Dr Nathan Palpant
Stem cells and cardiovascular development
Dr Nathan Palpant completed a BSc in Biology (magna cum laude) from Whitworth University in 2001 and a PhD in Molecular and Integrative Physiology from the University of Michigan in 2009. He then completed a postdoctoral fellowship at the University of Washington Institute for Stem Cell and Regenerative Medicine in 2015 studying the genetic and signaling basis of lineage decisions in cardiovascular development. In 2015 he was recruited as Group Leader at The University of Queensland’s Institute for Molecular Bioscience where he now heads the Stem Cell and Cardiovascular Development Laboratory. His laboratory focuses on mechanisms underlying mesoderm cell lineage decisions using human pluripotent stem cells, genomics, genome engineering, and bioengineering.
- The Genetic Basis of Cardiovascular Development
The mechanisms by which cells navigate developmental pathways into specific tissues requires the complex orchestration of transcriptional changes that ultimately give rise to the functional identity of a cell. My lab focuses on studying novel genetic regulators governing the identity of cells in the cardiovascular system. Understanding the genetics of cell identity is an essential part of learning how to manipulate cell states. We can use this knowledge to enhance tissue regenerative approaches, learn how to enrich cell subtypes from stem cells, and study the basis of developmental diseases.
- Chromatin Dynamics Underlying Cell Identity Genes
Differential methylation and acetylation at specific amino acid residues on histones has emerged as a central mechanism for identifying functionally distinct parts of the genome including promoters, enhancers, open/closed regions of the genome, transcriptionally active DNA and more. My lab studies chromatin dynamics in cardiovascular development as a means to understand how changes in the nucleus translate to changes in cell fate and use unbiased bioinformatics algorithms that analyze chromatin states to identify genes governing cell identity.
- Methodological Advances in Stem Cell Differentiation Protocols
Developmental biology has formed the groundwork for defining differentiation protocols from pluripotency. Efficient differentiation protocols are required to generate the diverse array of cell types represented in the body either for therapeutic purposes or to understand the basis of complex tissue formation and disease etiology. My lab uses computational approaches in combination with insights from developmental biology to identify simple and efficient methods for deriving cardiovascular cell lineages from pluripotency. One major issue in the field currently is the derivation of cell subtypes (e.g. atrial vs ventricular heart cells or endocardial vs hemogenic endothelium) which is a key area of focus in my lab.
- Stem Cells in Cardio-respiratory Critical Care
According to current global burden of disease metrics, cardiovascular diseases contribute to 22% of deaths in Australia and costs our healthcare systems in excess of $1 billion pa. In collaboration with Prof John Fraser who heads up the Critical Care Research Group at the Prince Charles Hospital, we are establishing a program to elucidate new knowledge about cardio-respiratory diseases, develop novel point-of-care diagnostics, and advance new therapeutics involving stem cells and mechanical assist devices.
Research training opportunities
Please see IMB’s postgraduate website for more information.
- 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, In Press
- Nakano A, Nakano H, Smith K, Palpant NJ. The developmental origins and lineage contributions of endocardial endothelium. Biochim Biophys Acta. 2016 Jan 29. pii: S0167-4889(16)30012-X. doi: 10.1016/j.bbamcr.2016.01.022.
- Szabo L; Morey R; Palpant NJ; Wang PL; Afari N; Jiang C; Parast MM; Murry CE; Laurent LC; Salzman J. Tissue-specific induction of circular RNA during human fetal development revealed by statistically based splicing detection. Genome Biology. 2015 Jun 16;16(1):126.
- Palpant NJ*, Pabon L*, Roberts M, Hadland B, Jones D, Jones C, Moon R, Ruzzo W, Bernstein I, Zheng Y, Murry CE. Inhibition of β-catenin signaling re-specifies anterior-like endothelium into beating human cardiomyocytes. Development. 2015 Jul 7. pii: dev.117010.
- Palpant NJ, Hofsteen P, Pabon L, Reinecke H, Murry CE. Cardiac Development in Human Embryonic Stem Cells and Zebrafish is Inhibited by Exposure to Tobacco Cigarettes and E-Cigarettes. PLoS One. 2015 May 15;10(5):e0126259.
- Zhu WZ, Filice D, Palpant NJ and Laflamme MA. Methods for assessing the electromechanical integration of human pluripotent stem cell-derived cardiomyocyte grafts. Chapter in L. Black and M. Radisic (eds) Cardiac Tissue Engineering Methods and Protocols. Methods Mol Biol. 2014;1181:229-47.
- Palpant NJ and Murry CE. Proliferation at the Heart of Preadolescence. Cell. 2014 May 8;157(4):765-7.
- 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.
- Palpant NJ. Pabon L. Rabinowitz JS, Stoick-Cooper C, Paige SL, Moon RT, Murry CE. Transmembrane protein 88: a Wnt regulatory protein that specifies cardiovascular progenitor cell fate. Development. 2013 Aug 7
- Murry CE, Palpant NJ, Maclellan WR. Cardiopoietry in Motion: Primed Mesenchymal Stem Cells for Ischemic Cardiomyopathy. J Am Coll Cardiol. 2013 Apr 10.
- Palpant NJ and Dudzinski D. Zinc Finger Nucleases: Looking Toward Translation. Gene Therapy. 2013 Feb;20(2):121-7. doi: 10.1038/gt.2012.2. Epub 2012 Feb 9.
- Gantz J*, Palpant NJ*, Welikson RE, Hauschka SD. Murry CE, Laflamme M. Targeted genomic integration of a selectable floxed dual fluorescence reporter in human embryonic stem cells. PLoS One. 2012;7(10):e46971, Epub 2012 Oct 10.
- 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.
- Davis J, Yasuda S, Palpant NJ, Martindale J, Stevenson T, Converso K, Metzger JM. Diastolic dysfunction and thin filament dysregulation resulting from excitation–contraction uncoupling in a mouse model of restrictive cardiomyopathy. Journal of Molecular and Cellular Cardiology. J Mol Cell Cardiol. 2012 Sep;53(3):446-57.
- Palpant NJ, Murry CE. Regenerative medicine: Reprogramming the injured heart. Nature. 2012 May 31;485(7400):585-6.
- Palpant NJ, Houang EM, Sham YY, Metzger JM. pH responsive titratable inotropic performance of histidine-modified cardiac troponin I. Biophysical Journal. 2012 Apr 4;102(7):1570-9.
- Palpant NJ, Bedada FB, Peacock B, Blazar BR, Metzger JM, Tolar J. Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies. American Journal of Physiology – Heart and Circulatory Physiology. 2011 Jan;300(1):H356-65.
- Barnabei M, Palpant NJ, MetzgerJM. Influence of genetic backgroundon ex vivo and in vivo cardiac function in several commonly used inbredmouse strains. Physiological Genomics. 2010 Sep;42A(2):103-13.
- Palpant NJ, Houang EM, Delport W, Hastings KEM, Unofriev AV, Sham YY, and Metzger JM. Pathogenic peptide deviations support a model of adaptive evolution of chordate cardiac performance by troponin mutations. Physiological Genomics. 2010 Jul 7;42(2):287-99.
- PalpantNJ, Metzger JM. AestheticCardiology: adipose-derived stem cells for myocardial repair. CurrentStem Cell Research and Therapy. 2010 Jun;5(2):145-52.
- Palpant NJ, Szatkowski ML, Townsend D, Wang W, Koch LG, Britton SL, Metzger JM. Artificial Selection for Whole Animal Low Intrinsic Aerobic Capacity Co-Segregates with Hypoxia-Induced Cardiac Pump Failure. PLoS One. 2009 Jul 1;4(7):e6117.
- Palpant NJ, D’Alecy LG, Metzger JM. Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo. The FASEB Journal. 2009 May;23(5):1529-40.
- Turner II, Wang W, Townsend D, Palpant NJ, Bedada F, Fomicheva EV, Metzger JM. Molecular cardiology in translation: gene, cell and chemical-based experimental therapeutics for the failing heart. Journal of Translational Cardiovascular Research. 2008; 1:317-327.
- Palpant NJ, Day SM, Herron TJ, Metzger JM. Single histidine substituted cardiac troponin I confers protection from age-related systolic and diastolic dysfunction. Cardiovascular Research. 2008 Nov 1;80(2):209-18.
- Palpant NJ, Yasuda S, MacDougald OA, Metzger JM. Non-canonical Wnt signaling enhances differentiation of Sca1+/c-kit+ adipose-derived murine stromal vascular cells into spontaneously beating cardiac myocytes. Journal of Molecular and Cellular Cardiology. 2007 Sep;43(3):362-70.