Dr. Roger Johns is a professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine. He is a world-renowned NIH-funded expert in both pulmonary hypertension as well as the neurosciences underlying the molecular mechanisms and actions of anesthesia and pain.
Dr. Roger Johns, a clinician-scientist who specializes in cardio-thoracic anesthesia, has a multitude of interests and is equally enthusiastic about each. He began his scientific career in the race to discover the identity of “Endothelium-Derived Relaxing Factor” or EDRF, which proved to be nitric oxide. This small, unassuming molecule (NO) has led him in a pursuit of the mechanisms underlying anesthesia, analgesia, pain, and lung vascular biology. Discoveries include the regulation of NO production by high and low oxygen concentrations and NO’s role in lung biology and cardiac failure including pulmonary hypertension, ciliary motility, development, and transition of the fetal pulmonary circulation and inflammation based pathologic remodeling of the lung vasculature and heart. Dr. Johns and his group discovered the role of the NO pathway in mechanisms of anesthesia and have published important work implicating this pathway in the mechanism of plasticity associated with chronic inflammatory and neuropathic pain.
In one of Dr. Johns’ current projects, he and his team are investigating the molecular mechanisms that underlie the onset and maintenance of chronic pain, particularly neuropathic pain. This research has helped to elucidate a vast network of molecules at neuronal synapses, particularly the post-synaptic density (PSD), that are critical for pain signal propagation. Within the PSD, Dr. Johns’ focus is on small molecular scaffolding proteins, such as PSD-95 and PSD-93, that help to regulate trafficking of receptors (e.g., NMDA, AMPA). Importantly, these scaffolding proteins link these receptors to their downstream signaling pathways that include enzymes such as NO synthase, guanylyl cyclase, and protein kinase G. This work includes the development of new analgesics to interfere with the PSD protein interactions in the hopes of providing relief for those who suffer from debilitating chronic pain.
Another of Dr. Johns’ interests is in the mechanism of inhalational anesthetics, such as the commonly used sevoflurane. Although anesthetics have been used for surgery for at least 150 years, surprisingly, their mechanism of action is not understood. This part of his lab group is focused on the ability of these anesthetics to specifically disrupt critical protein-protein interactions that mediate excitatory neurotransmission and contribute to the anesthetic state.
Recently, Dr. Johns and his team identified a gene that was highly upregulated in a hypoxia-induced model of pulmonary hypertension and named it hypoxia-induced mitogenic factor (HIMF). They found that the HIMF protein is upregulated by hypoxia and by TH2 stimulation and that it is expressed in the remodeling pulmonary vessels. They also showed that recombinant HIMF has mitogenic, angiogenic, vasoconstricting, and chemokine-like properties in lung. They have now proven a role for HIMF as a pleiotropic cytokine that mediates the vascular remodeling and induced hemodynamic changes of hypoxia-induced pulmonary hypertension. HIMF is also upregulated in some human forms of pulmonary hypertension and asthma. Large-scale human genomic and gene polymorphism studies are underway. HIMF is a member of the Resistin-like family of proteins, which have adipokine and insulin resistance and pro-inflammatory properties, suggesting that HIMF may mediate vascular pathology associated with obesity and metabolic syndrome. The Johns lab is actively involved in defining the detailed mechanisms of how HIMF and the Resistin-like proteins cause the pro-inflammatory remodeling of the lung vasculature and heart in cardiopulmonary disease and the lung inflammation in COVID-19. The lab has most recently defined HIMF/human Resistin as the critical regulator of the priming and activation of the NLRP3 inflammasome, a critical mediator of inflammatory disease and remodeling in pulmonary hypertension, heart failure, atherosclerosis and neuroinflammation.
Dr. Johns also has an interest in health policy. He was a Robert Wood Johnson Health Policy Fellow of the Institute of Medicine, National Academy of Sciences (2005–2008) and served as a health and science policy advisor in the US Senate 109th Congress. Since 2010 he has been an elected member of the National Academy of Medicine of the National Academies. Current policy research interests and experience include approaches to coverage decisions for new technologies and pharmaceuticals, the impact of an aging population on health systems funded through pay-as-you-go social insurance, elder abuse, the factors influencing diffusion of new health technology, and the science and politics of biogeneric drugs.
Dr. Johns has trained more than 60 students and fellows now in independent academic and industrial research positions around the world. He has been continuously funded by the National Institutes of Health for 37 years, generating over $100,000,000 in NIH funding.
Current Laboratory Members/Key Associates
John Skinner, BS
Lior Levy, BS
Qing Lin, MD, PhD
Swati Agarwal, PhD
Udeshika Kariyawasam, PhD
Christy Gray, MD
Selected Publications (from >220)
- Angelini DJ, Su Q, Yamaji-Kegan K, Fan C, Skinner JT, Poloczek A, El-Haddad H, Cheadle C, Johns RA. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMa) in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling. Respir Res. doi: 10.1186/1465-9921-14-1, 2013 PMID: 23289668.
- Tao F, Chen Q, Sato Y, Skinner J, Tang P, Johns RA: Inhalational Anesthetics Disrupt Postsynaptic Density Protein-95, Drosophila Disc Large Tumor Suppressor, and Zonula Occludens-1 Domain Protein Interactions Critical to Action of Several Excitatory Receptor Channels Related to Anesthesia. 2015 122:776-86 PMID: 25654436
- 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. 36(1):134-44. PMID: 26586659
- Li C, Schaefer M, Gray C, Yang Y, Furmanski O, Liu S, Worley P, Mintz CD, Tao F, Johns RA. Sensitivity to isoflurane anesthesia increases in autism spectrum disorder Shank3+/∆cmutant mouse model. Neurotoxicol Teratol. 2016 Nov 14. pii: S0892-0362(16)30133-7. doi: 10.1016/j.ntt.2016.11.002. PMID: 27856360
- Precision Medicine Workshop Group [Newman JH…..Johns RA…..Xiao L]: Enhancing Insights Into Pulmonary Vascular Diseases Through a Precision Medicine Approach. American J Resp Crit Care Med 195:1661-1670 2017
- Eunchai Kang1,2*, Danye Jiang3*, Yun Kyoung Ryu3*, Sanghee Lim3, Minhye Kwak3, Christy D. Gray3, Michael Xu3, Michele Schaefer3, Roger A Johns3, Honjung Song1,2,4, C. David Mintz3 Isoflurane Causes Cognitive Deficits and Disruption of Brain Circuit Development via Activation of the mTOR Pathway in a Mouse Model of Pediatric Anesthetic Neurotoxicity. PLoS Biol 15(7):e2001246., 2017 PMID: 28683067
- Schaefer ML, Wand M, Perez PJ, Coca Peralta W, Xu J, Johns RA: Nitric Oxide donor prevents neonatal isoflurane-induced impairments in synaptic plasticity and memory. Anesthesiology 2019 130:247-262 PMID: 30601214
- Lin Q, Fan C, Skinner JT, Hunter EN, MacDonald AA, Illei PB, Yamaji-Kegan K, Johns RA. HIMF Licenses Macrophages for DAMP Activation to Initiate Pulmonary Vascular Remodeling. J Immunology, 2019 203:2862-2871 PMID: 31611261
- Lin Q, Fan C, Gomez-Arroyo J, Meuchel LW, Skinner JT, Fang X, Shu Z, Yamaji-Kegan, Johns RA. 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. Arterio Thromb Vasc Biol, 2019 39(12):2505-2519 PMID: 31597444
- Ren X, Johns RA, Gao WD. EXPRESS: Right heart in pulmonary hypertension: From adaptation to heart failure. Pulm Circ 2019 Apr 3;9(3):204589401984561.doi: 10.1177/2045894019845611. PMID39042134
- Lin Q, Johns RA. Resistin family proteins in pulmonary diseases. Am J Physiol, 2020 319: L422-434. PMID: 32692581
- Lin Q, Price SA, Skinner JH, Hu B, Fan C, Yamaji-Kegan K, Johns RA. Systematic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody. PLoS One. 2020, 15(7) :e0235546 PMID: 3260943
- Schaefer ML, Perez PJ, Wang M, Gray C, Krall C, Sun X, Hunter E, Skinner J, Johns RA. Neonatal isoflurane anesthesia or disruption of postsynaptic denity-95 protein interactions change dendritic spine densities and cognitive function. Anesthesiology 2020, Oct 1;133(4)812-823 PMID: 32773681
- Bracamonte-Baran W, Gilotra TW, Rodriguez K, Talor M, Oh BC, Griffin J, Wittstein I, Sharma K, Skinner J, Johns R, Russell S, Anders R, Zhu Q, Halushka M, Branadacher G, Cihakova D: Endothelial stromal PD-L1 modulates CD8+ T cell infiltration after heart transplantation. Circ Heart Fail. 2021 Oct;14(10):e007982. doi: 10.1161/CIRCHEARTFAILURE.120.007982. Epub 2021 Sep 24.PMID: 34555935
- Won T, Wood MK, Hughes DM, Talor MV, Ma Z, Schneider J, Skinner JT, Asady B, Goerlich E, Halushka MK, Hays AG, Kim DH, Parikh CR, Rosenberg AZ, Coppens I, Johns RA, Gilotra NA, Hooper JE, Pekosz A, Čiháková D. Endothelial thrombomodulin downregulation caused by hypoxia contributes to severe infiltration and coagulopathy in COVID-19 patient lungs. 2022 Jan;75:103812. doi: 10.1016/j.ebiom.2022.103812. Epub 2022 Jan 13.PMID: 35033854
- Nakahara M, Ito H, Skinner JT, Lin Q, Tamosiuniene R, Nicolls MR, Keegan AD, Johns RA, Yamaji-Kegan K.
The inflammatory role of dysregulated IRS2 in pulmonary vascular remodeling under hypoxic conditions. Am J Physiol Lung Cell Mol Physiol. 2021 Aug 1;321(2):L416-L428. doi: 10.1152/ajplung.00068.2020. Epub 2021 Jun 30
- Tao BD, Kumar S, Lin Q, Gomez-Arroyo J, Skinner JA, Gao W, Johns RA: Resistin-like Molecule α Dysregulates Cardiac Bioenergetics in Neonatal Rat Cardiomyocytes. Frontiers in Cardiovascular Medicine. Front Cardiovasc Med. 2021 Apr 26;8:574708. doi: 10.3389/fcvm.2021.574708. eCollection 2021.PMID: 33981729
- Agarwal S, Schaefer ML, Krall C, Johns RA.
Isoflurane Disrupts Postsynaptic Density-95 Protein Interactions Causing Neuronal Synapse Loss and Cognitive Impairment in Juvenile Mice Via Canonical Nitric Oxide Mediated Protein Kinase-G Signaling. 2022 May 3. doi: 10.1097/ALN.0000000000004264..PMID: 35504002
- Lin Q, Kumar, S, Kariyawasam U, Yang Xiaomei, Yang Wei, Skinner JT, Gao WD, Johns RA: Human Resistin Induces Cardiac Dysfunction in Pulmonary Hypertension. J Am Heart Assoc. 2023 e027621. DOI 10.1161/JAHA.122.027621