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Research Interests
- Airway nerves
- Acute and chronic airway inflammation
- Airway remodeling and histopathology
Past Research
In the lower airways, airway smooth muscle, vasculature, and glands are under constant control by the parasympathetic nervous system. By controlling the activity of these cell types, parasympathetic nerves play an important role in regulating air flow to the lungs. For over 50 years, we’ve known that increased parasympathetic nerve activity contributes to reversible airway hyperactivity associated with certain pulmonary diseases such as bronchial asthma and emphysema but the cellular mechanism for abnormal parasympathetic tone is still poorly understood. Most research has concentrated on airway smooth muscle and prejunctional release of acetylcholine with relatively few studies focused on the parasympathetic ganglionic neurons "upstream" from the nerve-muscle junction. Due to their pivotal role in regulation of autonomic tone, our past research involved developing a combination of techniques to study how parasympathetic ganglionic neurons function.
Using these techniques, we were able to determine the effects of immediate hypersensitivity reactions on membrane characteristics of bronchial† parasympathetic ganglia neurons and identify several mediator and neurotransmitter receptors associated with regulation of neuronal activity.†† We also spent considerable amount of time to development techniques for anatomical and functional analysis of human bronchial parasympathetic ganglia neurons and analysis of these cells is currently being used for a number of different studies.
Current Research
Airway Remodeling and Airway Nerves. In chronic allergy and asthma, the airways are remodeled with increased growth or number of infiltrating cells, fibroblasts, smooth muscle, sensory nerves, and glands, all of these are potential sources of neurotrophins and all are in contact with parasympathetic nerves. Neurotrophins are growth factors that are usually associated with development of the peripheral nervous system but recently we have shown that adult neurons continue to express neurotrophin receptors and activation of these receptors can affect neuronal excitability and morphology. Our research centers on the hypothesis that the neurotrophins serve as an important neuro-modulatory autacoids that can regulate the physiology and anatomy and, consequently, the function of adult parasympathetic neurons. Results from these studies will shed new light on the complex pathophysiology of airway diseases such as asthma and COPD and may ultimately determine new therapeutic treatments for these complex diseases.
Current research in our labs addresses how neurotrophins, especially nerve growth factor (NGF), are involved in dysregulation of parasympathetic nerves at the level of the ganglionic neurons in mice and humans. For example, the neurotrophin, NGF, is increased in asthmatic airways and acutely affects synaptic transmission in airway parasympathetic ganglia: One effect is an increase the amplitude of the synaptic potential to action potential threshold, thus decreasing integration (filtering) by the neurons. In our studies, we will directly address the hypothesis that NGF affects nicotinic receptor channels and electrophysiological properties of human and mouse ganglionic neurons. We will also address hypotheses pertaining to the mechanisms by which NGF modulates parasympathetic neuronal excitability via alteration of potassium currents underlying action potential afterhyperpolarization.
We also plan to address the hypothesis that chronic NGF exposure changes neuroanatomical features of mouse and human bronchial ganglionic neurons. We will determine how the effect of NGF on dendritic growth ultimately affects synaptic efficacy. We will also address the hypothesis that neurotrophins regulate the cholinergic and non-adrenergic non-cholinergic (NANC) neurotransmitter phenotypes of mouse and human parasympathetic neurons. We will also determine how neurotrophin-induced changes in neurotransmitter phenotype alters functional (smooth muscle) responses to nerve stimulation.
Future studies
The subunit composition of nicotinic acetylcholine receptors of airway ganglia neurons will be studied using antibodies, which recognize different alpha subunits and, specifically, will be used to identify these subunits with immunohistochemistry and by blocking acetylcholine-induced membrane currents. RNAi, introduced by adeno-associated virus, directed at receptor subunits, as well as single cell RT-PCR of identified receptors, are planned. Transgenic manipulation of neurotrophin and neurotrophin receptors are also planned.
Bayview Histology Core
In addition to our own basic research program, we provide histological procedures for basic research investigators at the Johns Hopkins Bayview Campus. During the past 20 years, a comprehensive range of histological expertise and methodologies were developed for our own research as well as for other investigators’ grants, program projects, and industry-related studies (see Dr. Myers’s Biosketch). This service includes all aspects of tissue fixation, processing, embedding and sectioning techniques (frozen, paraffin, plastic), and staining (routine differential stains as well as special stains to highlight specific cells or tissue components). Dr. Myers also provides expertise with immunohistochemical staining using brightfield (peroxidase and alkaline phosphatase) and double and triple immunofluorescence histochemistry. In situ hybridization is also available to identify mRNA in tissue samples. Thick (100µm to 4mm) Vibratome sectioning of fresh or fixed specimens can also be performed in this lab. Dr. Myers provides expertise for histological techniques that are sensitive to different methods of fixing, freezing or staining of different tissues and/or tissue targets (e.g. GFP, antigen retrieval). The Core also provides training and supervision of laboratory personnel who may then use the histology lab facilities (embedding, sectioning, staining, microscopy, imaging) on a fee-for-use basis, allowing investigators to perform their own tissue preparation and staining on their own schedule and to their own specifications. This Histology Core is supported entirely by internal and external grant funding, and fee-for-service income from investigators.
Laboratory
Allen C. Myers, Ph.D. Associate Professor of Medicine - senior laboratory investigator; Director, Bayview Histology Core
Holly K. Rohde - Senior Laboratory Technician
Positions available
Post-doctoral research fellowships are available:
1. Electrophysiological (patch and intracellular recording) and functional studies of airway parasympathetic innervation. Tissue culture experience is also necessary.
2. Anatomical (basic pathology, immunohistology) and biochemical (ELISA, immunoblotting, PCR) studies on the effects of chronic inflammation and airway remodeling.
Pre-doctoral positions leading to Ph.D degree are also available.
For information, contact Dr. Myers directly at amyers@jhmi.edu
Last Updated: 2/15/08
