Biomedical Research Education & Training
Faculty Member

Knapik, Ela W., M.D.
Associate Professor of Medicine
Associate Professor of Cell & Developmental Biology

Lab Url: N/A

Phone Number: (615) 322-7569

Email Address:

Knapik, Ela's picture
Academic history
M.D., Jagiellonian University, Cracow, Poland
Postdoctoral, Colorado State University, Fort Collins
Postdoctoral, Massachusetts General Hospital and Harvard Medical School, Boston, MA

Office Address   Mailing Address

Light Hall 1165

529 Light Hall 0275

Research Keywords
membrane trafficking, extracellular matrix, chondrocyte differentiation, cardiovascular functions, neural crest stem cells, cell and developmental biology, genetics, zebrafish

Research Specialty
Protein Secretion and Extracellular Matrix, Regulation of Cell Shape Changes in Morphogenesis

Research Description
Our laboratory is interested in understanding mechanisms and pathways that direct neural crest stem cells, and mediate their differentiation into various derivatives. We use a particularly effective approach to dissect the complex processes of cell specification and differentiation namely a combination of embryological and genetic methods and ask how gene networks control cell behavior and cell fate.
The first steps en route to answer these questions, beginning with individual genes, is to develop and characterize mutations that produce specific neural crest phenotypes, and establish gene hierarchy and cooperation among regulators that will control neural crest progenitors specification and differentiation. Neural crest stem cell genes and the genetic mutations are our primary tools to study gene expression, regulation, epistasis, cell fate, behavior, proliferation and survival.
Our main model system, zebrafish (Danio rerio) lends itself superbly to genetic and developmental analysis because of abundant availability of transparent embryos developing outside the mother that are accessible to manipulation and direct observation. This small fish can be used in a mutagenesis screen and its genome is amenable to efficient positional cloning of mutations and phenotypic analysis. In parallel, we use mammalian cells in culture and biochemical approaches to address our questions.

We have focused our investigation on two areas:
(i) the genetic network of transcription factors orchestrating transition of neural crest stem cell to derivatives like craniofacial cartilage,
(ii) and the role of cellular secretory pathway in chondrocyte maturation.

We use positional cloning approaches to help us identify point mutations responsible for craniofacial malformations. We have already found a set of factors critical for neural crest specification in the mutations mont blanc, mother superior and quadro. Now, we are dissecting the genetic interactions among these factors and further search for novel components of the genetic network.
Concurrently, we are investigating a phenotypic series of mutations affecting chondrocyte differentiation. Chondrocytes originate from neural crest stem cells and constitute most of the larval head skeleton. Surprisingly, we have discovered that the mutations in crusher and bulldog loci disrupt genes in the cellular secretory pathway, while the stumpf locus is critical in posttranslational protein modification and folding. These results open a new vista for research on the role of secretory pathway in a global context of embryonic morphogenesis and disease.

Our long-term goal is not only to understand the molecular mechanisms governing neural crest biology, but also to provide insight to the etiology and pathogenesis of human congenital and environmentally induced birth defects affecting neural crest derivatives (face, cranial ganglia, heart, skin, fetal alcohol syndrome) and crest derived tumors (melanomas, neuroblastoma, and teratocarcinomas).

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 Development. J Biol Chem, 289(17), 11971-85, 2014

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 pathway. Stem Cells, 2014

Unlu, G, Levic, DS, Melville, DB, Knapik, EW. Trafficking mechanisms of extracellular matrix macromolecules: insights from vertebrate development and human diseases. Int J Biochem Cell Biol, 47, 57-67, 2014

Vacaru, AM, Unlu, G, Spitzner, M, Mione, M, Knapik, EW, Sadler, KC. In vivo cell biology in zebrafish - providing insights into vertebrate development and disease. J Cell Sci, 127(Pt 3), 485-95, 2014

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 development. Cancer Res, 74(1), 38-43, 2014

Lee, RT, Knapik, EW, Thiery, JP, Carney, TJ. An exclusively mesodermal origin of fin mesenchyme demonstrates that zebrafish trunk neural crest does not generate ectomesenchyme. Development, 140(14), 2923-32, 2013

Muller, 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 rhythm. Dis Model Mech, 6(2), 332-41, 2013

Bradley, KM, Breyer, JP, Melville, DB, Broman, KW, Knapik, EW, Smith, JR. An SNP-Based Linkage Map for Zebrafish Reveals Sex Determination Loci. G3 (Bethesda), 1(1), 3-9, 2011 PMCID:3178105

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 maturation. PLoS Genet, 7(8), e1002246, 2011

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 epiboly. Dev Dyn, 240(6), 1613-25, 2011

Melville, DB, Knapik, EW. Traffic jams in fish bones: ER-to-Golgi protein transport during zebrafish development. Cell Adh Migr, 5(2), 114-8, 2011

Melville, DB, Montero-Balaguer, M, Levic, DS, Bradley, K, Smith, JR, Hatzopoulos, AK, Knapik, EW. The feelgood mutation in zebrafish dysregulates COPII-dependent secretion of select extracellular matrix proteins in skeletal morphogenesis. Dis Model Mech, 2011

Wang, WD, Melville, DB, Montero-Balaguer, M, Hatzopoulos, AK, Knapik, EW. Tfap2a and Foxd3 regulate early steps in the development of the neural crest progenitor population. Dev Biol, 360(1), 173-85, 2011

Sarmah, S, Barrallo-Gimeno, A, Melville, DB, Topczewski, J, Solnica-Krezel, L, Knapik, EW. Sec24D-dependent transport of extracellular matrix proteins is required for zebrafish skeletal morphogenesis. PLoS One, 5(4), e10367, 2010 PMCID:2860987

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, 29(48), 15187-94, 2009 PMCID:2837368

Granero-Molt??, F, Sarmah, S, O''Rear, L, Spagnoli, A, Abrahamson, D, Saus, J, Hudson, BG, Knapik, EW. Goodpasture antigen-binding protein and its spliced variant, ceramide transfer protein, have different functions in the modulation of apoptosis during zebrafish development. J Biol Chem, 2008 PMCID:2459293

Bradley, KM, Elmore, JB, Breyer, JP, Yaspan, BL, Jessen, JR, Knapik, EW, Smith, JR. A major zebrafish polymorphism resource for genetic mapping. Genome Biol, 8(4), R55, 2007 PMCID:1896001

Lang, MR, Lapierre, LA, Frotscher, M, Goldenring, JR, Knapik, EW. Secretory COPII coat component Sec23a is essential for craniofacial chondrocyte maturation. Nat Genet, 38(10), 1198-203, 2006

Montero-Balaguer, M, Lang, MR, Sachdev, SW, Knappmeyer, C, Stewart, RA, De La Guardia, A, Hatzopoulos, AK, Knapik, EW. The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish. Dev Dyn, 235(12), 3199-212, 2006

M??ller, 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 zebrafish. Dev Dyn, 235(10), 2881-8, 2006

Barrallo-Gimeno, A, Holzschuh, J, Driever, W, Knapik, EW. Neural crest survival and differentiation in zebrafish depends on mont blanc/tfap2a gene function. Development, 131(7), 1463-77, 2004

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, 24(2), 380-94, 2003

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 phenotype. Development, 130(23), 5741-54, 2003

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 morphogenesis. Mech Dev, 105(1-2), 157-62, 2001

Chevrette, M, Joly, L, Tellis, P, Knapik, EW, Miles, J, Fishman, M, Ekker, M. Characterization of a zebrafish/mouse somatic cell hybrid panel. Genomics, 64(1), 119-26, 2000

Knapik, EW. ENU mutagenesis in zebrafish--from genes to complex diseases. Mamm Genome, 11(7), 511-9, 2000

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 markers. Genomics, 58(3), 219-32, 1999

Fornzler, D, Her, H, Knapik, EW, Clark, M, Lehrach, H, Postlethwait, JH, Zon, LI, Beier, DR. Gene mapping in zebrafish using single-strand conformation polymorphism analysis. Genomics, 51(2), 216-22, 1998

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, 18(4), 338-43, 1998

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. Vertebrate genome evolution and the zebrafish gene map. Nat Genet, 18(4), 345-9, 1998

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 polymorphisms. Development, 123, 451-60, 1996

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 regions. Eur J Neurosci, 5(4), 311-8, 1993

Nornes, HO, Dressler, GR, Knapik, EW, Deutsch, U, Gruss, P. Spatially and temporally restricted expression of Pax2 during murine neurogenesis. Development, 109(4), 797-809, 1990

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