Faculty Profile

Dr. Ales Cvekl, Ph.D.

Ales Cvekl, Ph.D.

Professor, Department of Ophthalmology & Visual Sciences

Professor, Department of Genetics

The Max Berger Chair in Ophthalmology

Vice Chair for Research, Department of Ophthalmology & Visual Sciences

Areas of Research: Chromatin structure and remodeling; 3D organization of the nucleus; DNA-binding transcription factors; Pax6; BMP and FGF signaling; eye development; lens induction; eye evolution; differentiation of human ES cells

Professional Interests

We are studying mouse eye as a model system to elucidate molecular mechanisms of embryonic development, transcriptional regulation, signal transduction, cellular differentiation, nuclear organization, and aging. We are particularly interested in the genes that control embryonic lens induction and differentiation. We seek to identify and characterize the complet set of genetic and epigenetic instructions that control mammalian lens development. We are studying DNA-binding transcription factors (e.g. Pax6, c-Maf, Hsf4, Gata3, and Prox1), BMP and FGF signaling, and chromatin remodeling (e.g. CBP, p300, Brg1, Snf2h, and Ncoa6) and their role in lens induction and differentiation. Aberrant function of these genes causes not only lens abnormalities in mouse embryos, but also other human congenital (existing at birth) eye diseases affecting the cornea, lens, iris, and retina. Mutations in PAX6 cause aniridia, characterized by the absence of iris, as well as early onset cataract, foveal hypoplasia and glaucoma. Mutations in p300, HSF4, and MAF cause distinct types of lens opacities resulting in cataracts.

Transcriptional regulatory mechanisms of Pax6, c-Maf, Prox1, and Gata3 are investigated through the identification and functional characterization of lens-specific enhancers of these genes. Gene regulatory networks (GRNs) of crystallin gene expression are comprised of multiple feed-forward loops and represent excellent models to study principles of tissue morphogenesis.

We are also studying the biology of lens fiber cell nuclei as transcriptional factories for crystallin gene synthesis. The crystallin encode highly abundant lens structural proteins that accumulate in elongating lens fiber cells and are required for lens transparency and its refraction. We are interested in nascent transcription/transcriptional bursting, mRNA splicing and transport, crystallin mRNA stability control, and their translational regulation. Multiple RNA-binding proteins were recently identified in different lens compartments.

The differentiating lens fiber cells degrade all intracellular organelles to reduce linght scattering. Or recent studies revealed that Bnip3l is required for degradation of mitochondria, endoplasmic reticulum nad Golgi apparatus. Mutations in ATP-dependent chromatin remodeling enzymes Brg1/Smarca4 and Snf2h/Smarca5 and transcription factor Gata3 in lens prevent nuclear degradation. The molecular processes that govern nuclear degradation in mature lens fibers remain poorly understood. Novel insights include use of single molecule RNA FISH and bi-directional transfer of proteins between the nucleus and cytoplasm.

Recently, we developed a new procedure to differentiate lens progenitor cells and differentiated lentoid bodies from human embryonic stem (ES) cells. This system is currently being used to study the earliest stages of human lens formation and to generate lens organoids. In addition, we are interested to develop high-throughput drug screening platforms using differentiated ES cells to manipulate gene expression in lentoid bodies and retinal pigmented epithelium to study mechnaisms in cataractogenesis and age-related macular degeneration. 

Our research has implications for the identification, prevention, and treatment of inherited ocular diseases, and for a better understanding of the genetic components of age-related ocular diseases, such as cataract and age-related macular degeneration. In addition, some genes essential for eye development, such as Pax6, play important roles in the formation of other organs, including brain and pancreas. Several novel roles of PAX6 are used to explain differences between primate and rodent brains. Our studies also have impact on understanding of eye evolution and formation of new genes through gene duplication.

Methods: ChIP-seq, 3C, 4C, ATAC-Seq, RNA-seq, single cell RNA-seq, RNA-FISH, engineering of ES cells (CRISPR-Cas9), conditional gene targeting in mouse, in vivo reporter gene expression, computational biology and genomics, cell and tissue engineering, use of 3D scaffolds

Selected Publications

A.        Original Communications in Reviewed Journals:

 

1.         Kodicek, M., A. Cvekl and Z. Vodrazka. 1981. Fluorescence study of the molecular conformation of human haemopexin. Int. J. Biol. Macromol. 3:397-398.

2.         Cvekl, A., K. Horska and K. Sebesta. 1988. On the mechanism of rifampicin inhibition of DNA dependent RNA polymerase from Escherichia coli. Collect. Czechoslovak Chem. Commun. 53:181-185.

3.         Cvekl, A., K. Horska, K. Sebesta, I. Rosenberg and A. Holy. 1988. The effect of divalent cations and core polymerase in abortive initiation by Escherichia coli DNA dependent RNA polymerase using phosphonate dinucleotide primers. Biocatalysis 1:275-281.

4.         Cvekl, A., K. Horska, K. Sebesta, I. Rosenberg and A. Holy. 1989. Phosphonate analogues of dinucleotides as substrates for DNA dependent RNA polymerase in primed abortive initiation reaction. Int. J. Biol. Macromol. 11:33-38.

5.         Cvekl, A., K. Horska, K. Sebesta, I. Rosenberg and A. Holy. 1989. Trinucleotide AUA and UAU formation catalyzed by wheat germ RNA polymerase II on poly(dA-dT) template. Collect. Czechoslovak. Chem. Commun. 54:811-818.

6.         Schnapp, A., J. Clos, W. Haedelt, R. Schreck, A. Cvekl and I. Grummt. 1990. TIF-IB, a factor that confers promoter specificity to mouse RNA polymerase I. Nucleic Acids Res. 18:1385-1393.

7.         Horska, K., A. Cvekl, I. Rosenberg, A. Holy and K. Sebesta. 1990. DNA-dependent RNA polymerase mediated formation of methylphosphonyl internucleotide linkage. Coll. Czechoslovak Chem. Commun. 55:2769-2780.

8.         Cvekl, A. and K. Horska. 1990.Cibacron Blue inhibition of prokaryotic and eukaryotic DNA-dependent RNA polymerases. Collect. Czechoslovak Chem. Commun. 55:2769-2780.

9.         Cvekl, A., K. Horska, C. Vlcek and V. Paces. 1991. Protein binding AT-rich motifs flank the duck bA-globin enhancer. Gene (Amst.) 103:253-257.

10.       Cvekl, A. and V. Paces. 1992. Interactions between proteins bound to the duck bA-globin promoter and enhancer detected by the DNase I footprinting. Gene (Amst.) 110: 225-228.

11.       Kantorow, M., A. Cvekl, C.M. Sax and J. Piatigorsky.1993.Protein-DNA interactions of the mouse aA-crystallin control regions. Differences between expressing and non-expressing cells. J. Mol. Biol. 230:425-435.

12.       Klement, J.F., A. Cvekl* and J. Piatigorsky. 1993. Functional elements DE2A, DE2B and DE1A and the TATA box are required for activity of the chicken aA-crystallin gene in transfected lens epithelial cells. J. Biol. Chem. 268:6777-6784. (* Equal contribution of the first and second author).

13.       Tomarev, S.I., M. Duncan, H.J. Roth, A. Cvekl and J. Piatigorsky. 1994. Convergent evolution of crystallin gene regulation in squid and chicken: The AP-1/ARE connection. J. Mol. Evol. 39:134-143.

14.       Sax, C.M., A. Cvekl, M. Kantorow, B. Sommer, A.B. Chepelinsky and J. Piatigorsky. 1994. Identification of negative-acting and protein-binding elements in the mouse aA-crystallin -1556/-1165 region. Gene (Amst.) 144:163-169.

15.       Cvekl, A., C.M. Sax, E. H. Bresnick and J. Piatigorsky. 1994. Complex array of positive and negative elements regulates the chicken aA-crystallin gene: Involvement of Pax-6, USF, CREB and/or CREM and AP-1 proteins. Mol. Cell. Biol. 14:7363-7376.

16.       Cvekl, A., F. Kashanchi, C.M. Sax, J.N. Brady and J. Piatigorsky. 1995. Transcriptional regulation of the mouse aA-crystallin gene: Activation dependent on a cyclic AMP responsive element (DE1/CRE) and a Pax-6 binding site. Mol. Cell. Biol.15:653-660.

17.       Matlova, R., K. Horska, V. Benes, A. Cvekl and J. Sponar. 1995. Protein induced bending or flexing at the 5’-end of the duck bA-globin gene promoter. Gene (Amst.) 156:277-281.

18.       Cvekl, A., J.B. McDermott and J. Piatigorsky. 1995. cDNA encoding a chicken protein with homology to hnRNP type A/B. Biophys. Biochim. Acta. 1261:290-292.

19.       Sax, C.M., A. Cvekl, M. Kantorow, R. Gopal-Srivastava, J.G. Ilagan, N.P. Ambulos, Jr. and J. Piatigorsky. 1995. Lens-specific activity of the mouse aA-crystallin promoter in the absence of a TATA box: Functional and protein binding analysis of the mouse aA-crystallin PE1 region. Nucleic Acids Res. 23:442-451.

20.       Cvekl, A., C.M. Sax, X. Li, J.B. McDermott and J. Piatigorsky. 1995. Pax-6 and lens-specific transcription of the chicken d1-crystallin gene. Proc. Natl. Acad. Sci. USA 90:4681-4685.

21.       Richardson, J., A. Cvekl and G. Wistow. 1995. Pax-6 is essential for lens-specific expression of z-crystallin. Proc. Natl. Acad. Sci. USA 90:4676-4680.

22.       Duvall, J.F., F. Kashanchi, A. Cvekl, M.F. Radonovich and J.N. Brady. 1995. Transactivation of the HTLV-I Tax1-responsive 21 bp repeats requires holo-TFIID and TFIIA. J. Virol. 69:5077-5086.

23.       Chambers, C., A. Cvekl, C.M. Sax and P. Russell. 1995. Sequence, initial functional analysis and protein-DNA binding sites of the mouse bB2-crystallin-encoding gene. Gene (Amst.) 166: 287-292.

24.       McDermott, J.B., A. Cvekl and J. Piatigorsky. 1996. Lens-specific expression of the chicken bA3/A1-crystallin promoter fragment in transgenic mice. Biochem. Biophys. Res. Commun. 221:559-564.

25.       Gopal-Srivastava, R., A. Cvekl and J. Piatigorsky. 1996. Regulation of the mouse aB-crystallin/small heat shock protein gene in lens: involvement of Pax-6. J. Biol. Chem. 271:23029-23036.

26.       Sax, C.M., A. Cvekl and J. Piatigorsky. 1997. Transcriptional regulation of the mouse aA-crystallin gene: binding of USF to -7/+5 region. Gene (Amst.) 185:209-216.

27.       McDermott, J.B., A. Cvekl and J. Piatigorsky.1997.A complex enhancer of the chicken bA3/A1-crystallin gene depends on an AP-1/CRE element for activity. Invest. Ophthalmol. Vis. Sci. 38:951-959.

28.       Li, X., A. Cvekl, S. Bassnett, and J. Piatigorsky. 1997. Lens-preferred activity of chicken d1-and d2-crystallin enhancers in transgenic mice and evidence for retinoic acid-responsive regulation of the d1-crystallin gene. Dev. Genet. 20:258-266. 

29.       Gopal-Srivastava, A. Cvekl and J. Piatigorsky. 1998. Involvement of retinoic acid/retinoid receptors in the regulation of murine aB-crystallin/small heat shock protein gene expression in the lens. J. Biol. Chem. 273:17954-17961.

30.       Duncan, M.K., J.I. Haynes, A. Cvekl, and J. Piatigorsky. 1998. Dual roles for Pax-6: a transcriptional repressor of lens fiber-cell specific b-crystallin genes. Mol. Cell. Biol.18:5579-5586.

31.       Cvekl, A., F. Kashanchi, J.N. Brady and J. Piatigorsky. 1999. Pax-6 interactions with TATA-box binding protein and retinoblastoma protein.  Invest. Ophthalmol. Vis. Sci. 40:1343-1350.

32.       Ilagan, J.G., A. Cvekl, M. Kantorow, J. Piatigorsky, and C.M. Sax.1999. Regulation of aA-crystallin gene expression: lens-specificity achieved through the differential placement of similar transcriptional control elements in mouse and chicken. J. Biol. Chem. 274:19973-19978.

33.           Kozmik, Z., J. Paces, J. Kralova, P. Pfeffer, V. Paces, A. Kalousova & A. Cvekl.1999.Molecular cloning and expression of the human and mouse homologues of the Drosophila dachshund gene. Dev. Genes Evol. 209:537-545

34.           Kozmik, Z., and A. Cvekl. 1999.Localization of the human homologue of the Drosophila dachshund (DACH) gene to chromosome 13q21. Genomics 59:110-111.

35.           Duncan, M.K., A. Cvekl, X. Li, and J. Piatigorsky. 2000. Truncated forms of Pax-6 can disrupt lens morphology in transgenic mice. Invest. Ophthalmol. Vis. Sci. 41:464-473.

36.           Duncan, M.K., Z. Kozmik, K. Cveklova, J. Piatigorsky, and A. Cvekl.  2000. Overexpression of PAX6(5a) in lens fiber cells results in upregulation of a5b1 integrin expression.  J. Cell Sci. 113: 3173-3185.

37.           Kirstein, L., A. Cvekl, B.K. Chauhan, and E.R. Tamm. 2000. Regulation of human Myocillin/TIGR gene transcription in trabecular meshwork cells and astrocytes: role of Upstream Stimulator Factor. Genes Cells 5: 661-676.

38.           Zhang, W., K. Cveklova, B. Oppermann, M. Kantorow, and A. Cvekl. 2001. Quantitation of PAX6 and PAX6(5a) transcript levels in adult human lens, cornea, and monkey retina. Mol. Vis. 7:1-6.

39.           Chauhan, B.K., N.A. Reed, W. Zhang, M.K. Duncan, M. Kilimann, and A. Cvekl. 2002. Identification of genes downstream of Pax6 in the mouse lens using cDNA microarrays. J. Biol. Chem. 277: 11539-11548.

40.           Chauhan, B.K., W. Zhang, K. Cveklova, M. Kantorow, and A. Cvekl. 2002. Identification of differentially expressed genes in mouse Pax6 heterozygous lenses. Invest. Ophthalmol. Vis. Sci. 43: 1884-1890.

41.           Sheets, N., B.K. Chauhan, E. Wawrousek, F.J. Hejtmancik, A. Cvekl, and M. Kantorow. 2002. Cataract- and lens-specific up-regulation of ARK receptor tyrosine kinase in Emory mouse cataract. Invest. Ophthalmol. Vis. Sci. 43: 1870-1875.

42.           Kim, S.-S., R. Zhang, S.E. Braunstein, A. Joachimiak, A. Cvekl, and R.S. Hegde. 2002. Structure of the retinal determination protein Dachshund reveals a DNA binding motif. Structure 10: 787-795.

43.           Baulmann, D.C., A. Ohlmann, C. Flugel-Koch, S. Goswami, A. Cvekl, and E.R. Tamm. 2002. Pax6 heterozygous eyes show defects in chamber differentiation that are associated with a wide spectrum of other anterior eye segment abnormalities. Mech. Develop. 118: 3-17.

44.           Chauhan, B.K., N.A. Reed, Y. Yang, L. Cermak, L. Reneker, M.K. Duncan, M. and A. Cvekl.2002. A comparative cDNA microarray analysis reveals a spectrum of genes regulated by Pax6 in mouse lens. Genes Cells 7: 1267-1283.

45.           Goswami, S., N. L. Sheetz, J. Zavadil, B.K. Chauhan, E.P. Bottinger, V.N. Reddy, M. Kantorow, and A. Cvekl. 2003. The spectrum and range of oxidative stress responses of human lens epithelial cells to H2O2 insult. Invest. Ophthalmol. Vis. Sci. 44: 2084-2093.

46.           Wu, K., Y. Yang, C. Wang, M.A. Davoli, M. D'Amico, A. Li, K. Cveklova, Z. Kozmik, M.P. Lisanti, R.G. Russel, A. Cvekl, and R.G. Pestell. 2003.DACH1 inhibits TGF-b signaling through binding Smad4. J. Biol. Chem. 278:51673-51684.

47.           Chauhan, B.K., Y. Yang, K. Cveklova, and A. Cvekl. 2004. Functional properties of natural human PAX6 and PAX6(5a) mutants. Invest. Ophthalmol. Vis. Sci. 45: 385-392.

48.           Chauhan, B.K., Y. Yang, K. Cveklova, and A. Cvekl. 2004. Functional interactions between alternatively spliced forms of Pax6 in crystallin gene regulation and in haploinsufficiency. Nucleic Acids Res. 32:1696-1709.

49.           Zaniolo, K., S. Leclerc, A. Cvekl, R. Bazin, K. Larouche, and S.L. Guerin. 2004.Expression of the a4 integrin subunit gene promoter is modulated by the transcription factor Pax-6 in corneal epithelial cells. Invest. Ophthalmol. Vis. Sci. 45: 1692-1704.

50.           Cvekl, A., B.K. Chauhan, Y. Yang, and K. Cveklova. 2004. Regulation of gene expression by Pax6 in ocular cells: A case of tissue-preferred expression of crystallins in lens. Int. J. Dev. Biol. 48: 829-844.

51.           Yang, Y., B.K. Chauhan, K. Cveklova, and A. Cvekl. 2004. Transcriptional regulation of mouse aB- and gF-crystallin genes in lens: Dual promoter-specific functional interactions between Pax6 and large Maf transcription factors. J. Mol. Biol. 344: 351-368.

52.           Cvekl, A., Jr., J. Zavadil, B.K. Birshtein, M. Grotzer and A. Cvekl. 2004. Analysis of transcripts from 17p13.3 in medulloblastoma suggests ROX/MNT as a potential tumour suppressor gene. Eur. J. Cancer 40: 2525-2532.

53.           Ohlmann A., M. Scholz, A. Goldwich, B.K. Chauhan, K. Hudl, A.V. Ohlmann, E. Zrenner, W. Berger, A. Cvekl, M.W. Seelinger and E.R. Tamm. 2005. Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice. J. Neurosci. 25: 1701-1710.

54.           Yang, Y. and A. Cvekl. 2005. Tissue-specific regulation of the mouse aA-crystallin gene in lens via recruitment of Pax6 and c-Maf to its promoter. J. Mol. Biol. 351: 453-469.

55.           Castellini, M., L.V. Wolf, B.K. Chauhan, M.W. Kilimann, A. Cvekl and M.K. Duncan. 2005. Palm is expressed in both developing and adult mouse lens and retina. BMC Ophthalmology 5: 14.

56.           Yang Y., T. Stopka, N. Golestaneh, Y. Wang, K. Wu, A. Li, M.K. Duncan, K. Wu, B.K. Chauhan, C.Y. Gao, K. Cveklova, R.G. Pestell, A.B. Chepelinsky, A.I. Skoultchi and A. Cvekl. 2006. Regulation of aA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin. EMBO J. 25: 2107-2118.

57.           Wu, K., A. Li, C. Wang, M. Rao, Y. Lu, R.I. Glazer, S. Kristpati, D. Di Vizio, K. Cveklova, Y. Yang, M.P. Lisanti, A. Cvekl, and R.G. Pestell. 2006. DACH1 is a cell fate determination factor that inhibits cyclin D1 and breast tumor growth. Mol. Cell. Biol. 26: 7116-7129.

58.           Pirity, M.K., W.-L. Wang, L.V. Wolf, E.R. Tamm, N. Schreiber-Agus and A. Cvekl. 2007. Rybp, a Polycomb-complex associated protein, is required for mouse eye development. BMC Dev. Biol. 7: 39.

59.           Wu, K., M. Liu, A. Li, H. Donninger, M. Rao, X. Jiao, M.P. Lisanti, A. Cvekl, M. Birrer and R.G. Pestell. 2007. The cell fate determination factor DACH1 inhibits c-Jun induced contact-independent growth. Mol. Biol. Cell 18: 755-767.

60.           Yang, Y., L.W. Wolf and A. Cvekl. 2007. Distinct embryonic expression and localization of CBP and p300 histone acetyltransferases at the mouse aA-crystallin locus. J. Mol. Biol. 370: 917-926.

61.           Pontoriero, G.F., P. Deschamps, R. Ashery-Padan, R. Wong, Y. Yang, J. Zavadil, A. Cvekl, S. Sullivan, T. Williams and J.A. West-Mays. 2008. Cell autonomous roles for AP-2a in lens vesicle separation and maintenance of the lens epithelial cell phenotype. Dev. Dynam. 237: 602-617.

62.           Chen, Y., Y. Doughman, S. Gu, A. Jarrell, S. Aota, A. Cvekl, M. Watanabe, S.L. Dunwoodie, R.S. Johnson, V, van Heyningen, D.A. Kleinjan, D.C. Beebe and Y.-C. Yang. 2008. Cited2 is required for the proper formation of hyaloid vasculature and for lens morphogenesis. Development 135: 2939-2948.

63.           Wolf, L.V., Y. Yang, E.F. Wawrousek and A. Cvekl. 2008. Transcriptional regulation of mouse aA-crystallin gene studied by a 148 kb BAC and its derivates. BMC Dev. Biol. 8: 88.

64.           Oron-Karni, V., C. Farhi, M. Elgart, T. Marquardt, L. Ramizova, O. Yaron, Q. Xie, A. Cvekl, and R. Ashery-Padan. 2008. Dual requirement for Pax6 in retinal progenitor cells. Development 135: 4037-4047.

65.           Wolf, L.V., Yang, Y., J. Wang, Q. Xie, B. Braunger, E.R. Tamm, J. Zavadil, and A. Cvekl. 2009. Genome-wide identification and analysis of genes regulated by Pax6 in mouse lens. PLoS ONE 4: e4159.

66.           Yang, C., Y. Yang, L. Brennan, E.E. Bouhassira, M. Kantorow and A. Cvekl. 2010. Efficient generation of lens progenitor cells and lentoid bodies from human embryonic stem cells in chemically defined conditions. FASEB J. 24: 3274-3283.

67.           Frenz, D.A., W. Liu, A. Cvekl, Q. Xie, L. Wassef, L. Quadro, K. Niederreither, M. Maconochie and A. Shanske. 2010. Retinoid signaling in inner ear development: a “Goldilocks” phenomenon. Am. J. Med. Genet Part A 152A: 2947-2961.

68.           Wang, W-L, Q. Li, J. Xu, and A. Cvekl. 2010. Lens fiber cell differentiation and denucleation are disrupted through expression of the N-terminal nuclear receptor box Ncoa6 and result in p53-dependent and p53-independent apoptosis. Mol. Biol. Cell 21: 2453-468. (Cover article).

69.           Zhou, J., Y. Liu, W. Zhang, V.M. Popov, M. Wang, N. Patabiraman, C. Sune, A. Cvekl, K. Wu, J. Jiang, C. Wang, and R.G. Pestell. 2010. Transcription elongation regulator 1 is a co-integrator of the cell fate determination factor Dachshund homolog 1. J. Biol. Chem. 285: 40342-4050. 

70.           Caceres, A., F. Shang, E. Wawrousek, Q. Liu, O. Avidan, A. Cvekl, Y. Yang, A. Haririna, A. Storaska, D. Fushman, J. Kuszak, E. Dudek, D. Smith and A. Taylor. 2010. Intact K6 on ubiquitin is required to regulate proliferation and differentiation including hijacking mitosis to dump a nucleus. PLoS ONE 5: e13331.

71.           He, S., M. K. Pirity, W.-L. Wang, L. Wolf, B. K. Chauhan, K. Cveklova, E.R. Tamm, R. Ashery-Padan, D. Metzger, P. Chambon, J. Zavadil and A. Cvekl. 2010. Chromatin remodeling enzyme Brg1 is required for mouse lens fiber cell terminal differentiation and their denucleation. Epigenetics & Chromatin 3: 21.

72.           Ninkovic, J., L. Pinto, S. Petricca, J. Sun, M.A. Rieger, T. Schroeder, A. Cvekl, J. Favor and M. Gotz. 2010. The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin aA. Neuron 68: 682-694.

73.           Xie, Q. and A. Cvekl. 2011. The orchestration of mammalian tissue morphogenesis through a series of coherent feed forward loops. J. Biol. Chem 286: 43259-43271. (Cover article).

74.           Brennan, L.A., W. Lee Kantorow, D. Chauss, R. McGreal, S. He, L. Mattucci, J. Wei, S. A. Riazuddin, A. Cvekl, J. F. Hejtmancik and M. Kantorow. 2012. Spatial expression patterns of autophagy genes in the eye lens and induction of autophagy in lens cells. Mol. Vis. 18: 1773-1786.

75.           Qie, X., Y. Yang, J. Huang, J. Ninkovic, T. Walcher, L. Wolf, A. Vitenzon, D. Zheng, M. Gotz, D.C. Beebe, J. Zavadil and A. Cvekl. 2013. Pax6 interactions with chromatin and identification of its novel direct target genes in lens and forebrain. PLoS ONE 8: e54507.

76.           Walcher, T, Q. Xie, J. Sun, M. Imler, J. Beckers T. Ozturk, D. Niessing, A. Stoykova, A. Cvekl, J. Ninkovic and M. Gotz. 2013. Functional dissection of the paired domain of Pax6 reveals molecular mechanisms of coordinating neurogenesis and proliferation. Development 140: 1123-1136.

77.           Braunger, B.M., A. Ohlmann, M. Koch, N. Tanimoto, C. Volz, Y. Yang, M.R. Rosl, A. Cvekl, H. Jagle, M.W. Seelinger and E.R. Tamm. 2013. Constitutive overexpression of Norrin activates Wnt/b-catenin and endothelin-2 signaling to protect photoreceptors from light damage. Neurobiol. Disease 50: 1-12.

78.           Shaham, O., K. Gueta, E. Mor, P. Oren-Giladi, N. Davis, Q. Xie, A. Cvekl, N. Shomron, D. Gringberg, M. Pasmanik-Chor, R.E. Bell, C. Levy, R. Avellino, S. Banfi, I. Conte and R. Ashery-Padan. 2013. Pax6 regulates gene expression in the vertebrate lens through microRNA-204. PLoS Genetics 9: e1003357.

79.           Wolf, L., W. Harrison, H. Jie, Q. Xie, N. Xiao, J. Sun, L. Kong, S. A. Lachke, M.R. Kuracha, V. Govindarajan, P.K. Brindle, R. Ashery-Padan, D. C. Beebe, P.A. Overbeek, and A. Cvekl. 2013. Histone modifications and cell fate determination: Lens induction requires the lysine acetyltransferases CBP and p300. 2013. Nucleic Acids Res. 41: 10199-10214.

80.           Wolf, L., C.S. Gao, K. Gueta, Q. Xie, T. Chevalier, J. Sun, N. Podduturi, P.S. Zelenka, R. Ashery-Padan, J. Zavadil, and A. Cvekl. 2013. Identification and characterization of FGF2-dependent mRNA/microRNA networks during lens fiber cell differentiation. 2013. G3 (Bethesda) 3: 2239-2255.

81.           Xie, Q., D. Ung, K. Khafizov, A. Fiser, and A. Cvekl. 2014. Gene regulation by PAX6: Structural- functional correlations of missense mutants and transcriptional control of Trpm3/miR-204. Mol. Vis. 20: 270-282.

82.           Castellanos, R., Q. Xie, D. Zheng, A. Cvekl, and B.E. Morrow. 2014. Mammalian Tbx1 preferentially binds and regulates downstream targets via a tandem T-site repeat. PLoS ONE 9: e95151.

83.           Sun, J., S. Rockowitz, Q. Xie, R. Ashery-Padan, D. Zheng and A. Cvekl. 2015. Identification of in vivo DNA-binding mechanisms of Pax6 and reconstruction of Pax6-dependent gene regulatory network during forebrain and lens development. Nucleic Acids Res. 43: 6827-6846.

84.           Sun, J., S. Rockowitz, D. Chauss, P. Wang, M. Kantorow, D. Zheng and A. Cvekl. 2015. Chromatin features and comparative expression of lens genes: crystallins, RNA polymerase II, transcription factors and autophagy-mediators. Mol. Vis. 21: 955-973.

85.          Lyu, L., S. Jiang, M.-L. Chang, Y. Gu, M.K. Duncan, W.-L. Wang, S. Limi, A. Cvekl, L.W. Reneker, L. Du, F. Shang, E.A. Whitcomb, and A.Taylor. 2016. p27 stabilization due to an unfolded proteins response interferes with lens fiber cell denucleation and causes cataract. FASEB J. 30:1087-1095.

86.          Xie, Q., R. McGreal, R. Harris, C.Y. Gao, W. Liu, L. Reneker, L.S. Musil and A. Cvekl. 2016. Regulation of c-Maf and aA-crystallin by FGF signaling in lens. J. Biol. Chem. 291:3947-3958.          

87. Lowe, A., R. Harris, P. Bhansali, A. Cvekl, and W. Liu. 2016. Intercellular adhesion-dependent cell survival and ROCK-regulated actomyosin-driven forces mediate self-formation of a retinal organoid. Stem Cell Reports 6:743-756.

88.          He, S., S. Limi, R.S. McGreal, Q. Xie, L. Brennan, W. Lee Kantorow, J. Kokavec, R. Majumdar, H. Hou, Jr., W. Edelmann, R. Ashery-Padan, J. Zavadil, M. Kantorow, A. Skoultchi, T. Stopka and A. Cvekl. 2016. Chromatin remodeling enzyme Snf2h regulates lens fiber cell differentiation and denucleation. Development 143:1937-1947.

89.          Menuchin-Lasowski, Y., Oren-Giladi, P., Xie, Q., Ezra-Elia, R., Ofri, R., Peled-Hajaj, S., Farhy, C., Higashi, Y., Van de Putte, T., Kondoh, H., Huylebroeck, D., Cvekl, A., and Ashery-Padan, R. 2016. Sip1 regulates the generation of the inner nuclear layer retinal cell lineages in mammals. Development 143: 2829-2841.

90.          Sun, J., Y. Zhao, R. McGreal, Y. Cohen-Tayar, S.Rockowitz, C. Wilczek, R. Ashery-Padan, D. Zheng, D. Schechter, and A. Cvekl. 2016. Pax6 associates with H3K4-specific histone methyltransferases Mll1, Mll2, and Set1a and regulates H3K4 methylation at promoters and enhancers. Epigenetics Chromatin 9: 37.

91.          Esteban-Martinez, L., E. Sierra-Filardi, R.S. McGreal, M. Salazar-Roa, G. Marino, E. Seco, S. Durand, D. Enot, O. Grana, M. Malumbres, A. Cvekl, A.M. Cuervo, G. Kroemer, and P. Boya. 2017. Programmed mitophagy is essential for the glycolytic switch during cell differentiation. EMBO J. 36: 1688-1706.

92.          Liu, W., and A. Cvekl. 2017. Six3 in a small population of progenitors at E8.5 is required for neuroretinal specification via regulating cell signaling and survival in mice. Dev. Biol. 428: 164-175.

93.          Cavalheiro, G.R., G.E. Matos-Rodriguez, Y. Zhao, A.L. Gomes, D. Anand, D. Predes, J.G. de Abreu, D. Zheng, S.A. Lachke, A. Cvekl, and R.A.P. Martins. 2017. N-myc regulates growth and fiber cell differentiation in lens development. Dev. Biol. 429: 105-117.

94.          Cvekl, A., Y. Zhao, R.S. McGreal, Q. Xie, X. Gu, and D. Zheng. 2017. Evolutionary origin of Pax6 control of crystallin genes. Genome Biol. Evol. 9: 2057-2074.

95.          Brennan, L., R. McGreal, C.M. Logan, A. Cvekl, A.S. Menko, and M. Kantorow. 2018. Bnip3l/Nix is required for elimination of mitochondria, endoplasmic reticulum and Golgi apparatus to form the lens organelle-free zone. Exp. Eye Res. 174: 173-184.

96.          Zhao, Y., D. Zheng, and A. Cvekl. 2018. A comprehensive spatial-temporal transcriptomic analysis of differentiating nascent mouse lens epithelial and fiber cells. Exp. Eye Res.175: 56-72.

97.          Limi, S., A. Senecal, R. Coleman, M. Lopez-Jones, P. Guo, C. Polumbo, R.H. Singer, A.I. Skoultchi, and A. Cvekl. 2018. Transcriptional dynamics during lens fiber cell differentiation and novel insights into the denucleation process. J. Biol. Chem. 293: in press.

 

 B.             Books, Chapters in Books, and Review Articles

  1. Cvekl, A., K. Horska and K. Sebesta. 1986. Transcription in Escherichia coli. Chemicke listy 80:954-976 (in Czech).
  2. Cvekl, A., K. Horska and K. Sebesta.1989.Initiation of transcription in prokaryotes. Chemicke listy 83:29-56 (in Czech).
  3. Cvekl, A. 1990. Transcription in eukaryotic cell. In New Trends in Molecular Genetics II (V. Benes, ed.). Institute of Molecular Genetics, Prague, pp. 9-18 (in Czech).
  4. Cvekl, A. 1991. Transcription in eukaryotes. Vesmir 70:73-75 (in Czech).
  5. Cvekl, A.1991.Protein TFIID: A basic transcription factor in eukaryotes. Chemicke listym85:398-406 (in Czech).
  1. Cvekl, A. and Piatigorsky, J. 1996. Lens development and crystallin gene expression: Many roles for Pax-6. BioEssays 18:621-630. (Cover article).
  2. Duncan, M.K.*, Cvekl, A.*, Kantorow, M., and Piatigorsky, J. 2004. Lens crystallins. In Ocular lens development (M.L. Robinson and F.J. Lovicu, Eds.), Cambridge University Press, pp. 119 - 150. (* Equal contributions).
  3. Cvekl, A. and E.R. Tamm. 2004. Anterior eye development and ocular mesenchyme: new insights from studies of Pax6 and other DNA-binding transcription factors. BioEssays 26:374-386. (Cover article).
  4. Yang, Y. and A. Cvekl. 2007. Large Maf transcription factors: cousins of AP-1 proteins and important regulators of cellular differentiation. Einstein J. Biol. Med. 22: 2-11.
  5. Cvekl, A. and M.K. Duncan. 2007. Genetic and epigenetic mechanisms during lens development. Prog. Retinal Eye Res. 26:555-597.
  6. Cvekl, A. and W. Wang. 2009. Retinoic acid signaling in mammalian eye development. Exp. Eye Res. 89:280-291.
  7. Cvekl, A. and K. Mitton. 2010. Epigenetic regulatory mechanisms in mammalian eye development and disease. Heredity 105: 135-151.
  8. He, S and A. Cvekl. 2012. Focus on molecules: Brg1: A range of functions during eye development. Exp. Eye Res. 103: 117-118.
  9. Cvekl, A., Y. Yang, Y. Jing and Q. Xie. 2012. Lens differentiation from embryonic stem (ES) and induced pluripotent (iPS) cells. In Stem Cells In Ophthalmology (S. Tsang, Ed.) Springer Science+Business Media LLC, New York, pp.57-74.
  10. Cvekl, A., I. Friedman and E.V. Semina. 2014. Lens specific transcription factors: implications for congenital cataract. In Lens epithelium and posterior subcapsular opacification (S. Saika, L. Werner and F. Lovicu, Eds.) Springer Science+Business Media LLC, New York, pp.105-165.
  11. Cvekl, A. and R. Ashery-Padan. 2014. The cellular and molecular mechanisms of vertebrate lens development. Development 141: 4432-4447.
  12. Cvekl, A., R.S. McGreal, and W. Liu. 2015. Lens development and crystallin gene expression. Prog. Mol. Biol. Transl. Med. 134: pp-pp.
  13. Hejtmancik, J.F., A. Riazuddin, R.S. McGreal, A. Cvekl, and A. Shiels. 2015. Lens biology and biochemistry. Prog. Mol. Biol. Transl. Med. 134: pp-pp.
  14. Cvekl, A., and P. Callaerts. 2017. PAX6: 25thanniversary and more to learn. Exp. Eye Res. 156:10-21.
  15. Cvekl, A., and X. Zhang. 2017. Signaling and gene regulatory networks in mammalian lens development. Trends Genet. 33:677-702.

 C.             Book Reviews and Editorials

  1. Cvekl, A., and D. Zheng. 2009. Joram Piatigorsky: Gene Sharing and Evolution. Human Genomics 4: 66-67.


More Information About Dr. Ales Cvekl

http://www.aecom.yu.edu/thecvekllab/

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Research Information