A5054969234- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Bladder and Urothelial Cancer Treatments
- Proteoglycans and glycosaminoglycans research
- Renal cell carcinoma treatment
- Evolution and Genetic Dynamics
- Dupuytren's Contracture and Treatments
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- CRISPR and Genetic Engineering
- Chemotherapy-related skin toxicity
- Nail Diseases and Treatments
- Medical Imaging and Pathology Studies
- Lung Cancer Treatments and Mutations
- Carbohydrate Chemistry and Synthesis
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Platelet Disorders and Treatments
- Animal Genetics and Reproduction
- Pneumocystis jirovecii pneumonia detection and treatment
- Evolutionary Game Theory and Cooperation
- Urinary Bladder and Prostate Research
- Nutrition, Genetics, and Disease
- Nanoparticle-Based Drug Delivery
Chalmers University of Technology
2019-2024
Broad Institute
2017-2021
Harvard University
2021
University of Zurich
2013-2017
SIB Swiss Institute of Bioinformatics
2013-2015
Rudjer Boskovic Institute
2008-2010
Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine plasma free glycosaminoglycan profiles (GAGomes) tumor metabolism for multi-cancer early detection (MCED) of 14 types using 2,064 samples from...
Significance Translation is a fundamental biochemical process in which ribosomes use an mRNA’s nucleotide sequence as template to synthesize protein with specific amino acid sequence. Errors this are deleterious because they can alter protein’s structure. Yet such errors surprisingly frequent. Here we ask whether and how evolution affect the ability of proteins cope these errors. In principle, could reduce rate errors, or it leave unchanged but damaging effects We find that populations...
Abstract Precision oncology aims to tailor clinical decisions specifically patients with the objective of improving treatment outcomes. This can be achieved by leveraging omics information for accurate molecular characterization tumors. Tumor tissue biopsies are currently main source profiling. However, invasive and limited in resolving spatiotemporal heterogeneity tumor tissues. Alternative non-invasive liquid exploit patient’s body fluids access multiple layers tumor-specific biological...
Abstract The ribosome represents a promising avenue for synthetic biology, but its complexity and essentiality have hindered significant engineering efforts. Heterologous ribosomes, comprising rRNAs r-proteins derived from different microorganisms, may offer opportunities novel translational functions. Such heterologous ribosomes previously been evaluated in E. coli via complementation of genomic deficiency, this method fails to guide the refractory ribosomes. Here, we implement orthogonal...
Plasma and urine glycosaminoglycans (GAGs) are long, linear sulfated polysaccharides that have been proposed as potential noninvasive biomarkers for several diseases. However, owing to the analytical complexity associated with measurement of GAG concentration disaccharide composition (the so-called GAGome), a reference study normal healthy GAGome is currently missing. Here, we prospectively enrolled 308 adults analyzed their free GAGomes in plasma using standardized ultra-high-performance...
Abstract Phenotypic mutations are amino acid changes caused by mistranslation. How phenotypic affect the adaptive evolution of new protein functions is unknown. Here we evolve antibiotic resistance TEM-1 towards on cefotaxime in an Escherichia coli strain with a high mistranslation rate. populations evolved such strains endow host cells general growth advantage, not only but also several other antibiotics that ancestral had been unable to deactivate. High-throughput sequencing shows this...
In bacteria, ribosome kinetics are considered rate-limiting for protein synthesis and cell growth. Enhanced may augment bacterial growth biomanufacturing through improvements to overall yield, but whether this can be achieved by ribosome-specific modifications remains unknown. Here, we evolve 16S ribosomal RNAs (rRNAs) from Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae towards enhanced rates. We find that rRNA sequence origin significantly impacted evolutionary trajectory...
No liquid biomarkers are approved in renal cell carcinoma (RCC), making early detection of recurrence surgically treated nonmetastatic (M0) patients dependent on radiological imaging. Urine- and plasma free glycosaminoglycan profiles-or GAGomes-are promising reflective RCC metabolism.
Glycosaminoglycans (GAGs) are long linear sulfated polysaccharides implicated in processes linked to disease development such as mucopolysaccharidosis, respiratory failure, cancer, and viral infections, thereby serving potential biomarkers. A successful clinical translation of GAGs biomarkers depends on the availability standardized GAG measurements. However, owing analytical complexity associated with quantification concentration structural composition, a method simultaneously measure...
PURPOSE No liquid biomarkers are approved in metastatic renal cell carcinoma (mRCC) despite the need to predict and monitor response noninvasively tailor treatment choices. Urine plasma free glycosaminoglycan profiles (GAGomes) promising metabolic mRCC. The objective of this study was explore if GAGomes could PATIENTS AND METHODS We enrolled a single-center prospective cohort patients with mRCC elected for first-line therapy (ClinicalTrials.gov identifier: NCT02732665 ) plus three...
Abstract We aimed to investigate the use of free glycosaminoglycan profiles (GAGomes) and cfDNA in plasma differentiate between lung cancer benign disease. GAGs were analyzed using MIRAM® Free Glycosaminoglycan Kit with ultra-high-performance liquid chromatography electrospray ionization triple-quadrupole mass spectrometry. detected two GAGome features, 0S chondroitin sulfate (CS) 4S CS, cancer-specific changes. Based on observed changes, we devised a model predict cancer. The model, named...
3034 Background: Non-invasive liquid biopsies promise to enable early cancer detection and improve patient outcomes. However, virtually all rely on genomic biomarkers, with limited sensitivity early-stage tumors poor of cancers shedding little cell-free DNA, like genitourinary or brain tumors. Here, we explored the use plasma urine glycosaminoglycan (GAGs) profiles, GAGomes, as biomarkers reflective tumor metabolism serve an alternative pan-cancer biopsy. Methods: In this case-control study,...
Screening for bladder cancer (BCa) could reduce mortality via early detection of early-stage high-grade (Ta/T1 N0 M0 grade 2-3) disease. Noninvasive biomarkers aid in screening, but current markers lack the specificity required. The urinary free glycosaminoglycan profile (GAGome) is a promising biomarker BCa metabolism.
We aimed to investigate the use of free glycosaminoglycan profiles (GAGomes) and cfDNA in plasma differentiate between lung cancer benign disease, a cohort 113 patients initially suspected cancer. GAGomes were analyzed all samples using MIRAM
Abstract Darwinian evolution preferentially follows mutational pathways whose individual steps increase fitness. Alternative with that do not fitness are less accessible. Here, we show mistranslation, the erroneous incorporation of amino acids into nascent proteins, can accessibility such alternative and, ultimately, high genotypes. We subject populations beta‐lactamase TEM‐1 to directed in Escherichia coli under both low‐ and high‐mistranslation rates, selecting for activity on antibiotic...