Rebecca Burdine, Professor of Molecular Biology. Photo by Sameer A. Khan/Fotobuddy Rebecca D. Burdine Position Professor of Molecular Biology Website Burdine Lab CV Rebecca Burdine CV (PDF) Office Phone 609-258-7515 Email [email protected] Assistant Galo Guerrero Office Guyot Hall, M159 Bio/Description FocusUsing zebrafish to study development and disordersResearchIn my laboratory we are using the zebrafish to study how the left-right (LR) axis and pattern is established. Vertebrates appear bilaterally symmetric, but have internal asymmetries along the LR axis. This axis is revealed by the asymmetric placement of organs along the midline. For example, the human heart is located on the left of the body cavity, while the liver is located on the right. While genes implicated in LR patterning have been identified, we do not know how the LR axis is established, how the axis is aligned with the existing dorsal-ventral and anterior-posterior axes, or how LR information is received and interpreted by developing organs. Proper LR axis formation is critical for organogenesis as correct organ placement allows for proper connectivity with the developing vasculature. In humans, defects in LR patterning often manifest as congenital heart disease. Our current studies focus on the mechanisms of left-right patterning, and on identifying new genes involved in this process. Additionally, we use our work in zebrafish to understand human disorders including ciliopathies, RASopathies, idiopathic scoliosis and congenital heart defects.Left-Right Patterning in the Vertebrate EmbryoAsymmetric expression of the Nodal inhibitor dand5 (magenta) in the zebrafish ciliated (green) left-right organizer.We use the zebrafish to study how the left-right (LR) axis is established. Vertebrates appear bilaterally symmetric, but have internal asymmetries along the LR axis, as revealed by the asymmetric placement of organs. For example, the human heart is located on the left of the body cavity, while the liver is located on the right. Defects in LR patterning can lead to birth anomalies, including congenital heart defects, that are often fatal. Current models propose cilia driven flow is required to establish LR patterning, but we still lack a full understanding of how flow is translated into a signal that is understood and responded to by relevant cells to produce asymmetric gene expression in the embryo. Without a full understanding of the genes involved and the signaling pathways utilized, we are missing important information about a process that contributes substantially to congenital heart defects in humans. Our current studies focus on identifying new players in LR patterning that will help define the pathway downstream of flow that produces asymmetric gene expression.Selected Publications: Bicc1 and Dicer regulates left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5Gdf3 is required for robust Nodal signaling during germ layer formation and left-right patterningTwo additional midline barriers function with midline lefty1 expression to maintain asymmetric Nodal signaling during left-right axis specification in zebrafishUnderstanding how organs obtain asymmetric positionsHow an organ obtains its final asymmetric position is not well understood. Organs such as the heart and pancreas form at the midline and obtain asymmetric positions later in development. Asymmetry is governed by the left-sided expression of Nodal early in development, yet each organ responds differently to this signal; for example, the heart loops to the right, while the liver is positioned on the left. To better understand how organs respond to asymmetric information, we are investigating how the developing heart responds to Nodal. Our current studies focus on implementing genomic approaches to identify Nodal-induced transcriptomic changes that drive asymmetric organ morphogenesis. Using confocal imaging, we take advantage of the transparency of zebrafish embryos to image asymmetric heart development in real time to better understand the collective cell movements that occur in this process. These studies additionally shed light on cell migration mechanisms that can be utilized by cancer cells to metastasize.Selected Publications: Cooperation between Nodal and FGF signaling regulates zebrafish cardiac cell migration and heart morphogenesisLeft-right asymmetric heart jogging increases the robustness of dextral heart looping in zebrafishIntegration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetryUtilizing Zebrafish as a Model to Study Human Disease Zebrafish are an excellent model for studying human disease, in part thanks to their genetic similarity to humans, their ability to be easily manipulated biologically and chemically, and their transparency which allows for feasible observation of disease progression. Variants of unknown significance from patient whole genome sequencing can often be rapidly evaluated in zebrafish providing information critical for correct diagnoses. We have developed models to study genes involved in ciliopathies, idiopathic scoliosis, and RASopathies. Our studies provide insights into disease mechanisms, can identify potential therapeutic targets, and can enable screening of drug libraries for novel drug interventions.Selected Publications: Abrogration of MAP4K4 protein function causes congenital anomalies in humans and zebrafish(Link is external)Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature(Link is external)Divergent effects of intrinsically active MEK variants on developmental Ras signaling(Link is external)In vivo severity ranking of Ras pathway mutations associated with developmental disorders(Link is external)The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formationBiographyRebecca Burdine is a faculty member in the Department of Molecular Biology at Princeton University. Her lab focuses on understanding the developmental mechanisms that control left-right patterning and organ morphogenesis in order to understanding how structure birth anomalies arise. She was named the 44th Mallinckrodt Scholar for the Edward Mallinckrodt Jr. Foundation, and received a Scientist Development Career Award from the American Heart Association in 2003. She was elected as fellow to the American Association for the Advancement of Science (AAAS) in 2018. She is currently serving on the Board of The International Society of Differentiation, and previously served on the boards of the Genetics Society of America and the International Zebrafish Society. She is on the Editorial board for Zebrafish, and regularly serves on grant review panels for the NIH and NSF. Dr. Burdine graduated summa cum laude from Western Kentucky University, majoring in Recombinant Gene Technology with a minor in Chemistry. She received her Ph.D. from Yale University for her thesis work with Dr. Michael Stern. Dr. Burdine carried out her postdoctoral research in the laboratory of Alexander F. Schier (Harvard) when he was at the Skirball Institute of Biomolecular Medicine at New York University. Dr. Burdine is a parent to a child with Angelman Syndrome. She first served on the Angelman Syndrome Foundation (ASF) scientific advisory committee in 2007 by invitation from Dr. Joe Wagstaff. She has previously served as Chief Scientific Officer for the Pitt-Hopkins Research Foundation and for the Foundation for Angelman Syndrome Therapeutics. She is currently serving on the Board of Directors and the Chair of the Science Advisory Committee for the ASF.Honors & Awards2024 Elected member of the SDB Academy, Society for Developmental Biology2024 Clio Hall Award for Contributions to Graduate Student Professional Development at Princeton2018 Elected Fellow to the American Association for the Advancement of Science (AAAS)2016-2017 National Academies Education Mentor in the Life Sciences2013-2014 National Academies Education Fellow in the Life Sciences2012 Invited Speaker for Yale University Biology Alumni Reunion2011 Invited Speaker for NICHD National Advisory Meeting as an ARRA Success Story2003-2006 44th Mallinckrodt Scholar, Edward Mallinckrodt Jr. Foundation2003-2006 Scientist Development Award, American Heart Association2001-2002 American Heart Association Postdoctoral Fellowship1998-2001 Damon Runyon Cancer Research Foundation Fellowship1997 Selected speaker Yale Graduate Student Research Symposium1997 Anna Fuller Fund Fellowship in Molecular Oncology1991-1996 Howard Hughes Medical Institute Predoctoral Fellow1989 Department of Biology Scholarship, Western Kentucky University1988 Phi Eta Sigma Honor Society (Induction)1987-1990 President’s Honor List (3.8-4.0 GPA), Western Kentucky University1987-1990 Western Kentucky University Regents Scholarship1987 Florence and Basil C. Cole Scholarship, Western Kentucky Un Education Ph.D., Yale UniversityB.S., Western Kentucky University Selected Publications 1.Gonzalez V, Grant M, Suzuki M, Christophers B, Williams J, Burdine R. Cooperation between Nodal and FGF signals regulates zebrafish cardiac cell migration and heart morphogenesis. bioRxiv : the preprint server for biology. 2024;. PMCID: PMC10802409 1.Patterson V, Ullah F, Bryant L, Griffin J, Sidhu A, Saliganan S, Blaile M, Saenz M, Smith R, Ellingwood S, Grange D, Hu X, Mireguli M, Luo Y, Shen Y, Mulhern M, Zackai E, Ritter A, Izumi K, Hoefele J, Wagner M, Riedhammer K, Seitz B, Robin N, Goodloe D, Mignot C, Keren B, Cox H, Jarvis J, Hempel M, Gibson C, Mau-Them F, Vitobello A, Bruel A-L, Sorlin A, Mehta S, Raymond L, Gilmore K, Powell B, Weck K, Li C, van Silfhout A, Giacomini T, Mancardi M, Accogli A, Salpietro V, Zara F, Vora N, Davis E, Burdine R, Bhoj E. Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish. Science advances. 2023;9(17):eade0631. PMCID: PMC10132768 1.Khan N, Cabo R, Burdine R, Tan W-H, Keary C, Ochoa-Lubinoff C, Bird L, Investigators S. Health-related quality of life and medication use among individuals with Angelman syndrome. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. 2023;32(7):2059–2067. PMID: 37039911 1.Cheng K, Burdine R, Dickinson M, Ekker S, Lin A, Lloyd K, Lutz C, MacRae C, Morrison J, O’Connor D, Postlethwait J, Rogers C, Sanchez S, Simpson J, Talbot W, Wallace D, Weimer J, Bellen H. Promoting validation and cross-phylogenetic integration in model organism research. Dis Model Mech. 2022;15(9). PMCID: PMC9531892 1.Menon T, Burdine R. A twist in Pitx2 regulation of gut looping. Dev Cell. 2022;57(21):2445–2446. PMID: 36347237 1.Maerker M, Getwan M, Dowdle M, McSheene J, Gonzalez V, Pelliccia J, Hamilton D, Yartseva V, Vejnar C, Tingler M, Minegishi K, Vick P, Giraldez A, Hamada H, Burdine R, Sheets M, Blum M, Schweickert A. Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5. Nat Commun. 2021;12(1):5482. PMCID: PMC8446035 1.Willgoss T, Cassater D, Connor S, Krishnan M, Miller M, Dias-Barbosa C, Phillips D, McCormack J, Bird L, Burdine R, Claridge S, Bichell T. Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model. Child Psychiatry Hum Dev. 2021;52(4):654–668. PMCID: PMC8238699 1.Bird L, Ochoa-Lubinoff C, Tan W-H, Heimer G, Melmed R, Rakhit A, Visootsak J, During M, Holcroft C, Burdine R, Kolevzon A, Thibert R. The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome. Neurology. 2021;96(7):e1024-e1035. PMCID: PMC8055330 1.Grimes D, Patterson V, Luna-Arvizu G, Schottenfeld-Roames J, Irons Z, Burdine R. Left-right asymmetric heart jogging increases the robustness of dextral heart looping in zebrafish. Dev Biol. 2020;459(2):79–86. PMID: 31758943 1.Patterson V, Burdine R. Swimming toward solutions: Using fish and frogs as models for understanding RASopathies. Birth Defects Res. 2020;112(10):749–765. PMCID: PMC7968373 View all publications 1.Patel A, Yeung E, McGuire S, Wu A, Toettcher J, Burdine R, Shvartsman S. Optimizing photoswitchable MEK. Proc Natl Acad Sci U S A. 2019;116(51):25756–25763. PMCID: PMC6926043 1.Harris A, Siggers P, Corrochano S, Warr N, Sagar D, Grimes D, Suzuki M, Burdine R, Cong F, Koo B-K, Clevers H, Stévant I, Nef S, Wells S, Brauner R, Ben Rhouma B, Belguith N, Eozenou C, Bignon-Topalovic J, Bashamboo A, McElreavey K, Greenfield A. ZNRF3 functions in mammalian sex determination by inhibiting canonical WNT signaling. Proc Natl Acad Sci U S A. 2018;115(21):5474–5479. PMCID: PMC6003506 1.Goyal Y, Jindal G, Pelliccia J, Yamaya K, Yeung E, Futran A, Burdine R, Schüpbach T, Shvartsman S. Divergent effects of intrinsically active MEK variants on developmental Ras signaling. Nat Genet. 2017;49(3):465–469. PMCID: PMC5621734 1.Pelliccia J, Jindal G, Burdine R. Gdf3 is required for robust Nodal signaling during germ layer formation and left-right patterning. Elife. 2017;6. PMCID: PMC5745080 1.Stainier D, Raz E, Lawson N, Ekker S, Burdine R, Eisen J, Ingham P, Schulte-Merker S, Yelon D, Weinstein B, Mullins M, Wilson S, Ramakrishnan L, Amacher S, Neuhauss S, Meng A, Mochizuki N, Panula P, Moens C. Guidelines for morpholino use in zebrafish. PLoS Genet. 2017;13(10):e1007000. PMCID: PMC5648102 1.Jindal G, Goyal Y, Humphreys J, Yeung E, Tian K, Patterson V, He H, Burdine R, Goldsmith E, Shvartsman S. How activating mutations affect MEK1 regulation and function. J Biol Chem. 2017;292(46):18814–18820. PMCID: PMC5704466 1.Jindal G, Goyal Y, Yamaya K, Futran A, Kountouridis I, Balgobin C, Schüpbach T, Burdine R, Shvartsman S. In vivo severity ranking of Ras pathway mutations associated with developmental disorders. Proc Natl Acad Sci U S A. 2017;114(3):510–515. PMCID: PMC5255624 1.Grimes D, Burdine R. Left-Right Patterning: Breaking Symmetry to Asymmetric Morphogenesis. Trends Genet. 2017;33(9):616–628. PMCID: PMC5764106 1.Grant M, Patterson V, Grimes D, Burdine R. Modeling Syndromic Congenital Heart Defects in Zebrafish. Curr Top Dev Biol. 2017;124:1–40. PMID: 28335857 1.Burdine R, Grimes D. Antagonistic interactions in the zebrafish midline prior to the emergence of asymmetric gene expression are important for left-right patterning. Philos Trans R Soc Lond B Biol Sci. 2016;371(1710). PMCID: PMC5104502 1.Jaffe K, Grimes D, Schottenfeld-Roames J, Werner M, Ku T-S, Kim S, Pelliccia J, Morante N, Mitchell B, Burdine R. c21orf59/kurly Controls Both Cilia Motility and Polarization. Cell Rep. 2016;14(8):1841–9. PMCID: PMC4775428 1.Grimes D, Boswell C, Morante N, Henkelman R, Burdine R, Ciruna B. Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature. Science. 2016;352(6291):1341–4. PMCID: PMC5574193 1.Jindal G, Goyal Y, Burdine R, Rauen K, Shvartsman S. RASopathies: unraveling mechanisms with animal models. Dis Model Mech. 2015;8(8):769–82. PMCID: PMC4527292 1.Hjeij R, Onoufriadis A, Watson C, Slagle C, Klena N, Dougherty G, Kurkowiak M, Loges N, Diggle C, Morante N, Gabriel G, Lemke K, Li Y, Pennekamp P, Menchen T, Konert F, Marthin J, Mans D, Letteboer S, Werner C, Burgoyne T, Westermann C, Rutman A, Carr I, O’Callaghan C, Moya E, Chung E, UK10K Consortium, Sheridan E, Nielsen K, Roepman R, Bartscherer K, Burdine R, Lo C, Omran H, Mitchison H. CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. Am J Hum Genet. 2014;95(3):257–74. PMCID: PMC4157146 1.Kim C, Miri A, Leung L, Berndt A, Mourrain P, Tank D, Burdine R. Prolonged, brain-wide expression of nuclear-localized GCaMP3 for functional circuit mapping. Front Neural Circuits. 2014;8:138. PMCID: PMC4244806 1.Tarkar A, Loges N, Slagle C, Francis R, Dougherty G, Tamayo J V, Shook B, Cantino M, Schwartz D, Jahnke C, Olbrich H, Werner C, Raidt J, Pennekamp P, Abouhamed M, Hjeij R, Köhler G, Griese M, Li Y, Lemke K, Klena N, Liu X, Gabriel G, Tobita K, Jaspers M, Morgan L, Shapiro A, Letteboer S, Mans D, Carson J, Leigh M, Wolf W, Chen S, Lucas J, Onoufriadis A, Plagnol V, Schmidts M, Boldt K, Roepman R, Zariwala M, Lo C, Mitchison H, Knowles M, Burdine R, Loturco J, Omran H. DYX1C1 is required for axonemal dynein assembly and ciliary motility. Nature genetics. 2013;45(9):995–1003. PMCID: PMC4000444 1.Park C, Wong A, Greene C, Rowland J, Guan Y, Bongo L, Burdine R, Troyanskaya O. Functional knowledge transfer for high-accuracy prediction of under-studied biological processes. PLoS computational biology. 2013;9(3):e1002957. PMCID: PMC3597527 1.Lenhart K, Holtzman N, Williams J, Burdine R. Integration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetry. PLoS genetics. 2013;9(1):e1003109. PMCID: PMC3554567 1.Burdine R, Caspary T. Left-right asymmetry: lessons from Cancún. Development (Cambridge, England). 2013;140(22):4465–70. PMCID: PMC3817937 1.Panizzi J, Becker-Heck A, Castleman V, Al-Mutairi D, Liu Y, Loges N, Pathak N, Austin-Tse C, Sheridan E, Schmidts M, Olbrich H, Werner C, Häffner K, Hellman N, Chodhari R, Gupta A, Kramer-Zucker A, Olale F, Burdine R, Schier A, O’Callaghan C, Chung E, Reinhardt R, Mitchison H, King S, Omran H, Drummond I. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. Nature genetics. 2012;44(6):714–9. PMCID: PMC3371652 1.Daily J, Nash K, Jinwal U, Golde T, Rogers J, Peters M, Burdine R, Dickey C, Banko J, Weeber E. Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome. PloS one. 2011;6(12):e27221. PMCID: PMC3235088 1.Becker-Heck A, Zohn I, Okabe N, Pollock A, Lenhart K, Sullivan-Brown J, McSheene J, Loges N, Olbrich H, Haeffner K, Fliegauf M, Horvath J, Reinhardt R, Nielsen K, Marthin J, Baktai G, Anderson K V, Geisler R, Niswander L, Omran H, Burdine R. The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nature genetics. 2011;43(1):79–84. PMCID: PMC3132183 1.Sullivan-Brown J, Bisher M, Burdine R. Embedding, serial sectioning and staining of zebrafish embryos using JB-4 resin. Nature protocols. 2011;6(1):46–55. PMCID: PMC3122109 1.McSheene J, Burdine R. Examining the establishment of cellular axes using intrinsic chirality. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(30):12191–2. PMCID: PMC3145736 1.Fogelgren B, Lin S-Y, Zuo X, Jaffe K, Park K, Reichert R, Bell D, Burdine R, Lipschutz J. The exocyst protein Sec10 interacts with Polycystin-2 and knockdown causes PKD-phenotypes. PLoS genetics. 2011;7(4):e1001361. PMCID: PMC3072367 1.Slagle C, Aoki T, Burdine R. Nodal-dependent mesendoderm specification requires the combinatorial activities of FoxH1 and Eomesodermin. PLoS genetics. 2011;7(5):e1002072. PMCID: PMC3102743 1.Miri A, Daie K, Burdine R, Aksay E, Tank D. Regression-based identification of behavior-encoding neurons during large-scale optical imaging of neural activity at cellular resolution. Journal of neurophysiology. 2011;105(2):964–80. PMCID: PMC3059183 1.Lenhart K, Lin S-Y, Titus T, Postlethwait J, Burdine R. Two additional midline barriers function with midline lefty1 expression to maintain asymmetric Nodal signaling during left-right axis specification in zebrafish. Development (Cambridge, England). 2011;138(20):4405–10. PMCID: PMC3177310 Related News Patel, Burdine, Shvartsman release study: Optical switch illuminates cells' development Advisee(s): Cullen B. Young Research Area Cell Biology, Development & Cancer