About

Diane Lipscombe was appointed director of the Carney Institute for Brain Science in May 2016, after serving as interim director since January 2015. She has been on the Brown faculty since 1990 and formerly served as the co-director of the Neuroscience Graduate Program. Her laboratory, the Lipscombe Lab, studies the expression, regulation, and function of voltage-gated calcium ion channels in different regions of the nervous system. She is also interested in their role in chronic pain and psychiatric disorders. As director of the Carney Institute, she guides the scientific vision of the Institute and advocates for the Institute and its researchers. Diane works with members of the Brown senior administration as well as leaders of other initiatives on campus. She also represents the Carney Institute nationally and internationally and raises private philanthropy to support Carney Institute activities.

Research topics

• Computer Science
• Sociology
• Political Science
• Data science
• Engineering
• Engineering ethics
• Management science
• Epistemology

Selected publications

• A bioluminescent activity dependent platform, BLADe, for converting intracellular activity to photoreceptor activation

  Scientific Reports · 2026-05-11

  articleOpen access

  Genetically encoded sensors and actuators have advanced the ability to observe and manipulate cellular activity, yet few non-invasive strategies enable cells to directly couple their intracellular states to user-defined outputs. We promote a bioluminescent activity-dependent (BLADe) platform that facilitates programmable feedback through genetically encoded light generation. Using calcium (Ca2+) flux as a model, we engineered a Ca2+-dependent luciferase that functions as an activity-gated light source capable of photoactivating light-sensing actuators. As an initial demonstration of the versatility of this platform we present two separate use cases in neurons. In the first application, the presence of luciferin triggers Ca2+ dependent local illumination that provides activity dependent gene expression by activating a light-sensitive transcription factor. In the second application, neuronal activity-driven Ca2+ fluctuations via locally generated bioluminescence control neural dynamics through opsin activation in single cells, populations and intact tissue. BLADe can be expanded to couple any signal that bioluminescent enzymes can be engineered to detect with the wide variety of photosensing actuators. This modular strategy of coupling an activity dependent light emitter to a light sensing actuator offers, in principle, a generalizable framework for state dependent cell-autonomous control across biological systems.

  PublisherOA PDFDOI

• <i>Trpv1</i> -dependent <i>Cacna1b</i> gene inactivation reveals cell-specific functions of Ca _V 2.2 channels <i>in vivo</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-10 · 1 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Voltage-gated Ca V 2.2 channels underlie the N-type current, and they regulate calcium entry at many presynaptic nerve endings to control transmitter release. A role for Ca V 2.2 channels has been well-established in the transmission of pain information using pharmacological and global gene inactivated mouse models. However, investigation of the cell-specific actions of Ca V 2.2 channels would benefit from the availability of cell-restricted knockout mouse models and particularly in dissecting behavioral responses that depend on Ca V 2.2 channel activity. Here, we show the importance of Ca V 2.2 channels in Trpv1 -lineage neurons in behavioral responses to sensory stimuli using Cre-dependent inactivation of the Cacna1b gene. Our work shows the cell- type specificity of Ca V 2.2 channels in mediating rapidly developing heat hypersensitivity and the utility of Cre-dependent inactivation of Cacna1b to discern cell-specific Ca V 2.2 channel functions.

  PublisherOA PDFDOI

• Control of Synaptic Communication through Molecularly Engineered Bioluminescence Light Emission and Sensing

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-28 · 2 citations

  preprintOpen access

  Abstract Synapses are sites of intercellular communication between neurons and from neurons to target organs, and of signal integration that underly physiological and behavioral responses. We have developed a modular platform, Interluminescence (Int), for experimental control of synaptic transmission: bioluminescent light, generated by a luciferase oxidizing a luciferin, from a presynaptic neuron is used to activate transsynaptic optogenetic ion channels in the postsynaptic neuron. Two strategies can activate or silence postsynaptic neurons in vivo in the presence of luciferin. In the ‘Act-Int’ approach, a luciferase is genetically expressed in synaptic vesicles and released during depolarization-induced presynaptic vesicle fusion and exocytosis. In the ‘Persist-Int’ approach, a luciferase is tethered to the presynaptic membrane where it can support sustained transsynaptic signaling. Both strategies can activate postsynaptic neurons with similar efficacy. By design, the modularity of the platform permits the use of luciferases and opsins ranging in brightness and light sensitivity, and the luciferase can be targeted to different subcellular regions of the presynaptic neuron. Our results demonstrate the utility and versatility of Interluminescence to mediate synapse-specific transmission that is either activity-dependent or activity-independent.

  PublisherOA PDFDOI

• <i>Trpv1</i>-dependent <i>Cacna1b</i> gene inactivation reveals cell-specific functions of Ca_V2.2 channels <i>in vivo</i>

  Figshare · 2025-01-01

  datasetOpen accessSenior author

  Voltage-gated Ca_V2.2 channels underlie the N-type current, and they regulate calcium entry at many presynaptic nerve endings to control transmitter release. A role for Ca_V2.2 channels has been well established in the transmission of sensory signals including noxious information using pharmacological and global gene knockout mouse models. However, investigation of the cell-specific actions of Ca_V2.2 channels has been difficult due to the lack of gene-dependent knockout mouse models and particularly in dissecting behavioral responses that depend on Ca_V2.2 channel activity. Here, we show the importance of Ca_V2.2 channels in <i>Trpv1</i>-lineage neurons in behavioral responses to sensory stimuli using Cre-dependent inactivation of the <i>Cacna1b</i> gene. Our work shows the cell-type specificity of Ca_V2.2 channels in mediating rapidly developing heat hypersensitivity and the utility of Cre-dependent inactivation of <i>Cacna1b</i> to discern cell-specific Ca_V2.2 channel functions.

  PublisherDOI

• <i>Trpv1</i> -dependent <i>Cacna1b</i> gene inactivation reveals cell-specific functions of Ca _V 2.2 channels <i>in vivo</i>

  Channels · 2025-12-22 · 1 citations

  articleOpen accessSenior authorCorresponding

  2.2 channel functions.

  PublisherDOI

• CaBLAM: a high-contrast bioluminescent Ca2+ indicator derived from an engineered Oplophorus gracilirostris luciferase

  Nature Methods · 2025-12-02 · 9 citations

  articleOpen access

  Monitoring intracellular calcium is central to understanding cell signaling across nearly all cell types and organisms. Fluorescent genetically encoded calcium indicators (GECIs) remain the standard tools for in vivo calcium imaging, but require intense excitation light, leading to photobleaching, background autofluorescence and phototoxicity. Bioluminescent GECIs, which generate light enzymatically, eliminate these artifacts but have been constrained by low dynamic range and suboptimal calcium affinities. Here we show that CaBLAM ('calcium bioluminescence activity monitor'), an engineered bioluminescent calcium indicator, achieves an order-of-magnitude improvement in signal contrast and a tunable affinity matched to physiological cytosolic calcium. CaBLAM enables single-cell and subcellular activity imaging at video frame rates in cultured neurons and sustained imaging over hours in awake, behaving animals. These capabilities establish CaBLAM as a robust and general alternative to fluorescent GECIs, extending calcium imaging to regimes where excitation light is undesirable or infeasible.

  PublisherDOI

• <i>Trpv1</i>-dependent <i>Cacna1b</i> gene inactivation reveals cell-specific functions of Ca_V2.2 channels <i>in vivo</i>

  Figshare · 2025-01-01

  datasetOpen accessSenior author

  Voltage-gated Ca_V2.2 channels underlie the N-type current, and they regulate calcium entry at many presynaptic nerve endings to control transmitter release. A role for Ca_V2.2 channels has been well established in the transmission of sensory signals including noxious information using pharmacological and global gene knockout mouse models. However, investigation of the cell-specific actions of Ca_V2.2 channels has been difficult due to the lack of gene-dependent knockout mouse models and particularly in dissecting behavioral responses that depend on Ca_V2.2 channel activity. Here, we show the importance of Ca_V2.2 channels in <i>Trpv1</i>-lineage neurons in behavioral responses to sensory stimuli using Cre-dependent inactivation of the <i>Cacna1b</i> gene. Our work shows the cell-type specificity of Ca_V2.2 channels in mediating rapidly developing heat hypersensitivity and the utility of Cre-dependent inactivation of <i>Cacna1b</i> to discern cell-specific Ca_V2.2 channel functions.

  PublisherDOI

• Peripheral Ca _V 2.2 Channels in the Skin Regulate Prolonged Heat Hypersensitivity during Neuroinflammation

  eNeuro · 2024-10-21 · 4 citations

  articleOpen accessSenior author

  Neuroinflammation can lead to chronic maladaptive pain affecting millions of people worldwide. Neurotransmitters, cytokines, and ion channels are implicated in neuroimmune cell signaling, but their roles in specific behavioral responses are not fully elucidated. Voltage-gated Ca V 2.2 channel activity in skin controls rapid and transient heat hypersensitivity induced by intradermal (i.d.) capsaicin via IL-1ɑ cytokine signaling. Ca V 2.2 channels are not, however, involved in mechanical hypersensitivity that developed in the i.d. capsaicin animal model. Here, we show that Ca V 2.2 channels are also critical for heat hypersensitivity induced by i.d. complete Freund adjuvant (CFA). i.d. CFA, a model of chronic neuroinflammation, involves ongoing cytokine signaling for days leading to pronounced edema and hypersensitivity to sensory stimuli. Peripheral Ca V 2.2 channel activity in the skin was required for the full development and week-long time course of heat hypersensitivity induced by i.d. CFA, but paw edema and mechanical hypersensitivity were independent of Ca V 2.2 channel activity. CFA induced increases in several cytokines in hindpaw fluid including IL-6 which was also dependent on Ca V 2.2 channel activity. Using IL-6–specific neutralizing antibodies in vivo, we show that IL-6 contributes to heat hypersensitivity and that neutralizing both IL-1ɑ and IL-6 was even more effective at reducing the magnitude and duration of CFA-induced heat hypersensitivity. Our findings demonstrate a functional link between Ca V 2.2 channel activity and the release of IL-6 in the skin and show that Ca V 2.2 channels have a privileged role in the induction and maintenance of heat hypersensitivity during chronic forms of neuroinflammation in the skin.

  PublisherOA PDFDOI

• Interleukin-1α links peripheral CaV2.2 channel activation to rapid adaptive increases in heat sensitivity in skin

  Scientific Reports · 2024-04-20 · 7 citations

  articleOpen accessSenior author

  Abstract Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated Ca V 2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1α (IL-1α), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1α was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1α levels were also dependent on peripheral Ca V 2.2 channel activity. Neutralizing IL-1α in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1α enhances behavioral responses to stimuli and, in culture, IL-1α enhances the responsiveness of Trpv1 -expressing sensory neurons. Together, our data suggest that IL-1α is the key cytokine that underlies rapid and reversible neuroinflammatory responses in skin.

  PublisherOA PDFDOI

• Peripheral Ca _V 2.2 channels in skin regulate prolonged heat hypersensitivity during neuroinflammation

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-17 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Neuroinflammation can lead to chronic maladaptive pain affecting millions of people worldwide. Neurotransmitters, cytokines, and ion channels are implicated in neuro-immune cell signaling but their roles in specific behavioral responses are not fully elucidated. Voltage-gated Ca V 2.2 channel activity in skin controls rapid and transient heat hypersensitivity induced by intradermal capsaicin via IL-1α cytokine signaling. Ca V 2.2 channels are not, however, involved in mechanical hypersensitivity that developed in the same animal model. Here, we show that Ca V 2.2 channels are also critical for heat hypersensitivity induced by the intradermal ( id ) Complete Freund’s Adjuvant (CFA) model of chronic neuroinflammation that involves ongoing cytokine signaling for days. Ongoing CFA-induced cytokine signaling cascades in skin lead to pronounced edema, and hypersensitivity to sensory stimuli. Peripheral Ca V 2.2 channel activity in skin is required for the full development and week-long time course of heat hypersensitivity induced by id CFA. Ca V 2.2 channels, by contrast, are not involved in paw edema and mechanical hypersensitivity. CFA induced increases in cytokines in hind paws including IL-6 which was dependent on Ca V 2.2 channel activity. Using IL-6 specific neutralizing antibodies, we show that IL-6 contributes to heat hypersensitivity and, neutralizing both IL-1α and IL-6 was even more effective at reducing the magnitude and duration of CFA-induced heat hypersensitivity. Our findings demonstrate a functional link between Ca V 2.2 channel activity and the release of IL-6 in skin and show that Ca V 2.2 channels have a privileged role in the induction and maintenance of heat hypersensitivity during chronic forms of neuroinflammation in skin. Significance Statement Neuroinflammation can lead to chronic maladaptive pain. Neurotransmitters, ion channels, cytokines, and cytokine receptors are implicated in neuron-immune signaling, but their importance in mediating specific behavioral responses are not fully elucidated. We show that the activity of peripheral Ca V 2.2 calcium ion channels in skin play a unique role in the induction and maintenance of heat hypersensitivity in the CFA model of prolonged neuroinflammation, without accompanying effects on edema and mechanical hypersensitivity. Blocking peripheral Ca V 2.2 channel activity reduces local cytokine levels in hind paws injected with CFA including IL-6 and neutralizing IL-6 reduces CFA- induced heat hypersensitivity. Our studies define key signaling molecules that act locally in skin to trigger and maintain heat hypersensitivity during chronic neuroinflammation.

  PublisherDOI

Recent grants

• NIH Grant R01NS029967

  NIH · $3.6M · 2011

• NIH Grant T32MH019118

  NIH · $2.5M · 2014

• Voltage-Gated Calcium Channels in Nociceptors and Mechanoreceptors

  NIH · $9.1M · 2006–2026

• NIH Grant K02NS001927

  NIH · $362k · 2001

• Interdisciplinary Predoctoral Neuroscience Training Program in the Neuroscience Graduate Program.

  NIH · $7.8M · 1999–2026

Frequent coauthors

• Christopher I. Moore

  Providence College

  97 shared

• Eduardo Javier López Soto

  88 shared

• Weifeng Xu

  57 shared

• Andreas Björefeldt

  University of Gothenburg

  52 shared

• Jeremy W. Murphy

  Providence College

  44 shared

• Nina Friedman

  Brown University

  43 shared

• Ute Hochgeschwender

  Central Michigan University

  41 shared

• Arturo Andrade

  John Brown University

  40 shared

Awards & honors

• 2023 Landis Award for Outstanding Mentorship