Diane Lipscombe
Lipscombe was named one of Fast Company’s most creative people in 2019 for her leadership at the Carney Institute,[3] by encouraging collaboration to spur development of innovative treatments.
By 2020, Lipscombe had authored 50 scientific articles characterizing the voltage-gated calcium ion channel family of genes and their protein products.
Voltage-gated calcium channels are found in cell membranes, they typically consist of several associated proteins encoded by separate genes.
She studies how the cellular process of alternative splicing generates multiple protein isoforms from single calcium channel genes.
In a collaboration with Robert Darnell, Lipscombe’s lab validated the role of Nova2, a neuronal-specific RNA-binding protein, in controlling tissue and developmental specific alternative splicing of CaV channels in neurons.
[13] They also found that Rbfox2, another RNA-binding protein, regulates alternative splicing during development of a cassette exon in Cacna1b, impacting CaV2.2 channel expression levels.
Over her career, Lipscombe established herself as an expert on how CaV channels participate in the nociceptive pathways and their possibilities as drug targets for treating chronic pain.
They showed that a rare CACNA1B mutation identified in a three-generation family with a myoclonus dystonia-like syndrome impacts single CaV2.2 channel activity by altering ion flow.
[16] In collaborations with colleagues at the Stanley Center for Psychiatric Research at Broad Institute, the Lipscombe Lab described the electrophysiological consequences of rare missense variations in CACNA1.
They also showed that rare de novo variants of CACNA1I linked to schizophrenia impacts membrane trafficking of CaV3.3 with expected alterations in burst firing in thalamic relay neurons.
[18] Through a collaboration with Brown University researcher Christopher Moore and other institutions, the Lipscombe Lab is also developing new genetically encoded tools to monitor calcium signals in cells using bioluminescent proteins.
She was elected to the American Academy of Arts and Sciences, served as President of the Society for Neuroscience in 2019[20] and was named Fast Company Top 100 most creative people of 2019.
