Chronic Pulmonary Diseases
My research also involves the study of redox-sensitive calcium signaling mediated by the calcium channel Transient Receptor Potential Melastatin-2 (TRPM2). TRPM2 is a unique channel that possesses an enzymatic domain fused to its calcium-permeable pore. The binding of ADPR to the enzymatic domain activates channel activity and induces intracellular calcium influx. Furthermore, TRPM2 can be activated by direct oxidation by hydrogen peroxide, as well as binding of intracellular calcium (iCa2+) to the Calmodulin-binding site at the N-terminus of the protein. These direct and indirect modes of activation make TRPM2 an efficient cellular redox sensor capable of regulating a variety of cellular processes, such as apoptosis, inflammation and motility.
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I have been investigating the role of TRPM2 in lung inflammation and damage using in vivo animal models of lung diseases of oxidative stress, such as chronic obstructive pulmonary disease (COPD)[Botta, D. et al. (2012) Am. J. Respir. Crit. Care Med. 185:A1305 (Abst.)], acute lung injury/acute respiratory distress syndrome (ALI/ARDS) [Botta, D. et al. (2014) J. Immunol. 192:120.13 (Abst.)], and interstitial pulmonary fibrosis (IPF) [Bauer, C.M.T., Botta, D. et al. (2013) Eur. Respir. J. 42:Suppl. 57, P3930 (Abst.)].
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Figure 2. Hyperattenuation in normal (A5) and fibrotic (B4) mouse lung tissue.