Stem cells and cardiovascular development

Discovering the genetic basis of cardiovascular development and disease

The Palpant laboratory focuses on mechanisms controlling cardiovascular development and disease, drawing on three core themes spanning genomics, cell biology, and cardiac physiology. We are studying mechanisms controlling human pluripotent stem cell differentiation to derive functional human cell types for disease modelling and cell therapeutics, using consortium-scale data and systems biology methods to identify mechanisms controlling cell identity and function, and studying molecules discovered in Australia’s venomous flora and fauna as new drug therapeutics for cardiovascular disease.

The lab expertise covers multidisciplinary approaches involving stem cell biology, genomics, statistical genetics, bioinformatics, gene editing, drug discovery, and animal physiology. We draw on national and international clinical and industry partnerships to orient our priorities toward translational opportunities that address key areas of unmet need in clinical care and industry discovery pipelines.

Group leader

Dr Nathan Palpant

Associate Professor
Nathan Palpant

Group Leader, Stem cells and cardiovascular development

  +61 7 334 62054 
  n.palpant@imb.uq.edu.au
  UQ Researcher Profile

1.    Organization of gene programs revealed by unsupervised analysis of diverse gene–trait associations.
Mizikovsky D, Sanchez MN, Nefzger CM, Cuellar Partida G*, Palpant NJ*.
Nucleic Acids Research, 2022; gkac413

2.    Therapeutic inhibition of acid sensing ion channel 1a recovers heart function after ischemia-reperfusion injury.
Redd MA, Scheuer SE, Saez NJ, Yoshikawa Y, Chiu HS, Gao L, Hicks M, Villanueva JE, Joshi Y, Chow CY, Cuellar-Partida G, Peart JN, See Hoe LE, Chen X, Sun Y, Suen JY, Hatch RJ, Rollo B, Alzubaidi MAH, Maljevic S, Quaife-Ryan GA, Hudson JE, Porrello ER, White MY, Cordwell SJ, Fraser JF, Petrou S, Reichelt ME, Thomas WG, King GF*, Macdonald PS*, Palpant NJ*.
Circulation. 2021;144:947–960

3.   Integrating single-cell genomics pipelines to discover mechanisms of stem cell differentiation.
Sophie Shen S, Sun Y, Matsumoto M, Sinniah E, Wilson SB, Little MH, Powell JE, Nguyen Q, Palpant NJ.
Trends in Molecular Medicine. 2021, 27, 1135-1158.

4.    Conserved epigenetic regulatory logic infers genes governing cell identity.
Shim WJ, Sinniah E, Xu J, Vitrinel B, Alexanian M, Andreoletti G, Shen S, Sun Y, Balderson B, Boix C, Peng G, Jing N, Wang Y, Kellis M, Tam P, Smith A, Piper M, Christiaen L, Nguyen Q, Boden M**, Palpant NJ**.
Cell Systems. 11, 625-639 e613 (2020).

5.    Single-Cell Transcriptomic Analysis of Cardiac Differentiation from Human PSCs Reveals HOPX-Dependent Cardiomyocyte Maturation.
Friedman CE, Nguyen Q, Lukowski SW, Chiu HS, Helfer A, Miklas J, Suo SS, Han JDJ, Osteil P, Peng G, Jing N, Baillie GJ, Senabouth A, Christ AN, Bruxner TJ, Murry CE, Wong ES, Ding J, Wang Y, Hudson J, Ruohola-Baker H, Bar-Joseph Z, Tam PPL, Powell JE**, and Palpant NJ**.
Cell Stem Cell. 2018 Oct 4;23(4):586-598.e8.

View all Publications

Dr Meredith ReddInstitute for Molecular Bioscience Impact Award for Paper of the Year (2021)
Dalia MizikovskyBest First Year PhD Student Short Oral Presentation Award Australian Society for Stem Cell Research (ASSCR) ECR Symposium (2021)
Dr Meredith ReddRalph Reader Basic Science Prize of Cardiac Society of Australia and New Zealand (CSANZ) (2021)
Dalia MizikovskyMichael F. Hickey Memorial Honours Prize, The University of Queensland (2020)
Enakshi Sinniah

ISSCR Zhong Mei Chen Yong Award for Scientific Excellence International Society for Stem Cell Research (ISSCR)
Annual International Meeting held in Boston, USA (2020)

Dr Nathan PalpantLorne Genome Millennium Science Mid-Career Award (2019)
Dr Nathan PalpantGlobal Strategy and Partnerships Award, The University of Queensland (2019)
Dr Nathan PalpantWellcome Trust Award, The International Congress of the Society for Developmental Biology, held in Singapore (2019)
Dr Meredith ReddOutstanding Poster Presentation Award at ISSCR/KSSCR Annual Meeting, held in Seoul, South Korea (2019)
Dr Meredith ReddTravel Award for Best ECR/MCR Presentation at NIH Cardiovascular Bioengineering Symposium, held in Sydney, Australia (2019)
Enakshi SinniahBest Oral Presentation Award Australian Society for Stem Cell Research (ASSCR) Annual Meeting held in Brisbane, Australia (2019)
Enakshi SinniahISSCR/KSSCR Travel Grant for Outstanding Oral Presentation Award ISSCR/KSSCR Annual Meeting held in Seoul, South Korea (2019)
Enakshi SinniahBest PhD Talk Award Oz Single Cell Conference Annual Meeting held in Melbourne, Australia – Enakshi Sinniah (2019)
Dr Nathan PalpantResearch Excellence Award, The University of Queensland Foundation (2019)

Infensa Bioscience (Australia) – Developing novel therapeutics for ischemic heart disease

Stroke and heart attack have two important things in common: (1) they both cause ischemic injury of the heart or brain due to lack of blood supply to the affected tissue, and (2) there are no drugs available to treat the ensuing tissue damage. Infensa Bioscience is developing drugs that directly target the underlying tissue damage and which in preclinical experiments have been shown to massively reduce tissue injury whether they are delivered before or after the re-establishment of blood flow to the brain or heart. These drugs are designed to decrease the mortality associated with these diseases, greatly improve functional outcomes and quality-of-life for survivors, and drastically reduce the burden of these diseases on healthcare systems worldwide. A/Prof Palpant is scientific co-founder and Scientific Advisory Board member.

Relevant Grants
Development of drugs to prevent ischemic injuries of the heart and brain. Medical Research Future Fund Cardiovascular Mission. APP2007625. 2021-2023.

ASIC1a, a new therapeutic drug target for cardiac ischemia. NHMRC Ideas Grant. APP2002857. 2021-2024.
Development of a first-in-class therapeutic for protecting the ischemic heart. NHMRC Development Grant APP2000178. 2021-2023.

Relevant Publications
Redd MA, Scheuer SE, Saez NJ, Yoshikawa Y, Chiu HS, Gao L, Hicks M, Villanueva JE, Joshi Y, Chow CY, Cuellar-Partida G, Peart JN, See Hoe LE, Chen X, Sun Y, Suen JY, Hatch RJ, Rollo B, Alzubaidi MAH, Maljevic S, Quaife-Ryan GA, Hudson JE, Porrello ER, White MY, Cordwell SJ, Fraser JF, Petrou S, Reichelt ME, Thomas WG, King GF*, Macdonald PS*, Palpant NJ*. Therapeutic inhibition of acid sensing ion channel 1a recovers heart function after ischemia-reperfusion injury. Circulation. 2021;144:947–960


HAYA Therapeutics (Switzerland) –
Identifying novel non-coding RNA elements controlling organ fibrosis.

HAYA Therapeutics is a precision therapeutics company that discovers and develops innovative tissue- and cell-selective genomic medicines for fibrotic diseases and other serious health conditions associated with aging, including cancer. The Palpant laboratory is embedded in the company’s discovery engine focusing on identifying long non-coding RNAs (lncRNAs) within the “dark matter” of the human genome to identify key tissue and cell-specific drivers of fibrosis and other disease processes. The long term goal is to develop novel targets and drug candidates with the potential for greater efficacy and safety than existing treatments. HAYA’s lead therapeutic candidate is an antisense molecule targeting Wisper, a cardiac-enriched master driver of fibrosis, which has shown in preclinical testing the ability to halt and potentially reverse the fibrotic processes underlying heart failure.


Relevant Grants
Assessing the role of noncoding RNAs in fibroblast remodeling after cardiac injury. Grant # 31003A_182322. Swiss National Foundation.
Commercial contract with HAYA Therapeutics, Switzerland. Uniquest AG-024694. 2020-2022

Relevant Publications
Shim WJ, Sinniah E, Xu J, Vitrinel B, Alexanian M, Andreoletti G, Shen S, Sun Y, Balderson B, Boix C, Peng G, Jing N, Wang Y, Kellis M, Tam P, Smith A, Piper M, Christiaen L, Nguyen Q, Boden M**, Palpant NJ**. Conserved epigenetic regulatory logic infers genes governing cell identity. Cell Systems. 11, 625-639 e613 (2020).

 

Merck (Germany) –
Multiplexed single cell RNA-sequencing to accelerate discovery into genetic mechanisms of cell differentiation

The Palpant laboratory is working with Merck to commercialise a method for barcoding human cells with proprietary barcodes that enables scalable multiplexed single cell RNA-seq. The platform provides unique capabilities for discovery exceeding design limits of existing commercially available barcoding methods. It enables 100 trillion possible unique barcode options to customise complexity and scale of multiplexing, has no sample handling requirements between cell isolation and single cell capture pipelines, involves simple workflow for amplifying barcode library to enhance data quality, and is compatible with any computational demultiplexing method.
The approach expands experimental design options beyond limitations of existing external barcoding. It provides the ability to scale barcoding of any human cell type to maximise data output with current best-practice capture efficiencies, multiplexed analysis of gene, drug, signalling, or other perturbations at scale, parameter testing protocol development such as disease modelling or cell differentiation assays, analysis of high-resolution time-course assays, and dissecting cell-cell interactions by cell mixing assays such as organoid models.

Relevant Grants
Merck Research Grant. 2021-2022

 

ConcR (UK) – Machine learning methods to improve diagnostic prediction

We are developing methods for statistical inference between multiple imaging and cellular data for predictive computational models. Our goal is identify complex biomarkers, specifically joint imaging-molecular markers, and causal inference methods to identify mechanism of actions to predict therapeutic effects across biological models that can be applied to preclinical in-vitro screening data and retrospective clinical data.

Relevant Publications
Shim WJ, Sinniah E, Xu J, Vitrinel B, Alexanian M, Andreoletti G, Shen S, Sun Y, Balderson B, Boix C, Peng G, Jing N, Wang Y, Kellis M, Tam P, Smith A, Piper M, Christiaen L, Nguyen Q, Boden M**, Palpant NJ**. Conserved epigenetic regulatory logic infers genes governing cell identity. Cell Systems. 11, 625-639 e613 (2020).

 

Sana Biotechnology (USA) - Advancing stem cells toward clinical testing    

Work by Dr Palpant on iPSC genome engineering and differentiation protocols resulted in a licensed patent (US Patent 10,612,002; 2020) on derivation of hPSCs-endothelial cells. This patent and seminal studies on regenerating the mammalian heart with iPSC-derived heart muscle (Nature) formed the basis for Sana Biotechnology (USA; USD $700M series A VC investment in 2019). The Palpant group is working with Sana CSO Professor Charles Murry to advance methods that control cell differentiation and improve engraftment of cells during transplantation.

Relevant Grants
Induced pluripotent stem cell derived cardiomyocytes: a new therapy for "no-option" end stage heart failure. Medical Research Future Fund Stem Cell Therapies Mission. APP2007625. 2021-2025.

Global Strategy and Partnerships Award, The University of Queensland, 2017, 2019

Relevant Publications
Friedman CE, Nguyen Q, Lukowski SW, Chiu HS, Helfer A, Miklas J, Suo SS, Han JDJ, Osteil P, Peng G, Jing N, Baillie GJ, Senabouth A, Christ AN, Bruxner TJ, Murry CE, Wong ES, Ding J, Wang Y, Hudson J, Ruohola-Baker H, Bar-Joseph Z, Tam PPL, Powell JE**, and Palpant NJ**. Single-Cell Transcriptomic Analysis of Cardiac Differentiation from Human PSCs Reveals HOPX-Dependent Cardiomyocyte Maturation. Cell Stem Cell.  2018 Oct 4;23(4):586-598.e8.

Palpant NJ*, Pabon L, Friedman CE, Roberts M, Hadland B, Zaunbrecher RJ, Bernstein I, Zheng Y, Murry CE. Generating high-purity cardiac and endothelial derivatives from patterned mesoderm using human pluripotent stem cells. Nature Protocols, 2017 Jan;12(1):15-31.

Chong JJ, Yang X, Don CW, Minami E, Liu Y, Weyers JJ, Mahoney WM, Van Biber B, Palpant NJ, Gantz J, Fugate JA, Muskheli V, Gough GM, Vogel KW, Astley CA, Hotchkiss CE, Baldessari A, Pabon L, Reinecke H, Gill EA, Nelson V, Kiem H, Laflamme MA, Murry  CE. Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts. Nature. 2014 Apr 30.

Shiba Y, Fernandes S, Zhu W, Kim J, Palpant NJ, Gantz J, Moyes KW, Muskheli V, Reinecke H, Van Biber B, Dardas T, Mignone JL, Izawa A, Hanna R, Viswanathan M, Gold JD, Kotlikoff MI, Murry CE, Laflamme MA. Human ESC-Derived Cardiomyocytes Electrically Integrate and Suppress Arrhythmias in a Guinea Pig Infarct Model. Nature. 2012 Sep 13;489(7415):322-5.

 

The Palpant lab is comprised of members with a range of career development from honours and PhD students to research assistants and postdocs that enable training at all levels. The lab has diverse areas of expertise including wet lab work on stem cell biology and animal models to dry lab work with expertise analysing large scale genomic data. This diversity provides an ideal environment for interdisciplinary collaborations across the lab that result in high impact papers delivered by members at all levels of training. I am engaged with project design and analysis across the lab and aim to mentor groups to work together on projects to facilitate team involvement while ensuring each member has a clear and distinct project to work on.

Our Strategy

The Palpant laboratory aims to identify the decision-making DNA elements of cells, design approaches to control cell differentiation decisions during development, and discover new approaches to control heart cell functions including development of new therapeutics for heart disease.

We implement diverse wet and dry lab approaches linking genome regulation with cell function using computational bioinformatics, cell biology, gene editing, animal physiology, and drug discovery.

Outcomes from the group have led to translational impact including formation of a new UQ spinout company, Infensa Bioscience, as well as partnerships with companies in Europe, Canada, and the US. The team has expertise in pluripotent stem cell biology, cardiac muscle cells, and genomics with our publications cited 7-fold higher than the field average (Topic E 4031 FWCI of 7.37, SciVal). Our research has been featured on the ABC (including a Catalyst documentary), Newsweek, The Guardian, and The Washington Post.  
 

 

 

Key areas of interest

  • Genome sequencing is a powerful tool for studying the biological basis of disease, yet out of millions of data points, finding the underlying cause of development and disease can be difficult. We are using methods in systems biology and genomics to develop innovative computational approaches that reveal how the genome controls cell decisions. These tools not only reveal novel processes controlling development but can also identify regions of the genome underpinning mechanisms of disease.
     
  • Our inability to accurately guide cell differentiation pathways currently limits the utility of iPSC-derived cell products in research, tissue engineering, and drug discovery. We are delivering benchmark data and iPSC tools that are accelerating discovery into mechanisms of cell differentiation. We use iPSCs with cell barcoding technology and new sequencing approaches to evaluate mechanisms of cell differentiation decisions at single cell resolution and develop models of cardiovascular disease for drug discovery.
     
  • Conditions caused by obstruction of blood flow to the heart are the most common emergency manifestation of cardiovascular disease and the leading cause of death in the world. We work closely with chemists and clinicians to discover and test new drugs to address this key area of unmet need. Our recent work has focused on a spider-venom derived inhibitor of ASIC1a, Hi1a, which we are advancing into large animal models and FDA approved safety tests for clinical development to treat ischemic heart disease.

Our Team

  Group Leader

  Researchers

  • Han Chiu

    Mr Han Chiu

    Research Assistant
    Institute for Molecular Bioscience
  • Dr Woo Jun Shim

    Dr Woo Jun Shim

    Postdoctoral Research Fellow
    Institute for Molecular Bioscience
  • Yuanzhao Cao

    Dr Yuanzhao Cao

    Postdoctoral Research Fellow
    Institute for Molecular Bioscience
  • Jun Chen

    Miss Jun Chen

    Research Assistant
    Institute for Molecular Bioscience
  • Dr Enakshi Sinniah

    Dr Enakshi Sinniah

    Postdoctoral Research Fellow
    Institute for Molecular Bioscience
  • Dr Amy Hanna

    Dr Amy Hanna

    Postdoctoral Research Fellow
    Institute for Molecular Bioscience

  Students