Venkateswar Addala
A5072077716- Cancer Genomics and Diagnostics
- Occupational and environmental lung diseases
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Esophageal Cancer Research and Treatment
- Pleural and Pulmonary Diseases
- Pancreatic and Hepatic Oncology Research
- Machine Learning and Data Classification
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Explainable Artificial Intelligence (XAI)
- Gastric Cancer Management and Outcomes
- Immune Cell Function and Interaction
- Melanoma and MAPK Pathways
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Genetic factors in colorectal cancer
- Lymphoma Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Protein Degradation and Inhibitors
- Cutaneous Melanoma Detection and Management
- Lung Cancer Research Studies
- Proteoglycans and glycosaminoglycans research
- PARP inhibition in cancer therapy
QIMR Berghofer Medical Research Institute
2018-2024
The University of Queensland
2021-2022
Abstract Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote restrain disease progression. Here, we interrogate how cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence a p53-driven hierarchy, where with gain-of-function (GOF) mutant educate dominant population CAFs that establish pro-metastatic environment for GOF null alike. also demonstrate educated by may be reprogrammed either or...
Abstract To increase understanding of the genomic landscape acral melanoma, a rare form melanoma occurring on palms, soles or nail beds, whole genome sequencing 87 tumors with matching transcriptome for 63 was performed. Here we report that mutational signature analysis reveals subset tumors, mostly subungual, an ultraviolet radiation signature. Significantly mutated genes are BRAF, NRAS , NF1 NOTCH2 PTEN and TYRP1 . Mutations amplification KIT also common. Structural rearrangement copy...
Abstract The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance this crosslinking and stabilizing fibrillar collagens its known role tumor desmoplasia. Using small-molecule drug-design approaches, we generated validated PXS-5505, first-in-class highly selective potent pan-lysyl inhibitor. We demonstrate vitro vivo that inhibition decreases chemotherapy-induced pancreatic desmoplasia stiffness, reduces cancer cell invasion metastasis,...
Critical immune-suppressive pathways beyond programmed death 1 (PD-1) and ligand (PD-L1) require greater attention. Nectins nectin-like molecules might be promising targets for immunotherapy, since they play critical roles in cell proliferation migration exert immunomodulatory functions pathophysiological conditions. Here, we show CD155 expression both malignant cells tumor-infiltrating myeloid humans mice. Cd155–/– mice displayed reduced tumor growth metastasis via DNAM-1 upregulation...
Cells within the tumour microenvironment (TME) can impact development and influence treatment response. Computational approaches have been developed to deconvolve TME from bulk RNA-seq. Using scRNA-seq profiling breast tumours we simulate thousands of mixtures, representing purities cell lineages, compare performance nine deconvolution methods (BayesPrism, Scaden, CIBERSORTx, MuSiC, DWLS, hspe, CPM, Bisque, EPIC). Some are more robust in deconvolving mixtures with high purity levels. Most...
Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups PanNETs, termed T1, T2 T3, distinct patterns methylation. The T1 subgroup was enriched for functional ATRX, DAXX MEN1 wild-type genotypes. contained mutations in recurrent chromosomal losses half genome no association between regions loss levels. were larger had lower MGMT gene body, which showed positive...
Abstract Background Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined the immune features of MPM offers prospect identifying changes that could inform future clinical trials. Methods We analysed somatic mutations from 229 samples, including previously published data and 58 samples had undergone WGS within this study. This was RNA-seq analysis to characterize tumour environment. Results The comprehensive...
Abstract Background Brain cancer is the leading cause of cancer-related death in children. Early detection and serial monitoring are essential for better therapeutic outcomes. Liquid biopsy has recently emerged as a promising approach detecting these tumors by screening body fluids presence circulating tumor DNA (ctDNA). Here we tested limits liquid using patient-specific somatic mutations to detect monitor primary metastatic pediatric brain cancer. Methods Somatic were identified 3...
Technological innovation and increased affordability have contributed to the widespread adoption of genome sequencing technologies in biomedical research. In particular large cancer research consortia embraced next generation sequencing, used technology define somatic mutation landscape multiple types. These studies primarily utilised Illumina HiSeq platforms. this study we performed whole three malignant pleural mesothelioma matched normal samples using a new platform, BGISEQ-500, compared...
Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic methylation data from 115 oesophageal patients mostly DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in study protocol of trial. report genomic associated poorer overall survival, such as APOBEC mutational RS3-like...
Oesophageal adenocarcinoma (OAC) is a highly heterogeneous cancer with poor survival. Standard curative treatment chemotherapy or without radiotherapy followed by oesophagectomy. Genomic heterogeneity feature of OAC and has been linked to resistance.
BACKGROUND Immunotherapy has improved patient survival for multiple cancer types, including melanoma. While a variety of molecular features have been linked to response immune checkpoint inhibitors (ICI) treatment, clinically established biomarkers, such as tumour mutation burden (TMB) and PD-L1 expression, shown limitations in accurately categorising responders versus non-responders. Due the complex nature ICI response, which includes intrinsic extrinsic within microenvironment (TME), using...
•Genome analysis revealed that treatment biomarkers are shared across solid tumours, highlighting repurposing opportunities.•Comprehensive panels detect most known biomarkers; however, WGS detects more for treatments in clinical trials.•TMB is well correlated between sequencing methods, but absolute values vary and dependent on mutation types considered. BackgroundNext-generation used cancer research to identify somatic germline mutations, which can predict sensitivity or resistance...
A plateau in treatment effect can be seen for the current ‘one-size-fits-all’ approach to oesophageal adenocarcinoma (OAC) management using neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). In OAC, tumour microenvironment (TME) is largely immunosuppressed, however a subgroup of patients with an immune-inflamed TME exist and show improved outcomes. We aimed understand overall immune-based mechanisms underlying responses patient outcomes relation therapy modality. This study included...
The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical signalling PDAC remains largely unknown. Only one study has investigated prognostic significance receptor, PDAC. No studies have PDAC.Here, we performed analysis mRNA expression three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD 150)...
Uncertainty estimation is crucial for understanding the reliability of deep learning (DL) predictions, and critical deploying DL in clinic. Differences between training production datasets can lead to incorrect predictions with underestimated uncertainty. To investigate this pitfall, we benchmarked one pointwise three approximate Bayesian models predicting cancer unknown primary, using RNA-seq 10,968 samples across 57 types. Our results highlight that simple scalable significantly improves...
Abstract Trust and transparency are critical for deploying deep learning (DL) models into the clinic. DL application poses generalisation obstacles since training/development datasets often have different data distributions to clinical/production that can lead incorrect predictions with underestimated uncertainty. To investigate this pitfall, we benchmarked one pointwise three approximate Bayesian used predict cancer of unknown primary independent RNA-seq covering 10,968 samples across 57...