HIF is also present in other disease states. Further, many aspects of normal physiological response include activation of HIF: HIF expression is seen in normal embryonic development, it is seen whenever wound healing or inflammation occur, and is essential for adjustment to high altitude or whenever the organism experiences a lower than normal level of oxygen. Cancer: our work has for many years focussed on how malignant cells and the tissues that surround and infiltrate them react to oxygen levels. The levels of oxygen found vary tremendously both from cancer to cancer, and within individual tumors. One of the key findings from our recent work has been that each cell type found within tumors utilizes the HIF response differently; the malignant cells, tumor-associated fibroblasts, myeloid cells, endothelial cells and lymphoid cells all have different spectra of response via HIF, and these differences impact how tumors grow, survive and, ultimately, metastasize. Inflammation, infection and immunity: We have investigated how T cells and macrophages utilize hypoxic response to allow immune response. We are actively investigating this in terms of models of infection, inflammation, and immunological response to cancer; and we are also asking how myeloid/lymphoid interactions are affected by the response to oxygenation. Physiology: a critical aspect of ventilatory control is the normative response of the carotid body and other tissues to the organisms overall oxygenation. This response in turn can affect various aspects of homeostasis, including pulmonary vascular tension and even systemic blood pressure. We have found that this control is highly related to the function of HIF and hypoxic response, in a way that is tightly controlled by complex interactions amongst tissue types.
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Palazon A, Goldrath AW, Nizet V, Johnson RS, (2014), HIF transcription factors, inflammation, and immunity, Immunity, 41(4):518-28 Lee YS, Kim JW, Osborne O, Oh da Y, Sasik R, Schenk S, Chen A, Chung H, Murphy A, Watkins SM, Quehenberger O, Johnson RS*, Olefsky JM* (*=Co-corresponding authors), (2014), Increased Adipocyte O2 Consumption Triggers HIF-1?, Causing Inflammation and Insulin Resistance in Obesity, Cell, 157:1339-1352 Cowburn AS, Takeda N, Boutin AT, Kim J, Sterling J, Nakasaki M, Southwood M, Goldrath AW, Jamora C, Nizet V, Chilvers E*, Johnson RS* (*=Co-corresponding authors), (2013), Differential regulation of systemic arterial pressure by the skin: role of HIF isoforms,Proceedings of the National Academy of Sciences, 110:17570-17575 Doedens AL, Phan AT, Stradner MH, Fujimoto JK, Nguyen JV, Yang E, Johnson RS, Goldrath AW, (2013), Hypoxia inducible factors enhance CD8+ T cell effector responses to persistent antigen, Nature Immunology, 14:1173-1182 Kim J, Evans C, Weidemann A, Takeda N, Lee YS, Stockmann C, Branco-Price C, Brandberg F, Leone G, Ostrowski MC, Johnson RS, (2012), Loss of Fibroblast HIF-1a accelerates tumorigenesis, Cancer Research, 72:3187-3195 Branco-Price C, Zhang N, Schnelle M, Evans C, Katschinski DM, Liao D, Ellies L, Johnson RS, (2012), Endothelial cell HIF-1a and HIF-2a differentially regulate metastatic success, Cancer Cell, 21:52-65 Doedens A, Stockmann C, Rubinstein M, Liao D, Zhang N, DeNardo D, Coussens LM, Karin M, Goldrath A, Johnson RS, (2010), Macrophage expression of HIF-1 suppresses T cell function and promotes tumor progression, Cancer Research, 70:7465-7475 Zhang N, Fu Z, Linke S, Chicher J, Gorman JJ, Poellinger L, Peet DJ, Powell F, Johnson RS, (2010), The asparaginyl hydroxylase FIH is an essential regulator of metabolism, Cell Metabolism, 11:364-378 Takeda N, O?Dea EL, Doedens A, Kim J-W, Weidemann A, Stockmann C, Asagiri M, Simon MC, Hoffmann A, Johnson RS, (2010),Differential activation and antagonistic function of HIF-a isoforms in macrophages are essential for NO homeostasis, Genes and Development, 24:491-501 Stockmann C, Kerdiles Y, Nomaksteinsky M, Weidemann A, Takeda N, Doedens A, Torres-Collado AX, Iruela-Arispe L, Nizet V, Johnson RS, (2010), Loss of myeloid cell-derived growth factor accelerates fibrosis, Proceedings of the National Academy of Sciences, 107:4329-4334 Nizet V, Johnson RS, (2009), Interdependence of hypoxic and innate immune responses, Nature Reviews Immunology, 9:609-617 Stockmann C, Doedens A, Weidemann A, Zhang N, Greenberg J, Cheresh D, Johnson RS, (2008), Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis, Nature, 456:814-818 Boutin A, Weidemann A, Fu Z, Mesropian L, Gradin K, Jamora C, Wiesener M, Eckardt K-U, Koch CJ, Ellies LG, Haddad G, Haase VH, Simon MC, Poellinger L, Powell FL, Johnson RS, (2008), Epidermal sensing of oxygen is essential for systemic hypoxic response, Cell, 133:223-234 Mason S, Ameln H, Duh R, McNulty WJ, Howlett RA, Olfert IM, Sundberg CJ, Poellinger L, Johnson RS, (2007), HIF-1? in endurance training: suppression of oxidative metabolism, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 293:R2059-206 Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S, Haase VH, Nizet V, Johnson RS, (2007), Regulation of iron homeostasis by the hypoxia inducible transcription factors (HIFs), Journal of Clinical Investigation, 117:1926-1932 Liao D, Corle C, Seagroves TN, Johnson RS, (2007), HIF-1? is a key regulator of metastasis in a transgenic model of cancer initiation and progression, Cancer Research, 67:563-572
