Department of Anesthesiology and Critical Care Medicine
The Johns Hopkins University School of Medicine
720 Rutland Ave, Ross 359
Baltimore, MD 21205
Dr. Feng Tao’s research interests focus on the central mechanisms of analgesia and anesthesia. The goal of his work is to understand how the effects of analgesics and anesthetics on their neuronal targets are regulated. Specifically, he is interested in the regulation of central sensitization mediated by glutamate receptors and their interacting proteins. It is through these pathways that pain sensation is modulated in the central nervous system, especially at the spinal cord level. Dr. Tao uses a DNA antisense technique to knock down PSD-95/SAP90, a molecular scaffolding protein that has been identified to attach NMDA receptors to internal signaling molecules at neuronal synapses. He revealed for the first time that the PSD-95/SAP90 antisense oligodeoxynucleotide dose-dependently attenuated nerve injury-induced mechanical and thermal hyperalgesia during both the development and maintenance phases of chronic neuropathic pain. He also found that PSD-95/SAP90 knockdown by the PSD-95/SAP90 antisense oligodeoxynucleotide reduced the minimum alveolar anesthetic concentration (MAC) of halothane. These studies provide novel insights into the mechanisms that underlie the chronic neuropathic pain state and clinical inhalational anesthetic application.
Dr. Tao has further investigated the role of PSD-95/SAP90 in chronic pain and anesthesia mechanisms by using peptide to disrupt NMDA receptor-PSD-95/SAP90 protein interactions. He constructed and purified an HIV Tat fusion peptide, “pTat-PSD-95 PDZ2,” which can be delivered intracellularly by the Tat protein transduction domain. GST pull-down and co-immunoprecipitation experiments have shown that this peptide dose-dependently inhibits the protein-protein interactions between NMDA receptors and PSD-95/SAP90. In vivo pharmacologic studies have demonstrated that intraperitoneal injection of the cell-permeant fusion peptide pTat-PSD-95 PDZ2 significantly diminishes complete Freund’s adjuvant-induced chronic inflammatory pain and reduces halothane MAC in mice. These results indicate that this fusion peptide can potentially be developed for the treatment of chronic pain and used as an adjuvant agent in clinical anesthesia.
As an extension of his pain research, Dr. Tao has begun a collaboration with Dr. John McDonald’s laboratory in the International Center for Spinal Cord Injury at Kennedy Krieger Institute to address the problems of central chronic pain after spinal cord injury using a unique stem cell approach. This research project has been funded by a Maryland Stem Cell Research Grant. In 2012, he developed a new line of research to investigate stress-induced pain transition after surgery. His research proposal was funded with a 5-year NIH R01 grant.