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-dependant 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).
- PhD, City University of Hong Kong - China, 12/11/2002
- Bachelor of Science (Applied Biology)(Honours), City University of Hong Kong - China, 18/11/1997
- Endocrine disrupting chemicals
- Environmental estrogens
- Molecular Toxicology
- Sydney rock oyster
Development of bioassays for EDC screening and detection
Fields of Research
|060199||Biochemistry And Cell Biology Not Elsewhere Classified||40|
|111599||Pharmacology And Pharmaceutical Sciences Not Elsewhere Classified||40|
|050199||Ecological Applications Not Elsewhere Classified||20|
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. CityU Seed Grant, City University of Hong Kong – 2013 (Project no. 7003027)
Investigators: A/P Richard Kong, Dr Richard Yu
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
2. State Key Laboratory in Marine Pollution, China – 2012 (Project no. 9369101)
Investigator: A/P Richard Kong, Prof Rudolf Wu, Dr Richard Yu
Project Title: Interactive effects of climate change and hypoxia on fish sex determination: estrogen synthesis and masculinisation
Funding: $US 115,384
3. General Research Fund, Hong Kong Research Grants Council – 2011 (Project no. 160411)
Investigators: A/P Richard Kong, Prof John Giesy, Dr Richard Yu
Project Title: Uncovering the molecular links between hypoxia and endocrine disruption: A functional study of zebrafish leptin
Funding: $US 108,974
School Honours Coordinator - Environmental & Life Sciences
Discipline Honours Coordinator - B. Environmental Science & Management
Deputy Program Convenor - B. Environmental Science & Management (Honours)
BIOL1003 Professional Skills for Biological Sciences 1
Click on a category title below to expand the list of citations for that specific category.
Conference (3 outputs)
|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]|
|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]|
|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]|
Journal article (26 outputs)
|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]|
|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]|
|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]|
|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]|
|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]|
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Grants and Funding
|Number of grants||1|
For project grants received where the lead institution is other than the University of Newcastle, details are shown in italics.
Click on a grant title below to expand the full details for that specific grant.
2009 (1 grants)
Role of leptin in hypoxia-induced inhibition of sterodogenesis in zebrafish embryos$5,000
Funding Body: University of Newcastle
|Doctor Richard Yu|
|New Staff Grant||Chief Investigator|
|Total Amount||Funding Start||Funding Finish|
|Number of current supervisions||2|
|Total current UoN PhD EFTSL||1|
For supervisions undertaken at an institution other that the University of Newcastle, details are shown in italics, and the institution name is listed below the program name.
|Program||Supervisor Type||Research Title|
|2012||2016||PhD (Environmental Sc)||Principal Supervisor||Investigation of the Molecular Mechanisms Underlying Chemical-induced Endocrine Disruption in Sydney Rock Oysters (Saccostrea glomerata)|
|2009||2013||PhD (Biological Sciences)||Co-Supervisor||Discovering the Mechanisms of Estrogen Mediated Vitellogenesis in the Sydney Rock Oyster, Saccostrea Glomerata|
Dr Man Kit Richard (Richard) Yu
|Work Phone||(02) 4921 6990|
|Fax||(02) 4921 8977|
Environmental Water Science Group
School of Environmental and Life Sciences
Faculty of Science and Information Technology
The University of Newcastle, Australia
|Focus Area||Environmental Science and Management|
Callaghan NSW 2308