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Researchers
  • Dr.  Michal Shoshkes-Carmel
 
Research
The main interest of ShoshkesCarmelab is to understand the Telocyte. We study this using mammalian intestine as a model system. Telocytes are large stromal cells characterized by long cytoplasmic processes, have recently emerged as an important source of Wnt proteins, providing crucial support for intestinal stem cell renewal. Current projects are concerned with understanding telocytes in:

Development

development  
The mammalian gut is established as a cylinder with an outer mesodermal layer and an inner luminal endoderm. During embryonic and adult life, the endoderm and mesoderm are mutually dependent upon one another for instructive signals that eventually result in the organization of each layer with its functional characteristics. We will attempt to unravel the design principles of functional tissue patterning coordinated by telocytes

Homeostasis

homeostasis  
Telocytes have recently emerged as an important source of Wnt proteins, providing crucial support for intestinal stem cell renewal. However, the biology of these fascinating cells remains unclear. The overreaching goal of this project is to understand telocytes: their heterogeneity, structure-function relationship, sensing machinery and importance in intestinal homeostasis

Disease

disease  
80-90% of all cancer cases account for epithelial tissues. Accumulating evidence point at the profound affect of the tumor microenvironment in mediating its growth and progression. The establishment of tools for analyzing intestinal telocytes, along with the availability of organoid ex-vivo system to grow small intestine and colon in culture, will allow functional validation in humans. We will exploit colorectal mouse models together with human tissue to study the potential role of telocytes in contribution to fatal diseases
Team

We are recruiting passionate excellent curious students and postdocs

To apply please send CV and contact info to: Michal.Shoshkes@mail.huji.ac.il
Publications
Shoshkes-Carmel M, Wang YJ, Wangensteen KJ, Tóth B, Kondo A, Massasa EE, Itzkovitz S, Kaestner KH. Subepithelial telocytes are an important source of Wnts that support intestinal crypts. Nature 2018 May 2.
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Dou Z, Ghosh K, Vizioli MG, Zhu J, Sen P, Wangensteen KJ, Simithy J, Lan Y, Lin Y, Zhou Z, Capell BC, Xu C, Xu M, Kieckhaefer JE, Jiang T, Shoshkes-Carmel M, Tanim KMAA, Barber GN, Seykora JT, Millar SE, Kaestner KH, Garcia BA, Adams PD, Berger SL. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature. 2017 Oct 4.
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Aoki R*, Shoshkes-Carmel M*, Gao N, Shin S, May CL, Golson ML, Zahm AM, Ray M, Wiser CL, Wright CV, Kaestner KH. Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche. Cell Mol Gastroenterol Hepatol 2016 2(2), 175-188. Selected for cover
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Carmel MS., Kahane N., Oberman F., Miloslavski R., Sela-Donenfeld D., Kalcheim C., Yisraeli JK. A novel role for VICKZ proteins in maintaining epithelial integrity during embryogenesis. PLoS One 2015 10(8); e0136408
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Almeida, R., Almeida, J., Shoshkes, M., Mendes, N., Mesquita, P., Silva, E., Van Seuningen, E., Reis, C., Santos-Silva, F., David , L. OCT-1 is over-expressed in intestinal metaplasia and intestinal gastric carcinomas and binds to, but does not transactivate, CDX2 in gastric cells. J pathol 2005 207, 396-401.
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Ben-Shushan,E., Marshak, S., Shoshkes, M., Cerasi, E. & Melloul, D. A pancreatic beta-cell-specific enhancer in the human pdx-1 gene is regulated by HNF-3β, HNF-1α and SPs transcription factors. J Biol Chem 2001 276, 17533-17540.
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Marshak, S., Ben-Shushan, E., Shoshkes, M., Havin, L., Cerasi, E. & Melloul, D. Regulatory elements involved in human pdx-1 gene expression. Diabetes 2001 Feb; 50 Suppl 1: S37-8.
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Marshak, S., Ben-Shushan, E., Shoshkes, M., Leibovitz, G., Kaiser, N., Gross, D., Bertuzzi, F., Cerasi, E. & Melloul, D. (2001). Beta-cell-specific expression of insulin and pdx-1 genes. Diabetes Feb;50 Suppl 1: S131-2.
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Marshak, S., Ben-Shushan, E., Shoshkes, M., Havin, L., Cerasi, E. & Melloul, D. (2000) Functional conservation of regulatory elements in the pdx-1 gene: PDX-1 and HNF-3β transcription factors mediate beta-cell-specific expression. Mol Cell Biol. 2000 Oct;20(20):7583-90.
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