Dr Richard Yu

Dr Richard Yu

Lecturer

School of Environmental and Life Sciences (Environmental Science and Management)

Career Summary

Biography

I received my PhD from City University of Hong Kong in 2002. After my postdoctoral training with Prof. Rudolf Wu, I continued to work in the same institution as a Lecturer until joining the University of Newcastle in 2009. I am now an academic in the Discipline of Environmental Science and Management in the School of Environmental & Life Sciences (SELS).

My primary research interests are in the Molecular Toxicology of Environmental Stressors and Chemicals.

In particular, I am interested in (1) understanding the molecular mechanisms of endocrine disruption caused by hypoxia and environmental chemicals and (2) developing cell- and animal-based assays for the screening and detection of endocrine-disrupting chemicals (EDCs). Overall, my research covers both basic science aimed at understanding the fundamental mechanisms of environmental toxicity and applied science concerned with the development of diagnostic tools for assessing and monitoring environmental toxicity. Outlined below is a summary of my recent research activities and findings:   

1. Environmental Obesogens

The prevalence of obesity has been dramatically increasing worldwide during the last several decades. In recent years, there is growing epidemiological evidence indicating a positive correlation between the exposure of human population to EDCs and body weight, suggesting a possible role of EDCs in increasing obesity rates. The "obesogen hypothesis" is an emerging view proposing that exposure to a subset of these chemicals (obesogens) disrupts the weight-control mechanisms and ultimately increases obesity. To date, most of the known obesogens are those directly increasing adipogenesis and lipid accumulation, while the ones that contribute to diet-induced obesity (DIO) are understudied.

Leptin is an adipocyte-derived hormone that represses appetite and increases energy expenditure. Leptin inhibits appetite by decreasing the activity of the orexigenic NPY/AgRP/GABA neurons and increasing the activity of the anorexigenic POMC/CART neurons in the hypothalamus. Leptin action is exerted through its binding to the leptin receptor (OB-R) expressed on the surface of these neurons. Recent research showed that the disruption of OB-R activation (after treatment with leptin antagonists) during early development can lead to adult leptin resistance. Leptin resistance is a medical condition in which individuals are weakly responsive or unresponsive to high circulating levels of leptin and regarded as an important predisposing factor for DIO. Based on this existing knowledge, we hypothesise that early-life exposure to environmental chemicals that act as leptin antagonists can enhance the development of leptin-resistance and DIO in adults.  

In collaboration with my co-worker Dr Richard Kong at City University of Hong Kong, a pilot screening program was recently initiated to identify environmental chemicals that act as leptin antagonists using biophysical and cell-based assays. Further effort will be made to assess the ability of the identified candidates to induce the developmental programming of adult leptin resistance and DIO using zebrafish (an important human disease model). This project is anticipated to provide important information regarding the contribution of developmental programming to the obesity epidemic, through assessing the role of early-life exposure of environmental chemicals in the development of adult leptin resistance and obesity. Since the rising prevalence of obesity has been recently noticed in livestock, pets, and wild animals, the knowledge about the mechanism of action of environmental obesogens and the technologies developed in this research could also be applied to a much broader range of biota beyond humans. Eventually, the outcome of this research may aid in devising new regulations on the safety of animal feed and the release of obesogenic chemicals to the environment.

2. Estrogen-mediated Vitellogenesis in Oysters

Oysters respond to EDC mixtures with the induction of the female egg yolk protein, vitellogenin (Vtg), availing a biomarker which indicates the presence of estrogenic contaminants in sewage effluent receiving waters. Despite this, the precise mechanism through which estrogens exert their action to induce vitellogenesis is unknown. Estrogen receptors (ERs) with homology to vertebrate ERs have been identified in selected molluscan taxa, yet those found to date do not bind or are unresponsive to estrogen. We hypothesise that estrogens may bind to receptors yet to be identified in Mollusca, with lower structural similarity to vertebrate-like ERs, and such receptors act as estrogen-dependent transcriptional regulators of vitellogenin expression. In an effort to investigate this possibility, Dr Geoff MacFarlane (UoN) and I initiated a project to isolate and characterise novel “functional” ERs from the native Sydney rock oyster (Saccostrea glomerata). Our recent progress indicated that an invertebrate-like ER isolated from the Sydney rock oyster ovarian tissues shares a similar ligand (estrogen) binding pocket with that of the human ER and is expressed in response to estrogenic compounds. Further effort will be directed at clarifying its functional roles in mediating vitellogenesis and gonadal development and its epigenetic regulation in response to the exposure to estrogenic compounds. At the application level, this research will provide important information (an ER pathway specific to invertebrates) for the development of bioassays for screening xenoestrogens with ecotoxicological relevance to molluscs.

3. Fish Hypoxia

Previously, my co-workers and I have demonstrated for the first time that hypoxia can disrupt sex differentiation via modulation of gene expression for estrogen biosynthesis, leading to a male-biased sex ratio in zebrafish (Shang et al. 2006). This work has highlighted the alarming impacts of aquatic hypoxia on fish reproduction and sustainability, and thus attracted worldwide attention, as exemplified by cover stories written by Science and Nature as well as reports by CNN and ABC. This study has been cited 60 times since its publication in 2006. Later studies also provided scientific evidence that the transcription factor hypoxia-inducible factor-1 (HIF-1) regulates a number of genes involved in fish growth and reproduction in response to hypoxia (Yu et al. 2006a, 2008; Chu et al. 2010). To assess the applicability and specificity of HIF-1-regulated gene expression as biomarkers for monitoring aquatic hypoxia, we also made efforts to decipher the crosstalk between the xenobiotic transformation pathway and the HIF-1 pathway. Intriguingly, we demonstrated that the existence of xenobiotics can enhance HIF-1-mediated gene expression via increasing the cellular levels of reactive oxygen species (ROS), indicating that the presence of environmental xenobiotics must be considered when interpreting HIF-1-based hypoxia biomarker results (Yu et al. 2008). In 2012, my co-workers (Kong & Wu) and I obtained a seed fund ($US 115,384) from the State Key Laboratory in Marine Pollution, China to study the interactive effects of climate change and hypoxia on fish sex determination. 

4. Fish Leptin

The study of obesity and appetite control in fish models is an emerging field of research. In the last few years, my co-workers and I highlighted striking similarities in the function and regulation of leptin between fish and mammals. Our recent work suggests that leptin elevation under hypoxic conditions is a pathophysiological response common to both zebrafish and mammalian models (Chu et al. 2010). In another prior study, we reported for the first time the characterization of a fish long-form leptin receptor that contains all the signature motifs and domains found in the mammalian leptin receptors (Wong, Yu et al. 2007), implying the function of leptin receptor is conserved in both fish and mammals. Recently, using gain-or-loss gene function techniques, we demonstrated that leptin is the molecular link between hypoxia and endocrine disruption, leading to the suppression of the aromatase gene (cyp19a) and hence estrogen production in fish (Yu et al. 2012). Taken together, these findings provide novel insights into the molecular mechanism of endocrine disruption under hypoxia. This research successfully attracted $US 108,974 funding from Hong Kong General Research Fund (GRF) in 2011.

5. In-vitro bioassays for EDCs

For years, I have been collaborating with Prof. John Giesy (Canada Research Chair in Environmental Toxicology, University of Saskatchewan) on the development and validation of a H295R cell line screening test to evaluate toxicant-induced effects on steroid biosynthesis (steroidogenesis)—the H295R Steroidogenesis Assay (Gracia et al. 2004; Zhang et al. 2005; Gracia et al. 2006; Xu et al. 2006; Gracia et al. 2007; He et al. 2008; Song et al. 2008). This assay has been successfully used to assess the endocrine-disrupting potential and the mechanisms of action of various chemicals and environmental samples. This assay is currently being developed as part of Tier 1 of the US EPA Endocrine Disruptor Screening Program and an Organization for Economic Cooperation and Development (OECD) test method validation program.

6. In-vivo bioassays for EDCs

We recently demonstrated that induction of hepatic choriogenin H (ChgH, a fish egg-shell protein precursor) mRNA expression in male marine medaka can serve as a highly sensitive biomarker for environmental estrogens (its sensitivity is even better than vitellogenin) (Yu et al. 2006b; Cheng et al. 2008). This novel discovery led us to develop a ChgH-GFP transgenic marine medaka for monitoring environmental estrogens in marine water. Our recent progress indicated that this sentinel fish can detect 17β-estradiol (E2) at nominal concentrations as low as 1 μg/L. To make quantification of in vivo GFP expressed in developing fish embryos feasible, we previously developed an automatic 4D (3D plus time) acquisition system and the imaging processes of deconvolution and thresholding (Yu et al. 2006c). This 4D imaging system provides a simple but powerful means to quantify in vivo gene expression in a developmental toxicology context. The technologies have been successfully commercialised as environmental and food safety consultancy service in Hong Kong (Vitargent (International) Biotechnology Ltd). 

Research Expertise
Ecotoxicology Molecular toxicology Obesogen screening Embryotoxicity assays Development of bioassays for EDC screening and detection

Teaching Expertise
BIOL1003 Professional Skills for Biological Sciences, ENVS2004 Ecology, ENVS3004 Ecotoxicology, SCIT2500 Project and Advanced Studies, SCIT3500 Project and Advanced Studies II

Administrative Expertise
BSc Merit Pathway Convenor  

Collaborations
For years, I have been working in close collaboration with Prof Rudolf Wu (University of Hong Kong), Dr Richard Kong (City University of Hong Kong) and Prof John Giesy (University of Saskatchewan) on hypoxia and EDC research. Recent collaborative projects (funded) include: (1) National Natural Science Foundation of China – 2015 (Project no. 21577114), Investigators: A/P Richard Kong and Dr Richard Yu, Project title: Identification and molecular studies of environmental obesogens that cause overeating, Funding: $US 106,320. (2) CityU Strategic Research Grant, City University of Hong Kong – 2013 (Project no. 7003027), Investigators: A/P Richard Kong and Dr Richard Yu, Project Title: Pilot study to identify environmental obesogens (chemicals that cause overeating) using BRET (Bioluminescence Resonance Energy Transfer) and cell-based assays, Funding: $US 12,821. (3) SKLMP Seed Collaborative Research Fund, State Key Laboratory in Marine Pollution, China – 2012 (Project no. 9369101), Investigators: A/P Richard Kong, Prof Rudolf Wu and Dr Richard Yu, Project Title: Interactive effects of climate change and hypoxia on fish sex determination: estrogen synthesis and masculinisation, Funding: $US 115,384. (4) General Research Fund, Hong Kong Research Grants Council – 2011 (Project no. 160411), Investigators: A/P Richard Kong, Prof John Giesy and Dr Richard Yu, Project Title: Uncovering the molecular links between hypoxia and endocrine disruption: A functional study of zebrafish leptin, Funding: $US 108,974. 


Qualifications

  • PhD, City University of Hong Kong - China
  • Bachelor of Science (Applied Biology)(Honours), City University of Hong Kong - China

Keywords

  • EDC
  • Endocrine disrupting chemicals
  • Environmental estrogens
  • Fish
  • Hypoxia
  • Molecular Toxicology
  • Obesogens
  • Sydney rock oyster

Fields of Research

Code Description Percentage
050199 Ecological Applications not elsewhere classified 20
060199 Biochemistry and Cell Biology not elsewhere classified 40
111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified 40

Professional Experience

UON Appointment

Title Organisation / Department
Lecturer University of Newcastle
School of Environmental and Life Sciences
Australia

Invitations

Speaker

Year Title / Rationale
2011 Science Week Conference

Endocrine disrupting chemicals (EDCs) in the aquatic environment: Their mechanisms of action and detection strategies


Grant Reviews

Year Grant Amount
2015 PERIPHERAL: Variation in thermal and hypoxia sensitivities between peripheral and central fish populations, and its potential role in the resilience of populations experiencing ocean change
International - Competitive - 3IFA, International - Competitive - 3IFA
$807,541
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (28 outputs)

Year Citation Altmetrics Link
2015 Yu RMK, Chaturvedi G, Tong SKH, Nusrin S, Giesy JP, Wu RSS, Kong RYC, 'Evidence for microRNA-mediated regulation of steroidogenesis by hypoxia', Environmental Science and Technology, 49 1138-1147 (2015)

Environmental hypoxia can occur in both natural and occupational environments. Over the recent years, the ability of hypoxia to cause endocrine disruption via perturbations in ste... [more]

Environmental hypoxia can occur in both natural and occupational environments. Over the recent years, the ability of hypoxia to cause endocrine disruption via perturbations in steroid synthesis (steroidogenesis) has become increasingly clear. To further understand the molecular mechanism underlying hypoxia-induced endocrine disruption, the steroidproducing human cell line H295R was used to identify microRNAs (miRNAs) affecting steroidogenic gene expression under hypoxia. Hypoxic treatment of H295R cells resulted in the downregulation of seven steroidogenic genes and one of these, CYP19A1 (aromatase), was shown to be regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1). Using bioinformatic and luciferase reporter analyses, miR-98 was identified to be a CYP19A1- targeting miRNA from a subset of HIF-1-inducible miRNAs. Gain- and loss-of-function analysis suggested that under hypoxia, the increased expression of miR-98 led to the downregulation of CYP19A1 mRNA and protein expression and that it may have contributed to a reduction in estradiol (E2) production. Intriguingly, luciferase reporter assays using deletion constructs of a proximal 5'-flanking region of miR-98 did not reveal a hypoxia-responsive element (HRE)-containing promoter. Overall, this study provided evidence for the role of miRNAs in regulating steroidogenesis and novel insights into the molecular mechanisms of hypoxia-induced endocrine disruption. (Figure Presented).

DOI 10.1021/es504676s
2014 Lu X, Yu RMK, Murphy MB, Lau K, Wu RSS, 'Hypoxia disrupts gene modulation along the brain-pituitary-gonad (BPG)-liver axis', Ecotoxicology and Environmental Safety, 102 70-78 (2014) [C1]

Hypoxia alters sex hormone concentrations leading to reproductive impairment in fish; however the mechanisms underlying these effects remain largely unknown. Using zebrafish (Dani... [more]

Hypoxia alters sex hormone concentrations leading to reproductive impairment in fish; however the mechanisms underlying these effects remain largely unknown. Using zebrafish (Danio rerio), this study is the first to demonstrate that hypoxia causes endocrine disruption by simultaneously acting on multiple targets along the brain-pituitary-gonadal (BPG)-liver axis in fish. Alterations in the expression of key genes associated with reproductive endocrine pathways in the brain (sGnRH), pituitary (FSHß and LHß), gonads (FSH-R, LH-R, HMGR, StAR, CYP19A, CYP11A, CYP11ß and 20ß-HSD), and liver were correlated with significant reductions of estradiol in females and testosterone in males. Hypoxia also induced sex-specific and tissue-specific changes in the expression of estrogen, androgen, and membrane progestin receptors along the BPG axis, suggesting disruption of the feedback and synchronization of hormone signals. Furthermore, the hypoxia-induced upregulation of hepatic sex hormone-binding globulin suggests an increase in hormone transport and reduced bioavailability in blood, while upregulation of hepatic CYP3A65 and CYP1A in females suggests an increase in estrogen biotransformation and clearance. Given that the regulation of reproductive hormones and the BPG-liver axis are highly conserved, this study provides new insights into the hypoxia-induced endocrine disrupting mechanisms and reproductive impairment in other vertebrates. © 2014 Elsevier Inc.

DOI 10.1016/j.ecoenv.2014.01.017
Citations Scopus - 4
2012 Yu MKR, Chu DLH, Tan T-F, Li VWT, Chan AKY, Giesy JP, et al., 'Leptin-mediated modulation of steroidogenic gene expression in hypoxic zebrafish embryos: Implications for the disruption of sex steroids', Environmental Science & Technology, 46 9112-9119 (2012) [C1]
Citations Scopus - 8Web of Science - 8
2011 Lo KH, Hui MNYH, Yu MKR, Wu RSS, Cheng SH, 'Hypoxia impairs primordial germ cell migration in zebrafish (danio rerio) embryos', PLoS ONE, 6 e24540 (2011) [C1]
Citations Scopus - 10Web of Science - 9
2010 Chu DLH, Li VWT, Yu MKR, 'Leptin: Clue to poor appetite in oxygen-starved fish', Molecular and Cellular Endocrinology, 319 143-146 (2010) [C1]
DOI 10.1016/j.mce.2010.01.018
Citations Scopus - 17Web of Science - 17
2010 Ng PKS, Yu MKR, Kwong TFN, Wong MML, Kong RYC, 'Transcriptional regulation and functional implication of the grass carp CITED1 (gcCITED1) in the negative regulation of HIF-1', International Journal of Biochemistry and Cell Biology, 42 1544-1552 (2010) [C1]
DOI 10.1016/j.biocel.2010.06.007
Citations Scopus - 2Web of Science - 2
2009 Ng PKS, Chiu S-K, Kwong TFN, Yu MKR, Wong MML, Kong RYC, 'Functional characterization of two CITED3 homologs (gcCITED3a and gcCITED3b) in the hypoxia-tolerant grass carp, Ctenopharyngodon idellus', BMC Molecular Biology, 10 1-14 (2009) [C1]
DOI 10.1186/1471-2199-10-101
Citations Scopus - 3Web of Science - 2
2009 Zhou HW, Wong AHY, Yu RMK, Park YD, Wong YS, Tam NFY, 'Polycyclic Aromatic Hydrocarbon-Induced Structural Shift of Bacterial Communities in Mangrove Sediment', MICROBIAL ECOLOGY, 58 153-160 (2009) [C1]
DOI 10.1007/s00248-008-9456-x
Citations Scopus - 33Web of Science - 28
2008 Song R, He Y, Murphy MB, Yeung LWY, Yu RMK, Lam MHW, et al., 'Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidgenesis in the H295R cell line', Chemosphere, 71 1888-1894 (2008) [C1]
DOI 10.1016/j.chemosphere.2008.01.032
Citations Scopus - 31Web of Science - 30
2008 Chen X, Li VWT, Yu RMK, Cheng SH, 'Choriogenin mRNA as a sensitive molecular biomarker for estrogenic chemicals in developing brackish medaka (Oryzias melastigma)', Ecotoxicology and Environmental Safety, 71 200-208 (2008) [C1]
DOI 10.1016/j.ecoenv.2007.10.005
Citations Scopus - 16Web of Science - 16
2008 Yu RMK, Ng PKS, Tan T, Chu DLH, Wu RSS, Kong RYC, 'Enhancement of hypoxia-induced gene expression in fish liver by the aryl hydrocarbon receptor (AhR) ligand, benzo[a]pyrene (BaP)', Aquatic Toxicology, 90 235-242 (2008) [C1]
DOI 10.1016/j.aquatox.2008.09.004
Citations Scopus - 15Web of Science - 16
2008 He Y, Murphy MB, Yu RMK, Lam MHW, Hecker M, Gisey JP, et al., 'Effects of twenty PBDE metabolites on steroidgenesis in the H295R cell line', Toxicology Letters, 176 230-238 (2008) [C1]
DOI 10.1016/j.toxlet.2007.12.001
Citations Scopus - 70Web of Science - 67
2007 Kong RYC, Law SHL, Chu JKY, Ng PKD, Yu RMK, Wu RSS, 'Functional and molecular plasticity of the HIF transcription factors', COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, 148 S7-S7 (2007)
DOI 10.1016/j.cbpa.2007.06.016
2007 Shang EHH, Yu RMK, Wu RSS, 'Hypoxia alters sex hormones, sex ratio and favors a male-dominated population in fish', COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, 148 S118-S118 (2007)
DOI 10.1016/j.cbpa.2007.06.294
Citations Web of Science - 1
2007 Chen X, Kinoshita M, Hirata T, Yu RMK, Cheng SH, 'Transgenic marine medaka (Oryzias melastigma): a sensitive sentinel for estrogenic pollutants', MOLECULAR & CELLULAR TOXICOLOGY, 3 34-34 (2007)
Citations Web of Science - 8
2007 Wong MML, Yu RMK, Ng PKS, Law SHW, Tsang AKC, Kong RYC, 'Characterization of a hypoxia-responsive leptin receptor (omLepR(L)) cDNA from the marine medaka (Oryzias melastigma)', MARINE POLLUTION BULLETIN, 54 797-803 (2007) [C1]
DOI 10.1016/j.marpolbul.2007.01.025
Citations Web of Science - 24
2007 Gracia T, Hilscherova K, Jones PD, Newsted JL, Higley EB, Zhang X, et al., 'Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds', TOXICOLOGY AND APPLIED PHARMACOLOGY, 225 142-153 (2007) [C1]
DOI 10.1016/j.taap.2007.07.013
Citations Web of Science - 28
2006 Xu Y, Yu RMK, Zhang XW, Murphy MB, Giesy JP, Lam MHW, et al., 'Effects of PCBs and MeSO2-PCBs on adrenocortical steroidogenesis in H295R human adrenocortical carcinoma cells', CHEMOSPHERE, 63 772-784 (2006) [C1]
DOI 10.1016/j.chemosphere.2005.08.013
Citations Web of Science - 31
2006 Yu RMK, Lin CC, Chan PK, Chow ESH, Murphy MB, Chan BP, et al., 'Four-dimensional imaging and quantification of gene expression in early developing zebrafish (Danio rerio) embryos', TOXICOLOGICAL SCIENCES, 90 529-538 (2006) [C1]
DOI 10.1093/toxsci/kfj115
Citations Web of Science - 10
2006 Gracia T, Hilscherova K, Jones PD, Newsted JL, Zhang X, Hecker M, et al., 'The H295R system for evaluation of endocrine-disrupting effects', ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 65 293-305 (2006) [C1]
DOI 10.1016/j.ecoenv.2006.06.012
Citations Web of Science - 49
2006 Yu RMK, Wong MML, Kong RYC, Wu RSS, Cheng SH, 'Induction of hepatic choriogenin mRNA expression in male marine medaka: A highly sensitive biomarker for environmental estrogens', AQUATIC TOXICOLOGY, 77 348-358 (2006) [C1]
DOI 10.1016/j.aquatox.2006.01.003
Citations Web of Science - 22
2006 Law SHW, Wu RSS, Ng PKS, Yu RMK, Kong RYC, 'Cloning and expression analysis of two distinct HIF-alpha isoforms - gcHIF-1alpha and gcHIF-4alpha - from the hypoxia-tolerant grass carp, Ctenopharyngodon idellus', BMC MOLECULAR BIOLOGY, 7 (2006) [C1]
DOI 10.1186/1471-2199-7-15
Citations Web of Science - 42
2006 Yu RMK, Chen EXH, Kong RYC, Ng PKS, Mok HOL, Au DWT, 'Hypoxia induces telomerase reverse transcriptase (TERT) gene expression in non-tumor fish tissues in vivo: The marine medaka (Oryzias melastigma) model', BMC Molecular Biology, 7 (2006) [C1]
DOI 10.1186/1471-2199-7-27
2006 Shang EHH, Yu RMK, Wu RSS, 'Hypoxia affects sex differentiation and development, leading to a male-dominated population in zebrafish (Danio rerio)', ENVIRONMENTAL SCIENCE & TECHNOLOGY, 40 3118-3122 (2006) [C1]
DOI 10.1021/es0522579
Citations Web of Science - 105
2005 Zhang XW, Yu RMK, Jones PD, Lam GKW, Newsted JL, Gracia T, et al., 'Quantitative RT-PCR methods for evaluating toxicant-induced effects on steroidogenesis using the H295R cell line', ENVIRONMENTAL SCIENCE & TECHNOLOGY, 39 2777-2785 (2005) [C1]
DOI 10.1021/es048679k
Citations Web of Science - 60
2005 Yu RMK, Wong MML, Jack RW, Kong RYC, 'Structure, evolution and expression of a second subfamily of protein phosphatase 2A catalytic subunit genes in the rice plant (Oryza sativa L.)', PLANTA, 222 757-768 (2005) [C1]
DOI 10.1007/s00425-005-0018-x
Citations Web of Science - 7
2004 Hilscherova K, Jones PD, Gracia T, Newsted JL, Zhang XW, Sanderson JT, et al., 'Assessment of the effects of chemicals on the expression of ten steroidogenic genes in the H295R cell line using real-time PCR', TOXICOLOGICAL SCIENCES, 81 78-89 (2004) [C1]
DOI 10.1093/toxsci/kfh191
Citations Web of Science - 96
2003 Yu RMK, Zhou Y, Xu ZF, Chye ML, Kong RYC, 'Two genes encoding protein phosphatase 2A catalytic subunits are differentially expressed in rice', PLANT MOLECULAR BIOLOGY, 51 295-311 (2003) [C1]
DOI 10.1023/A:1022006023273
Citations Web of Science - 14
Show 25 more journal articles

Conference (3 outputs)

Year Citation Altmetrics Link
2010 Priestley MN, Dunstan RH, O'Connor W, Van Zweiten R, Yu MKR, Macfarlane GR, 'Molluscan bio-monitor for quantification and impcat assessment of estrogenically active compounds in Australian marine ecosystems', 20th SETAC Europe Annual Meeting, Seville, Spain: Science and Technology Environmental Protection: Programme Book, Seville, Spain (2010) [E3]
Co-authors Geoff Macfarlane, Hugh Dunstan
2010 Yu MKR, Chu DLH, Li VWT, 'Leptin: A molecular link between hypoxia and endocrine disruption in fish?', 6th International Conference on Marine Pollution and Ecotoxicology. Programme & Abstracts, Hong Kong (2010) [E3]
2009 Yu MKR, 'Leptin: A molecular link between hypoxia and endocrine disruption in fish?', 13th Australasian Society for Ecotoxicology Conference: Posters, Adelaide, SA (2009) [E3]
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Grants and Funding

Summary

Number of grants 7
Total funding $401,326

Click on a grant title below to expand the full details for that specific grant.


20161 grants / $144,654

Identification and Molecular Studies of Environmental Obesogens that Cause Overeating$144,654

Obesity is a global epidemic with rising trends in Asian countries, including China and Hong Kong. Because obesity is closely associated with chronic diseases, such as type 2 diabetes and cardiovascular diseases, the increase in obesity corresponds to a rise in mortality rates. There is growing epidemiological evidence indicating a positive correlation between the exposure of human population to endocrine-disrupting chemicals (EDCs, chemicals that affect hormone systems) and body weight, suggesting a possible role of EDCs in increasing obesity rates. The “obesogen hypothesis” proposes that exposure to a subset of these chemicals (obesogens) disrupts the body’s weight-control mechanisms and ultimately increases obesity. To date, most of the widely known obesogens are those that directly increase adipogenesis and lipid accumulation, while the ones which contribute to overeating (a major non-genetic cause of obesity) are understudied.

Leptin is an adipocyte-derived hormone that plays a key role in regulating food intake and inhibits appetite by decreasing the activity of the orexigenic NPY/AgRP/GABA neurons and increasing the activity of the anorexigenic POMC/CART neurons in the hypothalamus. Leptin action is exerted through its binding to the leptin receptor (OB-R) expressed on the surface of these neurons. Interestingly, chronically elevated leptin levels in “non-genetic obesity” individuals fail to cause appetite inhibition. This apparent leptin ineffectiveness (leptin resistance) is considered an important predisposing factor for diet-induced obesity (DIO). Although the concept of leptin resistance is widely accepted, its underlying mechanisms remain elusive. However, mounting evidence suggests that defective leptin transport across the blood-brain barrier (BBB) and disrupted hypothalamic leptin signaling are the potential causes for leptin resistance. Because leptin receptor (OB-R) plays an important role in regulating leptin transport and leptin signaling, it is highly likely that any disruption in OB-R activation will lead to leptin resistance. We hypothesize that certain environmental chemicals could act as leptin antagonists to enhance or promote obesity (as a result of leptin resistance) by the disruption of OB-R activity.

This study aims to conduct a screening program against a chemical library of representative environmental compounds (using biophysical and cell-based assays) to identify environmental chemicals that act as leptin antagonists. Chemicals identified by the screening program will be further tested in zebrafish to determine whether early developmental exposures to these chemicals could potentially lead to leptin resistance and DIO in adult life. We anticipate that the results of the proposed study will provide important new insights into the role of exposure to environmental chemicals in the development of obesity and thereby open new perspectives for the formulation of effective preventive strategies against obesity.

Funding body: National Natural Science Foundation of China

Funding body National Natural Science Foundation of China
Project Team
Scheme General Project Grant
Role Investigator
Funding Start 2016
Funding Finish 2019
GNo
Type Of Funding International - Competitive
Category 3IFA
UON N

20131 grants / $12,396

Pilot study to identify environmental obesogens (chemicals that cause overeating) using BRET (Bioluminescence Resonance Energy Transfer) and cell-based assays$12,396

Funding body: City University of Hong Kong

Funding body City University of Hong Kong
Project Team
Scheme CityU Strategic Research Grant
Role Investigator
Funding Start 2013
Funding Finish 2013
GNo
Type Of Funding International - Non Competitive
Category 3IFB
UON N

20122 grants / $127,023

Interactive effects of climate change and hypoxia on fish sex determination: estrogen synthesis and masculinisation$113,523

Funding body: State Key Laboratory in Marine Pollution

Funding body State Key Laboratory in Marine Pollution
Project Team
Scheme SKLMP Seed Collaborative Research Fund
Role Investigator
Funding Start 2012
Funding Finish 2014
GNo
Type Of Funding International - Non Competitive
Category 3IFB
UON N

Molecular mechanisms underpinning the induction of fish sex change by climate change stressors$13,500

Funding body: University of Newcastle - Faculty of Science & IT

Funding body University of Newcastle - Faculty of Science & IT
Project Team Doctor Richard Yu
Scheme Strategic Small Grant
Role Lead
Funding Start 2012
Funding Finish 2012
GNo G1401107
Type Of Funding Internal
Category INTE
UON Y

20111 grants / $102,253

Uncovering the molecular links between hypoxia and endocrine disruption: A functional study of zebrafish leptin $102,253

The ultimate goal of this project is to provide novel insights into the mechanistic role of leptin in endocrine disruption observed in hypoxic fish. Hypoxia (<2mg O2 L−1) arising as a result of euthrophication affects vast stretches of aquatic ecosystems worldwide and often leads to population decline and changes in community structure by eliminating oxygen-sensitive species. Endocrine disruption is one of the major causes of reproductive impairment observed in hypoxic fish. Our recent study demonstrated that hypoxia can alter both the levels and the balance of testosterone and estradiol, resulting in retarded gonadal development and altered phenotypic sex ratio in zebrafish. Reproductive impairments with concomitant perturbation of estrogens and androgens were similarly reported in several other fish species exposed to hypoxia. However, the mechanisms of such hypoxia-induced disruption of sex steroids are yet to be elucidated. One of the mechanisms of endocrine disruption is interference with steroidogenesis. In a previous study, we demonstrated that expression of cytochrome P450 cholesterol side chain cleavage enzyme (CYP11A) is down-regulated in hypoxic zebrafish embryos. Down-regulation of expression of CYP11A as well as the steroidogenic acute regulatory protein (StAR) gene has also been observed in human adrenocortical carcinoma H295R cells after short-term exposures to hypoxic conditions. Since both StAR and CYP11A represent the first and rate-determining steps of the steroidogenesis cascade, their suppression could contribute to the decreased sex steroid production observed in hypoxic fish. However, the regulatory mechanisms underlying hypoxia-mediated suppression of StAR and CYP11A remain elusive. The hormone leptin, apart from being a central regulator of food intake and metabolism, plays a role in modulating reproduction in mammals. This modulatory effect is likely due in part to the direct inhibitory effect of leptin on adrenal and gonadal steroidogenesis, mostly through attenuation of StAR and CYP11A gene expression. The molecular mechanisms accounting for this attenuation is still unclear, although steroidogenic factor 1 (SF1), a transcription factor essential for activation of multiple steroidogenic genes, may be involved. Hypoxia has been shown to increase leptin expression and secretion in various in vivo and in vitro mammalian systems, and the involvement of hypoxia-inducible factor 1 (HIF-1) in these responses was suggested. Our team recently demonstrated that HIF1-α overexpression can also elevate leptin gene expression in zebrafish embryos. Based on these observations, we hypothesize that the suppressive effects of hypoxia on steroidogenic gene expression in early zebrafish development is at least in part due to HIF-1α-enhanced leptin expression.

Funding body: University Grants Committee (Hong Kong)

Funding body University Grants Committee (Hong Kong)
Project Team
Scheme Research Grants Council - General Research Fund
Role Investigator
Funding Start 2011
Funding Finish 2014
GNo
Type Of Funding International - Competitive
Category 3IFA
UON N

20092 grants / $15,000

Discovery of Novel molecular targets in Caenorhabditis elegans for biomonitoring of endocrine disrupting chemicals$10,000

Endocrine disrupting chemicals (EDCs) can affect the normal growth and reproduction of the wildlife. Currently, bioassays to detect EDCs are largely based on the potential for direct interaction of chemicals with steroid hormone receptors, thus ignoring many chemicals that are able to interfere with the endocrine system by other non-receptor-mediated mechanisms. One of the important mechanisms by which EDCs cause endocrine disruption is via interfering with steroid synthesis (steroidogenesis). The nematode Caenorhabditis elegans has recently emerged as a useful invertebrate system for ecotoxicological monitoring of environmental chemicals. In an attempt to develop C. elegans bioassays for monitoring steroidogenesis disrupting chemicals, this project will identify novel molecular targets of EDCs in the biosynthetic pathway of dafachronic acids, hormones that are required for normal growth and reproductive development in C. elegans. The outcome of this project would advance the technology to detect endocrine disruption activities present in environmental samples.

Funding body: Faculty of Science and Information Technology,The University of Newcastle

Funding body Faculty of Science and Information Technology,The University of Newcastle
Project Team
Scheme Faculty Strategic Seed Grant
Role Lead
Funding Start 2009
Funding Finish 2009
GNo
Type Of Funding Internal
Category INTE
UON N

Role of leptin in hypoxia-induced inhibition of sterodogenesis in zebrafish embryos$5,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Richard Yu
Scheme New Staff Grant
Role Lead
Funding Start 2009
Funding Finish 2009
GNo G0189969
Type Of Funding Internal
Category INTE
UON Y
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Research Supervision

Number of supervisions

Completed0
Current3

Total current UON EFTSL

PhD1.6

Current Supervision

Commenced Level of Study Research Title / Program / Supervisor Type
2014 PhD Ecotoxicology of Metals in Estuarine Invertebrates
Environmental Studies, Faculty of Science and Information Technology, The University of Newcastle
Principal Supervisor
2012 PhD Investigation of the Molecular Mechanisms Underlying Chemical-induced Endocrine Disruption in Sydney Rock Oysters (Saccostrea glomerata)
Environmental Studies, Faculty of Science and Information Technology, The University of Newcastle
Principal Supervisor
2009 PhD Discovering the Mechanisms of Estrogen Mediated Vitellogenesis in the Sydney Rock Oyster, Saccostrea Glomerata
Biological Sciences, Faculty of Science and Information Technology, The University of Newcastle
Co-Supervisor
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Research Collaborations

The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.

Country Count of Publications
Hong Kong 28
China 8
Australia 7
United States 7
Canada 6
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Dr Richard Yu

Position

Lecturer
Environmental Water Science Group
School of Environmental and Life Sciences
Faculty of Science and Information Technology

Focus area

Environmental Science and Management

Contact Details

Email richard.yu@newcastle.edu.au
Phone (02) 4921 6990
Fax (02) 4921 8977

Office

Room LS2-45
Building Life Sciences
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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