Dr. Johns 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.
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 U.S. 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.
He 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.
- Tao F, Johns RA. “Tat-mediated peptide intervention in analgesia and anesthesia.” Drug Dev Res. 2010 Apr 1;71(2):99-105.
- Johns RA. “TH2 inflammation, hypoxia-induced mitogenic factor/FIZZ1, and pulmonary hypertension and vascular remodeling in schistosomiasis.” Am J Respir Crit Care Med. 2010 Feb 1;181(3):203-5.
- Johns RA, Yamaji-Kegan K. “Unveiling cell phenotypes in lung vascular remodeling.” Am J Physiol Lung Cell Mol Physiol 2009 Dec; 297(6):L1056-8.
- 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 2009. 6:329.
- Yamaji-Kegan K, Su Q, Angelini DJ, Johns RA. “IL-4 is proangiogenic in the lung under hypoxic conditions.” J Immunol 2009 May 1;182(9):5469-76.
Dr. Johns and his team are currently 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. The team’s 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, and their ability 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 the 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. 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. Roger Johns' Lab