Jose Polo

Professor Jose Polo

Director of Adelaide Centre for Epigenetics

School of Biomedicine

Faculty of Health and Medical Sciences

Eligible to supervise Masters and PhD - email supervisor to discuss availability.


Jose Maria Polo was born in Buenos Aires, Argentina where he graduated from Buenos Aires University as a Biochemist. In 2002, Jose began his graduate studies at Albert Einstein College of Medicine, New York under the supervision of Dr. Ari Melnick where he worked on the transcriptional mechanism of the BCL6 repression complex in B-cell lymphomas and B-cell maturation. In 2008, he obtained his PhD and moved to Boston to the laboratory of Dr. Konrad Hochedlinger at the Harvard Stem Cell Institute to work on reprogramming of adult cells into induced pluripotent stem (iPS) cells. In particular, his work focused on the acquisition of immortality and the existence of epigenetic memory during reprogramming.

In June 2011, established his independent research group at Monash University, where he holded appointments to the departments of Anatomy and Developmental Biology and to the Australian Regenerative Medicine Institute. In 2012, Jose was awarded a NHMRC Career Development Fellowship, in 2014 a Silvia and Charles Viertel Senior Medical Research Fellowship and in 2018 a Future Fellowship to continue his work in the molecular mechanism governing the reprogramming process and the epigenetic mechanism underpinning cell fate.

In October 2021, Jose was recruited to the University of Adelaide as the inaugural Director of the Adelaide Centre for Epigenetics (ACE) and group leader of the recently established South Australian Immunogenomics Cancer Institute (SAiGENCI). In Adelaide, he will continue his work in epigenetics and its application to reprogramming, early embryogenesis and cancer.

His work in epigenetics, reprogramming and cancer has been published in journals such as Nature, Cell, Nature Genetics, Cell Stem Cell and Nature Medicine among others as well as recognised with several awards including the Merit Award from the American Society of Haematology, the inaugural Metcalf Award, Victorian Young Tall Poppy Award, the Monash’s Vice-Chancellor award. In 2016, he co-founded Mogrify Ltd to translate reprogramming technologies into therapies, receiving several accolades including the 2019 Scrip Innovation Award.

My Research

The Polo group is interested in the transcriptional and epigenetic mechanisms that govern cell identity, in particular pluripotency, reprogramming of somatic cells into induced pluripotent stem (iPS) cells, development and cancer.

Being able to reprogram any specific mature cellular program into a pluripotent state and from there back into any other particular cellular program provides a unique tool to dissect the molecular and cellular events that permit the conversion of one cell type to another. Moreover, iPS cells and the reprogramming technology are of great interest in pharmaceutical and clinical settings, since the technology can be used to generate animal and cellular models for the study of various diseases as well in the future to provide specific patient tailor made cells for their use in cellular replacement therapies. By using a broad array of approaches through the use of mouse and human stem cells models combined with different molecular, biochemical, cellular techniques and genome wide approaches, our lab will aim to dissect the nature and dynamics of such events. Understanding the events leading to the generation of iPS cells has allowed us to not only she light into this process but it has led to the generation of complex models of humans development. Furthermore, we are using and translating the tools and knowledge gained through this work into the fields of development, cancer and several other diseases.

We are particularly interested in the following aspects:

1) The kinetics and universality of the epigenetic and genomic changes occurring during cell fate transitions.

2) The composition and assembly kinetics of transcriptional regulation complexes at  pluripotency genes and cancer associated transcription factors.

3) How the cell of origin influences the in vitro and in vivo plasticity potential of cells generated during the reprogramming process.

4) The role of transcription factors in cancer initiation and progression

5) Understanding mammalian development through the use of complex in vitro models

6) Synthetic cell biology

Professor Polo - iBlastoid background
Professor Polo
iBlastoid_CDX2 NANOG MERGED
iBlastoid

 

 

 

 

 

 

Higher Degree Research Projects

 

Understanding the epigenetic and transcriptional changes during reprogramming of cells to pluripotent stem cells.

The derivation of human embryonic stem cells (hESCs) and, more remarkably, the generation of human induced pluripotent stem cells (iPSCs) has revolutionised our understanding of pluripotency and opened new avenues for disease modelling, drug screening and regenerative medicine. The ability to reprogram any mature cell back to a pluripotent state, and then into another cell type, provides a unique opportunity to dissect the molecular and cellular events that occur during this conversion. Our lab aims to understand the kinetics and universality of the epigenetic and genomic changes occurring during reprogramming, the composition and assembly kinetics of transcriptional regulation complexes of pluripotency genes and how the cell of origin influences the in vitro and in vivo plasticity potential of cells generated during the reprogramming process. We will achieve this by combining stem cell technologies with several different molecular, biochemical, cellular techniques and genome-wide approaches; including ChIP, CUT&RUN, and single cell “omics”.

 

 

Molecular investigation of induced trophoblast cells (iTSC) and their derivatives.

The derivation of human embryonic stem cells (hESCs) and, more remarkably, the generation of human induced pluripotent stem cells (iPSCs) has revolutionised our understanding of pluripotency and opened new avenues for disease modelling, drug screening and regenerative medicine. However, the trophectoderm (TE) gives rise to the placenta and as such, iPSCs cannot provide models for TE or placenta. To address this important challenge, our lab has generated iTSCs for the first time. Our lab will use this model with both human and non-human primate cells, to understand the transcriptional and epigenomic changes that occur in vitro in the early human trophoblast and demonstrate that iTSCs can be used for disease modelling.

 

Pluripotency factors and cancer

Pluripotent stem cells can self-renew indefinitely and give rise to all cells of the adult organism. These remarkable capacities are the result of a core transcriptional network controlled by OCT4, SOX2 and NANOG, whose expression is lost upon differentiation.  Several cancers have been shown to reactivate OCT4, SOX2 and/or NANOG, with high expression levels positively correlating with cancer progression and severity.  Since they are linked to proliferative and multi-lineage differentiation capacity of cancer cells, they present attractive anticancer targets.  However, they are considered “undruggable” since they lack catalytic active sites for molecules to bind.

To provide therapeutic alternatives, the Polo lab has adapted and developed various novel techniques to determine how expression and function of the pluripotency factors OCT4, SOX2 and NANOG are controlled in various physiological and pathological cell types, including embryonic stem cells and cancer respectively.

 

Uncovering the regulatory complex of Bcl6 in lymphomas

Cellular identity is controlled by transcription factors, which bind to specific regulatory elements (REs) within the genome to regulate gene expression and cell fate changes. Recent advances in epigenome profiling techniques have significantly increased our understanding of which REs are utilised in which cell type, however, which factors interact with these REs remains largely elusive. A major impediment to dissecting protein complexes at specific genomic loci is the shortage of appropriate techniques. The most common technique to assess TF binding is chromatin immunoprecipitation (ChIP), which relies on antibodies to interrogate the binding sites of a single TF. Yet, ChIP does not allow dissection of the composition of a multi-protein complex at a specific locus. Importantly, the Polo lab has developed a novel epigenetic technique termed TINC (TALE-mediated Isolation of Native Chromatin), which allows us to do exactly that (Knaupp et al., Stem Cell Reports 2020).  TINC relies on epitope-tagged TALEs, which are DNA-binding proteins engineerable to target specific genomic regions. Upon cross-linking of the cells, the target regions are isolated based on affinity purification of the TALE and associated nucleic acid and protein molecules are analysed by next generation sequencing and mass spectrometry, respectively. In our proof-of-concept experiments, we dissected the protein complex formed at the Nanog promoter, a key pluripotency RE. We identified TFs previously known to bind to this locus as well as novel proteins whose role in pluripotency we further validated (Knaupp et al., Stem Cell Reports 2020). Consequently, with this valuable technique at hands, this PhD project aims at deciphering how the BTB/POZ transcriptional repressor and oncogene BCL6 is (mis)regulated in B-cell lymphomas, which in turn has major potential in identifying novel therapeutic targets.

  • Appointments

    Date Position Institution name
    2021 - ongoing Professor of Epigenetics and Director of the Adelaide Centre for Epigenetics University of Adelaide
    2018 - 2021 Unit coordinator for Master of Biotechnology Australian Regenerative Medicine Institute
    2011 - ongoing Professor and Group Leader in the Faculty of Medicine, Nursing and Health Sciences Monash University
    2011 - 2021 Dual appointment with the Australian Regenerative Medicine Institute (ARMI) and the Department of Anatomy and Developmental Biology (ADB) Monash University
    2008 - 2011 Research Fellow Harvard Stem Cell Institute and Centre for Regenerative Medicine,
    2002 - 2008 Graduate Student Albert Einstein College of Medicine
    2000 - 2002 Junior Lecturer University of Buenos Aires
    1998 - ongoing Visiting Student Memorial Sloan Kettering Cancer Center
    1995 - 2002 Research Assistant University of Buenos Aires
    1995 - 2000 Teaching Assistant University of Buenos Aires
  • Awards and Achievements

    Date Type Title Institution Name Country Amount
    2019 Award MSD’s Innovation Award at the 15th Annual Scrip Awards Mogrify Ltd United Kingdom -
    2018 Nomination Selected as Next Generation of Leaders of the International Society for Stem Cell Research International Society for Stem Cell Research Australia -
    2018 Fellowship ARC Future Fellowship ARC Australia -
    2017 Award Vice-Chancellor’s Diversity and Inclusion Award Monash University Australia -
    2015 Achievement Specialist Plenary Speaker, Australian Academy of Science’s Theo Murphy High-Flyer Think Tank, Australia Australian Academy of Science’s Theo Murphy High-Flyer Think Tank Australia -
    2014 Award Metcalf Award National Stem Cell Foundation of Australia Australia -
    2014 Achievement Invited as one of eight promising early career scientists (from all scientific disciplines across the world) of the Future Leaders program of the Science and Technology in Society Forum in Kyoto Future Leaders program of the Science and Technology in Society Forum in Kyoto Australia -
    2014 Award Deans Award for Excellence in Research (Early Career) Monash University Australia -
    2014 Fellowship Sylvia and Charles Viertel Senior Medical Research Fellowship Sylvia and Charles Viertel Australia -
    2013 Award Victorian Young Tall Poppy Science Award Victorian Young Tall Poppy Science Australia -
    2012 Fellowship Career Development Fellowship - NHRMC, Australia NHMRC Australia -
    2011 Fellowship Larkins Fellowship Monash Universit Australia -
    2009 Award Postdoctoral Fellowship Award Massachusetts General Hospital United States -
    2005 Award Pre-doctoral Fellowship National Cancer Centre Australia -
    2004 Award Merit Award and Plenary Speaker from the American Society of Haematology American Society of Haematology United States -
  • Education

    Date Institution name Country Title
    2002 - 2008 Albert Einstein College of Medicine United States Doctor of Philosophy (PhD)
    2002 - 2004 Albert Einstein College of Medicine United States Master of Science (MSci)
    1993 - 2000 University of Buenos Aires Argentina Biochemist (Professional Degree)

Research Grants

 

Date Details Title
2021–2023 NHMRC, Ideas Grant, CIA Developing an in vitro model of a human blastocyst
2021–2023 NHMRC, Ideas Grant, CIA Reprogramming human fibroblasts into induced trophoblast stem cells
2021-2023  ARC, Discovery Project, CIA How do transcription factors control cell fate transitions?
2020–2021  MRFF-Coronavirus Research Response–Rapid Screening of Approved Drugs in Stem Cell Models for COVID-19 Treatment, CI Stem cell-derived human tissue models for the identification of drugs to treat COVID-19.
2020–2023 Department of Health and Human Services Victoria, DHHS Evaluating direct and indirect effects of SARS-CoV-2 on multiple organ systems using stem cell-derived human tissues 
2020-2022 Cancer Council Victoria, PCI Targeted reprogramming of Prostate Cancer
2019–2020 The CASS Foundation, CI Targeting prostate cancer with maths.
2018–2022 ARC Future Fellowship

Unveiling the epigenome dynamics through the pluripotency continuum

The Fellowship supports Professor Polo salary.

2018–2021  NHMRC, CIB Exploring and Targeting the Anti-Inflammatory Signaling Mechanisms of IL-3.
2018–2020 ARC Discovery Project, CIB Regulatory architecture of the trunk-to-tail transition.
2017-2020 NHMRC, CIB Leveraging genomics strategies to generate adult neurons from iPSCs and somatic cells.
2017–2018 Prostate Cancer Foundation of Australia, CI A predictive computational framework for targeted reprogramming of castrate resistant prostate cancer.
2016–2019 NHMRC, CIA Unveiling the human reprogramming pathway.
2016–2019 NHMRC, CIA Using direct reprogramming to generate and rejuvenate Haematopoietic Stem Cells
2015-2019  NHMRC, CIB Bone Marrow Endothelial Stem Cells have the capacity to form both the endothelial and haematopoietic hierarchies.
2015-2017 NHMRC, CIA Inducing and controlling cellular plasticity.
2014-2016 NHMRC, CIA Epigenetic and functional decline of intestinal stem cells during aging.
2014–2018 Sylvia & Charles Viertel Foundation Senior Medical Research Fellowship The Fellowship supported Professor Polo salary from 2014-1018
2014-2016   NHMRC, CIB Advancing regenerative medicine by epigenetic engineering of human induced pluripotent stem cells.
2014-2018  Stem Cells Australia, Principal Investigator  
2014 ARC LIEF, Principal Investigator This Grant underpinned the establishment of a Single Cell Genomic Centre
2013-2015 NHMRC, CIA Determining how the germ layer of origin of adult somatic cells influences the differentiation potential of induced pluripotent stem cells.
2013-2015  NHMRC, CIA Does nuclear reprogramming of granulocytes induce reversal of the haematopoiesis pathway.
2012-2015 NHMRC, Chief Investigator, CDF The Fellowship supported Professor Polo salary from 2012-2013, it was discontinued upon being granted the Sylvia & Charles Viertel Foundation Senior Medical Research Fellowship.

                

Teaching, Mentoring and Research Supervision

Postdoctoral Fellows (Present)
Dr. Sandii Constable (Lab Manager)
Dr. Naiara Bediaga
Dr. German Moran

 

 

 

Postdoctoral Fellows (Past)
Dr. Christian Nefzger (Now group leader at UQ)
Dr. Fernando Rossello (Now Level C at University of Melbourne)
Dr. Kathryn Davidson (Now Project Manager at WEHI)
Dr. Alexandra Grubman (Now Medical Scientific Liaison at Biogen)
Dr. Jan Manent (Now postdoc at ARMI)

 

Higher Degree Research Graduate students
Monika Mohenska (Faculty Medicine, Nursing and Health Sciences PhD Program): Developing an algorithm to predict cellular identities given a spatial niche.
Joseph Chen (Industrial Partnership Fellowship) Using TFs to enhance induced pluripotency and direct reprogramming.
Jacob Michael Paynter (Faculty Medicine, Nursing and Health Sciences PhD Program): Generating human haematopoietic stem cells via transcription factor mediated reprogramming.
Michael Larcombe (Faculty Medicine, Nursing and Health Sciences PhD Program): Dissecting the regulatory complexes controlling pluripotency factors.
Jia Ping Tan (Faculty Medicine, Nursing and Health Sciences PhD Program): Understanding the molecular control and cell fate transitions of human induced trophoblast stem cells.
Esther Louise Miriklis (Australian Regenerative Medicine Institute): Spatial gene regulation via single cell analyses and advanced fluorescence microscopy.

 

Postgraduate students trained to date (PhD) Year
Xiaodong Ethan Liu (Monash Postgraduate Award Scholarship): Integrative molecular analyses reveal distinct reprogramming trajectories into states of naïve and primed human induced pluripotency. He was awarded the top 100 thesis from a Chinese student abroad by the Chinese government in 2019. Awarded the Stem Cell Biology Ridolfo award for best student of the year in 2018. Due to COVID19, he is doing a short postdoc in the Polo Lab. 2019
Xin Yi Choo (International Postgraduate Research Scholarship): Development of novel therapeutic approaches for treatment of Alzheimer’s disease. Now postdoc at Duke-NUS, Singapore. 2018
Jaber Firas: Towards an understanding of induced cellular plasticity. He was awarded the VC thesis Commendation. Awarded the Stem Cell Biology Ridolfo award for best student of the year in 2016. Now training as MD to become a Physician-Scientist. 2018
Suzan DeBoer: Modelling epigenetic dysregulation in developmental disorders. Now a postdoc in Leiden University Medical Center, Holland. 2017
Sara Alaei: Dynamics of transcription factor targeting and chromatin states during reprogramming. Now Postdoc at ARMI 2016
Bianca Borchin: Directed derivation and FACS-mediated purification of PAX3+/PAX7+ skeletal muscle precursors from human pluripotent stem cells. Professor Polo supervised her last year and thesis writing due to her first supervisor leaving the Institute. Bianca is now a Postdoc in Memorial Sloan Kettering. 2015

 

Honours students trained to date Year
Kayla Wong 2018
Jia Tan 2018
Matt Tiedemann 2017
Amber Rucinski 2016
Nathalia Tan 2015
Mitchel de Souza 2014
Jaber Firas 2013

 

Masters Student Year
Daniela Pufleau Valdes (Master of Biomedical & Health Science): Molecular and functional characterisation of iTSCs derived from reprogrammed human fibroblasts. 2019 - 2020

 

International Masters student Year
Frida Forsberg (Uppsala University) 2015

 

Research in Action undergraduate student Year
Neiloy Chowdhury 2018
Raymond Zhang 2018
Sheree Chen 2018
Pranjal Patel 2018
Natalie Saunders 2017
Kayla Wong 2017
Kesh Faye-Chauhan 2013
Laura Corfield 2013
Erica Min Joung Kim 2012

 

Research Assistant
Dr. Guizhi Sun

 

Research Assistants (Past)
Dr. Melissa Holmes
Ketan Mishra
Margeaux Hodgson-Garms
Joseph Chen
Jacob Paynter
Michael Larcombe
  • Current Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2024 Co-Supervisor The role of coding and non-coding RNA in atherosclerotic plaque phenotype in diabetic vs non-diabetic patients with peripheral arterial disease Doctor of Philosophy Doctorate Part Time Dr Benjamin Thurston
    2023 Principal Supervisor Somatic cell reprogramming of fibroblasts from different mammals to model early development. Doctor of Philosophy Doctorate Full Time Miss Elly Deidre Walters
    2023 Principal Supervisor How pluripotent transcription factors reshape the prostate cancer epigenetic landscape to reprogram the cell fate toward neuroendocrine-like with their cofactors Doctor of Philosophy Doctorate Full Time Mr Tianjun Zhang
  • Committee Memberships

    Date Role Committee Institution Country
    2020 - ongoing Chair ARMI Group Leader Meeting ARMI Australia
    2019 - ongoing Chair Academic Steering Committee Monash Micromon Genomics Platform Australia
    2019 - ongoing Member Co-organiser of the Single Cell Symposium, DUKE-NUS, Singapore Singapore
    2019 - ongoing Member International Society for Stem Cell Research (ISSCR) Education Committee International Society for Stem Cell Research (ISSCR) Australia
    2019 - ongoing Member Monash Proteomics Platform Steering Committee Monash Proteomics Australia
    2017 - ongoing Co-Chair Reprogramming Symposium Stem Cells Stream at ComBio - ASBMB 2017 Australia
    2017 - 2019 Member Pluripotency Stream Leader and member of the Scientific Leadership Group at ARC Stem Cells Australia Special Initiative. Australia
    2016 - 2018 Member Department of Anatomy and Developmental Biology Executive Committee Department of Anatomy and Developmental Biology Australia
    2016 - ongoing Chair Chair and Programme Co-organizer, Margaret River Regional Forum/ASSCR, 2017 Margaret River Regional Forum/ASSCR Australia
    2015 - 2018 Member ARMI HDR committee ARMI Australia
    2014 - ongoing Chair Lead organizer of the Australasian Society for Stem Cell Research Annual Meeting. Australasian Society for Stem Cell Research Australia
    2014 - ongoing Chair Pluripotency Symposium, Stem Cells Stream at ComBio - ASBMB 2014 Stem Cells Stream Australia
    2014 - 2017 Member Faculty of Biomedical and Psychological Sciences (FBPS) Gender Equity Committee Faculty of Biomedical and Psychological Sciences (FBPS) Australia
    2013 - 2018 Member MHTP Bioinformatics Committee Monash Institute of Medical Research Australia
    2013 - 2017 Member Cell Reprogramming Australia Cell Reprogramming Australia Australia
    2013 - 2015 Co-Chair Cell Reprogramming Australia Annual Conference Cell Reprogramming Australia Australia
  • Editorial Boards

    Date Role Editorial Board Name Institution Country
    2020 - ongoing Member Stem Cell Reports (Official Journal of the International Society for Stem Cell Research) International Society for Stem Cell Research Australia
  • Review, Assessment, Editorial and Advice

    Date Title Type Institution Country
    2016 - ongoing Silvia and Charles Viertel Foundation (External) Peer Review Silvia and Charles Viertel Foundation (External) -
    2016 - ongoing Biotechnology and Biological Sciences Research Council (UK) Peer Review Biotechnology and Biological Sciences Research Council (UK) -
    2013 - ongoing Fondation pour la Recherche Médicale (France) Peer Review Fondation pour la Recherche Médicale (France) -
    2013 - ongoing Reviewer for Academic Promotion Peer Review University of Melbourne, University of Edinburgh, Tokyo University, MRC LMS, Imperial College, John Hopkins University -
    2012 - ongoing Neurological Foundation of New Zealand Peer Review Neurological Foundation of New Zealand -
    2011 - ongoing NHMRC (Panel member and external) and ARC. Peer Review NHMRC and ARC -
  • Position: Director of Adelaide Centre for Epigenetics
  • Phone: 83133118
  • Email: jose.polo@adelaide.edu.au
  • Campus: West End Health Precinct
  • Building: AHMS - Adelaide Health and Medical Sciences, floor Sixth Floor
  • Room: 6067
  • Org Unit: Faculty of Health and Medical Sciences

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