About

Sean Conner, PhD, is an Associate Professor at the University of Minnesota Medical School. His research focuses on signaling between cells and the uptake of macromolecular nutrients mediated through cell surface receptors. His laboratory investigates the cellular mechanisms that control receptor trafficking through the endosomal compartment, emphasizing the importance of robust and high-fidelity processes since failures in receptor internalization or sorting can lead to serious health issues such as heart disease and cancer. Conner employs a combination of genetic and mammalian cell-based assays to understand how nutrient and signaling receptor transport is regulated, complementing these with biochemical and combinatorial approaches to resolve the molecular details of receptor endocytosis and intracellular sorting.

Research topics

• Computer Science
• Artificial Intelligence
• Medicine
• Internal medicine
• Data science
• Engineering management
• Endocrinology
• Management
• Economics
• Gastroenterology
• Engineering

Selected publications

• How students leverage assignment submission flexibility — A case study

  Heliyon · 2024 · 5 citations

  1st authorCorresponding
  • Computer Science
  • Artificial Intelligence
  • Computer Science

  Recent pedagogical trends in post-secondary education focus on how providing students with greater autonomy through assignment submission flexibility offers benefits ranging from increased learning to stress reduction. Unfortunately, the relationship between submission flexibility and any specific benefit is not firmly established. One explanation for this is a potential misalignment between anticipated benefits and an understanding of how most students leverage extended opportunities for assignment completion. The goal of this study was to investigate the relationship between assignment submission flexibility and how students used the opportunity. Quantitative evidence reveals that most students routinely maximized the time taken before submitting assignments. This occurred independent of assignment type, teaching modality, or the duration of assignment availability. The results support a conclusion that most students do not capitalize on increased flexibility to meet the demands of their unique schedules. Instead, they appear to adapt their schedules to submit assignments shortly before a perceived deadline.

  PublisherOA PDFDOI

• WS05.03 A phase 3b study of the effects of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on glucose tolerance in people with cystic fibrosis (CF) and abnormal glucose metabolism

  Journal of Cystic Fibrosis · 2023

  • Medicine
  • Internal medicine
  • Endocrinology
  PublisherOA PDFDOI

• Chondroitin sulfate proteoglycan 4 enhanced melanoma motility and growth requires a cysteine in the core protein transmembrane domain

  Melanoma Research · 2019-02-07 · 15 citations

  articleOpen access

  Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface proteoglycan that enhances malignant potential in melanoma and several other tumor types. CSPG4 functions as a transmembrane scaffold in melanoma cells to activate oncogenic signaling pathways such as focal adhesion kinase (FAK) and extracellular signal regulated kinases 1,2, that control motility, invasion and anchorage independent growth. Here, we demonstrate that CSPG4 promotes directional motility and anchorage independent growth of melanoma cells by organizing and positioning a signaling complex containing activated FAK to lipid rafts within the plasma membrane of migrating cells. This FAK-containing signal transduction platform, which consists of syntenin-1, active Src and caveolin-1 requires the cytoplasmic domain of CSPG4 for assembly. Enhanced directional motility promoted by this complex also requires a CSPG4 transmembrane cysteine residue C2230. Substituting C2230 with alanine (CSPG4) still permits assembly of the signaling complex, however Src remains in an inactive state. CSPG4 also fails to promote anchorage independent growth and activation of extracellular signal regulated kinases 1,2. Therapies that target the transmembrane domain of CSPG4 could be a novel strategy for limiting progression by disrupting its function as a compartmentalized motogenic and growth-promoting oncogenic signaling node.

  PublisherOA PDFDOI

• PI5P4Kγ functions in DTX1-mediated Notch signaling

  Proceedings of the National Academy of Sciences · 2018-02-12 · 35 citations

  articleOpen accessSenior authorCorresponding

  Significance The Notch signaling pathway performs a vital role in biological processes ranging from stem cell maintenance to cell viability. This highly conserved pathway must be tightly controlled, since defects in signaling can promote disease. The E3 ubiquitin ligase DTX1 has emerged as a key negative regulator of Notch signaling, where Notch ubiquitination by DTX1 is thought to control intracellular sorting decisions of the receptor. Here we show that DTX1 can regulate Notch activity independent of directly ubiquitinating the receptor, suggesting that DTX1 targets other factors involved in Notch transport. Using an activity-based screen for DTX1 substrates, we identify PI5P4Kγ, a lipid kinase, and discover that PI5P4Kγ and DTX1 have opposing activities in regulating Notch transit through recycling endosomes.

  PublisherOA PDFDOI

• A Novel Assay to Study Jagged-1 Trafficking

  University of Minnesota Digital Conservancy (University of Minnesota) · 2017-04-01

  dissertationOpen accessSenior author

  The Notch signaling pathway is an evolutionarily conserved cell-signaling system that plays an important role in cell differentiation and other processes. Notch signaling is activated when a ligand binds to the Notch protein at the cell surface, thereby initiating a series of events that leads to modification of gene expression. Notch and one of its ligands, Jagged-1, are found at elevated levels in metastatic prostate cancer, indicating that increased Notch signaling is responsible for metastasis of prostate cancer. If Jagged-1 were prevented from reaching the cell surface in the first place, prostate cancer metastasis could be averted. However, more knowledge about the trafficking of Jagged-1 is required to achieve that goal. This study hopes to develop a novel assay that could aid in the study of protein trafficking. A preliminary quantitative assay showed that the manufactured single chain variable fragment antibody bound to the Jagged-1 receptor at the cell surface and exhibited luciferase activity. Another qualitative assay showed that both receptor and antibody could be visualized fluorescently and that the internalization of the antibody could be tracked visually. These experiments will serve as a starting point for more extensive assays which will further optimize these techniques. This knowledge can then be utilized to combat cancer metastasis by blunting the expression of Jagged-1 at the cell surface.

  Publisher

• Glycogen synthase kinase 3β inhibition enhances Notch1 recycling

  Molecular Biology of the Cell · 2017-12-13 · 32 citations

  articleOpen accessSenior authorCorresponding

  The Notch signaling pathway is essential throughout development and remains active into adulthood, where it performs a critical role in tissue homeostasis. The fact that defects in signaling can lead to malignancy illustrates the need to control Notch activity tightly. GSK3β is an established regulator of the Notch signaling pathway, although its mechanism of action remains unclear. Given the emerging role for GSK3β in receptor trafficking, we tested the idea that GSK3β controls signaling by regulating Notch transport. Consistent with published reports, we find that GSK3β inhibition enhances Notch1 signaling activity. Immunolocalization analysis reveals that Notch1 localization within a tubulovesicular compartment is altered when GSK3β activity is disrupted. We also find that receptor cell surface levels increase following acute GSK3β inhibition. This is followed by elevated Notch intra-cellular domain (NICD) production and a corresponding increase in signaling activity. Moreover, Notch transport assays reveal that receptor recycling rates increase when GSK3β activity is inhibited. Collectively, results presented here support a model where GSK3β regulates signaling by controlling postendocytic transport of Notch1. Given that GSK3β activity is suppressed following stimulation by multiple signal transduction pathways, our findings also suggest that cells can modulate Notch1 activity in response to extracellular signals by mobilizing Notch1 from endosomal stores.

  PublisherOA PDFDOI

• Regulation of Notch Signaling Through Intracellular Transport

  International review of cell and molecular biology · 2016-01-01 · 40 citations

  review1st authorCorresponding
  PublisherDOI

• Dysfunction of Endocytic Kinase AAK1 in ALS

  International Journal of Molecular Sciences · 2014-12-10 · 41 citations

  articleOpen access

  Mechanisms of human mutant superoxide dismutase 1 (SOD1)-induced toxicity in causing the familial form of amyotrophic lateral sclerosis (ALS) remain elusive. Identification of new proteins that can selectively interact with mutant SOD1s and investigation of their potential roles in ALS are important to discover new pathways that are involved in disease pathology. Using the yeast two-hybrid system, we identified the adaptor-associated kinase 1 (AAK1), a regulatory protein in clathrin-coated vesicle endocytic pathway that selectively interacted with the mutant but not the wild-type SOD1. Using both transgenic mouse and rat SOD1-linked familial ALS (FALS) models, we found that AAK1 was partially colocalized with the endosomal and presynaptic protein markers under the normal physiological condition, but was mislocated into aggregates that contained mutant SOD1s and the neurofilament proteins in rodent models of ALS in disease. AAK1 protein levels were also decreased in ALS patients. These results suggest that dysfunction of a component in the endosomal and synaptic vesicle recycling pathway is involved in ALS pathology.

  PublisherOA PDFDOI

• Phenolic compounds in blackcurrant (Ribes nigrum L.) leaves relative to leaf position and harvest date

  Food Chemistry · 2014-09-16 · 77 citations

  article
  PublisherDOI

• Extraction and identification of antioxidant polyhydroxynaphthoquinone pigments from the sea urchin, Psammechinus miliaris

  LWT · 2014-05-23 · 63 citations

  articleOpen access

  Pigments were extracted from tests of individual sea urchins, Psammechinus miliaris, collected from a sea loch in Scotland. The extracts were red brown-to-orange in colour and yielded UV spectra with maxima at 475, 320 and 270 nm characteristic of polyhydroxylated naphthoquinone pigments (PHNQs) identified in other sea urchins. The yield of total phenols from the tests was relatively low (1–2 mg/g dry weight) but in line with levels found in tests from other sea urchin species. The extracts displayed reasonable antioxidant capacity assayed using the FRAP assay. After selection by solid phase extraction, the extracts were analysed by liquid chromatography-mass spectrometry (LC–MS). The LC–MS data suggested that the pigmentation was due to a range of spinochrome and echinochrome PHNQ components. Most of these components have been noted previously but there was evidence for sulphated forms which have not been identified before. The role and potential utility of these pigments in food applications is discussed.

  PublisherDOI

Recent grants

• NIH Grant F32GM020632

  NIH · $119k

• NIH Grant R01GM085029

  NIH · $1.4M · 2014

Frequent coauthors

• Gary M. Wessel

  Brown University

  25 shared

• Derek Stewart

  15 shared

• Howard V. Davies

  James Hutton Institute

  10 shared

• Susan R. Verrall

  James Hutton Institute

  10 shared

• Linnea Berg

  8 shared

• Gary Dobson

  James Hutton Institute

  7 shared

• Tom Shepherd

  James Hutton Institute

  7 shared

• Zheng Li

  6 shared

Awards & honors

• Dr. James E. Rubin Medical Memorial Award
• Graduating Medical Student Research Award
• Veneziale-Steer Award
• Dr. Marvin and Hadassah Bacaner Research Awards
• Schmidt Steer Award