GOALS
Electrical Patterning of the Heart
On the tissue/organ scale, the heart is one of the most rapid examples of autonomous, rhythmic, electrochemical oscillation in biology. Our group investigates core questions related to the developmental emergence and optimization of bioelectric signal generation and propagation.
Cell Fate Determination
Embryological development involves the progressive maturation of progenitor cells towards a terminally differentiated state. The long-term goals of our laboratory seek to understand the cellular, molecular, and biophysical events that dictate how cardiovascular cell lineages are established.
Cellular Integration/Organogenesis
Formation of multi-cellular organ systems requires the integration of divergent cell types. Using direct in vivo cell tracing techniques, we focus on identifying the developmental ontogeny and the molecular mechansims that integrate the various cellular components of the heart's electrical system.
RESEARCH
Current research projects in our laboratory are focused on the developmental emergence of cardiac biorythmicity. Effective pumping of blood depends on the rhythmic beating of cardiac muscle. In the mature heart, the timing and coordination of contraction is controlled by a specialized collection of cells referred to as the heart's conduction system. Development of this conduction system entails the de novo formation of a biorhythmic cellular circuit within a rudimentary, albeit functional, embryonic heart. The process of cardiac electrical maturation, therefore, provides a unique model system which informs core biological concepts related to the emergence and optimization of rhythmic electrochemical signal generation, as well as providing insight into the pathophysiology of human arrhythmic disorders. We are currently utilizing classical experimental embryological techniques in combination with state-of-the-art somatic transgenesis and cellular imaging to address: i) the developmental mechanisms that specify autonomous rhythmic signal generation, ii) the processes that allow for effective downstream transmission of these signals, and iii) the morphogenetic patterning events that align the various sub-components of the heart leading to proper spatiotemporal coordination of the cardiac cycle.
Right - High-speed imaging of electrical impulse propagation through a section of embryonic cardiac tissue.
DEVELOPMENTAL PHYSIOLOGY
Modern imaging modalities are allowing for a wide variety of previously inaccessible topics to now be explored in developing tissues. Our group is actively adapting and applying new technologies for labeling and imaging cells in the developing heart in order to gain novel insights into cardiac physiological maturation at subcellular resolution.
Calcium transients optically recorded from an embryonic cardiomyocyte
PUBLICATIONS
Thomas, K., Henley, T., Rossi, S., Costello, M.J., Polacheck, W., Griffith, B.E., and Bressan, M. (2021). Adherens junction engagement regulates functional patterning of the cardiac pacemaker cell lineage. Developmental Cell.
Easterling, M., Rossi, S., Mazzella, A.J., and Bressan, M. (2021). Assembly of the Cardiac Pacemaking Complex: Electrogenic Principles of Sinoatrial Node Morphogenesis. Journal of Cardiovascular Development and Disease 8, 40.
Wang L., Ma H., Huang P., Xie Y., Near D., Wang H., Xu J., Yang Y., Xu Y., Garbutt T., Zhou Y., Liu Z., Yin C., Bressan M., Taylor J.M., Liu J. and Qian L. (2020) Downregulation of Beclin1 promotes direct cardiac reprogramming. Sci Transl Med.
Guzzetta A, Koska M, Rowton M, Sullivan KR, Jacobs-Li J, Kweon J, Hidalgo H, Eckart H, Hoffmann AD, Back R, Lozano S, Moon AM, Basu A, Bressan M, Pott S, Moskowitz IP. Hedgehog-FGF signaling axis patterns anterior mesoderm during gastrulation. Proc Natl Acad Sci U S A. 2020 Jun 19;. doi: 10.1073/pnas.1914167117. PubMed PMID: 32561646.
Goudy J, Henley T, Méndez HG, Bressan M. Simplified platform for mosaic in vivo analysis of cellular maturation in the developing heart. Sci Rep. 2019 Jul 24;9(1):10716. doi: 10.1038/s41598-019-47009-7. PubMed PMID: 31341189; PubMed Central PMCID: PMC6656758.
Henley, T., Thomas, K., Bressan, M. Microinjection-based System for In Vivo Implantation of Embryonic Cardiomyocytes in the Avian Embryo. J. Vis. Exp. (144), e59267, doi:10.3791/59267 (2019).
Bressan M, Henley T, Louie JD, Liu G, Christodoulou D, Bai X, Taylor J, Seidman CE, Seidman J, Mikawa T. Dynamic cellular integration drives functional assembly of the heart's pacemaker complex. Cell Reports. 2018 May 22;23(8):2283-91.
Thomas K, Goudy J, Henley T, Bressan M. Optical Electrophysiology in the Developing Heart. J Cardiovasc Dev Dis. 2018 May 11;5(2). pii: E28. doi: 10.3390/jcdd5020028. Review. PubMed PMID: 29751595.
Kuyumcu-Martinez MN, Bressan MC. Rebuilding a broken heart: lessons from developmental and regenerative biology. Development. 2016 Nov 1;143(21):3866-3870. Review. PubMed PMID: 27803055.
Bressan M, Liu G, Louie JD, Mikawa T. Cardiac Pacemaker Development from a Tertiary Heart Field. Etiology and Morphogenesis. Chapter 39. 2016; PMID:29787147.
Bressan M, Mikawa T. Avians as a model system of vascular development. Methods Mol Biol. 2015;1214:225-42. doi: 10.1007/978-1-4939-1462-3_14. PubMed PMID: 25468608; PubMed Central PMCID: PMC4582444.
Bressan M, Louie JD, Mikawa T. Hemodynamic forces regulate developmental patterning of atrial conduction. PLoS One. 2014; 9(12):e115207.
Bressan M, Yang PB, Louie JD, Navetta AN, Garriock RJ, Mikawa T. Reciprocal myocardial-endocardial interactions pattern atrioventricular junction conduction delay. Development. 2014 Oct; 141: 4149-4157.
Hua LL, Vedantham V, Barnes RM, Hu J, Robinson AS, Bressan M, Srivastava D, Black BL. Specification of the mouse cardiac conduction system in the absence of Endothelin signaling. Dev Biol. 2014 Sep 15; 393(2):245-54.
Bressan M, Liu G, Mikawa T. Early mesodermal cues assign avian cardiac pacemaker fate potential in a tertiary heart field. Science. 2013 May 10; 340(6133): 744-8.
Maya-Ramos L, Cleland J, Bressan M, Mikawa T. Induction of the Proepicardium. J. Dev. Biol. 2013, 1(2): 82-91
Liu J, Bressan M, Hassel D, Huisken J, Staudt D, Kikuchi K, Poss KD, Mikawa T, Stainier DY. A dual role for ErbB2 signaling in cardiac trabeculation. Development. 2010 Nov; 137(22):3867-75.
Bressan M, Davis P, Timmer J, Herzlinger D, Mikawa T. Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation. Dev Biol. 2009 Feb 1; 326(1):101-11.
Guillaume, R., Bressan, M., Hezlinger, D. Paraxial mesoderm contributes stromal cells to the developing kidney. Dev Biol. 2009 May; 329(2): 169-175.
Pallante BA, Duignan I, Okin D, Chin A, Bressan MC, Mikawa T, Edelberg JM. Bone marrow Oct3/4+ cells differentiate into cardiac myocytes via age-dependent paracrine mechanisms. Circ Res. 2007 Jan 5; 100(1):e1-11.
McDermott DA, Bressan MC, He J, Lee JS, Aftimos S, Brueckner M, Gilbert F, Graham GE, Hannibal MC, Innis JW, Pierpont ME, Raas-Rothschild A, Shanske AL, Smith WE, Spencer RH, St John-Sutton MG, van Maldergem L, Waggoner DJ, Weber M, Basson CT. TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome. Pediatr Res. 2005 Nov; 58(5):981-6.
Veugelers M, Bressan M, McDermott DA, Weremowicz S, Morton CC, Mabry CC, Lefaivre JF, Zunamon A, Destree A, Chaudron JM, Basson CT. Mutation of perinatal myosin heavy chain associated with a Carney complex variant. N Engl J Med. 2004 Jul 29; 351(5):460-9.
CONTACT
Employment Inquiries:
The laboratory is always looking for motivated postdocs and students. Please send a CV and a description of research interests to Michael Bressan.
Office
University of North Carolina, Chapel Hill
111 Mason Farm Rd. MBRB 6341c
Chapel Hill, NC
27599
Michael_Bressan(at)med.unc.edu
Tel: 919.843.9455
Laboratory
111 Mason Farm Rd. MBRB 6335
Chapel Hill, NC
27599
Tel: 919.962.3008
LAB MEMBERS
Michael Bressan PhD
Principle Investigator
Assistant Professor
Department of Cell Biology and Physiology
McAllister Heart Insititute
Training:
Postdoctoral Fellow
University of California, San Francisco
Cardiovascular Research Institute
PhD
Weill Medical College of Cornell University
Dept. of Physiology, Biophysics, and Systems Biology
B.S.
Lafayette College
Dept. of Biology
Trevor Maxwell Henley
Laboratory Manager
Training:
B.S.
University of North Carolina - Chapel Hill
Dept. of Biology
Minor: Chemistry
Julie Hulet Goudy
Research Technician
Training:
M.S.
Brigham Young University
Dept. of Physiology and Developmental Biology
B.S.
Brigham Young University
Dept. of Physiology and Developmental Biology
Minor: Editing
Kandace N. Thomas
Graduate Student
Training:
B.S.
Eastern University
Dept. of Biology
Simone Rossi PhD
Visiting Postdoctoral Fellow
Training:
PhD
IST-EPFL
Depart. of Mathematics
M.S.
Università degli Studi di Milano
Dept. of Physics
B.S.
Università degli Studi di Milano
Dept. of Physics
Marietta Easterling PhD
Postdoctoral Fellow
Training:
PhD
Washington State University
Dept. of Biology
B.S.
College of Charleston
Dept. of Biology
Anthony Mazzella MD
Chief Cardiology Fellow
Training:
MD
Virginia Commonwealth University School of Medicine
B.A.
University of North Carolina at Chapel Hill
Dept. Music Performance and Compisition
Dept. Chemistry