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Articles by Mitchell Levesque
A TERRA-NONO axis drives fibroblast reprogramming in cancer
Abstract INTRODUCTION RESULTS DISCUSSION MATERIALS AND METHODS Acknowledgments Supplementary Materials REFERENCES Information & Authors Metrics & Citations View Options References Figures Tables Media Share This article has 0 eLetter . Abstract The molecular mechanisms linking chromosome homeostasis to fibroblast reprogramming into cancer-associated fibroblasts (CAFs) remain poorly understood.
An automated high-resolution screening platform identifies regulators of anchor cell invasion in C. elegans
Abstract INTRODUCTION RESULTS DISCUSSION MATERIALS AND METHODS Acknowledgments Supplementary Materials REFERENCES Information & Authors Metrics & Citations View Options References Figures Tables Media Share This article has 0 eLetter . Abstract Microfluidic devices are valuable tools for live imaging. However, widespread adoption of microfluidic-based screening methods has been limited by the complexity of the existing techniques.
Targeting ABL kinases overcomes melanoma immune evasion following resistance to MAPK inhibition
Abstract MAPK inhibitors (MAPKi) are important treatment options for some patients with metastatic melanoma; however, resistance inevitably develops in the vast majority of cases (>70%).
Tumor-resident T cells and dendritic cells form an in situ archetype during immunotherapy response in melanoma
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Abstract Tumor-resident (TR) T cells, known as tissue-resident memory (TRM) T cells in mice, play a central role in melanoma immunosurveillance, yet their contribution to immune checkpoint inhibitor (ICI) therapy has not been comprehensively explored. We performed spatial and single-cell profiling on 32 metastatic melanoma lymph node samples, from treatment-naïve, ICI-resistant and ICI-responsive patients. Here we show that tumor areas in ICI-responders were enriched for both CD8+ and CD4+ TR.
By Andrea Di Pietro, Lewis Au, Niko Thio, Angela Pizzolla, Thu Nguyen, Thu Nguyễn, Sean MacDonald, Hugh Chalmers, Ruiqing Zhu, Marina Bacac, Petra C. Schwalie, Mitchell Levesque, Karen L Winch, Joanna Chan, George Yeung, Lavinia Spain, Aparna Rao, Shahneen Sandhu, David E Gyorki, Grant McArthur Verified, Laura K. Mackay, Paul Neeson, Patrick Crock, Alessia Airaghi, Tristan Molden-Hauer, Ramona Schlenker, Sonia Mailer, Kristy Barnes-Cullen
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Nature
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NLRP1 inflammasome activation in skin equivalents reveals mechanistic insights into the roles of keratinocytes in psoriasis
Abstract The pro-inflammatory cytokines interleukin(IL)-1β and IL-36γ are key drivers of psoriasis, an inflammatory skin disease for which a causal therapy is not available. However, the mechanisms underlying regulation of these cytokines in psoriasis remain poorly understood. Generation of IL-1β activity is regulated by inflammasomes. We activated the NLRP1 inflammasome in human keratinocytes cultivated in three-dimensional skin equivalents.
In vivo single-cell ribosome profiling reveals cell-type-specific translational programs during aging
Introduction Stem cells are characterized by two features: their ability to self-renew throughout life and to differentiate into other cell types. These functions are closely linked to their precise regulation of gene expression.
HLA export by melanoma cells decoys cytotoxic T cells to promote immune evasion
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STAR★Methods REAGENT or RESOURCESOURCEIDENTIFIER Antibodies 112Cd Rat Anti mouse CD45 BioLegend Clone:30-F11; Cat#103120; RRID: AB_312985 113In anti-mouse/human CD44 BioLegend Clone:IM7; Cat#103014; RRID: AB_312965 115In Rat anti-mouse CD3 BioLegend Clone: 145-2C11; Cat#100340; RRID: AB_11149115 141Pr Rat anti-mouse CD274 BioLegend Clone:10F.9G2; Cat#124302; RRID: AB_961228 142Nd Ratr anti-mouse Ly-6G/Ly-6C (Gr-1) BioLegend Clone: RB6-8C5; Cat#108449; RRID: AB_2563785 143Nd Ratr anti-mouse...
By Yoav Chemla, Orit Itzhaki, Stav Melamed, Chen Weller, Yuval Sade, Paulee Manich, Keren Reshef, Nicolas Xenidis, Avishai Maliah, Gilad Levy, Roma Parikh, Osnat Bartok, Itay Tal, Gal Aziel, Abraham Nissani, Sharon Yunger, Daniela Likonen, Tamar Golan, Coralie Capron, Ronen Levy, Diana Rasoulouniriana, Zohar Eyal, Yuval Barzilay, Aseel Khateeb, Tamar Ziv, Polina Greenberg, Xunwei Wu, Yael Amitay, Dov Hershkovitz, Tal Yardeni, Valentina Zemser-Werner, Oren Kobiler, David Bassan, Ron Shamir, Nadine Santana-Magal, Michael Milyavsky, Galit Eisenberg, Leeat Keren, Merav Cohen, Dvir Gur, Boaz Barak, Michal Lotem, David Sprinzak, Shoshana Greenberger, David Fisher, Michal J. Besser, Mehdi Khaled, Pierre Close, Ronnie Shapira, Sebastien Apcher, Asaf Madi, Mitchell Levesque, Yaron Carmi, Shivang Parikh, Yardena Samuels, Carmit Levy, Vitaly Kliminsky, Valentina Ace, Roi Balaban, Rami Khosravi, Amir Grau, Dvir Netanely, Hananya Vaknin, Ronen Brenner, Yael Friedmann, Lea Eisenbach, Francessca Rapino
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Cell Press
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The serum metabolome serves as a diagnostic biomarker and discriminates patients with melanoma from healthy individuals
ReportOnline now102283Open access 1Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland 2Department of Dermatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland 3Institute of Molecular Systems Biology, Federal Institute of Technology Zurich, 8093 Zurich, Switzerland 4Comprehensive Cancer Center Zurich, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland Publication...
Publisher Correction: Feasibility of multiomics tumor profiling for guiding treatment of melanoma - Nature Medicine
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Correction to: Nature Medicine https://doi.org/10.1038/s41591-025-03715-6, published online 27 May 2025. In the version of the article initially published, the far-right column of the lower panel in Fig. 2c was missing and has now been added, as seen in Fig. 1, below.
By Nora C Toussaint, Ximena Bonilla, Tarun Mehra, Francis Jacob, Parisa Rahimzadeh, Natalia Chicherova, Rebekka Wegmann, Julien Mena, Sandra Goetze, Franziska Singer, Anne Bertolini, Michael Prummer, Rudolf Aebersold, Holger Moch, Michael Weller, Markus G. Manz, Niko Beerenwinkel, Christian Beisel, Bernd Bodenmiller, Mitchell Levesque, Viktor H. Koelzer, Reinhard Dummer
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Nature
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Feasibility of multiomics tumor profiling for guiding treatment of melanoma - Nature Medicine
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Abstract There is limited evidence supporting the feasibility of using omics and functional technologies to inform treatment decisions. Here we present results from a cohort of 116 melanoma patients in the prospective, multicentric observational Tumor Profiler (TuPro) precision oncology project. Nine independent technologies, mostly at single-cell level, were used to analyze 126 patient samples, generating up to 500 Gb of data per sample (40,000 potential markers) within 4 weeks.
By Nora C Toussaint, Ximena Bonilla, Tarun Mehra, Francis Jacob, Rebekka Wegmann, Julien Mena, Sandra Goetze, Franziska Singer, Anne Bertolini, Michael Prummer, Rudolf Aebersold, Holger Moch, Michael Weller, Markus G. Manz, Niko Beerenwinkel, Christian Beisel, Bernd Bodenmiller, Mitchell Levesque, Viktor H. Koelzer, Reinhard Dummer, Parisa Rahimzadeh, Natalia Chicherova
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Nature
Verified
Single-cell landscape of innate and acquired drug resistance in acute myeloid leukemia - Nature Communications
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Abstract Deep single-cell multi-omic profiling offers a promising approach to understand and overcome drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML). Here, we combine single-cell ex vivo drug profiling (pharmacoscopy) with single-cell and bulk DNA, RNA, and protein analyses, alongside clinical data from 21 rrAML patients.
By Rebekka Wegmann, Ximena Bonilla, Ricardo Coelho, Sandra Goetze, Francis Jacob, Jack Kuipers, Ulrike Lischetti, Julien Mena, Michael Prummer, Franziska Singer, Nora C Toussaint, Rudolf Aebersold, Niko Beerenwinkel, Christian Beisel, Bernd Bodenmiller, Viktor H. Koelzer, Mitchell Levesque, Holger Moch, Lucas Pelkmans, Andreas Wicki, Bernd Wollscheid, Markus G. Manz, Berend Snijder
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Nature
Verified
Spatial proteomics identifies JAKi as treatment for a lethal skin disease - Nature
Abstract Toxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction triggered by common medications and is an emerging public health issue1,2,3. Patients with TEN undergo severe and sudden epidermal detachment caused by keratinocyte cell death. Although molecular mechanisms that drive keratinocyte cell death have been proposed, the main drivers remain unknown, and there is no effective therapy for TEN4,5,6.
A targetable type III immune response with increase of IL-17A expressing CD4+ T cells is associated with immunotherapy-induced toxicity in melanoma - Nature Cancer
Abstract Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine and chemokine assays from serum at baseline and at the adverse event onset indicated aberrant T cell activity with differential expression of type I and III immune signatures.
The genetic evolution of acral melanoma - Nature Communications
Abstract Acral melanoma is an aggressive type of melanoma with unknown origins. It is the most common type of melanoma in individuals with dark skin and is notoriously challenging to treat. We examine exome sequencing data of 139 tissue samples, spanning different progression stages, from 37 patients. We find that 78.4% of the melanomas display clustered copy number transitions with focal amplifications, recurring predominantly on chromosomes 5, 11, 12, and 22.
MHC-I upregulation safeguards neoplastic T cells in the skin against NK cell-mediated eradication in mycosis fungoides - Nature Communications
Abstract Cancer-associated immune dysfunction is a major challenge for effective therapies. The emergence of antibodies targeting tumor cell-surface antigens led to advancements in the treatment of hematopoietic malignancies, particularly blood cancers. Yet their impact is constrained against tumors of hematopoietic origin manifesting in the skin.
INPP5A phosphatase is a synthetic lethal target in GNAQ and GNA11-mutant melanomas - Nature Cancer
Abstract Activating mutations in GNAQ/GNA11 occur in over 90% of uveal melanomas (UMs), the most lethal melanoma subtype; however, targeting these oncogenes has proven challenging and inhibiting their downstream effectors show limited clinical efficacy.
Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment - Nature Communications
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Proteins and antibodies HIS-tagged recombinant human Growth and Differentiation Factor-15 was produced in HEK293T cells (Invigate GmbH, Jena). The anti-human GDF-15 antibody used in this manuscript was generated in female C57BL/6J GDF-15-/–mice kindly provided by Dr. Jens Strelau (Heidelberg, Germany) and validated for binding affinity by surface plasmon resonance at NMI (Reutlingen, Germany). Specificity was tested by tissue cross-reactivity studies.
By Carmen Reitinger, Kilian Wistuba-Hamprecht, Hubert Hackl, Hemant R. Joshi, Phil Cheng, Mitchell Levesque, Matthias Goebeler, Markus Sauer, Falk Nimmerjahn, Stefanie von Felten, Michel Mittelbronn, Andreas Beilhack, Reinhard Dummer, Markus Haake, Lena Sorger, Jacob Späth, Rudi Beschorner, Alexander Thiem, Manfred Rüdiger
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Nature
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Isolation and detection of extracellular vesicles from melanoma cells and liquid biopsies using size-exclusion chromatography and nano-flow cytometry
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Investigating the tumor-immune microenvironment through extracellular vesicles from frozen patient biopsies and 3D cultures
Skip to main page content Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Save citation to file Format: Add to My Bibliography Your saved search Name of saved search: Search terms: Frequency: Which day? Which day? Report format: Send at most: Send even when there aren't any new results Optional text in email: Create a file for external citation management software Front Immunol. Display options Format doi: 10.3389/fimmu.2023.1176175.
Hanson a leader in nurturing girls sports at Benson High School
By Mitchell Levesque Reporter Swift County Monitor-News Janel Hanson has always liked sports. When she was younger she remembers going to state basketball games where her dad would cheer for the underdog. When she was in high school during the 1960s her brother was a three-sport athlete, playing basketball and football, as well as running track. However, Hanson never played at the varsity level herself.
Vaccinations fall among children worrisome
Submitted by admin on August 3, 2022 - 9:25am By Mitchell Levesque Reporter Swift County Monitor-News Concern rises about infectious disease at Countryside Public Health, the regional community health service agency as childhood immunizations decrease. For more on this story, subscribe to the Monitor-News and support community journalism.
Petersons turn passions into reality on rural Swift County farm
By Mitchell Levesque Reporter Swift County Monitor-New A little past eight on a morning in July, when the robin’s call could still be heard and the sun in the sky was past introductions, Kent Peterson nimbly placed lettuce seeds the size of peppercorns into small holes. The seeds were being planted in a foam-looking sheet of nutrient-rich, artificial soil and smothered in water, making the whole thing look like a soggy brownie.
AccessU - More Than Stress
By Mikayla Scrignoli A University of Minnesota psychiatrist’s podcast that destigmatizes and promotes understanding of common mental health diagnoses- but took a break in November 2020. Thirty episodes are still available for anyone who needs them.
Highlights • Co-infection of M. bovis and H. pylori boosts gastric Th1 responses and immunopathology • Gastric presence of H. pylori compromises immune control of M. bovis • Both mutual effects result from redirection of Treg cells to sites of M. bovis infection • CXCR3 blockade restores M. bovis control, even if H. pylori is present Summary The two human pathogens Helicobacter pylori and Mycobacterium tuberculosis (Mtb) co-exist in many geographical areas of the world.
Survey: More Minnesotans rise to fight racism, educate themselves about social injustice
Minnesota's Diverse Communities Survey Photos by Evan Frost, Christine T. Nguyen, Nicole Neri, Kathryn Styer Martinez and Courtney Perry for MPR News Minnesotans from various racial and ethnic backgrounds name community involvement, growing awareness of racism, as well as cultural celebrations and awareness as some of the most positive things going on in their communities currently, according to a new survey.
Targeting complex, adaptive responses in melanoma therapy
Highlights • Future targeted therapies require knowledge of complex adaptive drug responses. • Drug combinations should target diverse mechanisms such as metabolism or signaling. • Combined targeted/immune therapies show promise, but tolerability is problematic. Abstract Our understanding of the complex, adaptive mechanisms of response to targeted therapies in metastatic melanoma is now leading to more effective combination treatments.
Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation
Highlights • RNF125 binds to, ubiquitinates, and promotes degradation of JAK1 • Low RNF125 increases JAK1 and EGFR expression in BRAFi-resistant melanoma • The combination of JAK, BRAF, and EGFR inhibitors overcomes drug resistance • RNF125 expression in melanoma specimens inversely correlates with BRAFi resistance Summary Despite the remarkable clinical response of melanoma harboring BRAF mutations to BRAF inhibitors (BRAFi), most tumors become resistant.
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