Research

It's what's on the outside (of cells) that counts

Cells are born, die, and function within the dynamic environment of the extracellular matrix (ECM). Therefore, the ongoing relationship between the parenchyma and the stroma, via the ECM, has the potential to dictate the entire fate of the tissue. My PhD focused on ECM dynamics in colitis, showing that ECM remodeling precedes histopathological signs of inflammation. While I appreciated the complexity of the murine models I was working with, I always thought that if I could reconstruct a custom-made tissue from scratch I would be able to better understand the contribution of each tissue component to the pathological process.
This inspired me to look to the world of tissue engineering, and specifically organs-on-chips, in my quest for that additional layer of understanding of tissue-level processes. In my research at the Wyss Institute, funded by Cancer Grand Challenges, I constructed esophageal organ-on-a-chip culture models with clinically derived human cells to study the role that the stroma plays in the progression of Barrett's esophagus and esophageal adenocarcinoma.
Now, at MIT, I am leveraging my experience in constructing complex 3D culture models to identify targets and test novel drugs for cancer.

Publications

Epithelial-Stromal Interactions in Barrett’s Esophagus Modeled in Human Organ Chips

Shimshoni E, Merry GE, Milot ZD, Oh CY, Horvath V, Gould RA, Caruso JA, Chen-Tanyolac C, Gascard P, Sangwan V, Bérubé J, Bailey SD, Hall S, Stachler MD, Ferri L, Tlsty TD, Ingber DE.

Gastro Hep Advances 2023 2(5):676-680. doi: 10.1016/j.gastha.2023.03.009.

Distinct extracellular–matrix remodeling events precede symptoms of inflammation

Shimshoni E, Adir I, Afik R, Solomonov I, Shenoy A, Adler M, Puricelli L, Sabino F, Savickas S, Mouhadeb O, Gluck N, Fishman S, Werner L, Salame TM, Shouval DS, Varol C, Auf dem Keller U, Podestà A, Geiger T, Milani P, Alon U, Sagi I. 

Matrix Biol. 2021 Feb;96:47-68. doi: 10.1016/j.matbio.2020.11.001.


Sample Preparation of Extracellular Matrix of Murine Colons for Scanning Electron Microscopy.

Shimshoni E, Sagi I.

Methods Mol Biol. 2019;1944:129-133. doi: 10.1007/978-1-4939-9095-5_9.


Enhanced Collagen Deposition in the Duodenum of Patients with Hyaline Fibromatosis Syndrome and Protein Losing Enteropathy.

van Rijn JM, Werner L, Aydemir Y, Spronck JMA, Pode-Shakked B, van Hoesel M, Shimshoni E, Polak-Charcon S, Talmi L, Eren M, Weiss B, H J Houwen R, Barshack I, Somech R, Nieuwenhuis EES, Sagi I, Raas-Rothschild A, Middendorp S, Shouval DS.

Int J Mol Sci. 2020 Nov 2;21(21):8200. doi: 10.3390/ijms21218200.


Tumor macrophages are pivotal constructors of tumor collagenous matrix.

Afik R, Zigmond E, Vugman M, Klepfish M, Shimshoni E, Pasmanik-Chor M, Shenoy A, Bassat E, Halpern Z, Geiger T, Sagi I, Varol C.

J Exp Med. 2016 Oct 17;213(11):2315-2331. doi: 10.1084/jem.20151193. 


ECM remodelling in IBD: innocent bystander or partner in crime? The emerging role of extracellular molecular events in sustaining intestinal inflammation.

Shimshoni E*, Yablecovitch D*, Baram L, Dotan I, Sagi I.

Gut. 2015 Mar;64(3):367-72. doi: 10.1136/gutjnl-2014-308048. 


Acetylation of lysine 382 and phosphorylation of serine 392 in p53 modulate the interaction between p53 and MDC1 in vitro.

Shahar OD, Gabizon R, Feine O, Alhadeff R, Ganoth A, Argaman L, Shimshoni E, Friedler A, Goldberg M.

PLoS One. 2013 Oct 23;8(10):e78472. doi: 10.1371/journal.pone.0078472. 


Live imaging of induced and controlled DNA double-strand break formation reveals extremely low repair by homologous recombination in human cells.

Shahar OD, Raghu Ram EV, Shimshoni E, Hareli S, Meshorer E, Goldberg M.

Oncogene. 2012 Jul 26;31(30):3495-504. doi: 10.1038/onc.2011.516.