Members
Konstantinos Zarbalis
Associate Investigator, Shriners Hospitals for Children
Associate Professor, Department of Pathology & Laboratory Medicine, UCD SOM
2425 Stockton Blvd, Room 671, Sacramento, CA 95817
(916) 453-2189
kzarbalis (at) ucdavis.edu
Education
- Postdoctoral Training, Developmental Neurobiology, UCSF
- PhD, Molecular Biology and Genetics, Technical University Munich, Germany
- MS, Biology, Technical University Munich, Germany
Research Interests
Our work focuses on the processes that guide the development of the brain and craniofacial skeleton and use this insight to expand our understanding of neurodevelopmental and craniofacial disorders. Our goal is to use knowledge gained into the mechanisms underlying these disorders to develop better diagnostic tools, preventive measures, and pathways to intervention.
Current work focuses on three main areas. First, investigating the mechanisms by which the autophagy and autism risk factor WDFY3 regulates the development of the brain by orchestrating neuronal migration and connectivity. Second, to research the interface between ribosomopathies and neurocristopathies and resulting birth defects, such as facial clefts. We are particularly interested on how possibly unique requirements of neural crest cells disproportionally affect craniofacial structures if ubiquitous ribosome biosynthesis is impaired. Third, we are conducting work on the role that maternal micronutrient supply during pregnancy may play in cerebral cortical development and how inadequate supply may precipitate neurodevelopmental disorders.
* equal contribution
2019
Le Duc D, Giulivi C, Hiatt SM, Napoli E, Panoutsopoulos A, Harlan De Crescenzo A, Kotzaeridou U, Syrbe S, Anagnostou E, Azage M, Bend R, Begtrup A, Brown NJ, Büttner B, Cho MT, Cooper GM, Doering JH, Dubourg C, Everman DB, Hildebrand MS, Santos FJR, Kellam B, Keller-Ramey J, Lemke JR, Liu S, Niyazov D, Payne K, Person R, Quélin C, Schnur RE, Smith BT, Strober J, Walker S, Wallis M, Walsh L, Yang S, Yuen RKC, Ziegler A, Sticht H, Pride MC, Orosco L, Martínez-Cerdeño V, Silverman JL, Crawley JN, Scherer SW, Zarbalis KS, Jamra R. Pathogenic WDFY3 variants cause neurodevelopmental disorders and opposing effects on brain size. Brain. 2019 Sep 1;142(9):2617-2630. doi: 10.1093/brain/awz198. Erratum in: Brain. 2019 Nov 1;142(11):e63. PMID: 31327001; PMCID: PMC6736092. Download PDF
2018
Napoli E, Song G, Panoutsopoulos A, Riyadh MA, Kaushik G, Halmai J, Levenson R, Zarbalis KS, Giulivi C. Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy. Sci Rep. 2018 Jul 27;8(1):11348. doi: 10.1038/s41598-018-29421-7. PMID: 30054502; PMCID: PMC6063930. Download PDF
2017
Napoli E, Liu S, Marsilio I, Zarbalis K, Giulivi C. Lipid-based DNA/siRNA transfection agents disrupt neuronal bioenergetics and mitophagy. Biochem J. 2017 Nov 10;474(23):3887-3902. doi: 10.1042/BCJ20170632. PMID: 29025974. Download PDF
Gompers AL, Su-Feher L, Ellegood J, Copping NA, Riyadh MA, Stradleigh TW, Pride MC, Schaffler MD, Wade AA, Catta-Preta R, Zdilar I, Louis S, Kaushik G, Mannion BJ, Plajzer-Frick I, Afzal V, Visel A, Pennacchio LA, Dickel DE, Lerch JP, Crawley JN, Zarbalis KS, Silverman JL, Nord AS. Germline Chd8 haploinsufficiency alters brain development in mouse. Nat Neurosci. 2017 Aug;20(8):1062-1073. doi: 10.1038/nn.4592. Epub 2017 Jun 26. PMID: 28671691; PMCID: PMC6008102. Download PDF
2016
Wu DJ, Gu R, Sarin R, Zavodovskaya R, Chen CP, Christiansen BA, Zarbalis KS, Adamopoulos IE. Autophagy-linked FYVE containing protein WDFY3 interacts with TRAF6 and modulates RANKL-induced osteoclastogenesis. J Autoimmun. 2016 Sep;73:73-84. doi: 10.1016/j.jaut.2016.06.004. Epub 2016 Jun 18. Erratum in: J Autoimmun. 2017 Nov;84:132. PMID: 27330028; PMCID: PMC5003737. Download PDF
Kaushik G, Huber DP, Aho K, Finney B, Bearden S, Zarbalis KS, Thomas MA. Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers. Biochem Biophys Res Commun. 2016 May 27;474(2):291-295. doi: 10.1016/j.bbrc.2016.04.088. Epub 2016 Apr 20. PMID: 27105911; PMCID: PMC4891464. Download PDF
Kaushik G, Zarbalis KS. Prenatal Neurogenesis in Autism Spectrum Disorders. Front Chem. 2016 Mar 15;4:12. doi: 10.3389/fchem.2016.00012. PMID: 27014681; PMCID: PMC4791366. Download PDF
2015
Sohn J, Orosco L, Guo F, Chung SH, Bannerman P, Mills Ko E, Zarbalis K, Deng W, Pleasure D. The subventricular zone continues to generate corpus callosum and rostral migratory stream astroglia in normal adult mice. J Neurosci. 2015 Mar 4;35(9):3756-63. doi: 10.1523/JNEUROSCI.3454-14.2015. PMID: 25740506; PMCID: PMC6605576. Download PDF
2014
Orosco LA, Ross AP, Cates SL, Scott SE, Wu D, Sohn J, Pleasure D, Pleasure SJ, Adamopoulos IE, Zarbalis KS. Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology. Nat Commun. 2014 Sep 8;5:4692. doi: 10.1038/ncomms5692. PMID: 25198012; PMCID: PMC4159772. Download PDF
Adamopoulos IE, Suzuki E, Chao CC, Gorman D, Adda S, Maverakis E, Zarbalis K, Geissler R, Asio A, Blumenschein WM, Mcclanahan T, De Waal Malefyt R, Gershwin ME, Bowman EP. IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis. Ann Rheum Dis. 2015 Jun;74(6):1284-92. doi: 10.1136/annrheumdis-2013-204782. Epub 2014 Feb 23. PMID: 24567524; PMCID: PMC4229480. Download PDF
Choe Y, Zarbalis KS, Pleasure SJ. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline. PLoS One. 2014 Feb 6;9(2):e86025. doi: 10.1371/journal.pone.0086025. PMID: 24516524; PMCID: PMC3916303. Download PDF
Ross AP, Zarbalis KS. The emerging roles of ribosome biogenesis in craniofacial development. Front Physiol. 2014 Feb 4;5:26. doi: 10.3389/fphys.2014.00026. PMID: 24550838; PMCID: PMC3912750. Download PDF
2013
Ross AP, Mansilla MA, Choe Y, Helminski S, Sturm R, Maute RL, May SR, Hozyasz KK, Wójcicki P, Mostowska A, Davidson B, Adamopoulos IE, Pleasure SJ, Murray JC, Zarbalis KS. A mutation in mouse Pak1ip1 causes orofacial clefting while human PAK1IP1 maps to 6p24 translocation breaking points associated with orofacial clefting. PLoS One. 2013 Jul 25;8(7):e69333. doi: 10.1371/journal.pone.0069333. PMID: 23935987; PMCID: PMC3723895. Download PDF
2012
Sohn J, Selvaraj V, Wakayama K, Orosco L, Lee E, Crawford SE, Guo F, Lang J, Horiuchi M, Zarbalis K, Itoh T, Deng W, Pleasure D. PEDF is a novel oligodendrogenic morphogen acting on the adult SVZ and corpus callosum. J Neurosci. 2012 Aug 29;32(35):12152-64. doi: 10.1523/JNEUROSCI.0628-12.2012. PMID: 22933798; PMCID: PMC3457640. Download PDF
Zarbalis K, Choe Y, Siegenthaler JA, Orosco LA, Pleasure SJ. Meningeal defects alter the tangential migration of cortical interneurons in Foxc1hith/hith mice. Neural Dev. 2012 Jan 17;7:2. doi: 10.1186/1749-8104-7-2. PMID: 22248045; PMCID: PMC3287125. Download PDF
2010
Endoh-Yamagami S, Karkar KM, May SR, Cobos I, Thwin MT, Long JE, Ashique AM, Zarbalis K, Rubenstein JL, Peterson AS. A mutation in the pericentrin gene causes abnormal interneuron migration to the olfactory bulb in mice. Dev Biol. 2010 Apr 1;340(1):41-53. doi: 10.1016/j.ydbio.2010.01.017. Epub 2010 Jan 22. PMID: 20096683. Download PDF
2009
Wizenmann A, Brunet I, Lam J, Sonnier L, Beurdeley M, Zarbalis K, Weisenhorn-Vogt D, Weinl C, Dwivedy A, Joliot A, Wurst W, Holt C, Prochiantz A. Extracellular Engrailed participates in the topographic guidance of retinal axons in vivo. Neuron. 2009 Nov 12;64(3):355-366. doi: 10.1016/j.neuron.2009.09.018. PMID: 19914184; PMCID: PMC4603356. Download PDF
Siegenthaler JA, Ashique AM, Zarbalis K, Patterson KP, Hecht JH, Kane MA, Folias AE, Choe Y, May SR, Kume T, Napoli JL, Peterson AS, Pleasure SJ. Retinoic acid from the meninges regulates cortical neuron generation. Cell. 2009 Oct 30;139(3):597-609. doi: 10.1016/j.cell.2009.10.004. Erratum in: Cell. 2011 Aug 5;146(3):486. PMID: 19879845; PMCID: PMC2772834. Download PDF
2007
Zarbalis K, Siegenthaler JA, Choe Y, May SR, Peterson AS, Pleasure SJ. Cortical dysplasia and skull defects in mice with a Foxc1 allele reveal the role of meningeal differentiation in regulating cortical development. Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14002-7. doi: 10.1073/pnas.0702618104. Epub 2007 Aug 21. PMID: 17715063; PMCID: PMC1955817. Download PDF
Konstantinova I, Nikolova G, Ohara-Imaizumi M, Meda P, Kucera T, Zarbalis K, Wurst W, Nagamatsu S, Lammert E. EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets. Cell. 2007 Apr 20;129(2):359-70. doi: 10.1016/j.cell.2007.02.044. PMID: 17448994. Download PDF
2006
Dow LE, Kauffman JS, Caddy J, Zarbalis K, Peterson AS, Jane SM, Russell SM, Humbert PO. The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge. Oncogene. 2007 Apr 5;26(16):2272-82. doi: 10.1038/sj.onc.1210016. Epub 2006 Oct 9. Erratum in: Oncogene. 2007 Aug 16;26(38):5692. Zarbalis, K [added]. PMID: 17043654. Download PDF
2005
May SR, Ashique AM, Karlen M, Wang B, Shen Y, Zarbalis K, Reiter J, Ericson J, Peterson AS. Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli. Dev Biol. 2005 Nov 15;287(2):378-89. doi: 10.1016/j.ydbio.2005.08.050. Epub 2005 Oct 17. PMID: 16229832. Download PDF
2004
Zarbalis K, May SR, Shen Y, Ekker M, Rubenstein JL, Peterson AS. A focused and efficient genetic screening strategy in the mouse: identification of mutations that disrupt cortical development. PLoS Biol. 2004 Aug;2(8):E219. doi: 10.1371/journal.pbio.0020219. Epub 2004 Aug 17. PMID: 15314648; PMCID: PMC509294. Download PDF
Bolz J, Uziel D, Mühlfriedel S, Güllmar A, Peuckert C, Zarbalis K, Wurst W, Torii M, Levitt P. Multiple roles of ephrins during the formation of thalamocortical projections: maps and more. J Neurobiol. 2004 Apr;59(1):82-94. doi: 10.1002/neu.10346. PMID: 15007829. Download PDF
2002
Uziel D, Mühlfriedel S, Zarbalis K, Wurst W, Levitt P, Bolz J. Miswiring of limbic thalamocortical projections in the absence of ephrin-A5. J Neurosci. 2002 Nov 1;22(21):9352-7. doi: 10.1523/JNEUROSCI.22-21-09352.2002. PMID: 12417660; PMCID: PMC6758033. Download PDF
2001
Knöll B, Zarbalis K, Wurst W, Drescher U. A role for the EphA family in the topographic targeting of vomeronasal axons. Development. 2001 Mar;128(6):895-906. PMID: 11222144. Download PDF
2000
Zarbalis K, Wurst W. Expression domains of murine ephrin-A5 in the pituitary and hypothalamus. Mech Dev. 2000 May;93(1-2):165-8. doi: 10.1016/s0925-4773(00)00252-5. PMID: 10781950. Download PDF