Dr. Hongzhen Hu
The University of Texas Health Science Center at Houston
Department of Integrative Biology & Pharmacology
- Mechanisms of neurogenic inflammation and pain
Sensory neurons inform the central nervous system of the thermal, mechanical and chemical conditions of the skin and internal organs. Noxious conditions such as extreme temperatures, tissue damage, or noxious chemicals are detected by a subpopulation of sensory neurons, the so-called nociceptors, which upon excitation signal pain and induce neurogenic inflammation. An in-depth molecular understanding of how these neurons receive and relay information from diverse stimuli and convey different perceptual modalities is still lacking. Over the past few years molecules involved in the direct gating of sensory modalities have been identified. These proteins belong to the transient receptor potential (TRP) family of non-selective cation channels. Several members of the TRP family are involved in the detection of temperature changes, thus acting as the molecular thermometers of our body. They have been referred to as “ThermoTRPs”. In addition to sensing temperature, they are also polymodal nociceptors integrating painful stimuli such as noxious temperatures and chemical insults. For example, TRPV1 channel is involved in thermal hyperalgesia and pain induced by capsaicin and acid. TRPA1 is activated by many noxious environmental stimuli including oxidants and electrophilic agents.
Our laboratory is interested in molecular dissection of sensory neuron function in temperature sensation, pain and inflammation and understanding how sensory neurons become sensitized during tissue injury and inflammation. A major emphasis in the laboratory is to understand the molecular mechanisms underlying thermal and chemical activation of temperature-sensitive ion channels, especially the mechanisms associated with initiation, transduction and gating of these channels by thermal energy. Another important direction in our laboratory is the molecular basis of visceral hypersensitivity which is a hallmark of gastrointestinal diseases such as irritable bowel syndrome (IBS). We aim to study the plasticity of TRP channels in the development of IBS and neuro-immune interactions between sensory neurons and immune cells. We are also interested in the sensitizing mechanisms of stretch-sensitive molecules that sense and transduce visceral mechanical stimuli in the gut during inflammation.
We use electrophysiological and pharmacological approaches in combination to molecular biology, mouse genetics and mouse behavioral methods to gain fundamental insights into the roles of ion channels that serve as sensors for temperature and noxious stimuli in sensory neurons under physiological and pathophysiological conditions
Hu H, Bandell M, Petrus M, Zhu MX, Patapoutian A (2009). Zinc irritation is mediated by direct activation of TRPA1. Nat Chem Biol 5: 183-190.
Hu H, Grandl J, Bandell M, Petrus M, and Patapoutian A (2009).Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4. PNAS 106: 1626-1631.
Grandl J, Hu H, Bandell M, Bursulaya B, Schmidt M, Petrus M, Patapoutian A (2008). Pore region of TRPV3 ion channel is specifically required for heat activation. Nat Neurosci 11: 1007 - 1013.
Kindt KS, Viswanath V, Macpherson L, Quast K, Hu H, Patapoutian A, Schafer WR (2007). Caenorhabditis elegans TRPA-1 functions in mechanosensation. Nat Neurosci 10: 568-577.