Marek Mlodzik, PhD
- PROFESSOR & CHAIR | Cell, Developmental & Regenerative Biology
- PROFESSOR | Ophthalmology
- PROFESSOR | Oncological Sciences
Research Topics:Cell Biology, Cellular Differentiation, Cytoskeleton, Developmental Neurobiology, Drosophila, Genetics, Genomics, Growth Factors and Receptors, Oncogenes, Signal Transduction
For more information, please visit the Mlodzik Laboratory website.
Multi-Disciplinary Training AreasCancer Biology [CAB], Development, Regeneration, and Stem Cells [DRS], Genetics and Genomic Sciences [GGS], Neuroscience [NEU]
Diploma, University of Basel
PhD, Biocenter, University of Basel
University of California
Member, NIH Scientific Review Group CDF-5
Marek Mlodzik’s laboratory studies the establishment of epithelial planar cell polarity (PCP) regulated by Wnt/Frizzled-PCP signaling and the mechanisms of Wnt-signaling specificity regulation between the PCP and canonical beta-catenin pathways. In addition, we are interested in cross-talk between the Wnt/Frizzled pathways and Notch and Egf-receptor signaling.
Epithelial cells - in the epidermis as well as in neural epithelia - are polarized with respect to the body axis. This is not only the case in Drosophila and other insects but is a widespread feature of epithelia in both invertebrates and vertebrates. The apparent difference between whole epithelial tissue (such as the disc-epithelia in Drosophila) and cells in tissue culture is that, in addition to the apical-basolateral polarity, epithelial tissues develop an obvious polarity with respect to body axes, planar cell polarity or PCP. The Drosophila tissue polarity genes are required for correct PCP generation and mutations in them affect all epithelial tissues (both neuronal and non-neuronal). Efforts to understand the mechanisms of PCP formation have focused on the wing and the eye. In the wing, PCP is reflected in the choice of the site at which hair out-growth initiates in each cell and the direction the hair points. In the eye, PCP is reflected in the mirror-symmetric arrangement of ommatidia relative to the dorso-ventral midline, the equator. PCP mutations result in the loss of hair/bristle polarity in the wing and loss of mirror-image symmetry in the eye, with ommatidia being misrotated and adopting the chiral forms randomly. Recent findings indicate that the underlying signaling pathway(s) are not only conserved throughout evolution and regulate related aspects of coordinated cellular polarization in mammals, but that they are also linked to several human diseases, ranging from gastrulation defects to cancer, and from ciliopathies (including obesity and mental retardation) to deafness and sterility.
For more information, please visit the Mlodzik Laboratory website.
Collu GM, Jenny A, Gaengel K, Mirkovic I, Chin ML, Weber U, Smith MJ, Mlodzik M. Prickle is phosphorylated by Nemo and targeted for degradation to maintain Prickle/Spiny-legs isoform balance during planar cell polarity establishment. PLoS genetics 2018 May; 14(5).
Haider A, Wei YC, Lim K, Barbosa AD, Liu CH, Weber U, Mlodzik M, Oras K, Collier S, Hussain MM, Dong L, Patel S, Alvarez-Guaita A, Saudek V, Jenkins BJ, Koulman A, Dymond MK, Hardie RC, Siniossoglou S, Savage DB. PCYT1A Regulates Phosphatidylcholine Homeostasis from the Inner Nuclear Membrane in Response to Membrane Stored Curvature Elastic Stress. Developmental cell 2018 May;.
Bala Tannan N, Collu G, Humphries AC, Serysheva E, Weber U, Mlodzik M. AKAP200 promotes Notch stability by protecting it from Cbl/lysosome-mediated degradation in Drosophila melanogaster. PLoS genetics 2018 Jan; 14(1).
Humphries AC, Mlodzik M. From instruction to output: Wnt/PCP signaling in development and cancer. Current opinion in cell biology 2017 Dec; 51.
Wu J, Mlodzik M. Wnt/PCP Instructions for Cilia in Left-Right Asymmetry. Developmental cell 2017 Mar; 40(5).
Weber U, Mlodzik M. APC/C(Fzr/Cdh1)-Dependent Regulation of Planar Cell Polarity Establishment via Nek2 Kinase Acting on Dishevelled. Developmental cell 2017 Jan; 40(1).
Carvajal-Gonzalez JM, Mulero-Navarro S, Mlodzik M. Centriole positioning in epithelial cells and its intimate relationship with planar cell polarity. BioEssays : news and reviews in molecular, cellular and developmental biology 2016 Dec; 38(12).
Carvajal-Gonzalez JM, Mulero-Navarro S, Smith M, Mlodzik M. A Novel Frizzled-Based Screening Tool Identifies Genetic Modifiers of Planar Cell Polarity in Drosophila Wings. G3 (Bethesda, Md.) 2016 Dec; 6(12).
Vega-Macaya F, Manieu C, Valdivia M, Mlodzik M, Olguín P. Establishment of the Muscle-Tendon Junction During Thorax Morphogenesis in Drosophila Requires the Rho-Kinase. Genetics 2016 Nov; 204(3).
Kelly LK, Wu J, Yanfeng WA, Mlodzik M. Frizzled-Induced Van Gogh Phosphorylation by CK1ε Promotes Asymmetric Localization of Core PCP Factors in Drosophila. Cell reports 2016 Jul; 16(2).
Carvajal-Gonzalez JM, Roman AC, Mlodzik M. Positioning of centrioles is a conserved readout of Frizzled planar cell polarity signalling. Nature communications 2016 Mar; 7.
Mlodzik M. The Dishevelled Protein Family: Still Rather a Mystery After Over 20 Years of Molecular Studies. Current topics in developmental biology 2016 Jan; 117.
Balmer S, Dussert A, Collu GM, Benitez E, Iomini C, Mlodzik M. Components of Intraflagellar Transport Complex A Function Independently of the Cilium to Regulate Canonical Wnt Signaling in Drosophila. Developmental cell 2015 Sep; 34(6).
Collu GM, Mlodzik M. Planar polarity: converting a morphogen gradient into cellular polarity. Current biology : CB 2015 May; 25(9).
Carvajal-Gonzalez JM, Balmer S, Mendoza M, Dussert A, Collu G, Roman AC, Weber U, Ciruna B, Mlodzik M. The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo. Nature communications 2015 Apr; 6.
Yang Y, Mlodzik M. Wnt-Frizzled/planar cell polarity signaling: cellular orientation by facing the wind (Wnt). Annual review of cell and developmental biology 2015; 31.
Carvajal-Gonzalez JM, Mlodzik M. Mechanisms of planar cell polarity establishment in Drosophila. F1000prime reports 2014 Nov; 6.
Serysheva E, Mlodzik M, Jenny A. WNKs in Wnt/β-catenin signaling. Cell cycle (Georgetown, Tex.) 2014 Nov; 13(2).
Mlodzik M, Halder G. Walter J Gehring (1939-2014). The EMBO journal 2014 Aug; 33(15).
Weber U, Rodriguez E, Martignetti J, Mlodzik M. Luna, a Drosophila KLF6/KLF7, is maternally required for synchronized nuclear and centrosome cycles in the preblastoderm embryo. PloS one 2014 Jun; 9(6).
Wu J, Roman AC, Carvajal-Gonzalez JM, Mlodzik M. Wg and Wnt4 provide long-range directional input to planar cell polarity orientation in Drosophila. Nature cell biology 2013 Sep; 15(9).
Chin ML, Mlodzik M. The Drosophila selectin furrowed mediates intercellular planar cell polarity interactions via frizzled stabilization. Developmental cell 2013 Sep; 26(5).
Yogev S, Djiane A. The apical determinants aPKC and dPatj regulate Frizzled-dependent planar cell polarity in the Drosophila eye. Cell 2005; 121: 621-631.
Singh J, Grumolato L, Aaronson SA, Mlodzik M. Abelson family kinases regulate Frizzled planar cell polarity signaling via Dsh phosphorylation. Genes & Development 2010; 24: 2157-2168.
Jenny A, Reynolds-Kenneally J, Mlodzik M, Burnett M, Das G. Dishevelled is protected by Diego from the antagonistic effect of the Stbm/Prickle complex during Fizzled-PCP signaling. Nature Cell Biology 2005; 7: 691-697.
Simons M, Gault WJ, Gotthardt D, Rohatgi R, Klein TJ, Shao Y, Lee HJ, Wu AL, Fang Y, Satlin LM, Dow JT, Chen J, Zheng J, Boutros M, Mlodzik M. Electrochemical cues regulate the assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization. Nature Cell Biology 2009; 11: 286-294.
Ciruna B, Jenny A, Schier AF, Mlodzik M, Lee D. Planar cell polarity signalling couples cell division and morphogenesis during neurulation. . Nature 2006; 439: 220-224.
Grumolato L, Liu G, Haremaki T, Mungamuri SK, Mong P, Akiri G, Lopez-Bergami P, Arita A, Anouar Y, Mlodzik M, Ronai ZA, Brody J, Weinstein DC, Aaronson SA. β-Catenin-independent activation of TCF1/LEF1 in human hematopoietic tumor cells through interaction with ATF2 transcription factors. PLoS genetics 2013; 9(8).
Wu J, Mlodzik M. The Frizzled extracellular domain is a ligand for Van Gogh/Strabismus during non-autonomous planar cell polarity signaling. Developmental Cell 2008; 15: 462-469.
Mirkovic I, Gault WJ, Rahnama M, Jenny A, Gaengel K, Bessette D, Gottardi CJ, Verheyen EM, Mlodzik M. The Nemo kinase connects core PCP factors to E-cadherin/b-catenin during ommatidial rotation in the Drosophila eye. Nature Struct. Mol. Biol. 2011; 18: 665–672.