Roger Johns, M.D., Ph.D.
February 1, 2020
Department of Anesthesiology and Critical Care Medicine
Johns Hopkins University
We discovered hypoxia-induced mitogenic factor (HIMF) as an unknown gene in lung from a hypoxia model of pulmonary hypertension. This was subsequently found to be a member of the resistin-like family of chemokine growth factors. We have defined a critical role for HIMF (also called retnla and FIZZ1) and its human counterparts (Resistin and RELM-β) in rodent and human pulmonary hypertension, lung vascular remodeling, immune and mesenchymal stem cell recruitment to remodeling vasculature, vasculogenesis, and inflammation. We defined many of its signaling pathways leading to HIF1, VEGF, IL6, STAT3 and BTK activation, alternative macrophage (Th2) activation and mobilization of chemokine pathways related to lung inflammation, asthma, and pulmonary hypertension. We have found its human isoforms to be biomarkers for idiopathic and scleroderma-related pulmonary hypertension and have recently developed human therapeutic antibodies to treat pulmonary hypertension and cardiac hypertrophy.
More recently we have been examining the early immune activation mechanism of HIMF/hresistin in the vascular and cardiac remodeling associated with pulmonary hypertension. We are studying the molecular and cellular mechanism of TLR4, RAGE, and S100A11 proteins and related miRNA and HDAC mechanisms in mediating inflammation, cell migration, and remodeling by using rat models and cells as well as human cells, tissues, and serum and genetic markers.
Members of the laboratory:
Michele Schaefer, PhD
Qing Lin, MD, PhD
Christy Gray, MD, PhD
Swati Agarwal, PhD
Santosh Kumar, PhD
Caroline Krall BVM&S, MSc
Bin Hu, MD
John Skinner, BS (Lab Manager)
Elizabeth Hunter, BS
- Lin Q, Fan C, Skinner JT, Hunter EN, Macdonald AA, Illei PB, et al. RELMalpha Licenses Macrophages for Damage-Associated Molecular Pattern Activation to Instigate Pulmonary Vascular Remodeling. J Immunol. 2019 Dec 1;203(11):2862-2871. doi: 10.4049/jimmunol.1900535. PubMed PMID: 31611261. Featured in the 2020 January issue of the "Vascular Biology Publication Alerts".
- Lin Q, Fan C, Gomez-Arroyo J, Van Raemdonck K, Meuchel LW, Skinner JT, et al. HIMF (Hypoxia-Induced Mitogenic Factor) Signaling Mediates the HMGB1 (High Mobility Group Box 1)-Dependent Endothelial and Smooth Muscle Cell Cross Talk in Pulmonary Hypertension. Arterioscler Thromb Vasc Biol. 22019 Dec;39(12):2505-2519. doi: 10.1161/ATVBAHA.119.312907. PubMed PMID: 31597444. Chosen as the "Editor's Pick".
- Lin Q, Fan C, Skinner JT, Bejia D, Van Raemdonck K, Nakahara M, et al. Therapeutic effects of the generated antibodies targeting human resistin in pulmonary hypertension. ATS (American Thoracic Society) International Conference; May 23, 2018; San Diego, CA, USA: American Journal of Respiratory and Critical Care Medicine; 2018. p. A7398.
- Johns RA, Takimoto E, Meuchel LW, Elsaigh E, Zhang A, Heller NM, Semenza GL, Yamaji-Kegan K. Hypoxia-inducible factor 1α is a critical downstream mediator for hypoxia-induced mitogenic factor (FIZZ1/RELMα)-induced pulmonary hypertension. Arterio Thromb Vasc Biol 2016. 36:134-144. PMCID: PMC5518796
- Fan C, Meuchel LW, Su Q, Angelini DJ, Zhang A, Cheadle C, et al. Resistin-Like Molecule alpha in Allergen-Induced Pulmonary Vascular Remodeling. Am J Respir Cell Mol Biol. 2015;53(3):303-13. doi: 10.1165/rcmb.2014-0322OC. PubMed PMID: 25569618; PubMed Central PMCID: PMCPMC4566066.
- Yamaji-Kegan K, Takimoto E, Zhang A, Weiner NC, Meuchel LW, Berger AE, et al. Hypoxia-induced mitogenic factor (FIZZ1/RELMa) induces endothelial cell apoptosis and subsequent interleukin-4-dependent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2014;306(12):L1090-103. doi: 10.1152/ajplung.00279.2013. PubMed PMID: 24793164; PubMed Central PMCID: PMC4060011. Angelini DJ, Su Q, Yamaji-Kegan K, Fan C, Skinner JT, Poloczek A, et al. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMa) in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling. Respir Res. 2013;14:1. doi: 10.1186/1465-9921-14-1. PubMed PMID: 23289668; PubMed Central PMCID: PMC3547770.
“Innovation through hypothesis based science”