About

Alyce Anderson, MD, PhD, is an Assistant Professor in the Department of Dermatology at the University of Minnesota. She is a Dermatologist and Dermatopathologist with a special interest in serving patients who are high risk for skin cancers. Dr. Anderson completed her medical degree at the University of Pittsburgh within the NIH-funded Medical Scientist Training Program, earning both an MD and a PhD in Clinical and Translational Sciences. She furthered her training at Northwestern University, where she completed her Dermatology residency, serving as the Academic Chief resident, and her Dermatopathology fellowship. Her clinical focus includes clinical pathologic correlation and assisting dermatology colleagues in diagnosis and treatment. Her research interests encompass costs of care, cost-effectiveness modeling, and utilizing large clinical datasets to improve patient care. She is also interested in gender representation within academic medicine.

Research topics

• Biology
• Chemistry
• Genetics
• Physics
• Pharmacology
• Biophysics
• Neuroscience
• Medicine
• Internal medicine
• Cell biology

Selected publications

• Receptor-dependent influence of R7 RGS proteins on neuronal GIRK channel signaling dynamics

  Progress in Neurobiology · 2024-11-13 · 6 citations

  articleOpen access
  PublisherOA PDFDOI

• Characterization of VU0468554, a New Selective Inhibitor of Cardiac G Protein–Gated Inwardly Rectifying K+ Channels

  Molecular Pharmacology · 2021 · 2 citations

  1st authorCorresponding
  • Medicine
  • Pharmacology
  • Neuroscience
  PublisherOA PDFDOI

• GPCR-dependent biasing of GIRK channel signaling dynamics by RGS6 in mouse sinoatrial nodal cells

  Proceedings of the National Academy of Sciences · 2020 · 27 citations

  1st authorCorresponding
  • Biology
  • Chemistry
  • Cell biology

  R-GIRK signaling dynamics in mouse SAN cells.

  PublisherOA PDFDOI

• Influence of RGS6 on Inhibitory G Protein Signaling in Mouse Sinoatrial Nodal Cells

  The FASEB Journal · 2020-04-01

  article1st authorCorresponding

  Introduction M2 muscarinic (M 2 R) activation of G protein‐gated inwardly rectifying K + (GIRK) channels in sinoatrial nodal (SAN) cells is a key mediator of vagal/parasympathetic slowing of heart rate. The strength of M 2 R‐GIRK signaling is negatively regulated by Regulator of G protein Signaling 6 (RGS6). Adenosine, used clinically to diagnose and treat certain arrhythmias, exerts these actions through A1 adenosine receptor (A 1 R) activation of GIRK channels. The extent to which RGS6 regulates A 1 R‐GIRK signaling, however, is unclear. Here, we investigated the impact of RGS6 on A 1 R‐GIRK and M 2 R‐GIRK signaling in mouse SAN cells. Methods and Results We measured the efficacy and potency of M 2 R‐ and A 1 R‐GIRK signaling in adult SAN cells from wild‐type and RGS6 −/− mice using whole‐cell patch‐clamp electrophysiology. As previously reported, SAN cells from RGS6 −/− mice displayed prolonged channel deactivation kinetics and increased channel sensitivity to the non‐selective cholinergic agonist carbachol (CCh), relative to wild‐type counterparts. In contrast, we observed a striking increase in the amplitude of the GIRK response evoked by adenosine (Ado) in RGS6 −/− SAN cells compared to wild‐type controls, with no impact on channel deactivation kinetics or sensitivity. Further recordings in wild‐type SAN cells revealed that M 2 R activation completely occludes the Ado‐induced response, whereas Ado application activates only a smaller fraction of GIRK channels. Both CCh‐ and Ado‐ induced currents were abolished in SAN cells treated by pertussis toxin (PTX), indicating these responses are mediated by Gi/o G proteins. Utilizing a bioluminescence resonance energy transfer (BRET) assay in transfected HEK cells, we found that RGS6 prefers G αo as a substrate for over G αi . Additionally, we found that while A 1 R does not discriminate between G αo and G αi , M 2 R displays a clear preference for G αo . We next employed a Cre/flox strategy to remove G αo from atrial tissue, including SAN cells. Loss of G αo yielded significantly blunted CCh‐induced responses, which also displayed prolonged activation and deactivation kinetics. While Ado‐induced responses had prolonged deactivation kinetics, activation kinetics and response amplitude were unaffected. Conclusions These results suggest that RGS6 negatively regulates A 1 R‐GIRK signaling distinct from its influence on M 2 R‐GIRK signaling in mouse SAN cells likely due to differing utilization of G ao by M 2 R and A 1 R. Support or Funding Information This work was supported by NIH grants R01 HL105550 and F31 HL139090.

  PublisherDOI

• VU0810464, a non‐urea G protein‐gated inwardly rectifying K⁺ (K_ir3/GIRK) channel activator, exhibits enhanced selectivity for neuronal K_ir3 channels and reduces stress‐induced hyperthermia in mice

  British Journal of Pharmacology · 2019-03-29 · 16 citations

  articleOpen access

  Background and Purpose G protein‐gated inwardly rectifying K + (K ir 3) channels moderate the activity of excitable cells and have been implicated in neurological disorders and cardiac arrhythmias. Most neuronal K ir 3 channels consist of K ir 3.1 and K ir 3.2 subtypes, while cardiac K ir 3 channels consist of K ir 3.1 and K ir 3.4 subtypes. Previously, we identified a family of urea‐containing K ir 3 channel activators, but these molecules exhibit suboptimal pharmacokinetic properties and modest selectivity for K ir 3.1/3.2 relative to K ir 3.1/3.4 channels. Here, we characterize a non‐urea activator, VU0810464, which displays nanomolar potency as a K ir 3.1/3.2 activator, improved selectivity for neuronal K ir 3 channels, and improved brain penetration. Experimental Approach We used whole‐cell electrophysiology to measure the efficacy and potency of VU0810464 in neurons and the selectivity of VU0810464 for neuronal and cardiac K ir 3 channel subtypes. We tested VU0810464 in vivo in stress‐induced hyperthermia and elevated plus maze paradigms. Parallel studies with ML297, the prototypical activator of K ir 3.1‐containing K ir 3 channels, were performed to permit direct comparisons. Key Results VU0810464 and ML297 exhibited comparable efficacy and potency as neuronal K ir 3 channel activators, but VU0810464 was more selective for neuronal K ir 3 channels. VU0810464, like ML297, reduced stress‐induced hyperthermia in a K ir 3‐dependent manner in mice. ML297, but not VU0810464, decreased anxiety‐related behaviour as assessed with the elevated plus maze test. Conclusion and Implications VU0810464 represents a new class of K ir 3 channel activator with enhanced selectivity for K ir 3.1/3.2 channels. VU0810464 may be useful for examining K ir 3.1/3.2 channel contributions to complex behaviours and for probing the potential of K ir 3 channel‐dependent manipulations to treat neurological disorders.

  PublisherOA PDFDOI

• Differential Impact of RGS6 on GIRK‐dependent Muscarinic and Adenosine Receptor Signaling in Mouse Sinoatrial Nodal Cells

  The FASEB Journal · 2019-04-01

  article1st authorCorresponding

  Introduction Parasympathetic slowing of heart rate is largely mediated by muscarinic receptor (M2R) activation of the G protein gated inwardly‐rectifying potassium (GIRK) channel on sinoatrial nodal (SAN) cells and atrial myocytes. The strength of M2R‐GIRK signaling is negatively regulated by regulator of G protein signaling 6, RGS6. Genetic ablation of RGS6 in mice gives rise to enhanced M2R‐GIRK signaling in SAN cells, resulting in both exaggerated M2R‐induced bradycardia and increased susceptibility to pacing‐induced atrial fibrillation. Adenosine, used clinically to both diagnose and treat certain arrhythmias, exerts these actions through adenosine receptor (A1R) activation of cardiac GIRK channels. The extent to which RGS6 regulates A1R‐GIRK signaling, however, is not understood. Here, we investigated and compared the impact of RGS6 on A1R‐GIRK and M2R‐GIRK signaling in mouse SAN cells and heart rate. Methods and Results Using whole‐cell patch‐clamp electrophysiology, we measured the efficacy and potency of M2R‐ and A1R‐GIRK channel signaling in adult SAN cells from wildtype and Rgs6 −/− mice. SAN cells from Rgs6 −/− mice displayed both prolonged channel deactivation kinetics and increased channel sensitivity to CCh‐induced currents as compared to wild‐type SAN cells. Surprisingly, we found no difference in kinetics or channel sensitivity of A1R‐GIRK responses in Rgs6 −/− SAN cells. We did observe a striking, significant increase in the amplitude of the A1R‐GIRK response in Rgs6 −/− SAN cells compared to wild‐type controls. Recordings from mice lacking cardiac GIRK channels ( Girk4 −/− ) confirm that M2R‐ and A1R‐induced currents are GIRK‐dependent. Furthermore, occlusion studies in wild‐type SAN cells suggest that M2R activates nearly all of the GIRK channels present in SAN cells, while A1R activates a smaller portion of GIRK channels. Intriguingly, RGS6 ablation seems to allow for the activation of a larger proportion of GIRK channels by A1R. Heart rate measurements from isolated Rgs6 −/− hearts show exaggerated bradycardia in response to the same doses of CPA, an A1R agonist, as compared to wild‐type controls. Significantly lower heart rates were observed in response to lower doses of CCh in isolated Rgs6 −/− hearts as compared to wild‐type hearts, suggesting a shift in sensitivity. Conclusions Our results suggest that A1R‐GIRK channel signaling displays distinct differences from M2R‐GIRK channel signaling, resulting in distinct negative regulation by RGS6 in mouse SAN cells and the isolated heart. Support or Funding Information This work was supported by NIH grants KW (HL105550) and AA (HL139090). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

  PublisherDOI

• Correction: The influences of the M2R-GIRK4-RGS6 dependent parasympathetic pathway on electrophysiological properties of the mouse heart

  PLoS ONE · 2018-07-06 · 1 citations

  erratumOpen access

  [This corrects the article DOI: 10.1371/journal.pone.0193798.].

  PublisherOA PDFDOI

• The influences of the M2R-GIRK4-RGS6 dependent parasympathetic pathway on electrophysiological properties of the mouse heart

  PLoS ONE · 2018-04-18 · 11 citations

  articleOpen access

  A large body of work has established the prominent roles of the atrial M2R-IKACh signaling pathway, and the negative regulatory protein RGS6, in modulating critical aspects of parasympathetic influence on cardiac function, including pace-making, heart rate (HR) variability (HRV), and atrial arrhythmogenesis. Despite increasing evidence of its innervation of the ventricles, and the expression of M2R, IKACh channel subunits, and RGS6 in ventricle, the effects of parasympathetic modulation on ventricular electrophysiology are less clear. The main objective of our study was to investigate the contribution of M2R-IKACh signaling pathway elements in murine ventricular electrophysiology, using in-vivo ECG measurements, isolated whole-heart optical mapping and constitutive knockout mice lacking IKACh (Girk4-/-) or RGS6 (Rgs6-/-). Consistent with previous findings, mice lacking GIRK4 exhibited diminished HR and HRV responses to the cholinergic agonist carbachol (CCh), and resistance to CCh-induced arrhythmic episodes. In line with its role as a negative regulator of atrial M2R-IKACh signaling, loss of RGS6 correlated with a mild resting bradycardia, enhanced HR and HRV responses to CCh, and increased propensity for arrhythmic episodes. Interestingly, ventricles from mice lacking GIRK4 or RGS6 both exhibited increased action potential duration (APD) at baseline, and APD was prolonged by CCh across all genotypes. Similarly, CCh significantly increased the slope of APD restitution in all genotypes. There was no impact of genotype or CCh on either conduction velocity or heterogeneity. Our data suggests that altered parasympathetic signaling through the M2R-IKACh pathway can affect ventricular electrophysiological properties distinct from its influence on atrial physiology.

  PublisherOA PDFDOI

• Expression and relevance of the G protein-gated K+ channel in the mouse ventricle

  Scientific Reports · 2018-01-15 · 29 citations

  articleOpen access1st authorCorresponding

  Abstract The atrial G protein-gated inwardly rectifying K + (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (M 2 R), and RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in mouse ventricle at relatively low levels. The cholinergic agonist carbachol (CCh) activated small GIRK currents in adult wild-type ventricular myocytes that exhibited relatively slow kinetics and low CCh sensitivity; these currents were absent in ventricular myocytes from Girk1 −/− or Girk4 −/− mice. While loss of GIRK channels attenuated the CCh-induced shortening of action potential duration and suppression of ventricular myocyte excitability, selective ablation of GIRK channels in ventricle had no effect on heart rate, heart rate variability, or electrocardiogram parameters at baseline or after CCh injection. Additionally, loss of ventricular GIRK channels did not impact susceptibility to ventricular arrhythmias. These data suggest that the mouse ventricular GIRK channel is a GIRK1/GIRK4 heteromer, and show that while it contributes to the cholinergic suppression of ventricular myocyte excitability, this influence does not substantially impact cardiac physiology or ventricular arrhythmogenesis in the mouse.

  PublisherDOI

• Abstract 17317: Differential Coupling and Regulation of GIRK-Dependent Muscarinic and Adenosine Receptor Signaling in Mouse Sino-Atrial Nodal Cells

  Circulation · 2018-11-06

  article1st authorCorresponding

  Introduction and Hypothesis: Parasympathetic slowing of heart rate is largely mediated by muscarinic receptor (M2R) activation of the G protein gated inwardly-rectifying potassium (GIRK) channel on sinoatrial-nodal (SAN) cells and atrial myocytes. The strength of M2R-GIRK signaling is negatively regulated by regulator of G protein signaling 6, RGS6. Genetic ablation of RGS6 in mice gives rise to enhanced M2R-GIRK signaling in SAN cells, resulting in both exaggerated M2R-induced bradycardia and increased susceptibility to pacing-induced atrial fibrillation. Adenosine receptor (A1R) activation, which can provoke atrial arrhythmias in human patients, can also activate GIRK channels, however, the details of A1R-GIRK signaling are poorly understood. Here, we investigated A1R-GIRK signaling in mouse SAN cells and tested the hypothesis that RGS6 negatively regulates A1R-GIRK signaling. Methods and Results: Using whole-cell patch-clamp electrophysiology, we measured the efficacy and potency of M2R- and A1R- GIRK signaling in adult SAN cells from wildtype and Rgs6 -/- mice. We found SAN cells from Rgs6 -/- mice displayed both prolonged channel deactivation kinetics and increased channel sensitivity to CCh-induced currents as compared to wild-type SAN cells. Surprisingly, we found no difference in kinetics or channel sensitivity of A1R-GIRK responses in Rgs6 -/- SAN cells. We did observe, however, a striking, significant increase in the amplitude of the A1R-GIRK response in Rgs6 -/- SAN cells compared to wild-type controls. Furthermore, occlusion studies in wild-type SAN cells suggest that M2R activates nearly all of the GIRK channels present in SAN cells, while A1R activation results in only partial GIRK channel activation. Intriguingly, RGS6 ablation seems to allow a larger proportion of GIRK channels to be activated by A1R. Recordings from mice lacking cardiac GIRK channels confirm that M2R- and A1R- induced currents are GIRK-dependent. Conclusions: Our results suggest that M2R-GIRK and A1R-GIRK are coupled differently within mouse sino-atrial nodal cells, resulting in differential regulation by RGS6.

  PublisherDOI

Recent grants

• Targeting the parasympathetic regulation of the heart to treat arrhythmias

  NIH · $120k · 2017–2020

Frequent coauthors

• Kevin Wickman

  University of Minnesota

  26 shared

• Ezequiel Marrón Fernández de Velasco

  University of Minnesota

  22 shared

• Baovi N. Vo

  University of Minnesota

  18 shared

• Corey R. Hopkins

  Nebraska Medical Center

  18 shared

• C. David Weaver

  Vanderbilt University

  17 shared

• Kirill A. Martemyanov

  University of Florida

  5 shared

• Lutz Birnbaumer

  4 shared

• Ikuo Masuho

  The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology

  3 shared