Background

Cilia and eukaryotic flagella are organelles that facilitate locomotion of single cells, such as algae, parasites and human sperm. Motile cilia are also found on epithelial cells in the brain, respiratory tract and female reproductive tract, where cilia beat in synchrony to transport cells, particles and nutrients. The motile cilium is considered the largest eukaryotic machine, and it has an extremely complicated beating mechanism that involves thousands of proteins beautifully organized in a cytoskeletal structure termed the axoneme. Mutations in any one of these proteins can result in ciliopathies characterized with breathing disorders, hydrocephalus and infertility.

Current Projects

We use methods in biochemistry and structural biology (especially single-particle cryo-EM) to understand the mechanism of ciliary beating and the molecular basis of mutations underlying ciliopathies. We are currently studying the assembly process and the functions of the radial spokes - huge complexes (over 20 proteins) that are crucial for ciliary beating.

Grossman-Haham, I., Coudray, N., Yu, Z., Wang, F., Zhang, N., Bhabha, G., and Vale, R. D. (2021). Structure of the radial spoke head and insights into its role in mechanoregulation of ciliary beating. Nat. Struct. Mol. Biol. 28: 20-28.
Feldman, T. Grossman-Haham, I., Elkis, Y., Vilela, P., Moskovits, N., Barshack, I., Salame, T. M., Fass, D., and Ilani, T. (2020). Inhibition of fibroblast secreted QSOX1 perturbs extracellular matrix in the tumor microenvironment and decreases tumor growth and metastasis in murine cancer models. Oncotarget 11: 386-398.

Javiit, G.#, Grossman-Haham, I.#, Alon, A., Resnick, E., Mutsafi, Y., Ilani, T., and Fass, D. (2019). cis-proline mutants of quiescin sulfhydryl oxidase 1 with altered redox properties undermine ECM integrity and cell adhesion in fibroblast cultures. Protein Sci. 28: 228-238. #equal contribution

Grossman-Haham, I., Rosenblum, G., Namani, T., and Hofmann, H. (2018). Slow domain reconfiguration causes power-law kinetics in a two-state enzyme. Proc. Natl. Acad. Sci. 115: 513-518.

Grossman, I., Ilani, T., Fleishamn, S. J., and Fass, D. (2016). Overcoming a species-specificity barrier in development of an inhibitory antibody targeting a modulator of tumor stroma. Protein Eng. Des. Sel. 29: 135-147.