Professor Nicholas Fisk

Contact details

Professor Nicholas Fisk, FAHMS
UQ Centre for Clinical Research, The University of Queensland
Building 71/918, Royal Brisbane & Women's Hospital Campus
Herston, Qld, 4029, Australia

T +61 7 3346 5300
F +61 7 3346 5304
E mabs.execdean@uq.edu.au

Nicholas Fisk is Executive Dean of the Faculty of Medicine and Biomedical Sciences at the University of Queensland. Previously he was the inaugural Director of the University of Queensland's state of the art $70M Centre for Clinical Research on the Herston campus, before becoming Executive Dean of the Faculty of Health Sciences in 2010 and the restructured Faculty of Medicine and Biomedical Sciences in 2014. He practices as a senior maternal-fetal medicine specialist / high risk obstetrician at the Royal Brisbane and Women's Hospital, and maintains a research group in UQCCR.

Between 1992-2007 he was Professor of Obstetrics /Fetal Medicine at Imperial College & Queen Charlotte's Hospital, London, where his laboratory and clinical research program achieved an international reputation in fetal diagnosis and treatment.

His main research interests have been in human fetal stem cell biology and monochorionic multiple pregnancy, but also spanned non-invasive prenatal diagnosis, fetal nociception, caesarean section, preterm labour, obstetric ultrasound and drug development in obstetrics. His group was the first to document pain-like stress response in the human fetus and show they could be blocked by opioid analgesia; he also devised the "natural caesarean" operation.

A fetal-medicine subspecialist with an MBA and a PhD in fetal physiology, he has authored over 400 publications, and is a past President of the International Fetal Medicine and Surgery Society. He reviews for numerous international grant bodies, and is a member of several editorial boards including PLoS Medicine and Stem Cell Translational Medicine.

His experimental fetal medicine group works on the role of fetal mesenchymal and endothelial stem cells in tissue repair, both the development of stem cell transplantation to repair debilitating early onset genetic disease, and its wider application to childhood and adult diseases. His clinical fetal medicine group together with colleagues in the hospital's Centre for Advanced Prenatal Care works on the twin twin transfusion syndromes, in particular optimising results of current laser and other therapies.

Research Interests

1. Fetal Mesenchymal Stem Cell (fMSC) Biology

Fetal Mesenchymal Stem Cells have therapeutic potential, being more primitive than adult MSC with greater differentiability, but lack the oncogenicity of embryonic cells. They are readily isolated from placenta, amniotic fluid, fetal blood, liver and bone marrow.

Our group showed that fMSC express pluripotency markers, grow faster and senesce later with longer telomeres, and show greater myogenic/osteogenic capacity. fMSC express adhesion molecules favouring engraftment, and their transplacental passage is implicated in fetomaternal microchimerism (FMC), whereby fMSC persist lifelong in women to participate in post-reproductive tissue repair. 

MSC hold promise to treat a range of unmet medical need in hereditary, acquired & degenerative disease. For genetic disorders we have shown intrauterine transplantation of fMSC prevents fractures in an animal model, while MSC have shown benefit in a clinical trial of children with osteogenesis imperfect. Supply side challenges with fetal MSC include sorting and culture strategies to overcome the high incidence of selective decidual MSC overgrowth, and in vitro production of scalable MSC by mesengenic induction of human embryonic or induced pluripotent stem cells.

2. Placental Endothelial Stem Cells

In collaborative work with Associate Professor Khosrotehrani, we have recently developed sorting strategies to harvest bulk quantities of the most primitive endothelial progenitors from the human placenta and demonstrate their contribution to wound healing and to angiogenesis. Combination strategies are applied separately to maternal and fetal MSC from the same placentae. This work has translational potential in a variety of vascular and reparative paradigms.

2. Monochorionic Intertwin Transfusion

tttsThis clinical program investigates the fetoplacental circulatory pathophysiology and treatment of twin-twin transfusion syndrome. This is a debilitating fetal condition, which arises from unbalanced transfusion along placental vascular anastomoses in monochorionic or single placenta twins where a net recipient develops volume overload and polyuria and a net donor growth restriction, oliguria and fetal compromise. Despite advances in treatment TTTS still results in a high rate of fetal death or long-term brain injury. Although considered rare, TTTS affects nearly as many babies as Down syndrome.

Key publications

Papers:

Patel J, Wong HY, Wang W, Alexis J, Shafiee A, Stevenson AJ, Gabrielli B, Fisk NM, Khosrotehrani K. Self-renewal and high proliferative colony forming capacity of late-outgrowth endothelial progenitors is regulated by cyclin-dependent kinase inhibitors driven by notch signaling. Stem Cells. 2016 Jan 6. doi:0.1002/stem.2262.

Millard SM, Pettit AR, Ellis R, Chan JK, Raggatt LJ, Khosrotehrani K, Fisk NM. Intrauterine bone marrow transplantation in osteogenesis imperfecta mice yields donor osteoclasts and osteomacs but not osteoblasts. Stem Cell Reports. 2015 Nov 10;5(5):682-9. doi: 10.1016/j.stemcr.2015.09.017. 

Ryan JM, Matigian N, Pelekanos RA, Jesuadian S, Wells CA, Fisk NM. Transcriptional ontogeny of first trimester human fetal and placental mesenchymal stem cells: Gestational age versus niche. Genom Data. 2014 Oct 25;2:382-5. doi: 10.1016/j.gdata.2014.10.016. eCollection 2014 Dec.

Shafiee A, Fisk NM, Hutmacher DW, Khosrotehrani K, Patel J. Fetal endothelial and mesenchymal progenitors from the human term placenta: potency and clinical potential. Stem Cells Transl Med. 2015 May;4(5):419-23. doi: 10.5966/sctm.2014-0224. 

Patel J, Shafiee A, Wang W, Fisk NM, Khosrotehrani K. Novel isolation strategy to deliver pure fetal-origin and maternal-origin mesenchymal stem cell (MSC) populations from human term placenta. Placenta. 2014 Nov;35(11):969-71. doi: 10.1016/j.placenta.2014.09.001.

Heazlewood CF, Sherrell H, Ryan J, Atkinson K, Wells CA, Fisk NM. High incidence of contaminating maternal cell overgrowth in human placental mesenchymal stem/stromal cell cultures: a systematic review. Stem Cells Transl Med. 2014 Nov;3(11):1305-11. doi: 10.5966/sctm.2014-0051. 

Seppanen E, Hodgson S, Khosrotehrani K, Bou-Gharious G, Fisk NM. Fetal microchimeric cells in a fetus-treats-its-mother paradigm do not contribute to dystrophin production in serially-parous mdx females. Stem Cells Development 10;21(15):2809-16, 2012

Pelekanos R, Chen YS, Ellis RL, Jesuadian S, Horne R, Wolvetang EJ, Fisk NM.  Small Molecule Mesengenic Induction of Human Induced Pluripotent Stem Cells to Generate Mesenchymal Stem/ Stromal Cells. Stem Cells Translational Medicine. 1:83-95, 2012

Danon D, Sekar R, Hack KE, Fisk NM. Increased Stillbirth in Uncomplicated Monochorionic Twin Pregnancies: A Systematic Review and Meta-analysis. Obstetrics and Gynecology 121 (6): 1318-1326, 2013

Ryan J, Pettit A, Guillot PV, Chan J, Fisk NM. Unravelling The Pluripotency Paradox In Fetal and Placental Mesenchymal Stem Cells: Oct-4 Expression and The Case Of The Emperor’s New Clothes. Stem Cells Review and Reports. 9(4):408-21, 2013

Patel J, Seppanen E, Chong MSK, Yeo JSL, Teo JSL, Chan JKY, Fisk NM, Khosrotehrani K. Prospective surface marker based isolation and expansion of fetal endothelial colony-forming cells (ECFC) from human term placenta. Stem Cells Translational Medicine. 2(11):839-47, 2013

Götherström C, Westgren M, Shaw SW, Aström E, Biswas A, Byers PH, Mattar CN, Graham GE, Taslimi J, Ewald U, Fisk NM, Yeoh AE, Lin JL, Cheng PJ, Choolani M, Le Blanc K, Chan JK. Pre-and postnatal transplanatation of fetal mesenchymal stem cells in osteogenisis imperfecta: a two-center experience. Stem Cells Translational Medicine, 3:255-64, 2014.

Roy E, Seppanen E, Ellis R, Lee E, Khosroterani K, Fisk NM, Bou-Gharios G. Biphasic recruitment of microchimeric fetal mesenchymal cells in acute kidney fibrosis: reparative role via involvement in fibrotic process. Kidney International. 85(3):600-10, 2014

Pelekanos RA, Ting MJ, Sardesai VS, Ryan JM, Lim YC, Chan JK, Fisk NM. Intracellular trafficking and endocytosis of CXCR4 in fetal mesenchymal stem/stromal cells. BMC Cell Biology, 15:15, 2014.

Guillot PV, Abass O, Bassett JH, Shefelbine SJ, Bou-Gharios G, Chan J, Kurata H, Williams GR, Polak J, Fisk NM: Intrauterine transplantation of human fetal mesenchymal stem cells from first trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice. Blood 111:1717-1725, 2008.

Galea P, Barigye O, Wee L, Jain V, Sullivan M, Fisk NM: The Placenta Contributes to Activation of the Renin Angiotensin System in Twin-Twin Transfusion Syndrome. Placenta 29:734-42, 2008.

Santos MA, O'Donoghue K, Wyatt-Ashmead J, Fisk NM: Fetal cells in the maternal appendix: a marker of inflammation or fetal tissue repair? Hum Reprod 23:2319-25, 2008.

Guillot PV, Gotherstrom CA, Chan J, Kurata H, Fisk NM: Human first trimester fetal mesenchymal stem cells (MSC) express pluripotency markers, grow faster, and have longer telomeres compared to adult MSC. Stem Cells 25: 646-54, 2007.

Chan J, Waddington SN, O'Donoghue K, Kurata H, Guillot PV, Gotherstrom C, Themis M, Morgan JE, Fisk NM: Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse. Stem Cells 25: 875-84, 2007.

Barigye O, Pasquini L, Galea P, Chappell L, Chambers H, Fisk NM: High risk of unexpected late fetal death in monochorionic diamniotic twins despite intensive ultrasound surveillance: a cohort study. PloS Medicine 2: 521-7, 2005.

O'Donoghue K, Chan J, de la Fuente J, Kennea N, Sandison A, Anderson JR, Roberts IAG, Fisk NM: Micro-chimerism in female bone marrow and bone decades after fetal mesenchymal stem cell trafficking in pregnancy. Lancet 364: 179-82, 2004.

O'Donoghue K, Cartwright E, Galea P, Fisk NM: Stage I twin-twin transfusion syndrome: rates of progression and regression in relation to outcome. Ultrasound Obstet Gynecol 30: 958-964, 2007.

Campagnoli C, Roberts IAG, Kumar S, Bennett PR, Bellantuono I, Fisk NM: Identification of mesenchymal stem/progenitor cells in human first trimester fetal blood, liver and bone marrow. Blood 98: 2396-402, 2001.

 

Reviews:

Millard S, Fisk NM. Mesenchymal stem cells for systemic therapy: shotgun approach or magic bullets? Bioessays. 35(3):173-82, 2013

Lee ESM, Bou-Gharios G, Seppanen E, Khosrotehrani K, Fisk NM:  Fetal Stem Cell Microchimerism: Natural Born Healers or Killers? Molecular Human Reproduction 2010, 16: 869-78, 2010

Fisk NM, Duncombe GJ, Sullivan MH: The basic and clinical science of twin-twin transfusion syndrome. Placenta 2009. 30:379-90

Bianchi D, Fisk NM: Gender matters: fetomaternal cell trafficking and the stem cell debate. JAMA 297: 1489-91, 2007.

Guillot P, O'Donoghue K, Kurata H, Fisk NM. Fetal stem cells: betwixt and between. Semin Reprod Med 24: 340-7, 2006.

Group Members 

Rebecca Pelekanos
Jatin Patel
Edwige Roy
Varda Sardesi
Abbas Shaffee
Carol Portmann
Johanna La Porte
Greg Duncombe

Funding Bodies

National Health and Medical Research Council
Australian Research Council
Richard & Jack Wiseman Trust
Institute of Obstetrics & Gynaecology Trust
Queensland Health 
Australian Stem Cell Centre
Royal Brisbane and Women's Hospital Foundation

Potential PhD Projects

  • Cancer association with reduced fetal stem cell microchimerism
  • Fetal stem cell transplantation
  • Generation of fetal like mesenchymal stem cells from induced pluripotent stem cell
  • Maximising homing and engraftment of stem cells for bone repair

Collaborations

Associate Professor Kiarash Khosrotehrani, UQ Centre for Clinical Research

Associate Professor Ernst Wolvetang, Australian Institute of Bioengineering and Nanotechnology, University of Queensland

Professor Kerry Atkinson, Mater Medical Research Institute, Queensland

Professor Justin Cooper-White, Australian Institute of Bioengineering and Nanotechnology, University of Queensland

Dr Roland Steck, School of Engineering Systems, Institute of Health and Biomedical Innovation, Queensland University of Technology

Dr George Bou-Gharios, Kennedy Institute, University of Oxford

Associate Professor Jerry Chan, Duke-NUS University, Singapore

Associate Professor Mahesh Choolani, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore

Dr Pascale Guillot, Institute of Child Health University College London

Professor John Golledge, James Cook University, Townsville

Associate Professor Christine Wells, University of Glasgow 

Dr Pascale Guillot, Institute for Women’s Health, University College London