160 results match your criteria: "Advanced Clinical Biosystems Research Institute.[Affiliation]"

Background: Inhibition of IL-4/IL-13 driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).

Objective: To assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.

Methods: Skin tape strip (STS) were collected from lesional/non-lesional skin of 20 AD patients during 16-week dupilumab treatment and from 20 healthy volunteers (HV) followed for 16-weeks.

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Cell Storage Conditions Impact Single-Cell Proteomic Landscapes.

J Proteome Res

January 2025

Department of Computational Biomedicine, Cedars Sinai Medical Center, Los Angeles, California 90048, United States.

Single cell transcriptomics (SCT) has revolutionized our understanding of cellular heterogeneity, yet the emergence of single cell proteomics (SCP) promises a more functional view of cellular dynamics. A challenge is that not all mass spectrometry facilities can perform SCP, and not all laboratories have access to cell sorting equipment required for SCP, which together motivate an interest in sending bulk cell samples through the mail for sorting and SCP analysis. Shipping requires cell storage, which has an unknown effect on SCP results.

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Single Cell Proteomics Reveals Specific Cellular Subtypes in Cardiomyocytes Derived from Human iPSCs and Adult Hearts.

Mol Cell Proteomics

January 2025

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048; Advanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048. Electronic address:

Single cell proteomics was performed on human induced pluripotent stem cells (iPSCs), iPSC-derived cardiomyocytes, and adult cardiomyocytes. Over 700 proteins could be simultaneously measured in each cell revealing unique subpopulations. A sub-set of iPSCs expressed higher levels of Lin28a and Tra-1-60 towards the outer edge of cell colonies.

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The prevalence of cardiovascular disease varies with sex, and the impact of intrinsic sex-based differences on vasculature is not well understood. Animal models can provide important insights into some aspects of human biology; however, not all discoveries in animal systems translate well to humans. To explore the impact of chromosomal sex on proteomic phenotypes, we used iPSC-derived vascular smooth muscle cells from healthy donors of both sexes to identify sex-based proteomic differences and their possible effects on cardiovascular pathophysiology.

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Author Correction: π-HuB: the proteomic navigator of the human body.

Nature

January 2025

State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.

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Silencing PADI-2 induces antitumor effects by downregulating NF-κB, Nrf2/HO-1 and AKT1 in A549 lung cancer cells.

Int Immunopharmacol

January 2025

Advanced Clinical Biosystems Research Institute, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Advanced Clinical Biosystems Research Institute, Precision Biomarker Laboratories, Cedars Sinai Medical Center, Los Angeles, CA, USA. Electronic address:

Objective: This study aimed to investigate the tumorigenic role and regulatory pathways of peptidyl arginine deiminase 2 (PAD-2) in A549 lung cancer cells following treatment with small interfering RNA (PADI-2 siRNA) or the pharmacological pan-PAD inhibitor BB-Cl amidine.

Materials And Methods: A549 lung cancer cells were treated with PADI-2 siRNA to knock down PADI-2 expression or with BB-Cl amidine to inhibit PAD2 activity. The effects on cell proliferation, migration, invasion, and cell cycle phases were assessed.

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Cisplatin-based chemotherapy is used across many common tumor types, but resistance reduces the likelihood of long-term survival. We previously found the puromycin-sensitive aminopeptidase, NPEPPS, as a druggable driver of cisplatin resistance in vitro and in vivo and in patient-derived organoids. Here, we present a general mechanism where NPEPPS interacts with the volume-regulated anion channels (VRACs) to control cisplatin import into cells and thus regulate cisplatin response across a range of cancer types.

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π-HuB: the proteomic navigator of the human body.

Nature

December 2024

State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

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Article Synopsis
  • * Researchers administered a drug called PR-364 to mice after a heart attack, finding it significantly reduced mortality, preserved heart function, and slowed heart failure progression.
  • * The findings revealed that PR-364 boosted the removal of damaged mitochondria and improved energy production in heart cells, suggesting it could be a promising treatment to protect heart tissue after a heart attack.
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Bioinformatics software tools are essential to identify informative molecular features that define different phenotypic sample groups. Among the most fundamental and interrelated tasks are missing value imputation, signature gene detection, and differential pattern visualization. However, many commonly used analytics tools can be problematic when handling biologically diverse samples if either informative missingness possess high missing rates with mixed missing mechanisms, or multiple sample groups are compared and visualized in parallel.

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Article Synopsis
  • The Human Proteome Project (HPP) aims to identify every protein-coding gene’s isoform and integrate proteomics into studies of human health and disease.
  • Major updates include the retirement of neXtProt as the knowledge base, with UniProtKB now serving as the reference proteome, and GENCODE providing the target protein list.
  • Recent data shows that 93% of protein-coding genes have been expressed, leaving 1,273 non-expressed proteins, along with the introduction of a new scoring system for functional annotation of proteins.
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PAD inhibition downregulates the cellular fibrotic behavior of senescent myofibroblasts derived from dilated cardiomyopathy.

Biomed Pharmacother

November 2024

Advanced Clinical Biosystems Research Institute, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Advanced Clinical Biosystems Research Institute, Precision Biomarker Laboratories, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address:

Background: Dilated cardiomyopathy (DCM) is characterized by enlarged, weakened heart ventricles due to chronic fibrosis. Dysfunctional senescent myofibroblasts and excessive citrullination have been implicated in fibrotic diseases. Peptidylarginine deiminases (PADs) are involved in the citrullination of ECM proteins.

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  • Huntington's disease (HD) is linked to a mutation in the Huntingtin gene that disrupts normal brain function, and the study investigates how SUMOylation affects proteins involved in neuronal activity in HD mice.* -
  • Using advanced mass spectrometry, researchers found changes in SUMOylated proteins related to synaptic function and signaling pathways in HD tissue, which were different from non-transgenic mice.* -
  • Experiments on neurons from HD and control mice revealed that altering SUMOylation, particularly via the Pias1 protein, can improve signaling and activity deficits observed in HD cells.*
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Article Synopsis
  • * In patients with morbid obesity and HFpEF, there are notable changes in heart muscle cells, including disrupted calcium response, altered gene expression, and cellular structure issues.
  • * Advanced imaging techniques revealed severe damage to heart muscle, particularly in the most obese patients, including mitochondrial dysfunction and reduced fatty acid processing, independent of diabetes.
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Article Synopsis
  • Proteomics is the extensive study of proteins, focusing on their structure and function through methods like identification and quantification.
  • The main approach, known as "shotgun" or "bottom-up proteomics," involves breaking proteins into smaller peptides for analysis via mass spectrometry.
  • This review aims to guide newcomers in proteomics by explaining various methods from basic biochemistry and protein extraction to interpretation and validation of results.
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This Technical Note presents a comprehensive proteomics workflow for the new combination of Orbitrap and Astral mass analyzers across biofluids, cells, and tissues. Central to our workflow is the integration of Adaptive Focused Acoustics (AFA) technology for cells and tissue lysis to ensure robust and reproducible sample preparation in a high-throughput manner. Furthermore, we automated the detergent-compatible single-pot, solid-phase-enhanced sample Preparation (SP3) method for protein digestion.

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Single-cell omics data analysis pipelines are complicated to design and difficult to share or reproduce. We describe a web platform that enables no-code analysis pipeline design, simple computing via the Open Science Grid, and sharing of entire data analysis pipelines, their input data, and interactive results. We expect this platform to increase the accessibility and reproducibility of single-cell omics.

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Proteomes are well known to poorly correlate with transcriptomes measured from the same sample. While connected, the complex processes that impact the relationships between transcript and protein quantities remains an open research topic. Many studies have attempted to predict proteomes from transcriptomes with limited success.

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Rapid Plasma Proteome Profiling via Nanoparticle Protein Corona and Direct Infusion Mass Spectrometry.

J Proteome Res

August 2024

Department of Computational Biomedicine, Cedars Sinai Medical Center, Los Angeles, California 90048, United States.

Noninvasive detection of protein biomarkers in plasma is crucial for clinical purposes. Liquid chromatography-mass spectrometry (LC-MS) is the gold standard technique for plasma proteome analysis, but despite recent advances, it remains limited by throughput, cost, and coverage. Here, we introduce a new hybrid method that integrates direct infusion shotgun proteome analysis (DISPA) with nanoparticle (NP) protein corona enrichment for high-throughput and efficient plasma proteomic profiling.

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Identification of retinal oligomeric, citrullinated, and other tau isoforms in early and advanced AD and relations to disease status.

Acta Neuropathol

July 2024

Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., A6212, Los Angeles, CA, 90048, USA.

Article Synopsis
  • * Researchers analyzed retinal samples from AD patients (both mild cognitive impairment and dementia) and matched controls, finding significant increases in various tau isoforms, particularly in advanced AD cases.
  • * Strong correlations were identified between specific retinal tau isoforms and brain pathology, indicating that changes in the retina could reflect the severity of cognitive decline and neurodegeneration in AD patients.
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Objectives: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG).

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Acoustic ejection mass spectrometry empowers ultra-fast protein biomarker quantification.

Nat Commun

June 2024

Advanced Clinical Biosystems Research Institute, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.

The global scientific response to COVID 19 highlighted the urgent need for increased throughput and capacity in bioanalytical laboratories, especially for the precise quantification of proteins that pertain to health and disease. Acoustic ejection mass spectrometry (AEMS) represents a much-needed paradigm shift for ultra-fast biomarker screening. Here, a quantitative AEMS assays is presented, employing peptide immunocapture to enrich (i) 10 acute phase response (APR) protein markers from plasma, and (ii) SARS-CoV-2 NCAP peptides from nasopharyngeal swabs.

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Bioinformatics software tools are essential to identify informative molecular features that define different phenotypic sample groups. Among the most fundamental and interrelated tasks are missing value imputation, signature gene detection, and differential pattern visualization. However, many commonly used analytics tools can be problematic when handling biologically diverse samples if either informative missingness possess high missing rates with mixed missing mechanisms, or multiple sample groups are compared and visualized in parallel.

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Article Synopsis
  • Hypertrophic cardiomyopathy (HCM) is a heart condition caused by gene mutations in about half of the patients, while the other half don't have these mutations.
  • Researchers studied heart tissue from patients to understand how energy use and fat processing changes in both groups of HCM patients.
  • They found different metabolic changes between the two groups that affect how the disease progresses in the heart.
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Background: Descending thoracic aortic aneurysms and dissections can go undetected until severe and catastrophic, and few clinical indices exist to screen for aneurysms or predict risk of dissection.

Methods: This study generated a plasma proteomic dataset from 75 patients with descending type B dissection (Type B) and 62 patients with descending thoracic aortic aneurysm (DTAA). Standard statistical approaches were compared to supervised machine learning (ML) algorithms to distinguish Type B from DTAA cases.

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