Senior Research Officer
BSc (Hons), PhD
Dr Vanessa Fear has a Bachelor of Science (honours) with a double major in Molecular Biology and Biochemistry from the University of Western Australia. (1990). She completed her PhD at the University of Western Australia (1998) in cellular biology and cell signalling under the supervision of Professor Peter Klinken. Subsequently she went on to a post-doctoral research placement at Murdoch University and developed an interest in the study of Type I interferon subtypes and their role in viral infection. Dr Fear then joined the Drug Discovery Unit at Telethon Kids Institute to develop their reverse yeast two hybrid screening technology. In 2009 Dr Fear commenced work with the Asthma and Allergy group at Telethon Kids Institute. In addition, Dr Fear initiated a research project investigating immune system dysfunction following burn injury and surgery with Professor Fiona Wood. Dr Fear then went on to investigate tumour surgery with lymph node resection and the corollary for onset of metastatic disease, and efficacy of immunotherapy.
Vanessa Fear has held a position with the Telethon Kids Institute, Genetic and Rare Diseases team as Senior Research Officer since 2018. Within this team her work focuses on application of CRISPR/Cas9 genome editing technology of pluripotent stem cells to assist with diagnoses of paediatric patients with genetic and rare diseases.
View her publications here.
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Publications
January 2024
CRISPR-Cas9-generated PTCHD1 2489T>G stem cells recapitulate patient phenotype when undergoing neural induction
An estimated 3.5%-5.9% of the global population live with rare diseases, and approximately 80% of these diseases have a genetic cause. Rare genetic diseases are difficult to diagnose, with some affected individuals experiencing diagnostic delays of 5-30 years. Next-generation sequencing has improved clinical diagnostic rates to 33%-48%. In a majority of cases, novel variants potentially causing the disease are discovered.
Autism Spectrum Published research Computational Biology Translational Genetics Child disability Rare diseases GeneticsDecember 2023Gene editing and cardiac disease modelling for the interpretation of genetic variants of uncertain significance in congenital heart disease
Genomic sequencing in congenital heart disease (CHD) patients often discovers novel genetic variants, which are classified as variants of uncertain significance (VUS). Functional analysis of each VUS is required in specialised laboratories, to determine whether the VUS is disease causative or not, leading to lengthy diagnostic delays.
Published research Early Childhood Development Computational Biology Child Physical Activity, Health and Development Mitochondrial Research Translational Genetics Genomics Child and adolescent health GeneticsNovember 2023The 8th International RASopathies Symposium: Expanding research and care practice through global collaboration and advocacy
Germline pathogenic variants in the RAS/mitogen-activated protein kinase (MAPK) signaling pathway are the molecular cause of RASopathies, a group of clinically overlapping genetic syndromes.
Published research Translational Genetics Child disability GeneticsJuly 2023A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence
Recurrences frequently occur following surgical removal of primary tumors. In many cancers, adjuvant therapies have limited efficacy. Surgery provides access to the tumor microenvironment, creating an opportunity for local therapy, in particular immunotherapy, which can induce local and systemic anti-cancer effects.
Children's Cancers Published research Subsite: Cancer Sarcoma Translational Research Translational GeneticsJun 2023Cardiometabolic disease risk markers are increased following burn injury in children
Burn injury in children causes prolonged systemic effects on physiology and metabolism leading to increased morbidity and mortality, yet much remains undefined regarding the metabolic trajectory towards specific health outcomes.
Published research Subsite: Cancer Translational GeneticsDecember 2022CD4+ T cells drive an inflammatory, TNF-α/IFN-rich tumor microenvironment responsive to chemotherapy
While chemotherapy remains the first-line treatment for many cancers, it is still unclear what distinguishes responders from non-responders. Here, we characterize the chemotherapy-responsive tumor microenvironment in mice, using RNA sequencing on tumors before and after cyclophosphamide, and compare the gene expression profiles of responders with progressors.
Children's Cancers Published research Computational Biology Sarcoma Translational Research Translational GeneticsJuly 2022Systemic long-term metabolic effects of acute non-severe paediatric burn injury
A growing body of evidence supports the concept of a systemic response to non-severe thermal trauma. This provokes an immunosuppressed state that predisposes paediatric patients to poor recovery and increased risk of secondary morbidity.
Published research Translational GeneticsApril 2022Non-severe burn injury increases cancer incidence in mice and has long-term impacts on the activation and function of T cells
Recent evidence suggests that burn patients are at increased risk of hospital admission for infection, mental health conditions, cardiovascular disease and cancer for many years after discharge for the burn injury itself.
Published research Sarcoma Translational Research Translational GeneticsSeptember 2021Temporally restricted activation of IFNβ signaling determines response to immune checkpoint therapy
The biological determinants of the response to immune checkpoint blockade (ICB) in cancer remain incompletely understood. Little is known about dynamic biological events that underpin therapeutic efficacy due to the inability to frequently sample tumours in patients.
Children's Cancers Published research Computational Biology Sarcoma Translational Research Translational GeneticsFebruary 2022Functional validation of variants of unknown significance using CRISPR gene editing and transcriptomics: A Kleefstra syndrome case study
There are an estimated > 400 million people living with a rare disease globally, with genetic variants the cause of approximately 80% of cases. Next Generation Sequencing (NGS) rapidly identifies genetic variants however they are often of unknown significance.
Published research Computational Biology Translational GeneticsFebruary 2022CRISPR single base editing, neuronal disease modelling and functional genomics for genetic variant analysis: pipeline validation using Kleefstra syndrome EHMT1 haploinsufficiency
Over 400 million people worldwide are living with a rare disease. Next Generation Sequencing identifies potential disease causative genetic variants. However, many are identified as variants of uncertain significance and require functional laboratory validation to determine pathogenicity, and this creates major diagnostic delays.
Published research Computational Biology Translational GeneticsSeptember 2021IFNβ Is a Potent Adjuvant for Cancer Vaccination Strategies
Cancer vaccination drives the generation of anti-tumor T cell immunity and can be enhanced by the inclusion of effective immune adjuvants such as type I interferons (IFNs). Whilst type I IFNs have been shown to promote cross-priming of T cells, the role of individual subtypes remains unclear. Here we systematically compared the capacity of distinct type I IFN subtypes to enhance T cell responses to a whole-cell vaccination strategy in a pre-clinical murine model.
Children's Cancers Published research Immunisation Systems Immunology Subsite: Cancer Translational Genetics Immune system Cancer Immunology and BiologyApril 2021Tumour draining lymph node-generated CD8 T cells play a role in controlling lung metastases after a primary tumour is removed but not when adjuvant immunotherapy is used
Surgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung cancer model, primary subcutaneous tumours were resected with associated dLNs remaining intact, completely resected or partially resected.
Children's Cancers Published research Computational Biology Cancer Immunology and BiologyNovember 2020Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy
Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICT.
Children's Cancers Published research Computational Biology Sarcoma Translational ResearchJuly 2020Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response
Epidemiological studies have demonstrated that survivors of acute burn trauma are at long-term increased risk of developing a range of morbidities. The mechanisms underlying this increased risk remain unknown. This study aimed to determine whether burn injury leads to sustained immune dysfunction that may underpin long-term morbidity. Plasma and peripheral blood mononuclear cells were collected from 36 pediatric burn survivors >3 years after a non-severe burn injury (<10% total body surface area) and from age/sex-matched non-injured controls.
Published research Nutrition in Early Life Vaccine Trials Group Subsite: Wesfarmers Centre of Vaccines and Infectious DiseasesMay 2020Bilateral murine tumor models for characterizing the response to immune checkpoint blockade
This protocol describes bilateral murine tumor models that display a symmetrical yet dichotomous response to immune checkpoint blockade
Children's Cancers Published research Systems Immunology Computational Biology Sarcoma Translational ResearchApril 2020Diverse Anti-Tumor Immune Potential Driven by Individual IFNα Subtypes
Our data shows that the expression of distinct IFNα subtypes within the tumor microenvironment results in different anti-tumor activities
Children's Cancers Published research Academic Biostatistics Cancer Immunology and BiologySeptember 2019Understanding acute burn injury as a chronic disease
The review will outline evidence of long-term health effects, possible mechanisms linking burn injury to long-term health and current research into burns as a chronic disease
Published research Cancer Immunology and BiologyAugust 2019The role and therapeutic implications of T cells in cancer of the lung
This review examines the role of T cells in lung cancer, discussing the direction and clinical significance of current and future immunotherapeutic strategies
Published research Computational Biology -
Education and Qualifications
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