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Kryn Stankunas

Kryn Stankunas

Assistant Professor, Biology
Member, IMB

Ph.D. Stanford University
B.S.. (Hon.), University of British Columbia

Office: Streisinger 245C
Office Phone: 541-346-7416
Lab: Streisinger 233/245

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Research Interests

The Stankunas laboratory pursues research on fundamental questions of vertebrate organ development and regeneration. We combine mouse and zebrafish genetics with cell, molecular, and systems biology approaches to determine how cell signals interface with epigenetic information to allow the heart, bone, and other organs/tissues to form and repair. We also develop chemical genetic technologies that enable high-resolution in vivo gene regulation studies to support these projects. The lab has three main research programs:

1) Heart Development

We pursue mouse genetic-based projects focused on understanding the contributions of 1) the BAF chromatin remodeling complex and 2) Wnt signaling to heart valve development and disease. Both projects characterize cellular and molecular origins of heart valve phenotypes that manifest in a collection of transgenic mouse models we have developed. From these observations, we determine origins and progression of congenital valve defects that affect up to 5% of humans. We also define molecular connections between the BAF complex and Wnt and other pathways and identify key target genes using candidate gene and transcriptome approaches. Additional heart development projects are studying mechanisms of myocardial trabeculation and the contributions of chromatin regulators to cardiac specification. This latter work includes zebrafish genetics research, which emerged as a field here at the University of Oregon.

2) Organ Regeneration

In collaboration with Scott Stewart, we use zebrafish as a model to determine roles of cell signals and chromatin reprogramming during vertebrate regeneration. Unlike humans, zebrafish possess the remarkable ability to perfectly regrow lost appendages (and other organs, including the heart). We intend to uncover the keys to zebrafish regeneration to inspire logical approaches to enhance mammalian organ repair. As an example, we showed how two signaling pathways (Wnt and BMP) direct formation of de-differentiated bone progenitors upon caudal fin amputation and then balance simultaneous needs for those cells to proliferate and re-differentiate into replacement bone cells. We are pursuing how additional pathways are integrated into this network and how the signals cooperate with chromatin regulators to “switch” gene expression programs that promote transitions between progenitor-like and differentiated states.

3) Chemical Genetic Technologies for Gene Regulation Studies

We collaborate closely with Chris Doe’s lab developing the “TU-tagging” technology to label newly synthesized RNA transcripts in specific cell types in mice, which are then purified and analyzed by RNA-Seq. Our initial TU-tagging studies identified novel heart and vasculature expressed genes whose developmental functions and regulation we are studying. Further, we are optimizing TU-tagging to expand its utility while applying the method to answer questions about dynamic gene regulation during organogenesis and regeneration.

Recent publications

(pulled from pubmed)

Recent publications

(pulled from pubmed)

Applying thiouracil tagging to mouse transcriptome analysis.
Gay L, Karfilis KV, Miller MR, Doe CQ, Stankunas K
Nat Protoc 2014 Feb;9(2):410-20
Sequential and opposing activities of Wnt and BMP coordinate zebrafish bone regeneration.
Stewart S, Gomez AW, Armstrong BE, Henner A, Stankunas K
Cell Rep 2014 Feb 13;6(3):482-98
Spatial and temporal control of transgene expression in zebrafish.
Akerberg AA, Stewart S, Stankunas K
PLoS One 2014;9(3):e92217
The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis.
Chen HI, Sharma B, Akerberg BN, Numi HJ, Kivelä R, Saharinen P, Aghajanian H, McKay AS, Bogard PE, Chang AH, Jacobs AH, Epstein JA, Stankunas K, Alitalo K, Red-Horse K
Development 2014 Dec;141(23):4500-12
Mouse TU tagging: a chemical/genetic intersectional method for purifying cell type-specific nascent RNA.
Gay L, Miller MR, Ventura PB, Devasthali V, Vue Z, Thompson HL, Temple S, Zong H, Cleary MD, Stankunas K, Doe CQ
Genes Dev 2013 Jan 1;27(1):98-115
Brg1 governs distinct pathways to direct multiple aspects of mammalian neural crest cell development.
Li W, Xiong Y, Shang C, Twu KY, Hang CT, Yang J, Han P, Lin CY, Lin CJ, Tsai FC, Stankunas K, Meyer T, Bernstein D, Pan M, Chang CP
Proc Natl Acad Sci U S A 2013 Jan 29;110(5):1738-43
Brg1 governs a positive feedback circuit in the hair follicle for tissue regeneration and repair.
Xiong Y, Li W, Shang C, Chen RM, Han P, Yang J, Stankunas K, Wu B, Pan M, Zhou B, Longaker MT, Chang CP
Dev Cell 2013 Apr 29;25(2):169-81
VEGF signaling has distinct spatiotemporal roles during heart valve development.
Stankunas K, Ma GK, Kuhnert FJ, Kuo CJ, Chang CP
Dev Biol 2010 Nov 15;347(2):325-36
Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis.
Stankunas K, Hang CT, Tsun ZY, Chen H, Lee NV, Wu JI, Shang C, Bayle JH, Shou W, Iruela-Arispe ML, Chang CP
Dev Cell 2008 Feb;14(2):298-311
SM22alpha-targeted deletion of bone morphogenetic protein receptor 1A in mice impairs cardiac and vascular development, and influences organogenesis.
El-Bizri N, Guignabert C, Wang L, Cheng A, Stankunas K, Chang CP, Mishina Y, Rabinovitch M
Development 2008 Sep;135(17):2981-91
Pbx/Meis deficiencies demonstrate multigenetic origins of congenital heart disease.
Stankunas K, Shang C, Twu KY, Kao SC, Jenkins NA, Copeland NG, Sanyal M, Selleri L, Cleary ML, Chang CP
Circ Res 2008 Sep 26;103(7):702-9
Pbx1 functions in distinct regulatory networks to pattern the great arteries and cardiac outflow tract.
Chang CP, Stankunas K, Shang C, Kao SC, Twu KY, Cleary ML
Development 2008 Nov;135(21):3577-86
Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126.
Kuhnert F, Mancuso MR, Hampton J, Stankunas K, Asano T, Chen CZ, Kuo CJ
Development 2008 Dec;135(24):3989-93
Engineering small molecule specificity in nearly identical cellular environments.
Sellmyer MA, Stankunas K, Briesewitz R, Crabtree GR, Wandless TJ
Bioorg Med Chem Lett 2007 May 15;17(10):2703-5
Rescue of degradation-prone mutants of the FK506-rapamycin binding (FRB) protein with chemical ligands.
Stankunas K, Bayle JH, Havranek JJ, Wandless TJ, Baker D, Crabtree GR, Gestwicki JE
Chembiochem 2007 Jul 9;8(10):1162-9
Exploiting protein destruction for constructive use.
Stankunas K, Crabtree GR
Proc Natl Acad Sci U S A 2007 Jul 10;104(28):11511-2
Rapamycin analogs with differential binding specificity permit orthogonal control of protein activity.
Bayle JH, Grimley JS, Stankunas K, Gestwicki JE, Wandless TJ, Crabtree GR
Chem Biol 2006 Jan;13(1):99-107
A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis.
Chang CP, Neilson JR, Bayle JH, Gestwicki JE, Kuo A, Stankunas K, Graef IA, Crabtree GR
Cell 2004 Sep 3;118(5):649-63
Conditional protein alleles using knockin mice and a chemical inducer of dimerization.
Stankunas K, Bayle JH, Gestwicki JE, Lin YM, Wandless TJ, Crabtree GR
Mol Cell 2003 Dec;12(6):1615-24
Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation.
Diehn M, Alizadeh AA, Rando OJ, Liu CL, Stankunas K, Botstein D, Crabtree GR, Brown PO
Proc Natl Acad Sci U S A 2002 Sep 3;99(18):11796-801
L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons.
Graef IA, Mermelstein PG, Stankunas K, Neilson JR, Deisseroth K, Tsien RW, Crabtree GR
Nature 1999 Oct 14;401(6754):703-8
Signaling through calcium, calcineurin, and NF-AT in lymphocyte activation and development.
Stankunas K, Graef IA, Neilson JR, Park SH, Crabtree GR
Cold Spring Harb Symp Quant Biol 1999;64:505-16