פרופ' לימור ברודאי

Associate Professor, Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University

Education

Molecular Analysis of Ubiquitin and SUMO Pathways in C. elegans and Schmidtea mediterranea

Protein modifications by ubiquitin and ubiquitin-like proteins are essential for cellular regulatory mechanisms. De-regulation of such processes are a cause for many human diseases. The main objective of our research is to understand, at a mechanistic and molecular level, how these processes are regulated. We use the nematode C. elegans as a model system to analyze various elements of the ubiquitin and ubiquitin-like  systems.

Recently we added to our laboratory another model, the planarian Schmidtea mediterranea that will help us to reveal the functions of SUMO during regeneration

Current lab projects:

1. Sumoylation dynamics during tissue morphogenesis

2. Regulation of assembly of cytoskeletal filaments by sumoylation 

3. SUMO in the mitochondria

4. Sumoylation dynamics in maintenance of germ cells identity

5. SUMO in planarian regeneration

Modeling a lung cancer oncogene in C. elegans 

Broday L., Kolotuev I., Didier C., Bhoumik A., Podbilewicz B., Ronai Z. 2004. The LIM domain protein UNC-95 is required for the assembly of muscle attachment structures and is regulated by the RING finger protein RNF-5 in C. elegans. J. Cell. Biol., 165(6): 857-867.

Broday L., Kolotuev I., Didier C., Bhoumik A., Gupta B.P., Sternberg P.W., Podbilewicz B., Ronai Z. 2004. The small ubiquitin-like modifier (SUMO) is required for gonadal and uterine-vulval morphogenesis in C. elegans. Genes. Dev., 18:2380-2391.

Broday L., Hauser C., Kolotuev I., Ronai Z. 2007. Muscle-epidermis interactions affect exoskeleton patterning in C. elegans. Dev. Dyn., 236:3129-3136. 

Kaminsky R., Denison C., Bening-Abu-Shach U., Chisholm A.D., Gygi S., Broday L. 2009.  SUMO regulates the assembly and function of a cytoplasmic intermediate filament protein in C. elegans. Dev Cell., 17:724-735.

• Featured in Research Highlight: Nature Reviews Molecular Cell Biology 11, 3 (January 2010).

Darom A., Bening-Abu-Shach U., Broday L. 2010. RNF-121 is an ER-membrane E3 ubiquitin ligase required for ER homeostasis and regulation of PAT-3/β-integrin levels. Mol. Biol. Cell., 21:1788-1798.

Zaidel-Bar R., Miller S., Kaminsky R., Broday L. 2010. Regulation of integrin adhesion complexes' dynamics by RNF-5 E3-ligase during molting in C. elegans. Biochem. Biophys. Res. Commun., 395:509-514. .

Kuang E., Okumura C., Sheffy-Levin S., Varsano T., Shu V.C., Qi J., Niesman I., Yang H.J., López-Otín C., Yang W., Reed J., Broday L.*, Nizet V.*, Ronai Z.* 2012. Regulation of ATG4B stability by RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection. PLoS Genet., e1003007. (*corresponding authors).

Sapir A., Tsur A., Koorman T., Ching K., Mishra P., Bardenheier A., Podolsky L., Bening-Abu-Shach U., Boxem  M., Chou T.F., Broday L.*, Sternberg P.W.*  2014. Controlled sumoylation of the mevalonate pathway enzyme HMGS-1 regulates metabolism during aging. Proc. Natl. Acad. Sci. USA, 111(37):E3880-9. (*corresponding authors).

Tsur A., Bening-Abu-Shach U., Broday L. 2015. ULP-2 SUMO protease regulates E-cadherin recruitment to adherens junctions. Developmental Cell, 35:1-15.

• Preview: Adhesion with a SUMO. Developmental Cell, 35, 2015.
• Featured in Research Highlight: SUMO controls a tug of war at junctions.  Nature Rev. Mol. Cell. Biol., 16:641, 2015.
• Developmental Cell cover         http://www.cell.com/developmental-cell/issue?pii=S1534-5807(14)X0044-4

Broday L. 2017. The SUMO system in C. elegans development. Int. J. Dev. Biol., 6:159-164.

Surana P., Gowda C., Tripathi V., Broday L., Das R. 2017. Structural and functional analysis of SMO-1, the SUMO homolog in C. elegans. PLoS One, 12(10):e0186622.

Thiruvalluvan M., Barghouth P.G., Tsur A., Broday L., Oviedo N.J. 2017. SUMOylation controls stem cell proliferation and regional cell death through hedgehog signaling in planarians. Cell. Mol. Life Sci., 2017.