bims-scepro Biomed News
on Stem cell proteostasis
Issue of 2026–11–15
fifteen papers selected by
William Grey, University of York
  1. Early hematopoietic fate decisions are independent of bone marrow niche.
  2. ADGRE2: A Promising Immunotherapeutic Target in Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia.
  3. Mediator kinase inhibition exposes a transcriptional vulnerability and synergizes with venetoclax in AML.
  4. Nuclear Receptor Nur77 Orchestrates Hematopoietic Lineage Commitment to Avert Anemia in Diabetes.
  5. CASM regulates lysosomal expansion and cell fate during senescence.
  6. Altered protein cysteine reactivity in senescent cells is a vulnerability for senolysis to ameliorate aging.
  7. Ultra-High-Throughput Tracking and Lineage Analysis of Cancer Stem Cells.
  8. Evolutionary dynamics in the years preceding acute myeloid leukaemia.
  9. Genomic characterization of patient derived xenograft models of multiple myeloma reveals selection of multiple pre-existing high risk clones.
  10. When cord blood grafts may be the preferred donor choice: a position statement from the ASTCT Cord Blood Special Interest Group.
  11. Non-cell-autonomous removal of protein aggregates via trogocytosis.
  12. Targeting a Calcium-Associated Mitochondrial Vulnerability in TET2-Deficient Myeloid Cells.
  13. A retinol-SREBP1-ELOVL6 lipogenic axis remodels NK cell biomechanics and constrains immune surveillance during aging.
  14. LAMPrEY: a Python-Based Automated Quality Control Tool for Large-Scale Proteomics Datasets.
  15. Genomic, single-cell, and functional profiling of the CD48-CD244 axis and NK cell dysfunction in multiple myeloma.
  1. bioRxiv. 2026 Oct 23. pii: 2026.10.20.760390. [Epub ahead of print]
    Early hematopoietic fate decisions are independent of bone marrow niche.
    Christian A Reardon-Lochbaum, Paolo Cadinu, Hao Zhang, Alan B Cantor, Jeffrey R Moffitt.
      Hematopoietic stem cells (HSCs) reside in specialized bone marrow microenvironments, termed niches, which regulate self-renewal and differentiation through local support programs. Although multiple anatomically distinct niches with unique cellular compositions have been described, it remains unclear to what degree these niches differentially shape HSC fate. In parallel, hematopoietic output is modulated with age, yet it remains unclear if this shift in HSC fate is driven by niche-specific modifications. To address these questions, we applied Multiplexed Error Robust Fluorescence in situ Hybridization to jointly define the cellular and spatial organization of the femoral marrow in young and aged mice. We find that while HSC niches are anatomically and compositionally distinct, stem cell lineage priming is not strongly associated with niche identity consistent with our demonstration that fate-shaping signals are provided redundantly across niches. Moreover, we find that while aging remodels the cellular composition of the marrow, reshapes cellular expression, and alters hematopoietic differentiation, HSC niches are preserved, and HSC fate remains niche agnostic. Together these findings separate anatomical niche identity from early HSC fate decisions and are consistent with a model in which hematopoietic support is distributed across different niche locations rather than partitioned among discrete sites.
    DOI:  https://doi.org/10.64898/2026.10.20.760390
  2. Cancer Med. 2026 Nov;pii: e72497. [Epub ahead of print]15(11):
    ADGRE2: A Promising Immunotherapeutic Target in Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia.
    Jennifer Neiss, Lisa Hemetsberger, Carolin Schaefer, Marc Rijksen, Antonia Schwab, Armin Zebisch, Andreas Reinisch, Heinz Sill, Annkristin Heine, Albert Wölfler.
      Acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) are heterogeneous myeloid malignancies with limited therapeutic options and often poor long-term prognosis due to persistence of therapy-resistant leukemic stem cells (LSC). Immunotherapeutic approaches have demonstrated high efficacy in lymphoid malignancies, but their application in AML and CMML remains challenging due to the lack of targetable (neo-)antigens. Here we investigated the expression of the adhesion G protein-coupled receptor E2 (ADGRE2) in diagnostic samples from 124 AML and 28 CMML patients using multiparameter flow cytometry and publicly available expression databases. ADGRE2 was significantly overexpressed on leukemic blasts in both AML and CMML compared to normal CD34+ hematopoietic stem and progenitor cells (HSPCs). ADGRE2 surface expression was high within the CD34+/38- and GPR56high LSC-enriched compartments, comparably distributed with minor differences among subgroups and high in distinct samples with low expression of established immunotherapeutic targets, such as CD33 and CLL-1. Our findings further corroborate ADGRE2 as a promising (complementary) immunotherapeutic target in myeloid malignancies.
    Keywords:  acute myeloid leukemia; chronic myelomonocytic leukemia; targeted therapy
    DOI:  https://doi.org/10.1002/cam4.72497
  3. Leukemia. 2026 Nov 11.
    Mediator kinase inhibition exposes a transcriptional vulnerability and synergizes with venetoclax in AML.
    Camille Aitchedji, Céline Moison, Simon Fortier, Rodrigo Mendoza-Sanchez, Deanne Gracias, Jean-François Spinella, Bounkham Thavonekham, Tara MacRae, Nadine Mayotte, Mélanie Fréchette, Valérie Blouin-Chagnon, Koryne Léveillé, Jalila Chagraoui, Réjean Ruel, Josée Hébert, Anne Marinier, Guy Sauvageau.
      Acute myeloid leukemia (AML) is a heterogeneous and aggressive hematologic malignancy associated with poor survival despite recent therapeutic advances. To identify novel anti-leukemic agents, we performed a high-throughput viability screen of 10,000 small molecules across 56 genetically diverse primary AML samples. Compounds with similar activity profiles were grouped into Compound Correlation Clusters (CCCs), leading to the identification of CCC163, which includes AML874, as a potent and selective hit. Integrated pharmacological and CRISPR-Cas9 approaches identified the Mediator complex as the molecular target of AML874. We demonstrated that AML874 acts as a selective CDK8/CDK19 inhibitor, disrupting Mediator-dependent transcription. FLT3-mutated AML showed increased sensitivity to AML874, suggesting a subtype-specific vulnerability. Notably, CDK8 inhibition synergized with venetoclax in AML cell lines and patient-derived xenograft models, resulting in enhanced anti-leukemic activity in vivo. Collectively, these findings establish CDK8/CDK19 inhibition as a therapeutically relevant strategy in AML.
    DOI:  https://doi.org/10.1038/s41375-026-03173-0
  4. Blood. 2026 Nov 10. pii: blood.2026034088. [Epub ahead of print]
    Nuclear Receptor Nur77 Orchestrates Hematopoietic Lineage Commitment to Avert Anemia in Diabetes.
    Qiao-Ling Huang, De-Yi Feng, Yinxiang Huang, Qi-Tao Chen, Wen-Xiu Zhao, Xiao-Xue Li, Qian Xiao, Heng-Hui Li, Rong Wu, Yi Zhang, Yue Chen, Xuejun Li, Qiao Wu, Caoxin Huang, Hang-Zi Chen.
      Anemia is a prevalent but poorly understood complication of diabetes mellitus. Here, we identify orphan nuclear receptor Nur77 as a critical suppressor of diabetic anemia. Nur77 expression was downregulated in hematopoietic stem and progenitor cells (HSPCs) from diabetic patients with anemia. In multiple diabetic mouse models, knockout of Nur77 induced anemia, a phenotype recapitulated by bone marrow transplantation. Mechanistically, Nur77 functioned as a transcriptional repressor in HSPCs, whose deficiency, together with diabetes-associated epigenetic modifications, enhanced chromatin accessibility and expression of genes involved in myeloid leukocyte differentiation. Consequently, this led to myeloid leukocyte-biased differentiation of HSPCs at the expense of erythroid lineage. Pharmacological upregulation of Nur77 with its agonist cytosporone B (Csn-B) effectively prevented anemia in diabetic mice. Clinically, Nur77 levels in HSPCs of diabetic patient negatively correlated with anemia occurrence. Collectively, our findings reveal a novel Nur77-mediated pathway in diabetic anemia pathogenesis and propose Nur77 as a new therapeutic target.
    DOI:  https://doi.org/10.1182/blood.2026034088
  5. JCI Insight. 2026 Nov 09. pii: e207890. [Epub ahead of print]11(21):
    CASM regulates lysosomal expansion and cell fate during senescence.
    Yu-Wei Cheng, Michael Z Gao, Jay Xiaojun Tan, Jie Liu, Toren Finkel.
      Cellular senescence, a hallmark of aging, is accompanied by a striking expansion of the cell's lysosomal compartment, yet the pathway leading to increased lysosomal content remains unresolved. Here, we demonstrate that the master lysosomal transcriptional regulator TFEB is activated during senescence through a pathway that involves conjugation of ATG8 onto single membranes (CASM). Using various senescence inducers, we show that senescence induction triggers robust TFEB nuclear translocation and upregulation of TFEB target genes. In contrast, inhibition of the core CASM machinery by CRISPR-mediated deletion of either ATG16L1, ATG12, or ATG5 markedly reduced senescence-induced TFEB nuclear translocation. In ATG16L1-KO cells, reconstitution with WT ATG16L1 but not the CASM-defective ATG16L1F467A mutant restored both ATG8 lipidation on the lysosomal surface and TFEB activation. Moreover, expression of the Salmonella effector protein SopF, a previously described specific CASM inhibitor, similarly blocked senescence-induced TFEB translocation. Functionally, upon stress, CASM-deficient cells exhibited a pronounced shift away from senescence and toward a cell death fate, a phenotype reversed by expressing a constitutively active form of TFEB. Together, these findings identify CASM-dependent TFEB activation as an essential mechanism enabling senescence-associated lysosomal expansion and suggest that lysosomal capacity modulates cell fate decisions in the aftermath of acute stress.
    Keywords:  Aging; Cell biology; Lysosomes
    DOI:  https://doi.org/10.1172/jci.insight.207890
  6. Nat Aging. 2026 Nov;6(11): 2469-2492
    Altered protein cysteine reactivity in senescent cells is a vulnerability for senolysis to ameliorate aging.
    Rong Wu, Fan Yang, Jiacheng Li, Tong Wu, Ruitu Lyu, Junhong Xiang, Xue Gao, Rukang Zhang, Hao Fan, Chunzhao Yin, Jiayi Tu, Zhicheng Xie, Chufan Cai, Freya Q Zhang, Kelly Xue, Jeronimo Najarro, Lei Dong, Rui Su, Angelo Y Meliton, Em Lundberg, Jonah K Chen, Janane Rahbani, Nickolai O Dulin, Nicole Arellano, Jun-Wei B Hughes, Shannon E Elf, Yu-Ying He, Bruce M Bissonnette, Robert B Hamanaka, Gökhan M Mutlu, Judith Campisi, Chuan He, Jing Chen.
      How diet shapes aging and age-related diseases marked by senescent cell accumulation remains unclear. Here we report vanadyl sulfate (VS), a mineral dietary supplement, as a senolytic agent. Oral VS ameliorates phenotypes of aging and diverse age-related disorders and extends lifespan in male mice. Integrated functional omics analyses show that senescent cells exhibit globally reduced proteome cysteine reactivity but increased expression and apparent cysteine reactivity of proteins essential for endoplasmic reticulum proteostasis. This redox-proteostasis state is linked to glutathione disulfide (GSSG) accumulation and can be recapitulated by GSSG delivery in nonsenescent cells. Mechanistically, VS inactivates reactive cysteines and promotes disulfide bond formation in senescent cells, leading to protein misfolding, aggregation and ultimately cell death. Glutathione reductase downregulation promotes GSSG accumulation, distinguishing senescent from nonsenescent cells and conferring selective susceptibility to VS. Our findings reveal an exploitable redox-proteostasis vulnerability of senescent cells with therapeutic potential to ameliorate aging.
    DOI:  https://doi.org/10.1038/s43587-026-01253-5
  7. Methods Mol Biol. 2026 Nov 13.
    Ultra-High-Throughput Tracking and Lineage Analysis of Cancer Stem Cells.
    Emeline Fontaine, Mathilde Brulé, Anaïs Horochowska, Chann Lagadec, François Anquez.
      Lineage analysis is a fundamental approach for understanding cellular dynamics and the propagation of phenotypic states across generation. In the context of cancer stem cells, longitudinal single-cell monitoring is particularly relevant for studying division patterns, phenotypic plasticity, and intergenerational propagation of stemness-associated traits. Recent advances in high-throughput time-lapse microscopy, combined with automated single-cell tracking and the use of fluorescent reporters provide a powerful framework for large-scale lineage reconstruction. Here we describe a complete and reproducible pipeline enabling the reconstruction of cell lineage trees from long-term two-dimensional live-cell imaging datasets, with a specific focus on cancer stem cells.This workflow integrates protocols for video-microscopy acquisition, image restoration, automated segmentation and data processing, statistical analysis, and output generation. This approach enables quantitative investigation of cell cycle dynamics, division symmetry, intergenerational phenotype propagation, and variability in lineage behavior. While illustrated using breast cancer stem cell models, the pipeline can be applied to any two-dimensional adherent cell line and long-term time-lapse microscopy.
    Keywords:  Cancer stem cells; Cell cycle dynamics; High-throughput time-lapse microscopy; Lineage reconstruction; Single-cell tracking
    DOI:  https://doi.org/10.1007/7651_2026_723
  8. Nature. 2026 Nov 11.
    Evolutionary dynamics in the years preceding acute myeloid leukaemia.
    Caroline J Watson, Gladys Y P Poon, Hamish A J MacGregor, Adriana V A Fonseca, Sophia Apostolidou, Aristi Damaskou, Christopher Boniface, Samuel Hackett, Aleksandra Gentry-Maharaj, Usha Menon, Jamie R Blundell.
      Somatic evolution in ageing tissues underlies many cancers1,2. However, our quantitative understanding of the rules governing this pre-cancerous evolution remains incomplete. Here we exploit a unique collection of serial blood samples3, collected annually for up to a decade and beginning as early as 15 years before diagnosis of acute myeloid leukaemia, to provide a quantitative description of pre-cancerous evolutionary dynamics. Using deep duplex sequencing and evolutionary theory, we quantify the acquisition ages and fitness effects of the key driver events in acute myeloid leukaemia development. The first driver mutations are typically acquired in the first few decades of life, when the blood remains highly polyclonal. These early slow-growing clones subsequently acquire multiple further driver mutations that confer selective advantages up to 100-fold larger than the early drivers. These faster-growing clones harbouring multiple driver mutations can cause complete somatic sweeps of the blood decades before diagnosis, a feature strongly associated with future acute myeloid leukaemia. Our data show that the clonal dynamics of blood are consistent with a set of remarkably simple evolutionary rules that strike a balance between chance and determinism.
    DOI:  https://doi.org/10.1038/s41586-026-11269-x
  9. bioRxiv. 2026 Oct 16. pii: 2026.10.14.755992. [Epub ahead of print]
    Genomic characterization of patient derived xenograft models of multiple myeloma reveals selection of multiple pre-existing high risk clones.
    Nathan J Becker, Enze Liu, Riya Sharma, Parvathi Sudha, Sara Ortega Bertran, Oumaima Jaouadi, Sreejeta Mondal, Nelia Luviano, Maurizio Affer, Kiran K Mangalaparthi, Akhilesh Pandey, Marios Papadimitriou, Benjamin T Diamond, David G Coffey, Abhishek Pandey, James Hoffman, Gil Hevroni, Dickran Kazandjian, Kelvin Lee, Gareth J Morgan, Faith E Davies, Attaya Suvannasankha, Aneta Mikulasova, Ola Landgren, Rafat Abonour, Brian A Walker.
      Multiple myeloma (MM) is a genomically complex malignancy of terminally differentiated plasma cells. Here, we have utilized the SCID-rab patient derived xenograft (PDX) model as a platform to expand scarce primary MM samples across disease stages and major cytogenetic subgroups for comprehensive molecular analysis. The model generated abundant CD138+ cells while retaining key genomic, transcriptomic and proteomic features of corresponding patient tumors. Compared with human myeloma cell lines, PDX cells more closely resembled primary MM in proliferative state and expression of therapeutically relevant targets. Whole genome sequencing (WGS) and single-cell WGS showed that PDXs arose from the selection of pre-existing subclones, including clones harboring high-risk alterations and convergent mechanisms of tumor suppressor inactivation. These findings establish SCID-rab PDX models as a platform for multi-omic profiling, studying clonal evolution, and determining therapeutic response in MM.
    DOI:  https://doi.org/10.64898/2026.10.14.755992
  10. Transplant Cell Ther. 2026 Nov 13. pii: S2666-6367(26)00896-1. [Epub ahead of print]
    When cord blood grafts may be the preferred donor choice: a position statement from the ASTCT Cord Blood Special Interest Group.
    American Society for Transplantation and Cellular Therapy Cord Blood Special Interest Group
      The introduction and wide adoption of post-transplant cyclophosphamide-based graft-versus host disease (GVHD) prophylaxis has changed the landscape of allograft donor selection such that allograft candidates now commonly have multiple potential graft sources, and there can be uncertainty over which graft source to prioritize. This position statement, written by the American Society for Transplantation and Cellular Therapy Cord Blood (CB) Special Interest Group and leading CB transplant physicians in the United States and abroad, discusses the state-of-the-art in CB transplantation (CBT). We highlight recent outcome data from multiple domestic and international centers with CBT expertise, across both adult and pediatric settings. Applying these data, we outline 4 clinical scenarios where CB may be the graft of choice: patients who lack a suitable, young, readily available donor, those in need of urgent transplantation, patients with difficult-to-cure acute leukemia or myelodysplastic syndrome, and patients with non-malignant diseases. We also present potential mechanisms underlying the unique graft-versus-leukemia effects mediating reduced relapse following CBT, along with the advantages of reduced chronic GVHD. This position statement emphasizes the critical, ongoing role of CBT in the transplant field, and will help guide transplant physicians to consider CBT as a preferred donor (or, as needed, referral to a center with CBT expertise) for patients in these scenarios.
    Keywords:  Allogeneic transplantation; Cord blood; Donor selection; alternative donor; graft choice; graft source
    DOI:  https://doi.org/10.1016/j.jtct.2026.11.025
  11. bioRxiv. 2026 Oct 19. pii: 2026.10.13.758691. [Epub ahead of print]
    Non-cell-autonomous removal of protein aggregates via trogocytosis.
    Yoshitaka Kimura, Kazuki Sato, Arun R Chavan, William Kasberg, Malan Silva, Wei Qiu, Nirmala Iyer, Michael Innerberger, Igor Siwanowicz, Scott D Pope, Athreya Rangavajhula, Gang-Qing Yao, Karl Insogna, Eric T Trautman, Christopher K E Bleck, Xiaolei Su, Jennifer Lippincott-Schwartz, Ruslan Medzhitov.
      Protein aggregate formation can cause cell damage and contribute to tissue pathologies including neurodegeneration. Protein aggregates are normally eliminated by cell-intrinsic mechanisms of lysosomal (autophagic) degradation. However, degradative capacity varies between cell types, raising the possibility that high-capacity cell types, such as macrophages, may contribute to aggregate disposal from the low-capacity cells. Here, we show that cellular protein aggregates are removed by macrophages via trogocytosis - a partial engulfment of the target cells. Lysosomal stress upon protein aggregate accumulation promotes cell surface expression of the transmembrane isoform of the macrophage growth factor CSF1 (tmCSF1), which is detected by macrophages through the CSF1 receptor to drive trogocytosis. Insufficient or impaired degradation of protein aggregates in lysosomes results in their transport along microtubules to the plasma membrane where they physically associate with tmCSF1. This enables macrophages to specifically trogocytose protein aggregates. These findings reveal a protein homeostasis system that eliminates protein aggregates in a non-cell-autonomous manner.
    DOI:  https://doi.org/10.64898/2026.10.13.758691
  12. Adv Sci (Weinh). 2026 Nov 09. pii: e78748. [Epub ahead of print]
    Targeting a Calcium-Associated Mitochondrial Vulnerability in TET2-Deficient Myeloid Cells.
    Yue Wang, Minh Duc Pham, Despina Stefanoska, Ting Yuan, Arka Provo Das, Chaonan Zhu, Meiqian Wu, Thanh Thuy Duong, Jaskiran Kaur, Yu Hao, Johannes Krefting, Marius Schwab, Jonathan Ward, Maria Duda, Wesley Abplanalp, Moritz von Scheidt, Andreas M Zeiher, Stefanie Dimmeler, Jaya Krishnan.
      Clonal hematopoiesis (CH) driven by loss-of-function mutations in TET2 is associated with increased cardiovascular risk, yet therapeutic strategies capable of preferentially targeting pathogenic TET2-deficient myeloid effector cells remain poorly defined. Here, we identify a TET2 loss-of-function-associated ion-mitochondrial vulnerability that enables preferential pharmacological suppression of TET2-deficient macrophages. Using chemical-genetic profiling, we find that perturbation of ion homeostasis preferentially compromises survival of TET2-deficient macrophages through increased mitochondrial-enriched Ca2+-sensitive signaling and activation of intrinsic apoptotic pathways. The cardiac glycoside Lanatoside C preferentially induces mitochondrial depolarization and apoptosis in TET2-deficient macrophages, with substantially smaller effects in control cells. In multicellular human cardiac organoids, preferential reduction of TET2-knockdown macrophages suppresses inflammatory remodeling, reduces cardiomyocyte apoptosis and fibrosis, and improves abnormal calcium-handling dynamics. In a murine partial donor-cell reconstitution model, Lanatoside C reduced relative donor-derived monocyte and neutrophil frequencies in Tet2-deficient donor-cell recipients; these findings do not establish effects on stem-cell fitness. Together, these findings identify a pharmacologically exploitable ion-mitochondrial vulnerability associated with TET2 loss-of-function and establish human cardiac organoids as a platform for causal interrogation of immune-driven cardiovascular pathology.
    Keywords:  Lanatoside C; TET2; cardiac organoids; cardioinflammation; clonal hematopoiesis; macrophages; mitochondrial calcium signaling
    DOI:  https://doi.org/10.1002/advs.78748
  13. Nat Aging. 2026 Nov 11.
    A retinol-SREBP1-ELOVL6 lipogenic axis remodels NK cell biomechanics and constrains immune surveillance during aging.
    Xinru Liu, Zhuanghao Hou, Tingting Liang, Mingming Zhu, Rui Zhao, Lili Qian, Tianfeng Jin, Xian Song, Guangming Huang, Fang Ni.
      Aging is associated with a progressive decline in immune surveillance, yet the mechanisms that constrain this process remain incompletely understood. Here we uncover a lipid-biomechanical mechanism in human natural killer (NK) cells that contributes to age-related immune decline. We show that aging drives a coordinated metabolic and physical state in NK cells, marked by lipid accumulation, increased membrane fluidity, reduced cortical stiffness and defective immune synapse organization, ultimately impairing target cell killing. Mechanistically, aging induces a retinoid-dependent metabolic shift in NK cells, characterized by enhanced retinol uptake and intracellular retinoic acid accumulation, which activates an SREBP1-dependent lipogenic program with ELOVL6 as a key downstream effector. This program remodels fatty-acyl composition, alters membrane and cortical mechanics, and constrains NK cell cytotoxic function. ELOVL6 inhibition restores membrane and cortical mechanics, rescues cytotoxicity in vitro and enhances antitumor activity in mouse models. These findings establish a targetable biomechanical mechanism linking aging to impaired immune surveillance.
    DOI:  https://doi.org/10.1038/s43587-026-01262-4
  14. Anal Chem. 2026 Nov 10. 98(44): 30098-30105
    LAMPrEY: a Python-Based Automated Quality Control Tool for Large-Scale Proteomics Datasets.
    Mario E Valdés-Tresanco, Soren Wacker, Mario S Valdés-Tresanco, Andriy Plakhotnyk, Nicholas I Brodie, Morgan Hepburn, Annegret Ulke-Lemée, Edward L Huttlin, Ian A Lewis.
      Over the past years, proteomics has moved increasingly towards the analysis of large cohorts of biological specimens. This has been made possible by significant improvements in mass spectrometry technology, chromatographic separation methods, and improved data acquisition strategies. These technological advances now routinely enable experiments that yield vast datasets that substantially outstrip the capacity of existing proteomics data analysis approaches. Processing such large datasets requires purpose-built, quality control tools designed to organize and analyze the data while recording all processing parameters for reproducibility. To address this need, we developed an open-source, Python-based software platform, Large-scale Automated Multi-level Proteomics Evaluation by Python (LAMPrEY), a comprehensive quality-control pipeline for Tandem-Mass-Tag (TMT) based quantitative proteomics analyses of large cohorts of samples. LAMPrEY features GUI-based file submission, automated processing with MaxQuant and RawTools, an interactive analytics dashboard, and an application programming interface (API) for programmatic usage that collectively enable rapid, reproducible analysis and interpretation of proteomics data. We demonstrate the longitudinal monitoring and analytical capabilities of LAMPrEY using TMT11 quantitative proteomics data generated from 910 Enterococcus faecium isolates collected from bloodstream infection patients. LAMPrEY is an open-source software that can be accessed at www.lewisresearchgroup.org/software.
    Keywords:  LC-MS; Python; Tandem-mass-tag; large-scale; open-source; proteomics; quality control
    DOI:  https://doi.org/10.1021/acs.analchem.6c02944
  15. JCI Insight. 2026 Nov 09. pii: e203794. [Epub ahead of print]11(21):
    Genomic, single-cell, and functional profiling of the CD48-CD244 axis and NK cell dysfunction in multiple myeloma.
    Bonell Patiño-Escobar, Torsten Steinbrunn, Lucy Perez-Lugo, Sham Rampersaud, Daniel D Waller, Daniela Ordoñez, Huimin Geng, Fernando Salangsang, Paul Phojanakong, Juan Antonio Camara Serrano, Yan Zeng, Veronica Steri, Oscar A Aguilar, Constantine S Mitsiades, Arun P Wiita.
      Multiple myeloma (MM) orchestrates immune evasion by subverting natural killer (NK) cell function. CD48, one of the most abundant NK ligands on MM cells, paradoxically enhances NK cell activation yet is associated with high-risk cytogenetics and poor patient survival. We integrated multiomics (bulk and single-cell RNA-seq, assay for transposase-accessible chromatin using sequencing [ATAC-seq], chromatin immunoprecipitation sequencing [ChIP-seq]), genome-wide CRISPR knockout/activation screens, and machine learning to dissect CD48 regulation and function. In human MM and Vκ*MYC mouse scRNA-seq datasets, NK cells exhibit stepwise increases in inflammatory and exhaustion signatures and loss of cytotoxic potential as disease progresses. In vitro coculture assays show that CD48 overexpression on MM enhances NK cell cytokine secretion, whereas chronic exposure leads to ex vivo NK dysfunction. In vivo, CD48-overexpressing Vκ*MYC tumors progress more slowly and extend host survival, while NK cell depletion accelerates disease. These findings support a context-dependent role for CD48, potentiating acute NK responses while coexisting with chronic NK exhaustion, and suggest strategies to modulate CD48 for therapeutic benefit.
    Keywords:  Cell biology; Hematology; Immunology; Machine learning; Molecular genetics; NK cells
    DOI:  https://doi.org/10.1172/jci.insight.203794
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