A5004219172- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Liver Disease Diagnosis and Treatment
- Reproductive Biology and Fertility
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Single-cell and spatial transcriptomics
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Diet and metabolism studies
- Tuberculosis Research and Epidemiology
- Chronic Lymphocytic Leukemia Research
- Mycobacterium research and diagnosis
- Asthma and respiratory diseases
- Antifungal resistance and susceptibility
- Complement system in diseases
- Genetic and phenotypic traits in livestock
- Prostate Cancer Treatment and Research
- Hepatitis C virus research
- Malaria Research and Control
- Cancer Risks and Factors
- Tracheal and airway disorders
- Cytomegalovirus and herpesvirus research
Garvan Institute of Medical Research
2017-2025
St Vincent's Clinic
2018-2025
UNSW Sydney
2019-2025
Symbiosis International University
2024
Gautam Buddha University
2023
All India Institute of Medical Sciences Bhubaneswar
2023
Jammu Hospital
2021-2023
Gulf Medical University
2023
The University of Texas MD Anderson Cancer Center
2023
The University of Texas Medical Branch at Galveston
2020-2023
High-throughput single-cell RNA sequencing is a powerful technique but only generates short reads from one end of cDNA template, limiting the reconstruction highly diverse sequences such as antigen receptors. To overcome this limitation, we combined targeted capture and long-read T-cell-receptor (TCR) B-cell-receptor (BCR) mRNA transcripts with short-read transcriptome profiling barcoded libraries generated by droplet-based partitioning. We show that Repertoire Gene Expression Sequencing...
Abstract Motivation The B-cell receptor (BCR) performs essential functions for the adaptive immune system including recognition of pathogen-derived antigens. vast repertoire and variation BCR sequences due to V(D)J recombination somatic hypermutation necessitates single-cell characterization sequences. Single-cell RNA sequencing presents opportunity simultaneous capture paired heavy light chains transcriptomic signature. Results We developed VDJPuzzle, a novel bioinformatic tool that...
The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co-existing autoimmunity. To investigate whether these are the cause or consequence of CD8+ clonal expansions autoimmunity, we analyzed patients mice germline GOF mutations. drove accumulation effector clones highly expressing NKG2D, receptor for stress-induced MHC-class-I-related molecules....
Summary Accurate identification of sparse heterozygous single-nucleotide variants (SNVs) is a critical challenge for identifying the causative mutations in mouse genetic screens, human diseases and cancer. When seeking to identify causal DNA that occur at such low rates, they are overwhelmed by false-positive calls arise from range technical biological sources. We describe strategy using whole-exome capture, massively parallel sequencing computational analysis, which identifies with rate...
Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse receptor-binding domains (RBDs) identify targeting of vulnerability. Antibodies broad reactivity clade B RBDs class 4 epitope, recurring IGHV/IGKV pairs, were readily elicited but...
The repeat region of the Plasmodium falciparum circumsporozoite protein (CSP) is a major vaccine antigen because it can be targeted by parasite neutralizing antibodies; however, little known about this interaction. We used isothermal titration calorimetry, X-ray crystallography and mutagenesis-validated modeling to analyze binding murine antibody CSP. Strikingly, we found that CSP bound multiple antibodies. This repeating pattern allows weak interactions single FAB domains accumulate yield...
Adoptive immunotherapy using donor-derived antigen-specific T-cells can prevent and treat infection after allogeneic haemopoietic stem cell transplant (HSCT).We treated 11 patients with a prophylactic infusion of 2 × 107 cells per square metre targeting seven infections (six viral one fungal) following HSCT. Targeted pathogens were cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, varicella zoster virus, influenza, BK (BKV) Aspergillus fumigatus.T-cell products successfully...
Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and implications infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in circulating T cell compartment children mild/asymptomatic COVID-19 compared adult household contacts same severity who had more evidence of systemic...
Multidrug resistant tuberculosis (MDR-TB) has been an area of growing concern and is posing a threat to the control (TB). The exact magnitude problem resistance anti-tuberculosis drugs worldwide was not known till 1994-97 global project on drug surveillance initiated by World Health Organization (WHO) International Union Against Tuberculosis Lung Diseases (IUATLD). Global Report 2014 estimated that 3.5% newly diagnosed 20.5% previously treated.TB cases had MDR-TB. It 480,000 emerged 210,000...
Abstract Chimeric antigen receptor (CAR) T cell therapy is effective in treating B malignancies, but factors influencing the persistence of functional CAR + cells, such as product composition, patients’ lymphodepletion, and immune reconstitution, are not well understood. To shed light on this issue, here we conduct a single-cell multi-omics analysis transcriptional, clonal, phenotypic profiles from pre- to 1-month post-infusion − cells patients CARTELL study (ACTRN12617001579381) who...
The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources B cell somatic mutation converged to drive accumulation a large disease-causing clone. A method quantifying low-affinity binding revealed recurring...
Abstract The thymus plays a crucial role in immune tolerance by exposing developing T cells (thymocytes) to myriad of self‐antigens. Strong T‐cell receptor ( TCR ) engagement induces self‐reactive thymocytes stimulating apoptosis or selection into specialized lineages, including intestinal αβ + CD 8αα intraepithelial lymphocytes IEL ). ‐intrinsic amino acid motifs that can be used predict whether will strongly remain elusive. Here, novel sequence alignment approach revealed lineages C57 BL...
Autologous haematopoietic stem cell transplantation (AHSCT) is a vital therapeutic option for patients with highly active multiple sclerosis (MS). Rates of remission suggest AHSCT the most effective form immunotherapy in controlling disease. Despite an evolving understanding biology immune reconstitution following AHSCT, mechanism by which enables sustained disease beyond period lymphopenia remains to be elucidated. Auto-reactive T cells are considered central MS pathogenesis. Here, we...
Background: Sebaceous carcinoma (SbCC) is a rare malignancy that often mimics benign conditions. Lymphatic involvement, large T3 tumors herald dismal survival for patients. We present our series of 13 cases locally advanced SbCC the eyelid treated at surgical oncology unit and describe clinical profile, patterns nodal spread recurrence pattern in this subset SbCC.Methods: A retrospective analysis case records was carried out patients presenting with orbital between January 1997 April 2010...
Abstract Intestinal inflammation continues in a subset of celiac disease (CD) patients despite gluten-free diet. Here, by applying multiomic single cell analysis to duodenal biopsies, we find low-grade malignancies with lymphoma driver mutations refractory CD type 2 (RCD2) comprise surface CD3 negative (sCD3-) lymphocytes stalled at an innate lymphoid (ILC) - progenitor T stage undergoing extensive TCR recombination. In people 1 (RCD1), who currently lack explanation, discover sCD3+ cells...
Background Long-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population order reduce ongoing disease burden. Methods We have investigated association between memory CD4 CD8 cells levels convalescent COVID-19 subjects. Findings Higher titres were associated with significantly higher RBD-specific cells, specific that proliferated vigorously vitro . Conversely, up half individuals had low...