Baskaran "BASKI" Thyagarajan, M. Pharm, Ph.D.,
Associate Professor of Pharmaceutics and Neuroscience
Molecular Signaling Laboratory
The major goal of Baskilab is to understand the regulatory role of Transient Receptor Potential (TRP) ion channels in the pathophysiology of neurodegenerative, neuromuscular and metabolic diseases and Pain.
Mammalian superfamily of TRP channels represent six related subfamilies – TRPC (canonical), TRPV (vanilloid), TRPM (melastatin) TRPP (polycystin), TRPML (mucolipin) and TRPA1 (ankyrin). All TRP channels are putative six-transmembrane polypeptide subunits that assemble as tetramers to form cation-permeable pores. TRP proteins coassemble to generate cation sensitive channels with specific biophysical properties. TRP channel proteins are ubiquitously expressed and most have splice variants. Therefore, many cells have a number of TRP channel proteins. TRP channels are involved in the regulation of several cellular functions including fertilization, development, thermosensation, nociception, taste, vision, mechanosensation, and intra- and extracellular Ca2+ and Mg2+ homeostasis.
To expand our knowledge of synaptic diversity in the expression and interactions among TRP channel proteins, PIP2, neurotoxins and lipid microdomains, we aim to uncover the potential role of novel partners that orchestrate neuronal exoendocytic mechanisms. We employ electrophysiology, intracellular Ca2+ imaging, optogenetics, confocal microscopy, biochemical, cell and molecular biological techniques and in vivo animal models to evaluate the role of PIP2 and TRP channels in physiology and pathophysiology.
We use in vivo animal models to study the behavioral changes during the development and progression of degenerative diseases and use in vitro isolated nerve-muscle preparations, primary and cultured cell lines and unrestrained worms (C elegans) to investigate the complex mechanisms that are involved in the cause and regulation of degenerative diseases by TRP channels, PIP2, and lipid microdomains. This will help our long-term goal to uncover the potentials of TRP channels as therapeutic targets against pain and metabolic and degenerative diseases.