Dr. Erez Dror

Research

Our Lab's Mission

We investigate if and how immune-metabolic stress influences β-cell health and function by altering chromatin dynamics. By studying the interplay between islet-associated immune cells and β-cells, we aim to identify novel therapeutic targets for diabetes. Our recent discovery of epigenetically distinct β-cell subsets with potential differences in immune responsiveness underscores the importance of understanding the impact of immune cell signaling on chromatin structure and gene expression in β-cells.

Key Research Areas

Immune-Endocrine Crosstalk
- Investigating the role of the different islet-resident immune cells in maintaining islet homeostasis.
- Exploring the functional outcome of interaction between specific immune cells and each of the newly identified β-cell subsets.
- Characterizing the role of CD24, a cell surface glycoprotein, in immune-endocrine crosstalk and its potential as a therapeutic target.
Chromatin Dynamics in β-Cell Response to Stress
- Investigating how immune-metabolic stress influences chromatin dynamics and gene expression in β-cells.
- Identifying novel (epigenetic) therapeutic targets to protect β-cells from stress-induced dysfunction.

Schematic representation of the SCANseq protocol

Chromatin modifications in islets

Studying the islet inside out

Our tools\methods

SCANseq (Surface Cytoplasmic and Nuclear epitope labelling coupled with scRNAseq): enables quantifications of cell surface markers and histone modifications together with gene expression in single cells.
Imaging (confocal, intravital)
Flow cytometry
Live cell Metabolic assays
Histone modification-reporting β cell lines
Pseudo-islet formation
Insulin secretion assays
Islet transplantations into the anterior chamber of the eye (ACE)
Mouse models of diabetes

The Ultimate Goal

Our long-term goal is to leverage these fundamental insights to develop innovative strategies for generating tailor-made islets for transplantation. By understanding the molecular mechanisms underlying islet function and dysfunction, we aim to create islets that are more resilient to immune-metabolic stress and capable of long-term function in transplant recipients.

Selected publications

Dror E, Fagnocchi L, Wegert V, Apostle S, Grimaldi B, Gruber T, Panzeri I, Heyne S, Höffler KD, Kreiner V, Ching R, Tsai-Hsiu Lu T, Semwal A, Johnson B, Senapati P, Lempradl A, Schones D, Imhof A, Shen H, Pospisilik JA. Epigenetic dosage identifies two major and functionally distinct β cell subtypes. Cell Metab. 2023 May 2;35(5):821-836.e7. doi: 10.1016/j.cmet.2023.03.008. Epub 2023 Mar 21. PMID: 36948185; PMCID: PMC10160009.

Dror et al 2023 - simply explained (video)

Wiedemann SJ, Trimigliozzi K, Dror E, Meier DT, Molina-Tijeras JA, Rachid L, Le Foll C, Magnan C, Schulze F, Stawiski M, Häuselmann SP, Méreau H, Böni-Schnetzler M, Donath MY. The cephalic phase of insulin release is modulated by IL-1β. Cell Metab. 2022 Jul 5;34(7):991-1003.e6. doi:10.1016/j.cmet.2022.06.001. Epub 2022 Jun 23. PMID: 35750050.

Brykczynska U, Geigges M, Wiedemann SJ, Dror E, Böni-Schnetzler M, Hess C, Donath MY, Paro R. Distinct Transcriptional Responses across Tissue-Resident Macrophages to Short-Term and Long-Term Metabolic Challenge. Cell Rep. 2020 Feb 4;30(5):1627-1643.e7. doi: 10.1016/j.celrep.2020.01.005. PMID: 32023474.

Lu TT, Heyne S, Dror E, Casas E, Leonhardt L, Boenke T, Yang CH, Sagar, Arrigoni L, Dalgaard K, Teperino R, Enders L, Selvaraj M, Ruf M, Raja SJ, Xie H, Boenisch U, Orkin SH, Lynn FC, Hoffman BG, Grün D, Vavouri T, Lempradl AM, Pospisilik JA. The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes. Cell Metab. 2018 Jun 5;27(6):1294-1308.e7. doi:10.1016/j.cmet.2018.04.013. Epub 2018 May 10. PMID: 29754954; PMCID: PMC5989056.

Dalmas E, Lehmann FM, Dror E, Wueest S, Thienel C, Borsigova M, Stawiski M, Traunecker E, Lucchini FC, Dapito DH, Kallert SM, Guigas B, Pattou F, Kerr-Conte J, Maechler P, Girard JP, Konrad D, Wolfrum C, Böni-Schnetzler M, Finke D, Donath MY. Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production. Immunity. 2017 Nov 21;47(5):928-942.e7. doi: 10.1016/j.immuni.2017.10.015. PMID: 29166590.

Nordmann TM, Dror E, Schulze F, Traub S, Berishvili E, Barbieux C, Böni-Schnetzler M, Donath MY. The Role of Inflammation in β-cell Dedifferentiation. Sci Rep. 2017 Jul 24;7(1):6285. doi: 10.1038/s41598-017-06731-w. PMID: 28740254; PMCID: PMC5524956.

Dror E, Dalmas E, Meier DT, Wueest S, Thévenet J, Thienel C, Timper K, Nordmann TM, Traub S, Schulze F, Item F, Vallois D, Pattou F, Kerr-Conte J, Lavallard V, Berney T, Thorens B, Konrad D, Böni-Schnetzler M, Donath MY. Postprandial macrophage-derived IL-1β stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat Immunol. 2017 Mar;18(3):283-292. doi: 10.1038/ni.3659. Epub 2017 Jan 16. PMID: 28092375.

​Research