Lindsay Wu

Senior Res Fellow (NH&MRC)

Less than a hundred years ago, we considered ourselves lucky to achieve sixty years of age, and supporting the old age pension for over 65 year olds was not an issue. Now, with Australia and much of the developed world facing an increasingly older population against a shrinking population of working age, declining health during old age is a "make or break" issue for healthcare systems and society at large. Old age increases (sometimes, exponentially so) the risk of health issues such as diabetes, cardiovascular disease, cancer, bone degeneration, inflammatory disorders and neurodegenerative diseases.

While billions are spent researching and treating these diseases as symptoms of ageing, in the Laboratory for Ageing Research we seek to identify the fundamental causes of ageing itself. We view ageing not as a result of a series of damages accumulated during a lifetime, but as a malleable biological program that can be intervened in and reversed. Indeed, experiments from simple organisms tell us that simple tweaks to single genes can greatly extend lifespan. The challenge is now on to translate these findings into mammalian systems, as well as uncover mechanisms that are unique to mammals. Treatments that intervene in this biological program may soon not only delay or even completely prevent diseases of old age, but may extend lifespan altogether. Such a strategy may allow us to stay healthy and productive well into what we today consider to be old age and beyond.

The Laboratory for Ageing Research is currently pursuing a number of ongoing projects in the search for understanding and interventions that may delay ageing, with a focus on female reproductive ageing: please see a recent article from the lab providing some background context to declining fertility with age

The following projects and more are available for study at both the honours and PhD level...

  • New treatments to maintain female fertility during biological ageing and following chemotherapy treatment
  • Role of the pentose phosphate pathway and the enzyme glucose-6-phosphate dehydrogenase in biological ageing
  • DNA transposons in genome instability and the regulation of lifespan
  • New treatments to reduce the side effects of chemotherapy
  • New treatments to maintain long term health and prevent accelerated biological ageing in cancer survivors
  • Studies of the metabolism of nicotinamide adenine dinucleotide (NAD+)

 

Journal articles
add
Bertoldo MJ; Listijono DR; Ho WHJ; Riepsamen AH; Goss DM; Richani D; Jin XL; Mahbub S; Campbell JM; Habibalahi A; Loh WGN; Youngson NA; Maniam J; Wong ASA; Selesniemi K; Bustamante S; Li C; Zhao Y; Marinova MB; Kim LJ; Lau L; Wu RM; Mikolaizak AS; Araki T; Le Couteur DG; Turner N; Morris MJ; Walters KA; Goldys E; O'Neill C; Gilchrist RB; Sinclair DA; Homer HA; Wu LE, 2020, 'NAD+ Repletion Rescues Female Fertility during Reproductive Aging', Cell Reports, vol. 30, pp. 1670 - 1681.e7, http://dx.doi.org/10.1016/j.celrep.2020.01.058
2020
Chalmers TJ; Wu LE, 2020, 'Transposable Elements Cross Kingdom Boundaries and Contribute to Inflammation and Ageing: Somatic Acquisition of Foreign Transposable Elements as a Catalyst of Genome Instability, Epigenetic Dysregulation, Inflammation, Senescence, and Ageing', BioEssays, vol. 42, http://dx.doi.org/10.1002/bies.201900197
2020
Bertoldo MJ; Listijono DR; Ho W-HJ; Riepsamen AH; Goss DM; Richani D; Jin XL; Mahbub S; Campbell JM; Habibalahi A; Loh W-GN; Youngson NA; Maniam J; Wong ASA; Selesniemi K; Bustamante S; Li C; Zhao Y; Marinova MB; Kim L-J; Lau L; Wu RM; Mikolaizak AS; Araki T; Le Couteur DG; Turner N; Morris MJ; Walters KA; Goldys E; O'Neill C; Gilchrist RB; Sinclair DA; Homer HA; Wu LE, 2020, 'NAD(+) Repletion Rescues Female Fertility during Reproductive Aging', CELL REPORTS, vol. 30, pp. 1670 - +, http://dx.doi.org/10.1016/j.celrep.2020.01.058
2020
Solon-Biet SM; McMahon AC; Ballard JWO; Ruohonen K; Wu LE; Cogger VC; Warren A; Huang X; Pichaud N; Melvin RG; Gokarn R; Khalil M; Turner N; Cooney GJ; Sinclair DA; Raubenheimer D; Le Couteur DG; Simpson SJ, 2020, 'Erratum: The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice (Cell Metabolism (2014) 19(3) (418–430), (S1550413114000655), (10.1016/j.cmet.2014.02.009))', Cell Metabolism, vol. 31, pp. 654, http://dx.doi.org/10.1016/j.cmet.2020.01.010
2020
Das A; Huang GX; Bonkowski MS; Longchamp A; Li C; Schultz MB; Kim LJ; Osborne B; Joshi S; Lu Y; Treviño-Villarreal JH; Kang MJ; Hung TT; Lee B; Williams EO; Igarashi M; Mitchell JR; Wu LE; Turner N; Arany Z; Guarente L; Sinclair DA, 2019, 'Erratum: Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging (Cell (2018) 173(1) (74–89.e20), (S0092867418301521) (10.1016/j.cell.2018.02.008))', Cell, vol. 176, pp. 944 - 945, http://dx.doi.org/10.1016/j.cell.2019.01.026
2019
Wu LE; Sinclair DA, 2019, 'The elusive NMN transporter is found', Nature Metabolism, vol. 1, pp. 8 - 9, http://dx.doi.org/10.1038/s42255-018-0015-6
2019
Latorre-Muro P; Baeza J; Armstrong EA; Hurtado-Guerrero R; Corzana F; Wu LE; Sinclair DA; López-Buesa P; Carrodeguas JA; Denu JM, 2018, 'Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity between Gluconeogenic and Anaplerotic Reactions', Molecular Cell, vol. 71, pp. 718 - 732.e9, http://dx.doi.org/10.1016/j.molcel.2018.07.031
2018
Das A; Huang GX; Bonkowski MS; Longchamp A; Li C; Schultz MB; Kim LJ; Osborne B; Joshi S; Lu Y; Treviño-Villarreal JH; Kang MJ; Hung TT; Lee B; Williams EO; Igarashi M; Mitchell JR; Wu LE; Turner N; Arany Z; Guarente L; Sinclair DA, 2018, 'Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging', Cell, vol. 173, pp. 74 - 89.e20, http://dx.doi.org/10.1016/j.cell.2018.02.008
2018
Bustamante S; Jayasena T; Richani D; Gilchrist RB; Wu LE; Sinclair DA; Sachdev PS; Braidy N, 2018, 'Quantifying the cellular NAD+ metabolome using a tandem liquid chromatography mass spectrometry approach', Metabolomics, vol. 14, http://dx.doi.org/10.1007/s11306-017-1310-z
2018
Chowdhury MKH; Turner N; Bentley NL; Das A; Wu LE; Richani D; Bustamante S; Gilchrist RB; Morris MJ; Shepherd PR; Smith GC, 2017, 'Niclosamide reduces glucagon sensitivity via hepatic PKA inhibition in obese mice: Implications for glucose metabolism improvements in type 2 diabetes', Scientific Reports, vol. 7, http://dx.doi.org/10.1038/srep40159
2017
Nelson ME; Lahiri S; Chow JDY; Byrne FL; Hargett SR; Breen DS; Olzomer EM; Wu LE; Cooney GJ; Turner N; James DE; Slack-Davis JK; Lackner C; Caldwell SH; Hoehn KL, 2017, 'Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival', Nature Communications, vol. 8, http://dx.doi.org/10.1038/ncomms14689
2017
Awan Z; Tay ESE; Eyre NS; Wu LE; Beard MR; Boo I; Drummer HE; George J; Douglas MW, 2016, 'Calsyntenin-1 mediates hepatitis C virus replication', Journal of General Virology, vol. 97, pp. 1877 - 1887, http://dx.doi.org/10.1099/jgv.0.000511
2016
Mohamad M; Mitchell SJ; Wu LE; White MY; Cordwell SJ; Mach J; Solon-Biet SM; Boyer D; Nines D; Das A; Catherine Li SY; Warren A; Hilmer SN; Fraser R; Sinclair DA; Simpson SJ; de Cabo R; Le Couteur DG; Cogger VC, 2016, 'Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance', Aging Cell, vol. 15, pp. 706 - 715, http://dx.doi.org/10.1111/acel.12481
2016
Wu LE; Levina A; Harris HH; Cai Z; Lai B; Vogt S; James DE; Lay PA, 2016, 'Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes', Angewandte Chemie, vol. 128, pp. 1774 - 1777, http://dx.doi.org/10.1002/ange.201509065
2016
Wu LE; Sinclair DA, 2016, 'Restoring stem cells-all you need is NAD+', Cell Research, vol. 26, pp. 971 - 972, http://dx.doi.org/10.1038/cr.2016.80
2016
Wu LE; Levina A; Harris HH; Cai Z; Lai B; Vogt S; James DE; Lay PA, 2016, 'Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes', Angewandte Chemie - International Edition, vol. 55, pp. 1742 - 1745, http://dx.doi.org/10.1002/anie.201509065
2016
Cagnone GLM; Tsai TS; Makanji Y; Matthews P; Gould J; Bonkowski MS; Elgass KD; Wong ASA; Wu LE; McKenzie M; Sinclair DA; John JCS, 2016, 'Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency', Scientific Reports, vol. 6, http://dx.doi.org/10.1038/srep23229
2016
Chowdhury MKH; Wu LE; Coleman JLJ; Smith NJ; Morris MJ; Shepherd PR; Smith GC, 2016, 'Niclosamide blocks glucagon phosphorylation of Ser552 on β-catenin in primary rat hepatocytes via PKA signalling', Biochemical Journal, vol. 473, pp. 1247 - 1255, http://dx.doi.org/10.1042/BCJ20160121
2016
Riepsamen A; Wu L; Lau L; Listijono D; Ledger W; Sinclair D; Homer H, 2015, 'Nicotinamide impairs entry into and exit from meiosis I in mouse oocytes', PLoS ONE, vol. 10, http://dx.doi.org/10.1371/journal.pone.0130058
2015
Riepsamen A; Wu L; Lau L; Listijono D; Ledger W; Sinclair DA; Homer H, 2015, 'Erratum: Nicotinamide impairs entry into and exit from meiosis I in mouse oocytes (PLoS ONE (2015) 10:5 (e0126194) DOI:10.1371/journal.pone.0126194)', PLoS ONE, vol. 10, http://dx.doi.org/10.1371/journal.pone.0126194
2015
Wu LE; Fazakerley DJ; Cantley J, 2015, 'Circulating AFABP promotes insulin secretion', Obesity, vol. 23, pp. 1525, http://dx.doi.org/10.1002/oby.21175
2015
Wu LE; Gomes AP; Sinclair DA, 2014, 'Geroncogenesis: Metabolic Changes during Aging as a Driver of Tumorigenesis', Cancer Cell, vol. 25, pp. 12 - 19, http://dx.doi.org/10.1016/j.ccr.2013.12.005
2014
Ma X; Yang P; Kaplan WH; Lee BH; Wu LE; Yang JYH; Yasunaga M; Sato K; Chisholm DJ; James DE, 2014, 'ISL1 regulates peroxisome proliferator-activated receptor γ activation and early adipogenesis via bone morphogenetic protein 4-dependent and -independent mechanisms', Molecular and Cellular Biology, vol. 34, pp. 3607 - 3617, http://dx.doi.org/10.1128/MCB.00583-14
2014
Wu LE; Samocha-Bonet D; Whitworth PT; Fazakerley DJ; Turner N; Biden TJ; James DE; Cantley J, 2014, 'Identification of fatty acid binding protein 4 as an adipokine that regulates insulin secretion during obesity', Molecular Metabolism, vol. 3, pp. 465 - 473, http://dx.doi.org/10.1016/j.molmet.2014.02.005
2014
Solon-Biet SM; McMahon AC; Ballard JWO; Ruohonen K; Wu LE; Cogger VC; Warren A; Huang X; Pichaud N; Melvin RG; Gokarn R; Khalil M; Turner N; Cooney GJ; Sinclair DA; Raubenheimer D; Le Couteur DG; Simpson SJ, 2014, 'The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice', Cell Metabolism, vol. 19, pp. 418 - 430, http://dx.doi.org/10.1016/j.cmet.2014.02.009
2014
Liu Y; Li Z; Wu L; Wang Z; Wang X; Yu Y; Zhao Q; Luo F, 2014, 'MiRNA-125a-5p: a regulator and predictor of gefitinib's effect on nasopharyngeal carcinoma', CANCER CELL INTERNATIONAL, vol. 14, http://dx.doi.org/10.1186/1475-2867-14-24
2014
Wu LE; Solon S; McMahon AC; Ballard JWO; Ruohonen K; Cogger VC; Warren A; Pichaud N; Melvin RG; Gokarn R; Khalil M; Huang X; Turner N; Cooney GJ; Sinclair DA; Raubenheimer D; Le Couteur DG; Simpson SJ, 2014, 'Disparate consequences of macronutrients on appetite, longevity and cardiometabolic health reconciled by nutritional geometry', Cell Metabolism
2014
Wu LE; Meoli CC; Mangiafico SP; Fazakerley DJ; Cogger VC; Mohamad M; Pant H; Kang MJ; Powter E; Burchfield JG; Xirouchaki CE; Mikolaizak AS; Stöckli J; Kolumam G; Van Bruggen N; Gamble JR; Le Couteur DG; Cooney GJ; Andrikopoulos S; James DE, 2014, 'Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction', Diabetes, vol. 63, pp. 2656 - 2667, http://dx.doi.org/10.2337/db13-1665
2014
North BJ; Rosenberg MA; Jeganathan KB; Hafner AV; Michan S; Dai J; Baker DJ; Cen Y; Wu LE; Sauve AA; Van Deursen JM; Rosenzweig A; Sinclair DA, 2014, 'SIRT2 induces the checkpoint kinase BubR1 to increase lifespan', EMBO Journal, vol. 33, pp. 1438 - 1453, http://dx.doi.org/10.15252/embj.201386907
2014
Wu LE; Sinclair DA, 2014, 'SIRT2 controls the pentose phosphate switch', EMBO Journal, vol. 33, pp. 1287 - 1288, http://dx.doi.org/10.15252/embj.201488713
2014
Poorten DVD; Samer CF; Ramezani-Moghadam M; Coulter S; Kacevska M; Schrijnders D; Wu LE; McLeod D; Bugianesi E; Komuta M; Roskams T; Hebbard L; George J, 2013, 'Hepatic fat loss in advanced nonalcoholic steatohepatitis: Are alterations in serum adiponectin the cause?†', Hepatology, vol. 57, pp. 2180 - 2188, http://dx.doi.org/10.1002/hep.26072
2013
Wu LE; Hocking SL; James DE, 2010, 'Macrophage infiltration and cytokine release in adipose tissue: angiogenesis or inflammation?', Diabetology International, vol. 1, pp. 26 - 34, http://dx.doi.org/10.1007/s13340-010-0003-x
2010
Hocking SL; Wu LE; Guilhaus M; Chisholm DJ; James DE, 2010, 'Intrinsic depot-specific differences in the secretome of adipose tissue, preadipocytes, and adipose tissue-derived microvascular endothelial cells', Diabetes, vol. 59, pp. 3008 - 3016, http://dx.doi.org/10.2337/db10-0483
2010
Wu LE; Carter EA; Rayner BS; McLeod AI; Marshall CP; Levina A; Aitken JB; Witting PK; Lai B; Cai Z; Vogt S; Lee YC; Tobin MJ; Harris HH; Lay PA, 2010, 'Silicon Nitride as a Versatile Growth Substrate for Microspectroscopic Imaging and Mapping of Individual Cells.', Molecular Biosystems, vol. 6, pp. 1316 - 1322, http://dx.doi.org/10.1039/c001499k
2010
Crowe SM; Wu LE; Economou C; Turpin S; Matzaris M; Hoehn KL; Hevener A; James DE; Duh E; Watt M, 2009, 'Pigment Epithelium-Derived Factor Contributes to Insulin Resistance in Obesity', Cell Metabolism, vol. 10, pp. 40 - 47, http://dx.doi.org/10.1016/j.cmet.2009.06.001
2009
Hoehn K; Hohnen-Behrens C; Cederberg A; Wu LE; Turner N; Yuasa T; Ebina Y; James DE, 2008, 'IRS1-independent defects define major nodes of insulin resistance', Cell Metabolism, vol. 7, pp. 421 - 433, http://dx.doi.org/10.1016/j.cmet.2008.04.005
2008
Vogt S; Lai B; Finney L; Palmer B; Wu LE; Harris H; Paunesku T; de Jonge M; Legnini D; Maser J; Glesne D; Lay P; Woloschak G, 2007, 'Imaging trace elements in cells with x-ray fluorescence microscopy', MICROSCOPY AND MICROANALYSIS, vol. 13, pp. 40 - 41, http://dx.doi.org/10.1017/S1431927607076283
2007
Conference Papers
add
Riepsamen A; Listijono D; Kalani S; Cooke S; Ledger W; Wu L; Sinclair D, 2019, 'Sirtuins are required for forming fertilization-ready eggs', in BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, BJOG: An International Journal of Obstetrics & Gynaecology, Brisbane, Australia, pp. 40 - 40, presented at Royal College of Obstetricians and Gynaecologists World Congress, Brisbane, Australia, 10 April 2019, http://dx.doi.org/10.1111/1471-0528.13368
2019
Homer H; Riepsamen A; Wu LE; Sinclair D, 2015, 'Sirt2-mediated BubR1 regulation promotes oocyte maturation', in HUMAN REPRODUCTION, OXFORD UNIV PRESS, Lisbon, PORTUGAL, pp. 11 - 11, presented at 31st Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), Lisbon, PORTUGAL, 14 June 2015 - 17 June 2015, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000359740300024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
2015
Wu LE; James DE; Cantley J, 2010, 'Secreted adipocyte fatty acid binding protein (FABP4) forms the molecular basis of the adipo-insular axis', in DIABETOLOGIA, SPRINGER, Stockholm, SWEDEN, pp. S58 - S58, presented at 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD), Stockholm, SWEDEN, 20 September 2010 - 24 September 2010, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000280689700124&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
2010
Working Papers
add
Bertoldo M; Listijono D; Ho W-HJ; Riepsamen A; Jin X; Selesniemi K; Goss D; Mahbub S; Campbell J; Habibalahi A; Loh W-GN; Youngson N; Maniam J; Wong ASA; Richani D; Li C; Zhao Y; Marinova M; Kim L-J; Lau L; Wu R; Mikolaizak S; Araki T; Le Couteur D; Turner N; Morris M; Walters K; Goldys E; O’Neill C; Gilchrist R; Sinclair D; Homer H; Wu L, 2019, NAD+ repletion rescues female fertility during reproductive ageing, http://dx.doi.org10.1101/721985
2019
Book Chapters
add
Massudi H; Wu LE; Sinclair DA, 2016, 'Sirtuin Activation by Small Molecules', in Houtkooper RH (ed.), SIRTUINS, edn. Proteins and Cell Regulation, SPRINGER, pp. 243 - 266, http://dx.doi.org/10.1007/978-94-024-0962-8_12
2016
Patents
add
Sinclair D; Gomes A; Wu L, NAD biosynthesis and precursors for the treatment and prevention of cancer and proliferation, Patent No. 9877981

“Translating new advances in oncofertility”: CIA A/Prof Robert Gilchrist, CIB Dr Lindsay Wu, CIC Prof Johan Smitz, CID Prof Teresa Woodruff, CIE Prof William Ledger, CIF Dr Kirsty Walters. NHMRC Project Grant APP1139763, (2018-2021).

“Preserving ovarian function during chemotherapy and old age”: NHMRC Career Development Fellowship (RD Wright Biomedical Fellowship) APP1127821 (2017-2020)

“Nicotinamide adenine dinucleotide (NAD+) raising agents for improving oocyte quality”: Chief Investigator C, NHMRC Development Grant APP1122484 (2017-2019)

“Female reproductive health preservation by nicotinamide adenine dinucleotide (NAD+) and Sirtuin2 (SIRT2)”: Chief Investigator C, NHMRC Project Grant APP1103689 (2016-2018)

“New drugs to prevent premature ageing and side effects of chemotherapy”: Chief Investigator A, NHMRC Development Grant APP1093643 (2015-2017)

“Calorie restriction mimetics for the treatment of hepatocellular carcinoma”: Early Career Fellowship, Cancer Institute NSW (2014-2016). 

 

 

 

 

Basic scientific research into the biology of ageing and age related disorders, especially type 2 diabetes.