Asthma in Adults
Asthma is a complex disease driven by inflammation that is induced by allergens, pollutants and other triggers. The two main aspects of asthma are increased bronchoconstriction (requiring inhalers that produce bronchodilation) and airway remodeling, a largely irreversible process of increased airway thickening, mucus production and fibrosis. Dr. Prakash's laboratory is currently focused on examining novel mechanisms that contribute to both bronchoconstriction and remodeling in the hopes of targeting these mechanisms to control asthma. The major ongoing projects are:
Neurotrophins in asthma
Neurotrophins are growth factors that are well-known to influence the nervous system. However, over the past four years, the lab has discovered and characterized the role of neurotrophins in the lung. Using human lung tissues from people with asthma verses non-asthma and animal models of asthma, progress is being made in a few areas. Recent work in the lab shows that neurotrophins such as brain-derived neurotrophic factor (BDNF) potentiate the effects of inflammation on bronchoconstriction (via airway smooth muscle calcium and epithelial nitric oxide) and airway remodeling (via matrix metalloproteinases and extracellular matrix proteins such as collagen).
The lab is now developing strategies targeting BDNF in the airway to suppress several key aspects of asthma pathophysiology. Ongoing work is focused on the neurotrophin effects of extracellular matrix regulation, mitochondrial metabolism, and cell proliferation and migration.
Cigarette smoke exposure and asthma
Both smoking itself and secondhand smoke exposure are known risk factors for airway diseases. Researchers are examining changes in airway smooth muscle structure and function induced by cigarette smoke exposure using both human tissues and, in collaboration with the Division of Pulmonary and Critical Care Medicine, mouse models of smoke exposure. Novel signaling mechanisms activated by cigarette smoke are being identified as early targets to prevent the detrimental effects of cigarette smoke.
Sex steroids and asthma in women
Unlike in coronary artery disease, asthma is actually worse in women of childbearing age. Menarche, pregnancy and menopause as well as use of estrogen replacement tone therapy can influence the incidence and severity of symptoms. Researchers in the lab are currently exploring how estrogens and progesterone can influence airway diseases by modulating bronchoconstriction and airway remodeling in the context of asthma. Novel signaling pathways activated by estrogen and progesterone receptors are being identified to understand why female sex hormones may be detrimental in asthma. This process helps to explore the possibility of modulating estrogen function to treat asthma in women.