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Department of Anesthesiology/Critical Care Medicine
The Johns Hopkins University School of Medicine
720 Rutland Avenue, Ross 361
Baltimore, MD 21205
Phone: (410) 614-1810 or (443) 287-3577
Fax: (410) 614-7711
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, including pulmonary hypertension, ciliary motility, development, and transition of the fetal pulmonary circulation. 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 FIZZ/resistin/RELMbeta family of proteins, which have adipokine and insulin resistance properties, suggesting that HIMF may mediate vascular pathology associated with obesity and metabolic syndrome. Much work is still required to clarify the exact role of HIMF, but it could be a key player in inflammatory lung diseases such as pulmonary hypertension and asthma.
Dr. Johns also has an interest in health policy. He is 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. 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, health information technology, and the science and politics of biogeneric drugs.
Dr. Johns has trained more than 30 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 over 20 years.
Current Laboratory Members/Key Associates
John Skinner, BS
Chunling Fan, PhD
Kazuyo Yamaji-Kegan, PhD
Michele Schaefer, PhD
Jose Gomez-Arroyo, PhD
Christy Gray, MD
Xia Fang, PhD
Katrien Van Raemdonck, PhD
Selected Publications (from >160)
- Fang M. Tao YX, He F, Zhang M, Levine CF, Mao P, Tao, F, Chou CL, Sadegh-Nasseri S, Johns RA. Synaptic PDZ domain-mediated protein interactions are disrupted by inhalational anesthetics. J Biol Chem 278:36669–75, 2003.
- Teng X, Li D, Champion HC, Johns RA. FIZZ1/RELMalpha, a novel hypoxia-induced mitogenic factor in lung with vasoconstrictive and angiogenic properties. Circ Res 92:1065–7, 2003.
- Tao F, Skinner J, Su Q, Johns RA. New role for spinal Stargazin in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated pain sensitization after inflammation. J Neurosci Res 84:867–73, 2006.
- Su Q, Zhou Y, Johns, RA. Bruton’s tyrosine kinase (BTK) is a binding partner for hypoxia induced mitogenic factor (HIMF/FIZZ1) and mediates myeloid cell chemotaxis. FASEB J 21:1376–82, 2007.
- Tao F, Johns RA. Effect of disrupting N-methyl-d-aspartate receptor/postsynaptic density protein-95 interactions on the threshold for halothane anesthesia in mice. Anesthesiology 108:882–887, 2008.
- Tao F, Su Q, Johns RA. Cell-permeable peptide Tat-PSD-95 PDZ2 inhibits chronic inflammatory pain behaviors in mice. Mol Ther 16:1776–1782, 2008.
- Sato Y, Tao YX, Su Q, Johns RA. PSD-93 mediates tyrosine-phosphorylation of the N-methyl-D-aspartate receptors. Neuroscience 153:700–708, 2008.
- Mao P, Tao Y-X, Fukaya M, Tao F, Li D, Watanabe M, Johns RA. Cloning and characterization of E-dlg, a novel splice variant of mouse homologue of the Drosophila discs large tumor suppressor binds preferentially to SAP102. IUBMB Life 60:684–692, 2008.
- Liaw WJ, Zhu XG, Yaster M, Johns RA, Gauda EB, Tao YX. Distinct expression of synaptic NR2A and NR2B in the central nervous system and impaired morphine tolerance and physical dependence in mice deficient in postsynaptic density-93 protein. Mol Pain 4:45, 2008.
- Fan C, Su Q, Li Y, Angelini DJ, Guggino WB, Johns RA. Hypoxia-induced mitogenic factor/FIZZ1 induces intracellular calcium release through the PLC-IP3 pathway. Am J Physiol Lung Cell Mol Physiol 297:L263–L270, 2009.
- Angelini DJ, Su Q, Yamaji-Kegan K, Fan F, Teng X, Hassoun PM, Yang SC, Champion HC, Tuder RM, Johns RA. Resistin-like molecule beta in scleroderma-associated pulmonary hypertension. Am J Respir Cell Mol Biol 41:553–61, 2009.
- Angelini DJ, Su Q, Yamaji-Kegan K, Fan C, Skinner JT, Champion HC, Crow MT, Johns RA. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMalpha) induces the vascular and hemodynamic changes of pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 296:L582–L593, 2009.
- Johns RA, Gao L, Rafaels NM, Grant AV, Stockton-Porter ML, Watson HR, Beaty TH, Barnes KC. Polymorphisms in resistin and resistin-like beta predict bronchial hyperreactivity in human asthma. Proc Am Thorac Soc 6:329, 2009.
- Yamaji-Kegan K, Su Q, Angelini DJ, Johns RA. IL-4 is proangiogenic in the lung under hypoxic conditions. J Immunol 182:5469–5476, 2009.
- Johns RA, Yamaji-Kegan K. Unveiling cell phenotypes in lung vascular remodeling. Am J Physiol Lung Cell Mol Physiol 297:L1056–L1058, 2009.
- Johns RA. TH2 inflammation, hypoxia-induced mitogenic factor/FIZZ1, and pulmonary hypertension and vascular remodeling in schistosomiasis. Am J Respir Crit Care Med 81:203–5, 2010.
- Tao F, Johns RA. Tat-mediated peptide intervention in analgesia and anesthesia. Drug Dev Res (in press).