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Ela W. Knapik, M.D.,

 

Associate Professor of Medicine, Cell & Developmental Biology

1165 Light Hall 2215 Garland Av.
Phone: 322-7569
Fax:322-7549

email: Dr. Ela Knapik

Our laboratory is interested in the molecular mechanisms of craniofacial morphogenesis and disease.  One aspect of our work focuses on cartilage biology taking advantage of the wealth of zebrafish mutations affecting chondrocyte differentiation.  We have recently discovered that lesions in sec23 genes, which code for proteins that take part in the assembly of secretory vesicles and other intracellular transport containers, specifically affect craniofacial chondrogenesis (Lang et al., Nature Genetics, 2006).  Although secretion is a fundamental property of every cell, our findings suggest that cranial chondrogenesis might be particularly sensitive to defects in protein trafficking.  Since abnormal ER to Golgi protein trafficking has been already linked to several human syndromes, our studies in zebrafish aim to provide insights on both the normal process of chondrocyte maturation and the molecular basis underlying human cranial and skeletal dysmorphologies. 

In parallel, we study how a set of early transcription and signaling factors regulate the specification and differentiation of neural crest stem cells (Holzschuh et al, Development 2003; Barrallo-Gimeno et al., Development, 2004; Muller et al., Developmental Dynamics, 2006; Montero-Balaguer et al., Developmental Dynamics 2006). We are dissecting the genetic interactions among these factors and further search for novel components of this regulatory network.  Our long-term goal is to explore this knowledge to develop novel ways to repair and regenerate craniofacial tissues using NC-like stem cells.  

Recent Publications

Zou P, Wu SY, Koteiche HA, Mishra S, Levic DS, Knapik E, Chen W, Mchaourab HS. A conserved role of aA-crystallin in the development of the zebrafish embryonic lensExp. Eye Res [print-electronic]. 2015 Sep; 138: 104-13. PMID: 26149094, PMCID: PMC4638411, PII: S0014-4835(15)00220-1, DOI: 10.1016/j.exer.2015.07.001, ISSN: 1096-0007. 

Levic DS, Minkel JR, Wang WD, Rybski WM, Melville DB, Knapik EWAnimal model of Sar1b deficiency presents lipid absorption deficits similar to Anderson diseaseJ. Mol. Med [print-electronic]. 2015 Feb; 93(2): 165-76. PMID: 25559265, PMCID: PMC4319984, DOI: 10.1007/s00109-014-1247-x, ISSN: 1432-1440. 

Levic DS, Minkel JR, Wang WD, Rybski WM, Melville DB, Knapik EWAnimal model of Sar1b deficiency presents lipid absorption deficits similar to Anderson diseaseJ. Mol. Med [print-electronic]. 2015 Feb; 93(2): 165-76. PMID: 25559265, PMCID: PMC4319984, DOI: 10.1007/s00109-014-1247-x, ISSN: 1432-1440. 

Tanwar V, Bylund JB, Hu J, Yan J, Walthall JM, Mukherjee A, Heaton WH, Wang WD, Potet F, Rai M, Kupershmidt S, Knapik EW, Hatzopoulos AK.Gremlin 2 promotes differentiation of embryonic stem cells to atrial fate by activation of the JNK signaling pathwayStem Cells. 2014 Jul; 32(7): 1774-88. PMID: 24648383, PMCID: PMC4123739, DOI: 10.1002/stem.1703, ISSN: 1549-4918. 

Niu X, Hong J, Zheng X, Melville DB, Knapik EW, Meng A, Peng J. The nuclear pore complex function of Sec13 protein is required for cell survival during retinal developmentJ. Biol. Chem [print-electronic]. 2014 Apr 4/25/2014; 289(17): 11971-85. PMID: 24627485, PMCID: PMC4002104, PII: M114.547190, DOI: 10.1074/jbc.M114.547190, ISSN: 1083-351X. 

Unlu G, Levic DS, Melville DB, Knapik EWTrafficking mechanisms of extracellular matrix macromolecules: insights from vertebrate development and human diseasesInt. J. Biochem. Cell Biol [print-electronic]. 2014 Feb; 47: 57-67. PMID: 24333299, PMCID: PMC3915713, PII: S1357-2725(13)00343-9, DOI: 10.1016/j.biocel.2013.11.005, ISSN: 1878-5875. 

Vacaru AM, Unlu G, Spitzner M, Mione M, Knapik EW, Sadler KC. In vivo cell biology in zebrafish - providing insights into vertebrate development and diseaseJ. Cell. Sci. 2014 Feb 2/1/2014; 127(Pt 3): 485-95. PMID: 24481493, PMCID: PMC4007761, PII: 127/3/485, DOI: 10.1242/jcs.140194, ISSN: 1477-9137. 

Venkateswaran A, Sekhar KR, Levic DS, Melville DB, Clark TA, Rybski WM, Walsh AJ, Skala MC, Crooks PA, Knapik EW, Freeman ML. The NADH oxidase ENOX1, a critical mediator of endothelial cell radiosensitization, is crucial for vascular developmentCancer Res [print-electronic]. 2014 Jan 1/1/2014; 74(1): 38-43. PMID: 24247717, PMCID: PMC3947320, PII: 0008-5472.CAN-13-1981, DOI: 10.1158/0008-5472.CAN-13-1981, ISSN: 1538-7445. 

Lee RT, Knapik EW, Thiery JP, Carney TJ. An exclusively mesodermal origin of fin mesenchyme demonstrates that zebrafish trunk neural crest does not generate ectomesenchymeDevelopment [print-electronic]. 2013 Jul; 140(14): 2923-32. PMID: 23739134, PMCID: PMC3699280, PII: dev.093534, DOI: 10.1242/dev.093534, ISSN: 1477-9129. 

Müller II, Melville DB, Tanwar V, Rybski WM, Mukherjee A, Shoemaker MB, Wang WD, Schoenhard JA, Roden DM, Darbar D, Knapik EW, Hatzopoulos AK. Functional modeling in zebrafish demonstrates that the atrial-fibrillation-associated gene GREM2 regulates cardiac laterality, cardiomyocyte differentiation and atrial rhythmDis Model Mech [print-electronic]. 2013 Mar; 6(2): 332-41. PMID: 23223679, PMCID: PMC3597016, PII: dmm.010488, DOI: 10.1242/dmm.010488, ISSN: 1754-8411. 

Wang WD, Melville DB, Montero-Balaguer M, Hatzopoulos AK, Knapik EWTfap2a and Foxd3 regulate early steps in the development of the neural crest progenitor populationDev. Biol [print-electronic]. 2011 Dec 12/1/2011; 360(1): 173-85. PMID: 21963426, PMCID: PMC3236700, PII: S0012-1606(11)01263-2, DOI: 10.1016/j.ydbio.2011.09.019, ISSN: 1095-564X. 

Melville DB, Montero-Balaguer M, Levic DS, Bradley K, Smith JR, Hatzopoulos AK, Knapik EWThe feelgood mutation in zebrafish dysregulates COPII-dependent secretion of select extracellular matrix proteins in skeletal morphogenesisDis Model Mech [print-electronic]. 2011 Nov; 4(6): 763-76. PMID: 21729877, PMCID: PMC3209646, PII: dmm.007625, DOI: 10.1242/dmm.007625, ISSN: 1754-8411. 

Eames BF, Yan YL, Swartz ME, Levic DS, Knapik EW, Postlethwait JH, Kimmel CB. Mutations in fam20b and xylt1 reveal that cartilage matrix controls timing of endochondral ossification by inhibiting chondrocyte maturationPLoS Genet [print-electronic]. 2011 Aug; 7(8): e1002246. PMID: 21901110, PMCID: PMC3161922, PII: PGENETICS-D-11-00175, DOI: 10.1371/journal.pgen.1002246, ISSN: 1553-7404. 

Liu D, Wang WD, Melville DB, Cha YI, Yin Z, Issaeva N, Knapik EW, Yarbrough WG. Tumor suppressor Lzap regulates cell cycle progression, doming, and zebrafish epibolyDev. Dyn [print-electronic]. 2011 Jun; 240(6): 1613-25. PMID: 21523853, PMCID: PMC3287344, DOI: 10.1002/dvdy.22644, ISSN: 1097-0177. 

Bradley KM, Breyer JP, Melville DB, Broman KW, Knapik EW, Smith JR. An SNP-Based Linkage Map for Zebrafish Reveals Sex Determination LociG3 (Bethesda). 2011 Jun 6/1/2011; 1(1): 3-9. PMID: 21949597, PMCID: PMC3178105, DOI: 10.1534/g3.111.000190, ISSN: 2160-1836. 

Melville DB, Knapik EWTraffic jams in fish bones: ER-to-Golgi protein transport during zebrafish developmentCell Adh Migr [print-electronic]. 2011 Mar; 5(2): 114-8. PMID: 21178403, PMCID: PMC3084976, PII: 14377, ISSN: 1933-6926. 

Sarmah S, Barrallo-Gimeno A, Melville DB, Topczewski J, Solnica-Krezel L, Knapik EWSec24D-dependent transport of extracellular matrix proteins is required for zebrafish skeletal morphogenesisPLoS ONE. 2010; 5(4): e10367. PMID: 20442775, PMCID: PMC2860987, DOI: 10.1371/journal.pone.0010367, ISSN: 1932-6203. 

Kucenas S, Wang WD, Knapik EW, Appel B. A selective glial barrier at motor axon exit points prevents oligodendrocyte migration from the spinal cord.J. Neurosci. 2009 Dec 12/2/2009; 29(48): 15187-94. PMID: 19955371, PMCID: PMC2837368, PII: 29/48/15187, DOI: 10.1523/JNEUROSCI.4193-09.2009, ISSN: 1529-2401. 

Granero-Moltó F, Sarmah S, O'Rear L, Spagnoli A, Abrahamson D, Saus J, Hudson BG, Knapik EWGoodpasture antigen-binding protein and its spliced variant, ceramide transfer protein, have different functions in the modulation of apoptosis during zebrafish developmentJ. Biol. Chem [print-electronic]. 2008 Jul 7/18/2008; 283(29): 20495-504. PMID: 18424781, PMCID: PMC2459293, PII: M801806200, DOI: 10.1074/jbc.M801806200, ISSN: 0021-9258. 

Bradley KM, Elmore JB, Breyer JP, Yaspan BL, Jessen JR, Knapik EW, Smith JR. A major zebrafish polymorphism resource for genetic mapping.Genome Biol. 2007; 8(4): R55. PMID: 17428331, PMCID: PMC1896001, PII: gb-2007-8-4-r55, DOI: 10.1186/gb-2007-8-4-r55, ISSN: 1474-760X. 

Montero-Balaguer M, Lang MR, Sachdev SW, Knappmeyer C, Stewart RA, De La Guardia A, Hatzopoulos AK, Knapik EWThe mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafishDev. Dyn. 2006 Dec; 235(12): 3199-212. PMID: 17013879, DOI: 10.1002/dvdy.20959, ISSN: 1058-8388. 

Lang MR, Lapierre LA, Frotscher M, Goldenring JR, Knapik EWSecretory COPII coat component Sec23a is essential for craniofacial chondrocyte maturationNat. Genet [print-electronic]. 2006 Oct; 38(10): 1198-203. PMID: 16980978, PII: ng1880, DOI: 10.1038/ng1880, ISSN: 1061-4036. 

Müller II, Knapik EW, Hatzopoulos AK. Expression of the protein related to Dan and Cerberus gene--prdc--During eye, pharyngeal arch, somite, and swim bladder development in zebrafishDev. Dyn. 2006 Oct; 235(10): 2881-8. PMID: 16921498, DOI: 10.1002/dvdy.20925, ISSN: 1058-8388. 

Barrallo-Gimeno A, Holzschuh J, Driever W, Knapik EWNeural crest survival and differentiation in zebrafish depends on mont blanc/tfap2a gene functionDevelopment [print-electronic]. 2004 Apr; 131(7): 1463-77. PMID: 14985255, PII: dev.01033, DOI: 10.1242/dev.01033, ISSN: 0950-1991. 

Holzschuh J, Barrallo-Gimeno A, Ettl AK, Durr K, Knapik EW, Driever W. Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and require tfap2a for expression of the neurotransmitter phenotypeDevelopment [print-electronic]. 2003 Dec; 130(23): 5741-54. PMID: 14534139, PII: dev.00816, DOI: 10.1242/dev.00816, ISSN: 0950-1991. 

Dethleffsen K, Heinrich G, Lauth M, Knapik EW, Meyer M. Insert-containing neurotrophins in teleost fish and their relationship to nerve growth factor.Mol. Cell. Neurosci. 2003 Oct; 24(2): 380-94. PMID: 14572460, PII: S1044743103001957, ISSN: 1044-7431. 

Sachdev SW, Dietz UH, Oshima Y, Lang MR, Knapik EW, Hiraki Y, Shukunami C. Sequence analysis of zebrafish chondromodulin-1 and expression profile in the notochord and chondrogenic regions during cartilage morphogenesisMech. Dev. 2001 Jul; 105(1-2): 157-62. PMID: 11429291, PII: S0925477301004178, ISSN: 0925-4773. 

Knapik EWENU mutagenesis in zebrafish--from genes to complex diseasesMamm. Genome. 2000 Jul; 11(7): 511-9. PMID: 10886014, PII: 10.1007/s003350010098, ISSN: 0938-8990. 

Chevrette M, Joly L, Tellis P, Knapik EW, Miles J, Fishman M, Ekker M. Characterization of a zebrafish/mouse somatic cell hybrid panelGenomics. 2000 Feb 2/15/2000; 64(1): 119-26. PMID: 10708527, PII: S0888-7543(99)96124-4, DOI: 10.1006/geno.1999.6124, ISSN: 0888-7543. 

Shimoda N, Knapik EW, Ziniti J, Sim C, Yamada E, Kaplan S, Jackson D, de Sauvage F, Jacob H, Fishman MC. Zebrafish genetic map with 2000 microsatellite markersGenomics. 1999 Jun 6/15/1999; 58(3): 219-32. PMID: 10373319, PII: S0888-7543(99)95824-X, DOI: 10.1006/geno.1999.5824, ISSN: 0888-7543. 

Förnzler D, Her H, Knapik EW, Clark M, Lehrach H, Postlethwait JH, Zon LI, Beier DR. Gene mapping in zebrafish using single-strand conformation polymorphism analysisGenomics. 1998 Jul 7/15/1998; 51(2): 216-22. PMID: 9722944, PII: S0888-7543(98)95386-1, DOI: 10.1006/geno.1998.5386, ISSN: 0888-7543. 

Knapik EW, Goodman A, Ekker M, Chevrette M, Delgado J, Neuhauss S, Shimoda N, Driever W, Fishman MC, Jacob HJ. A microsatellite genetic linkage map for zebrafish (Danio rerio)Nat. Genet. 1998 Apr; 18(4): 338-43. PMID: 9537415, DOI: 10.1038/ng0498-338, ISSN: 1061-4036. 

Postlethwait JH, Yan YL, Gates MA, Horne S, Amores A, Brownlie A, Donovan A, Egan ES, Force A, Gong Z, Goutel C, Fritz A, Kelsh R, Knapik E, Liao E, Paw B, Ransom D, Singer A, Thomson M, Abduljabbar TS, Yelick P, Beier D, Joly JS, Larhammar D, Rosa F, Westerfield M, Zon LI, Johnson SL, Talbot WS. Vertebrate genome evolution and the zebrafish gene mapNat. Genet. 1998 Apr; 18(4): 345-9. PMID: 9537416, DOI: 10.1038/ng0498-345, ISSN: 1061-4036. 

Knapik EW, Goodman A, Atkinson OS, Roberts CT, Shiozawa M, Sim CU, Weksler-Zangen S, Trolliet MR, Futrell C, Innes BA, Koike G, McLaughlin MG, Pierre L, Simon JS, Vilallonga E, Roy M, Chiang PW, Fishman MC, Driever W, Jacob HJ. A reference cross DNA panel for zebrafish (Danio rerio) anchored with simple sequence length polymorphismsDevelopment. 1996 Dec; 123: 451-60. PMID: 9007262, ISSN: 0950-1991. 

Neuman T, Keen A, Knapik E, Shain D, Ross M, Nornes HO, Zuber MX. ME1 and GE1: basic helix-loop-helix transcription factors expressed at high levels in the developing nervous system and in morphogenetically active regionsEur. J. Neurosci. 1993 Apr 4/1/1993; 5(4): 311-8. PMID: 8261111, ISSN: 0953-816X. 

Nornes HO, Dressler GR, Knapik EW, Deutsch U, Gruss P. Spatially and temporally restricted expression of Pax2 during murine neurogenesis.Development. 1990 Aug; 109(4): 797-809. PMID: 1977575, ISSN: 0950-1991.