A5004854900- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Chromosomal and Genetic Variations
- Colorectal Cancer Treatments and Studies
- Cytomegalovirus and herpesvirus research
- Cancer Genomics and Diagnostics
- Immunodeficiency and Autoimmune Disorders
- Lymphoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Osteoarthritis Treatment and Mechanisms
- Antimicrobial Peptides and Activities
- Silk-based biomaterials and applications
- Lung Cancer Research Studies
- Epigenetics and DNA Methylation
- Cancer Treatment and Pharmacology
Technical University of Denmark
2016-2025
Indian Institute of Technology Bombay
2022-2024
Swami Rama Himalayan University
2023
Bhagwan Mahaveer Cancer Hospital and Research Centre
2022
Danish Geotechnical Society
2022
University of California, Irvine
2021
European Molecular Biology Laboratory
2019
UNSW Sydney
2019
Copenhagen University Hospital
2019
Constructor University
2013-2019
The cellular ancestry of tumor antigens One contributing factor in antitumor immunity is the repertoire neoantigens created by genetic mutations within cells. Like corresponding mutations, these show intratumoral heterogeneity. Some are present all cells (clonal), and others only a fraction (subclonal). In study lung cancer melanoma, McGranahan et al. found that high burden clonal correlated with improved patient survival, an increased presence tumor-infiltrating lymphocytes, durable...
T cells are important for effective viral clearance, elimination of virus-infected and long-term disease protection. To examine the full-spectrum CD8
Abstract Human endogenous retroviruses (HERV) form a substantial part of the human genome, but mostly remain transcriptionally silent under strict epigenetic regulation, yet can potentially be reactivated by malignant transformation or therapies. Here, we evaluate potential for T cell recognition HERV elements in myeloid malignancies mapping transcribed genes and generating library 1169 antigenic HERV-derived peptides predicted presentation 4 HLA class I molecules. Using DNA barcode-labeled...
Abstract A concentric cylinder bioreactor has been developed to culture tissue engineered cartilage constructs under hydrodynamic loading. This operates in a low shear stress environment, large growth area for construct production, allows dynamic seeding of constructs, and provides uniform loading environment. Porous poly‐lactic acid seeded dynamically the using isolated bovine chondrocytes, were cultured 4 weeks at three densities (60, 80, 100 × 10 6 cells per bioreactor) different stresses...
Abstract Computational fluid dynamics (CFD) models to quantify momentum and mass transport under conditions of tissue growth will aid bioreactor design for development tissue‐engineered cartilage constructs. Fluent CFD are used calculate flow fields, shear stresses, oxygen profiles around nonporous constructs simulating in our concentric cylinder bioreactor. The stress distribution ranges from 1.5 12 dyn/cm 2 across the construct surfaces exposed varies little with relative number or...
Disulfide-stabilized MHC class I are empty peptide-receptive molecules that rapidly load peptide and improve T cell detection. See the related Research Article by Moritz et al . in this issue.
The intracellular trafficking of major histocompatibility complex class I (MHC-I) proteins is directed by three quality control mechanisms that test for their structural integrity, which correlated to the binding high-affinity antigenic peptide ligands. To investigate molecular features MHC-I these detect, we have followed hypothesis suboptimally loaded are characterized conformational mobility in F pocket region site. We created a novel variant an protein, Kb-Y84C, two alpha helices this...
Suboptimal immunity to SARS-CoV-2 mRNA vaccination has frequently been observed in individuals with various immunodeficiencies. Given the increased antibody evasion properties of emerging subvariants, it is necessary assess whether other components adaptive generate resilient and protective responses against infection. We assessed T cell 279 individuals, covering five different immunodeficiencies healthy controls, before after booster vaccination, as well Omicron infection a subset patients....
MHC class I molecules bind only those peptides with high affinity that conform to stringent length and sequence requirements. We have now investigated which can aid the in vitro folding of molecules, we find dipeptide glycyl-leucine efficiently supports HLA-A*02:01 H-2K b into a peptide-receptive conformation rapidly binds high-affinity peptides. Treatment cells induces accumulation at surface cells. Other dipeptides hydrophobic second amino acid show similar enhancement effects. Our data...
Patients with hematological malignancies are prioritized for COVID-19 vaccine due to their high risk severe SARS-CoV-2 infection-related disease and mortality. To understand T cell immunity, its long-term persistence, correlation antibody response, we evaluated the BNT162b2 mRNA vaccine-specific immune response in chronic lymphocytic leukemia (CLL) myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8 + cells using DNA-barcoded peptide-MHC multimers covering full...
Significance We have shown previously that dipeptides can support efficient in vitro folding of the MHC class I molecules. Here, we describe discovery catalyze dissociation low- and high-affinity peptides from their replacement for exogenous interest, on both recombinant cell surface HLA-A*02:01, HLA-B*27:05, H-2K b Understanding peptide exchange will help us understand optimization live cells. demonstrate peptide-exchange technology be used to produce epitope-specific tetramers much faster...
Abstract Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumour cell intrinsic and microenvironmental features underpinning CPI sensitization. Here we collated whole-exome transcriptomic data for >1000 CPI-treated patients across eight tumor-types, utilizing standardized bioinformatics-workflows clinical outcome-criteria to validate multivariate predictors CPI-sensitization. Clonal-TMB was strongest predictor...
CD8+ T-cells are essential for controlling and resolving SARS-CoV-2 infection, yet their antigen-specific resolution in relation to disease severity, functional dynamics during acute long-term memory formation remain incompletely understood. Using comprehensive longitudinal profiling of 553 immunogenic antigens across globally prevalent HLAs, we identified T-cell responses that were either critical early viral clearance or associated with severe outcomes. During patients COVID-19 exhibited a...
Treatment of large segmental bone defects remains an unsolved clinical challenge, despite a wide array existing graft materials. This project was designed to rapidly assess and compare promising biodegradable osteoconductive scaffolds for use in the systematic development new regeneration methodologies that combine scaffolds, sources osteogenic cells, bioactive scaffold modifications. Promising biomaterials fabrication methods were identified laboratories at Rutgers, MIT, Integra Life...
Major histocompatibility complex (MHC) class I molecules (proteins) bind peptides of eight to ten amino acids present them at the cell surface cytotoxic T cells. The binding groove binds peptide via hydrogen bonds with termini and diverse interactions anchor residue side chains peptide. To elucidate which these is most important for thermodynamic kinetic stability peptide-bound state, we have combined molecular dynamics simulations experimental approaches in an investigation conformational...
Abstract Purpose: We hypothesized that resistance to hypomethylating agents (HMA) among patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) would be overcome by combining a programmed death-ligand 1 antibody an HMA. Patients Methods: conducted Phase I/II, multicenter clinical trial for MDS not achieving International Working Group response after at least 4 cycles of HMA (“refractory”) or progressing (“relapsed”) 3+ higher risk the revised Prognostic...
Pain is the most common symptom in admitted cancer patients. The association between severity of pain and distress symptoms such as depression anxiety a subject research.The aim to study prevalence pain, anxiety, patients determine at tertiary care institute.This was prospective observational study.We enrolled 393 inpatients prospectively after written informed consent. Their disease details, presence, severity, character were recorded. Numerical Scale used for scores, self-reporting...