Ruby C Y Lin

Ruby C Y Lin
Westmead Institute for Medical Research · Centre for Infectious Diseases and Microbiology

PhD, MSc (Hons), BSc

About

119
Publications
18,112
Reads
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4,845
Citations
Citations since 2016
51 Research Items
2906 Citations
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20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
Introduction
My research is focussed on non-coding RNA species e.g., microRNA -driven dysfunctions that lead to pathogenesis. My overall strength is in transcriptomics (mRNA and microRNA), genomics and systems biology of cardiovascular disease, obesity and infectious diseases in humans and in rodent models. I am working on: 1. Immunomodulation (phage and human interactions). 2. Duality of microRNA function 3. Infective endocarditis: lncRNAs and miRNAs perspective 4. Meta-transcriptomes in disease systems
Additional affiliations
June 2021 - present
Westmead Institute for Medical Research
Position
  • Managing Director
Description
  • Medical Research Future Fund Frontiers Stage 1 funding scheme awarded. Phage Australia - integrating a network of clinicians, researchers and industry partners to develop phage therapy to deal with antimicrobial resistant infections.
January 2021 - present
Westmead Institute for Medical Research
Position
  • Business Development Manager
Description
  • I help CIDM build academia-industry relationships to advance research specifically in the infectious diseases and genomics space.
October 2017 - April 2020
The University of Sydney
Position
  • Co-supervision of HRD research students
Education
June 1998 - March 2002
The University of Sydney
Field of study
  • Medicine
March 1995 - June 1997
University of Canterbury
Field of study
  • Molecular and Cellular Genetics
March 1992 - December 1994
University of Canterbury
Field of study
  • Zoology

Publications

Publications (119)
Article
Full-text available
We previously showed that paternal high-fat diet (HFD) consumption programs β-cell dysfunction in female rat offspring, together with transcriptome alterations in islets. Here we investigated the retroperitoneal white adipose tissue (RpWAT) transcriptome using gene and pathway enrichment and pathway analysis to determine whether commonly affected n...
Article
Full-text available
Maintenance of cardiac structure and Z-disc signaling are key factors responsible for protecting the heart in a setting of stress, but how these processes are regulated is not well defined. We recently demonstrated that PI3K(p110α) protects the heart against myocardial infarction. The aim of this study was to determine whether PI3K(p110α) directly...
Article
Full-text available
The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic. Having either parent obese is an independent risk factor for childhood obesity. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offsp...
Article
Full-text available
Myocardial infarction (MI) is a serious complication of atherosclerosis associated with increasing mortality attributable to heart failure. Activation of phosphoinositide 3-kinase [PI3K(p110 alpha)] is considered a new strategy for the treatment of heart failure. However, whether PI3K(p110 alpha) provides protection in a setting of MI is unknown, a...
Article
Full-text available
A possible link between the glucocorticoid receptor gene ( GRL , 5q31-q32) and overweight has been suggested in a study of 42 families with morbid obesity.1 Data from another small study—of pairs of siblings—although not significant, showed a trend towards similar body mass index (weight(kg)/(height(m)2); difference=2.4) for 20 pairs sharing simila...
Article
Full-text available
Distal hereditary motor neuropathies (dHMNs) are a group of inherited diseases involving the progressive, length-dependent axonal degeneration of the lower motor neurons. There are currently 29 reported causative genes and 4 disease loci implicated in dHMN. Despite the high genetic heterogeneity, mutations in the known genes account for less than 2...
Preprint
Distal hereditary motor neuropathies (dHMNs) are a group of inherited diseases involving the progressive, length-dependent axonal degeneration of the lower motor neurons. There are currently 29 reported causative genes and 4 disease loci implicated in dHMN. Despite the high genetic heterogeneity, mutations in the known genes account for less than 2...
Article
Full-text available
Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics in...
Article
The escalating issue of multidrug-resistant (MDR) bacteria indicates the urgent need for new and effective strategies to combat this global health challenge. Here, we describe a new combinatorial approach that can be put forward for experimental therapy application against MDR bacteria. Specifically, we have developed a tri-system that includes the...
Article
Phage Directory has recently partnered with Phage Australia to help optimize Australia's data-centric standardized approach to personalized phage therapy. Here is a behind-the-scenes look at the genesis of Phage Australia, how the Phage Directory-Phage Australia partnership started, and what it is working toward.
Cover Page
Report: Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child. https://www.embopress.org/toc/17574684/2021/13/9
Article
Full-text available
Adjunctive phage therapy was used in an attempt to avoid catastrophic outcomes from extensive chronic Pseudomonas aeruginosa osteoarticular infection in a 7-year-old child. Monitoring of phage and bacterial kinetics allowed real-time phage dose adjustment, and along with markers of the human host response, indicated a significant therapeutic effect...
Article
The mechanisms underpinning beta cell compensation for obesity-associated insulin resistance and beta cell failure in type 2 diabetes remain poorly understood. We used a large-scale strategy to determine the time-dependent transcriptomic changes in islets of diabetes-prone db/db and diabetes-resistant ob/ob mice at 6 and 16 weeks of age. Differenti...
Article
After a century of use in human infection, the preparation and administration of therapeutic bacteriophages (phages) still relies on ad hoc partnerships of researchers, biotech companies, clinicians and regulators. There is a clear need to improve the reproducibility, safety and speed of the provision of suitable phages. Here we discuss the specifi...
Article
Full-text available
Approximately 10% of global health research is devoted to 90% of global disease burden (the so-called ‘10/90 Gap’) and it often neglects those diseases most prevalent in low-income countries. Antibiotic resistant bacterial infections are known to impact on healthcare, food security and socio-economic fabric in the developing countries. With a globa...
Preprint
Full-text available
Successful phage therapy for extensive chronic osteoarticular infection in a child resulted in an initial flush of bacterial contents into the bloodstream with an inflammatory response marked by fever, local pain and upregulation of genes associated with autophagy and innate immunity. Monitoring of phage and bacterial kinetics and the human host re...
Article
Full-text available
Objective: Aging and chronic glucocorticoid excess share a number of critical features, including the development of central obesity, insulin resistance and osteoporosis. Previous studies have shown that skeletal glucocorticoid signalling increases with aging, and that osteoblasts mediate the detrimental skeletal and metabolic effects of chronic gl...
Article
Circulating plasma TRAIL levels are suppressed in patients with cardiovascular and diabetic diseases. To identify novel targets in vascular metabolic diseases, genome-wide transcriptome of aortic tissue from Trail-/- vs. Trail+/+ mice were interrogated. We found 861 genes differentially expressed with TRAIL deletion. Gene enrichment analyses showed...
Article
Full-text available
In this single-arm non-comparative trial, 13 patients in an Australian hospital with severe Staphylococcus aureus infections were intravenously administered a good manufacturing practice-quality preparation of three Myoviridae bacteriophages (AB-SA01) as adjunctive therapy. AB-SA01 was intravenously administered twice daily for 14 d and the clinica...
Article
Full-text available
The effect of intravenous administration of bacteriophages manufactured under Good Manufacturing Practice (GMP) conditions in severe Staphylococcus aureus bacteraemia is unknown. A GMP-quality preparation of three Myoviridae bacteriophages (AB-SA01), was administered intravenously to thirteen patients with severe S. aureus infections receiving anti...
Article
Full-text available
Objectives: Evaluate the role of porins in the susceptibility of Klebsiella pneumoniae to ceftaroline and ceftaroline-avibactam. Methods: Susceptibility to ceftaroline and ceftaroline-avibactam was tested by broth microdilution method in Klebsiella pneumoniae isolates (n = 65), including isogenic mutants (n = 30) and clinical isolates (n = 35), wit...
Conference Paper
Full-text available
Introduction: Bacteriophage therapy is emerging as an approach to highly resistant and severe infection. Randomised studies are lacking but there have been some high-profile examples of successful salvage therapy using phages for highly antibiotic-resistant infection in critically ill patients. Here we describe the likely place of these agents in t...
Article
Background: Polyclonal, coagulase-negative staphylococci are common contaminants of blood cultures (1), but polyclonal, coagulase-positive staphylococci (Staphylococcus aureus) have yet to be unambiguously identified as a cause of bacteremia. Objective: To describe a patient with simultaneous and persistent bacteremia from 2 strains of S aureus. Ca...
Article
• Bacteriophage (phage) therapy is re-emerging a century after it began. • Activity against antibiotic-resistant pathogens and a lack of serious side effects make phage therapy an attractive treatment option in refractory bacterial infection. • Phages are highly specific for their bacterial targets but the relationship between in vitro activity and...
Article
Pseudomonas aeruginosa is a frequent causative agent of ventilation-associated pneumonia (VAP) with high attributable mortality (~13%), which may double in patients with multi-drug resistant (MDR) infection. Bacteriophage therapy was first utilised as antibacterial therapy in the early 1900s. Losing favour in the West with the advent of antibiotics...
Technical Report
This letter describes our experience of phage therapy using nebulised and intravenous phage therapy in a patient with ventilator-associated pneumonia and empyema caused by Pseudomonas aeruginosa here at Westmead Hospital, Australia. American Journal of Respiratory and Critical Care Medicine 2019, in press.
Method
Phage researchers and clinicians from the Westmead Institute and Westmead Hospital brief us on how phage therapy is regulated in Australia, through the lens of their experience treating 14 patients with IV phage therapy.
Preprint
Full-text available
Importance: The effect of IV administration of a bacteriophage cocktail produced under GMP conditions on patients with severe S. aureus infection, including complicated bacteraemia, endocarditis and septic shock, is unknown. Objective: To assess safety and tolerability of adjunctive bacteriophage therapy in patients with severe S. aureus infections...
Article
The rise of multiple antibiotic resistance in clinically relevant bacteria has created a global crisis with increasing burden on healthcare systems. The need to optimise alternative therapies to antibiotics, particularly in high risk nosocomial settings, is therefore immediate. Bacteriophages are specialised lethal viruses of bacteria, and an under...
Article
Full-text available
Circulating TNF-related apoptosis-inducing ligand (TRAIL) levels are reduced in patients with cardiovascular disease, and TRAIL gene deletion in mice exacerbates atherosclerosis and inflammation. How TRAIL protects against atherosclerosis, and why levels are reduced in disease is unknown. Here, multiple strategies were used to identify the protecti...
Conference Paper
Aims: Definitive diagnosis of malignant pleural mesothelioma (MPM) is difficult and requires invasive tumour biopsy.MicroRNAs are proven to be dysregulated in MPM and have therapeutic potential. Circular RNAs (circRNAs) are noncoding competitive endogenous RNAs (ceRNAs) that interact with microRNAs as ‘sponges’ via direct binding, subsequently lead...
Article
Full-text available
Malignant pleural mesothelioma (MPM), an aggressive malignancy affecting pleural surfaces, occurs in three main histological subtypes. The epithelioid and sarcomatoid subtypes are characterized by cuboid and fibroblastoid cells, respectively. The biphasic subtype contains a mixture of both. The sarcomatoid subtype expresses markers of epithelial–me...
Article
Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy linked to asbestos exposure. On a genomic level, MPM is characterised by frequent chromosomal deletions of tumour suppressors, including microRNAs. MiR-137 plays a tumour suppressor role in other cancers, so the aim of this study was to characterise it and its target Y-bo...
Article
Full-text available
Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of vitamin D are mediated through binding to the vitamin D receptor (VDR). Here, we report on the unexpected finding that stable knockdown of VDR expres¬sion in the human breast and...
Article
Repopulation of brain circuits by neural precursors is a potential therapeutic strategy for neurodegenerative disorders, however choice of cell is critical. Previously, we introduced a two-step culture system that generates a high yield of neural precursors from small samples of adult canine skin. Here we probe their gene and protein expression pr...
Data
Document S1. Supplemental Experimental Procedures, Figures S1–S7, and Tables S1–S3
Article
Full-text available
Malignant pleural mesothelioma (MPM) is a tumor originating in the mesothelium, the membrane lining the thoracic cavities, and is induced by exposure to asbestos. Australia suffers one of the world's highest rates of MPMand the incidence is yet to peak. The prognosis for patients withMPMis poor and median survival following diagnosis is 4–18 months...
Article
Full-text available
Background Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional r...
Article
Full-text available
Key points: MicroRNA (miRNA)-based therapies are in development for numerous diseases, including heart disease. Currently, very limited basic information is available on the regulation of specific miRNAs in male and female hearts in settings of disease. The identification of sex-specific miRNA signatures has implications for translation into the c...
Article
Full-text available
Expression of the miR-34 family (miR-34a, -34b, -34c) is elevated in settings of heart disease, and inhibition with antimiR-34a/antimiR-34 has emerged as a promising therapeutic strategy. Under chronic cardiac disease settings, targeting the entire miR-34 family is more effective than targeting miR-34a alone. The identification of transcription fac...
Article
Full-text available
Expression of miR-154 is upregulated in the diseased heart and was previously shown to be upregulated in the lungs of patients with pulmonary fibrosis. However, the role of miR-154 in a model of sustained pressure overload-induced cardiac hypertrophy and fibrosis had not been assessed. To examine the role of miR-154 in the diseased heart, adult mal...
Article
Full-text available
miRNAs are small non-coding RNAs (ncRNAs), which regulate gene expression. Here, the authors describe the contribution of miRNAs to cardiac biology and disease. They discuss various strategies for manipulating miRNA activity including antisense oligonucleotides (antimiRs, blockmiRs), mimics, miRNA sponges, Tough Decoys and miRNA mowers. They review...
Article
Full-text available
Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be in...
Article
Full-text available
We generated two hiPSC clones from a patient with sporadic late-onset Alzheimer's disease (AD-iPSCs), which expressed typical undifferentiated markers and passed standard pluripotency assays. Genome-wide microarray analysis revealed that AD-iPSCs were highly similar to control hiPSCs and hESCs, albeit with some noticeable differences in few genes,...
Article
Full-text available
Prognosis of malignant pleural mesothelioma (MPM) is poor, and predicting the outcomes of treatment is difficult. Here we investigate the potential of microRNA expression to estimate prognosis of MPM patients. Candidate microRNAs from microarray profiling of tumor samples from 8 long (median: 53.7 months) and 8 short (median: 6.4 months) survivors...
Article
Full-text available
Paternal high fat diet (HFD) consumption triggers unique gene signatures, consistent with premature aging and chronic degenerative disorders, in both white adipose tissue (RpWAT) and pancreatic islets of daughters. In addition to published data in Nature, 2010, 467, 963–966 (GSE: 19877, islet) and FASEB J 2014, 28, 1830–1841 (GSE: 33551, RpWAT), we...
Article
Full-text available
Expression of microRNA-652 (miR-652) increases in the diseased heart, decreases in a setting of cardioprotection, and is inversely correlated with heart function. The aim of this study was to assess the therapeutic potential of inhibiting miR-652 in a mouse model with established pathological hypertrophy and cardiac dysfunction due to pressure over...
Article
Introduction: MicroRNAs (miRNAs) are altered in heart disease and have emerged as promising therapeutic targets. We recently reported that therapeutic inhibition of the miR-34 family (with an 8 mer antimiR) was effective in attenuation of pathological cardiac remodeling. We hypothesized the efficacy of antimiR-34 may be due to its regulation of oth...
Article
Introduction: Targeting microRNAs differentially regulated in settings of stress and protection could represent a new approach for the treatment of heart failure. miR-652 expression increased in hearts of a cardiac stress mouse model and was downregulated in a model of cardiac protection. Aim: To assess the therapeutic potential of silencing miR-65...
Article
Full-text available
Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy, characterized by an almost complete loss of adipose tissue and severe insulin resistance. BSCL2 is caused by loss-of-function mutations in the BSCL2/SEIPIN gene, which is upregulated during adipogenesis and abundantly expressed in the adipose t...
Article
Full-text available
Therapeutic inhibition of the miR-34 family (miR-34a,-b,-c), or miR-34a alone, have emerged as promising strategies for the treatment of cardiac pathology. However, before advancing these approaches further for potential entry into the clinic, a more comprehensive assessment of the therapeutic potential of inhibiting miR-34a is required for two key...