Diane Lipscombe

Lipscombe has been recognized for her teaching, mentoring and scholarship. She was elected to the American Academy of Arts and Sciences in 2020, and she was elected a fellow of the American Association for the Advancement of Science in 2013.

Lipscombe’s research focuses on expression, regulation and function of voltage-gated calcium ion channels. By 2020, Lipscombe had authored 50 scientific articles characterizing the voltage-gated calcium ion channel family of genes and their protein products. The topics of Lipscombe’s articles range from individual channel biophysics to the regulation of specific channel isoforms by RNA- and DNA-binding proteins, and the contribution of tissue specific channel isoforms to disease states such as chronic pain and psychiatric disorders.

In addition to characterizing CaV channel behavior, Lipscombe’s team is also dedicated to investigating how regulation of calcium channel genes and transcripts leads to cell-specific expression patterns of individual CaV channel isoforms. The lab has confirmed multiple mechanisms that control exon selection during the processing of calcium ion channels pre-mRNAs. 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. 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. In 2020, the lab discovered a novel role of CTCF binding to DNA in nociceptor-specific splicing of Cacna1b exons, and they showed aberrant DNA methylation, disrupted CTCF binding and altered splicing of Cacna1b in nociceptors in neuropathic pain. These experiments informed the field’s understanding of the different splicing factors, and epigenetic regulation, that are critical for controlling cell-specific exon inclusion/exclusion during alternative splicing of calcium ion channel pre mRNAs across the nervous system.

Lipscombe was named one of Fast Company’s most creative people in 2019 for her leadership at the Carney Institute, by encouraging collaboration to spur development of innovative treatments. Her lab studies the expression, regulation, and function of voltage-gated calcium channels in different regions of the nervous system. Lipscombe is interested in the role of voltage-gated calcium channels in chronic pain and neurodegenerative and psychiatric disorders. Since 1992, she has worked closely with undergraduate and graduate students at Brown, as well as postdoctoral trainees.

Lipscombe has received multiple awards throughout her career in neuroscience. She was elected to the American Academy of Arts and Sciences, served as President of the Society for Neuroscience in 2019 and was named Fast Company Top 100 most creative people of 2019.

At postsynaptic sites, CaV1 channels (L-type currents) can couple membrane depolarization to activity-dependent gene expression. In 2001, Lipscombe’s lab demonstrated novel features of the neuronal CaV1.3 channels, with important implications for their contribution to control of neuronal function. In 2001, CaV1.2 channels were extensively studied, so the discovery that CaV1.3 channels open at membrane voltages significantly more hyperpolarized than CaV1.2 channels was unexpected and important for understanding their different physiological roles. The unique characteristics of CaV1.3 channels were not recognized previously because others had recorded the activity of cloned CaV1.3 channels using high concentrations of divalent cations to achieve larger currents. These non-physiological recording conditions obscured the true low threshold activation characteristics of CaV1.3 channels; a feature that has turned out to be critically important for their role in pacemaking and for supporting calcium entry into neurons at membrane voltages close to the resting membrane potential. Lipscombe’s lab provided calcium ion channel clones including CaV1.3 to many groups facilitated various exciting studies. CaV1.3 is now implicated in Parkinson Disease, and drives pacemaking in several excitable cells.

Lipscombe joined the Department of Neuroscience at Brown University in 1992, where she is currently the Thomas J. Watson Sr. Professor of Science. She has also taught courses at the Marine Biological Laboratory in Woods Hole, MA. Lipscombe serves as the director of Brown’s Robert J. and Nancy D. Carney Institute for Brain Science.

A first-generation university student, Lipscombe received a B.Sc. with honors in pharmacology in 1982 and a Ph.D. in pharmacology in 1986 from the University College London, under the supervision of Humphrey P. Rang and benefitting from many wonderful discussions with David Colquhoun and the C-floor group. She completed postdoctoral work in the laboratory of Richard W. Tsien at the Yale School of Medicine from 1986 to 1988, and at the Stanford University School of Medicine from 1989 to 1990.

Diane Lipscombe, Ph.D. (born March 31, 1960) is a professor of neuroscience and the Reliance Dhirubhai Ambani Director of Brown University’s Robert J. and Nancy D. Carney Institute for Brain Science. She served as the president of the Society for Neuroscience in 2019, the world’s largest organization for the study of the brain and nervous system.

Diane Lipscombe was born on March 31, 1960 in Edinburgh, UK. Her family moved to England in 1964, and she grew up in Orpington, Kent. In 1978, she worked as a technician at the Wellcome Research Laboratories in Kent, England, under the supervision of Sir James W. Black.