Welcome to the

LANDSMAN LAB

The pancreas is essential for blood glucose regulation and food digestion.

 

Our lab studies how the function of insulin-producing beta-cells is maintained in health, and why it is lost in diabetes.

 

We further study how the different pancreatic cell types develop in the embryo.

 

To better understand these processes, we focus on the role of the pancreas microenvironment.

 

Research

Our lab studies the development and function of insulin-producing beta-cells, focusing on the role of the pancreatic microenvironment. 

How do mesenchymal cells regulate pancreas development?

The pancreas comprises various cell types that share common progenitors in the embryo. We showed that mesenchymal cells guide pancreas and beta-cell development, and are required to establish organ size and shape (Landsman et al., 2011). We further showed that mesenchymal cells dictate the ratio between pancreatic endocrine cell populations (Hibsher et al., 2016). Our findings facilitate cell replacement therapy for diabetes. Recently, we demonstrated that the pancreatic mesenchyme gives rise to pericytes of the adult organs (Harari et al., 2019)

 

How do pericytes support beta-cell function and glucose regulation?

Insulin-producing beta-cells rely on their microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the islets of Langerhan's dense capillary network. However, while the role of endothelial cells in beta-cell function is well-established, our understanding of the role of pericytes lags behind. We showed that pericytes are required for maintaining beta-cell function and glucose-stimulated insulin secretion (Sasson, Rachi, Sakhneny, et al., 2016). In part, this activity is mediated by the production of ECM components (Sakhneny et al., 2021). Moreso, we found that in the neonatal pancreas, pericytes promote beta-cell proliferation (Epshtein et al., 2017). We now use transgenic mouse models to further define the pericyte/beta-cell axis and its requirement for glucose homeostasis.

Does abnormal pericyte function contribute to diabetes?

The impaired function of beta-cells is a critical factor in type 2 diabetes. We recently showed that TCF7L2, which confers a high genetic risk of type 2 diabetes through a yet-to-be-described mechanism, is required for the proper function of pancreatic pericytes. Inactivation of this transcription factor specifically in pancreatic pericytes leads to impaired glucose response due to impaired beta-cell function (Sakhneny et al., 2018). Our findings thus implicate abnormalities in the islet microenvironment as an underlying cause of diabetes. We now explore how pericyte dysfunction contributes to diabetes. 

Our research is funded by:
Current funding
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Past funding
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Lab Members

LIMOR LANDSMAN
Principle Investigator
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ALONA EPSHTEIN
Research Associate
LINA SAKHNENY
PhD student
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GUZEL BURGANOVA
PhD student
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ANAT SCHONBLUM
PhD student

Former members:

Adi Sasson

Maria Becker

Helen Guez

Michal Lisnyansky

Daniel Hibsher

Daria Baer

Eleonor Rachi

Laura Khalifa-Malka

Neta Harari

Sivan Azaria

Recent Publications

From virus to diabetes therapy: Characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment.

Nash Y, Ganoth A, Borenstein-Auerbach N, Levy-Barazany H, Goldsmith G, Kopelevich A, Pozyuchenko K, Sakhneny L, Lazdon E, Blanga-Kanfi S, Alhadeff R, Benromano T, Landsman L, Tsfadia Y, Frenkel D.
FASEB J. 2021 May;35(5):e21374. doi: 10.1096/fj.201901945R.

Pericytes contribute to the islet basement membranes to promote beta-cell gene expression.

Sakhneny L, Epshtein A, Landsman L.
Sci Rep. 2021 Jan 27;11(1):2378. doi: 10.1038/s41598-021-81774-8

NF-κB activity during pancreas development regulates adult β-cell mass by modulating neonatal β-cell proliferation and apoptosis.

Sever D, Hershko-Moshe A, Srivastava R, Eldor R, Hibsher D, Keren-Shaul H, Amit I, Bertuzzi F, Krogvold L, Dahl-Jørgensen K, Ben-Dov IZ, Landsman L, Melloul D.

Cell Death Discov. 2021 Jan 4;7(1):2. doi: 10.1038/s41420-020-00386-9.

Beta cell dysfunction in diabetes: the islet microenvironment as an unusual suspect.

Almaça J, Caicedo A, Landsman L.

Diabetologia. 2020 Oct;63(10):2076-2085. doi: 10.1007/s00125-020-05186-5. Review

Pancreatic Pericytes in Glucose Homeostasis and Diabetes.

Landsman L.

Adv Exp Med Biol. 2019 ;1122:27-40. doi: 10.1007/978-3-030-11093-2_2.Book Chapter

 

Pancreas organogenesis: Approaches to elucidate the role of epithelial-mesenchymal interactions.

Sakhneny L, Khalifa-Malka L, Landsman L.

Semin Cell Dev Biol. 2019 Aug;92:89-96. doi: 10.1016/j.semcdb.2018.08.012. Review.

Pancreatic pericytes originate from the embryonic pancreatic mesenchyme.

Harari N, Sakhneny L, Khalifa-Malka L, Busch A, Hertel KJ, Hebrok M, Landsman L

Dev Biol. 2019 May 1;449(1):14-20. doi: 10.1016/j.ydbio.2019.01.020.

Pancreatic Pericytes Support β-Cell Function in a Tcf7l2-Dependent Manner.

Sakhneny L, Rachi E, Epshtein A, Guez HC, Wald-Altman S, Lisnyansky M, Khalifa-Malka L, Hazan A, Baer D, Priel A, Weil M, Landsman L.

Diabetes. 2018 Mar;67(3):437-447. doi: 10.2337/db17-0697. Epub 2017 Dec 15.

 

Amphiphilic nanocarrier-induced modulation of PLK1 and miR-34a leads to improved therapeutic response in pancreatic cancer.

Gibori H, Eliyahu S, Krivitsky A, Ben-Shushan D, Epshtein Y, Tiram G, Blau R, Ofek P, Lee JS, Ruppin E, Landsman L, Barshack I, Golan T, Merquiol E, Blum G, Satchi-Fainaro R.

Nat Commun. 2018 Jan 2;9(1):16. doi: 10.1038/s41467-017-02283-9.

 

Neonatal pancreatic pericytes support β-cell proliferation.

Epshtein A, Rachi E, Sakhneny L, Mizrachi S, Baer D, Landsman L.

Mol Metab. 2017 Oct;6(10):1330-1338. doi: 10.1016/j.molmet.2017.07.010. Epub 2017 Jul 19.

 

Isolating and Analyzing Cells of the Pancreas Mesenchyme by Flow Cytometry.

Epshtein A, Sakhneny L, Landsman L.

J Vis Exp. 2017 Jan 28;(119). doi: 10.3791/55344.

 

Pancreatic Mesenchyme Regulates Islet Cellular Composition in a Patched/Hedgehog-Dependent Manner.

Hibsher D, Epshtein A, Oren N, Landsman L.

Sci Rep. 2016 Nov 28;6:38008. doi: 10.1038/srep38008.

 

Islet Pericytes Are Required for β-Cell Maturity.

Sasson A, Rachi E, Sakhneny L, Baer D, Lisnyansky M, Epshtein A, Landsman L.

Diabetes. 2016 Oct;65(10):3008-14. doi: 10.2337/db16-0365. Epub 2016 Jul 7.

 

Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation.

Russ HA, Landsman L, Moss CL, Higdon R, Greer RL, Kaihara K, Salamon R, Kolker E, Hebrok M.

Stem Cells Int. 2016;2016:6183562. doi: 10.1155/2016/6183562.

 

On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells.

Avraham-Davidi I, Yona S, Grunewald M, Landsman L, Cochain C, Silvestre JS, Mizrahi H, Faroja M, Strauss-Ayali D, Mack M, Jung S, Keshet E.

J Exp Med. 2013 Nov 18;210(12):2611-25. doi: 10.1084/jem.20120690. Epub 2013 Oct 28.

 

Factors expressed by murine embryonic pancreatic mesenchyme enhance generation of insulin-producing cells from hESCs.

Guo T, Landsman L, Li N, Hebrok M.

Diabetes. 2013 May;62(5):1581-92. doi: 10.2337/db12-0167. Epub 2013 Jan 10.

 

Elevated Hedgehog/Gli signaling causes beta-cell dedifferentiation in mice.

Landsman L, Parent A, Hebrok M.

Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17010-5. doi: 10.1073/pnas.1105404108. Epub 2011 Oct 3.

 

Pancreatic mesenchyme regulates epithelial organogenesis throughout development.

Landsman L, Nijagal A, Whitchurch TJ, Vanderlaan RL, Zimmer WE, Mackenzie TC, Hebrok M.

PLoS Biol. 2011 Sep;9(9):e1001143. doi: 10.1371/journal.pbio.1001143. Epub 2011 Sep 6.

 

 
 

Contact us

Dept. of Cell and Developmental Biology

Room 307, 3rd floor

Sackler Faculty of Medicine

Tel Aviv University

Ramat Aviv, Tel Aviv 69978 Israel
 
Tel : 972-3-640 6913 

Fax: 972-3-640 7432

Dr. Limor Landsman contact info:

Office : 972-3-640 6149
Mobile: 972-52-366 8201
Email: limorl@tauex.tau.ac.il