Timothy Sadlon

ORCID: 0000-0002-4821-2462
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About
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Research Areas
  • T-cell and B-cell Immunology
  • Immune Cell Function and Interaction
  • CAR-T cell therapy research
  • Diabetes and associated disorders
  • Immunotherapy and Immune Responses
  • Porphyrin Metabolism and Disorders
  • Hematopoietic Stem Cell Transplantation
  • Single-cell and spatial transcriptomics
  • Pancreatic function and diabetes
  • Genomics and Phylogenetic Studies
  • Advancements in Semiconductor Devices and Circuit Design
  • MicroRNA in disease regulation
  • Cancer Cells and Metastasis
  • Cancer-related molecular mechanisms research
  • Bioinformatics and Genomic Networks
  • Genomics and Chromatin Dynamics
  • Acute Myeloid Leukemia Research
  • Virus-based gene therapy research
  • Heme Oxygenase-1 and Carbon Monoxide
  • RNA Interference and Gene Delivery
  • Cannabis and Cannabinoid Research
  • Blood transfusion and management
  • Mesenchymal stem cell research
  • Chemokine receptors and signaling
  • Neonatal Health and Biochemistry

The University of Adelaide
2009-2024

Women's and Children's Health Network
2018-2023

Robinson Memorial Hospital
2021

University of South Australia
2021

Women's and Children's Hospital
2004-2019

Women's & Children's Health Research Institute
2004-2012

Center of Molecular Immunology (Cuba)
2010

The transcription factor FOXP3 is essential for the formation and function of regulatory T cells (Tregs), Tregs are maintaining immune homeostasis tolerance. This demonstrated by a lethal autoimmune defect in mice lacking Foxp3 immunodysregulation polyendocrinopathy enteropathy X-linked syndrome patients. However, little known about molecular basis human or relationship between direct indirect targets Tregs. To investigate this, we have performed comprehensive genome-wide analysis target...

10.4049/jimmunol.1000082 article EN The Journal of Immunology 2010-06-17

Chimeric antigen receptor (CAR)-T cell immunotherapy is a novel treatment that genetically modifies the patients' own T cells to target and kill malignant cells. However, identification of tumour-specific antigens expressed on multiple solid cancer types, remains major challenge. P2X purinoceptor 7 (P2X7) surface ATP gated cation channel, dysfunctional version P2X7, named nfP2X7, has been identified from tissues, while being undetectable healthy We present prototype -human CAR-T construct...

10.1038/s41467-023-41338-y article EN cc-by Nature Communications 2023-09-08

CD4+ T-cell subsets play a major role in the host response to infection, and healthy immune system requires fine balance between reactivity tolerance. This is part maintained by regulatory T cells (Treg), which promote tolerance, loss of tolerance contributes autoimmunity. As drive immunity are diverse, identifying understanding how these function specific biomarkers. From human CD4 Tconv/Treg cell genome wide analysis we identified peptidase inhibitor 16 (PI16) as subset biomarker now show...

10.1002/eji.201948094 article EN European Journal of Immunology 2019-05-25

Abstract Epigenetic features such as DNA accessibility dictate transcriptional regulation in a cell type- and state- specific manner, mapping this health vs. disease clinically relevant material is opening the door to new mechanistic insights targets for therapy. Assay Transposase Accessible Chromatin Sequencing (ATAC-seq) allows chromatin profiling from low input, making it tractable on rare populations, regulatory T (Treg) cells. However, little known about compatibility of assay with...

10.1038/s41598-023-32256-6 article EN cc-by Scientific Reports 2023-04-04

Control of oncogenes, including ZEB1 and ZEB2, is a major checkpoint for preventing cancer, loss this control contributes to many cancers, breast cancer. Thus tumour suppressors, such as FOXP3, which mutated or lost in cancer tissues, play an important role maintaining normal tissue homeostasis. Here we show the first time that ZEB2 selectively down regulated by FOXP3 also induced microRNA, miR-155. Interestingly, neither nor miR-155 directly altered expression ZEB1. In cells repression...

10.18632/oncotarget.25523 article EN Oncotarget 2018-06-11

Abstract Objectives Recent studies have identified expression of the non‐functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not normal cells, which makes it a promising tumour‐associated antigen candidate for chimeric (CAR)‐T‐cell immunotherapies. In this study, we assessed cytotoxic effects nfP2X7‐CAR‐T cancer using in vitro and vivo models. Methods We evaluated cell lines (SKOV‐3, OVCAR3, OVCAR5), peritoneal (LP‐9) primary serous derived from patient...

10.1002/cti2.1512 article EN cc-by Clinical & Translational Immunology 2024-01-01

Brown and colleagues report on a lentiviral vector platform that enables for tightly regulated, fully reversible, doxycycline-responsive knockdown of target genes using single short hairpin RNAs. The authors demonstrate the feasibility this system in vitro. Manipulation gene expression is an invaluable tool to study function vitro vivo. application small inhibitory RNAs knock down provides relatively simple, elegant, but transient approach many cell types as well whole animals. Short...

10.1089/hum.2009.107 article EN Human Gene Therapy 2010-07-08

Haem is essential for the health and function of nearly all cells. 5-Aminolaevulinic acid synthase-1 (ALAS-1) catalyses first rate-controlling step haem biosynthesis. ALAS-1 repressed by induced strongly lipophilic drugs that also induce CYP (cytochrome P450) proteins. We investigated effects on avian gene promoter a phenobarbital-like chemical, Glut (glutethimide), synthesis inhibitor, DHA (4,6-dioxoheptanoic acid), using reporter assay in transiently transfected LMH (Leghorn male hepatoma)...

10.1042/bj20050354 article EN Biochemical Journal 2005-11-08

Abstract Adult stem cells are capable of generating all the hematopoietic system, and this process is orchestrated in part by interactions between these stroma. T cell progenitors emerge from compartment migrate to thymus, where their terminal differentiation maturation occur, it during phase that selection shapes immune repertoire. Notch ligands, including Delta-like 1 (DL1), play a critical role lymphoid differentiation. To mimic vitro, stroma-expressing DL1 have been used generate...

10.1189/jlb.1008620 article EN Journal of Leukocyte Biology 2008-12-22

Background: Rural/remote blood collection can cause delays in processing, reducing PBMC number, viability, cell composition and function. To mitigate these impacts, was stored at 4 °C prior to processing. Viable immune phenotype, Interferon-γ (IFN-γ) release were measured. Furthermore, the lowest protective volume of cryopreservation media concentration investigated. Methods: Blood from 10 individuals for up days. Flow cytometry IFN-γ ELISPOT used measure phenotype function on thawed PBMC....

10.3390/ijms22179129 article EN International Journal of Molecular Sciences 2021-08-24

Natural Regulatory T cells (Tregs) are defined by stable expression of the cell surface proteins CD4 and CD25, low CD127 transcription factor FOXP3. The contribution Treg to prevention autoimmunity maintenance immune homoestasis is subject ongoing interest, as alterations in numbers function implicated a wide range diseases. vitro benchmark for determining suppression proliferation unmatched effector mixed lymphocyte reaction (MLR) over 3–6‐day time period. As an alternative this assay, we...

10.1038/icb.2012.18 article EN Immunology and Cell Biology 2012-06-12

Abstract Colorectal cancer (CRC) is the third most diagnosed and incidence rates are rapidly increasing among young adults. Despite current treatments, 5-year survival rate approximately 65%, highlighting an urgent need for new therapies. Leucine-rich repeat-containing G-protein coupled receptor (LGR5) a promising antigen target chimeric (CAR)-T cell therapy, which may represent novel effective treatment CRC. LGR5 binds R-spondins functions to enhance Wnt β-catenin signalling involved in...

10.1158/1538-7445.am2022-5574 article EN Cancer Research 2022-06-15

Abstract Background Genome-wide association studies (GWAS) have enabled the discovery of single nucleotide polymorphisms (SNPs) that are significantly associated with many autoimmune diseases including type 1 diabetes (T1D). However, identified variants lie in non-coding regions, limiting identification mechanisms contribute to disease progression. To address this problem, we developed a variant filtering workflow called 3DFAACTS-SNP link genetic target genes cell-specific manner. Here, use...

10.1186/s13072-022-00456-5 article EN cc-by Epigenetics & Chromatin 2022-06-30

Abstract Colorectal cancer is the third most diagnosed worldwide, and responsible for second largest number of related deaths, warranting need new treatments. The successful use chimeric antigen receptor T (CAR-T) cells against B-cell malignancies has inspired search CAR-T cell therapies solid tumours such as colorectal cancer. Cancer stem (CSC) are a small population within tumour with capacity to self-renew, differentiate, initiate tumours. CSC resistant chemotherapy radiotherapy enriched...

10.1158/1538-7445.am2024-6311 article EN Cancer Research 2024-03-22
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