Douglas A. Bayliss, Ph.D., PI
Joseph & Frances Larner Chair and Professor of Pharmacology
Professor of Anesthesiology
Email: bayliss at virginia dot edu
Serapio M Baca, Ph.D.
Senior Research Scientist
Email: serapio.baca at virginia.edu
My research focuses on understanding the relationship, under various conditions, between respiratory centers in the brainstem that are chemosensitive (e.g., CO2 and pH) and those that are involved in driving inspiration and expiration. To understand these relationships requires a number of techniques including whole cell patch-clamp, nerve recordings, and optical imaging of populations of cells—neurons and glia—in reduced preparations. My approaches are complimented by a number of molecular approaches in the Bayliss lab that aim to uniquely identify the molecular components of the chemosensors and to identify cell-specific markers to better delineate the relevant cell networks present in the Retrotrapezoid nucleus (RTN) and other identified respiratory centers.
Email: ecg4sd at virginia dot edu
I study the role of the proton-sensing G protein coupled receptor GPR4 in the regulation of central chemosensitivity in the retrotrapezoid nucleus. This receptor is thought to sense the pH changes in CSF which occur due to CO2 accumulation in the blood and subsequently modulate the activity of RTN neurons to induce altered respiration. I am using CRISPR/Cas9 genome editing to introduce pH-desensitizing mutations in mouse GPR4 and studying physiological changes induced in the whole animal or at the cellular level using plethysmography, immunocytochemistry, in situ hybridization, and/or patch clamp electrophysiology. I am also interested in studying the roles of metabotropic versus ionotropic signaling in regulation of neurotransmitter and neuromodulator release. We are using the RTN as a model system. It expresses both the “fast” transmitter glutamate as well as multiple neuropeptides which activate slower peptidergic signals. Additionally, it can be activated by protons in both ionotropic (via TASK2) and metabotropic (via GPR4) mechanisms. These characteristics make it an ideal system to study the regulation of transmitter release during different behaviors or activation contexts. My work is supported by F31 HL154660.
Keyong Li, Ph.D.
Email: kl4jd at virginia dot edu
I am interested in how ion channels contribute to the activity of brain cells and how that modifies the relevant behaviors in animal models, which may provide potential targets for the future treatments of channelopathies. My current studies focus on Retrotrapezoid Nucleus (RTN) neurons that sense CO2/H+ and control breathing. My recent work shows that TRPM4, a calcium-activated cationic channel, along with L-type calcium channels and various potassium channels (Kv and M channels), mediates a large subthreshold membrane potential oscillation that drives RTN neuron activity and breathing in mice (Cell Reports: 108714, 2021). I am currently investigating: ① the contribution of astrocytes in RTN to CO2-induced breathing in mice; and ② an RTN neuronal potassium channel that may be downstream of GPR4, which acts together with TASK-2 channels to sense CO2/H+. I use multiple tools for these studies, including patch clamp electrophysiology, qPCR, molecular histochemistry, imaging, viral-mediated gene expression injection and plethysmography in genetic mouse models.
Visiting Master's Student
Email: pwo3gc at virginia dot edu
I am currently looking at the differential ion permeability of Pannexin 1 channels. My research utilizes proteoliposome-based assay systems with purified channels to limit variables associated with cell-based experiments. My broader interests are focused on gap junctions, ephaptic coupling and in general computational neuroscience, especially different ways of impacting information processing in neural cells.
Yingtang Shi, Ph.D.
Assistant Professor of Research
Email: ys6c at virginia dot edu
I am interested in understanding the cellular and molecular mechanisms controlling the retrotrapezoid nucleus (RTN), a key brainstem chemoreceptor region that controls breathing. In my earlier work, I focused on identifying ion channels and receptors that contribute to regulating the firing activity and CO2/pH sensitivity of RTN neurons and CO2-regulated breathing (e.g., NALCN, TASK-2, GPR4). Later, I used single cell RNA-seq to characterize the expression profile for RTN neurons. This led directly to the discovery of Neuromedin B as a highly specific marker for RTN neurons. More recently, I found a striking birth-related upregulation of the peptide PACAP in mouse RTN neurons, and demonstrated that this neuropeptide and its related circuit stimulates breathing and protects neonatal mice from breathing disturbances. I am currently characterizing the roles of other neuropeptides and transcription factors in regulating RTN neuronal activity and their relevance to central respiratory diseases.