Associate Professor, Department of Cell and Developmental Biology, Sackler Faculty of Medicine
Associate Professor, Department of Cell and Developmental Biology, Sackler Faculty of Medicine
Prof. Limor Landsman joined the Department of Cell and Developmental Biology at Sackler Faculty of Medicine in 2012. She received both her M.Sc. and Ph.D. degrees from the Weizmann Institute of Science and completed her postdoctoral training at the University of California San Francisco (UCSF) Diabetes Center.
The role of the pancreatic microenvironment in glucose regulation and diabetes
Maintenance of blood glucose levels depends on the tight regulation of insulin secretion from pancreatic beta-cells. Insufficient insulin secretion, whether due to reduced beta-cell numbers, or impaired beta-cell function, leads to diabetes. Our group studies how beta-cell function and mass are established and maintained in health and why they are lost in diabetes. To this end, we research the crosstalk between beta-cells and cells in their microenvironment. Our results indicate the pivotal role of pericytes in regulating insulin secretion and further link diabetes-related changes in these cells with loss of glucose regulation. We further study the role of the pancreatic microenvironment in the embryonic and postnatal development of beta-cells to facilitate cell-replacement therapy for diabetes. Using genetically engineered mice, we study how pancreatic cells communicate with one another and how this communication is affected in diabetes.
Schonblum A, Ali Naser D, Ovadia S, Egbaria M, Puyesky S, Epshtein A, Wald T, Mercado Medrez S, Ashery-Padan R, and Landsman L. Beneficial islet inflammation in health depends on pericytic TLR/MyD88 signaling. J Clin Invest. (2024) Jun 17;134(14):e179335.
Edri S, Frisch AN, Safina D, Machour M, Zavin J, Landsman L, Pierreux CE, Spagnoli FM, and Levenberg S. 3D bioprinting of multicellular stem cell-derived constructs to model pancreatic cell differentiation. ADVANCED FUNCTIONAL MATERIALS (2024) 10.1002/adfm.202315488
Burganova G, Schonblum A, Sakhneny L, Epshtein A, Wald T, Tzaig M, Landsman L. Pericytes modulate islet inflammation and insulin secretion through IL-33 production. Frontiers in Endocrinology (2023). 14:1142988
Briggs JK, Schonblum A, Landsman L, Benninger RKP. Going With the Flow: Pericyte-Regulated Islet Blood Flow Influences Glucose Homeostasis. DIABETES (2022) Aug 1;71(8):1611-1613. doi: 10.2337/dbi22-0016. Commentary.
Glorieux L, Sapala A, Willnow D, Moulis M, Salowka A, Darrigrand JF, Edri S, Schonblum A, Sakhneny L, Schaumann L, Gómez HF, Lang C, Conrad L, Guillemot F, Levenberg S, Landsman L, Iber D, Pierreux CE, Spagnoli FM. Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions. DEVELOPMENT (2022) 149(3):dev199655. doi: 10.1242/dev.199655.
Sakhneny L, Mueller L, Schonblum A, Azaria S, Burganova G, Epshtein A, Isaacson A, Wilson H, Spagnoli FM, and Landsman L. The postnatal pancreatic microenvironment guides beta-cell maturation through BMP4 production. DEVELOPMENTAL CELL (2021) Oct 11;56(19):2703-2711.e5
Burganova G, Bridges C, Thorn P, and Landsman L. The role of vascular cells in pancreatic beta-cell function. FRONTIERS IN ENDOCRINOLOGY (2021) 12, 667170. Review
Nash Y, Ganoth A, Borenstein-Auerbacha N, Levy-Barazany H, Goldsmith G, Kopelevich A, Pozyuchenko K, Sakhneny L, Lazdon K, Blanga-Kanfi S, Alhadeff R, Benromano T, Landsman L, Tsfadia Y, and Frenkel D. From virus to diabetes therapy: characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment. FASEB J (2021) 35(5):e21374
Sakhneny L, Epshtein A, and Landsman L. Pericytes contribute to the islet basement membranes to promote beta-cell gene expression. SCIENTIFIC REPORTS (2021) 11:2378
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, and Melloul D. NF-κB activity during pancreas development regulates adult β-cell mass by modulating neonatal β-cell proliferation and apoptosis. CELL DEATH DISCOVERY (2021) 7:2
Almaça J, Caicedo A, Landsman L. Beta-cell dysfunction in diabetes: the islet microenvironment as an unusual suspect. DIABETOLOGIA (2020). 63(10):2076-2085. Review.
Harari N, Sakhneny L, Khalifa-Malka L, Busch A, Hertel KJ, Hebrok M, Landsman L. Pancreatic pericytes originate from the embryonic pancreatic mesenchyme. DEVELOPMENTAL BIOLOGY (2019) 449(1):14-20.
Sakhneny L, Khalifa-Malka L, and Landsman L. Pancreas organogenesis: approaches to elucidate the role of epithelial-mesenchymal interactions. SEMINARS IN CELL AND DEVELOPMENTAL BIOLOGY (2019). 92:89-96. Review.
Sakhneny L, Rachi E, Epshtein A, Guez HC, Wald-Altman C, Lisnyansky M, Khalifa-Malka L, Hazan A, Baer D, Priel A, Weil M and Landsman L. Pancreatic pericytes support ß-cell function in a Tcf7l2-dependent manner. DIABETES (2018) 67, 437-447
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, and Satchi-Fainaro R. Amphiphilic nanocarrier-induced modulation of PLK1 and miR-34a leads to improved therapeutic response in pancreatic cancer. NATURE COMMUNICATIONS (2018) 9, 16
Epshtein A, Rachi E, Sakhneny L, Mizrachi S, Baer D and Landsman L. Neonatal pancreatic pericytes support ß-cell proliferation. MOLECULAR METABOLISM (2017) 6, 1330-1338
Epshtein A, Sakhneny L and Landsman L. Isolating and analyzing cells of the pancreas mesenchyme by flow-cytometry. JoVE (2017) 119, e55344
Hibsher D, Epshtein A, Oren N and Landsman L. Pancreatic Mesenchyme Regulates Islet Cellular Composition in a Patched /Hedgehog-Dependent Manner. SCIENTIFIC REPORTS (2016) 6, 38008
Sasson A, Rachi E, Sakhneny L, Baer D, Lisnyansky M, Epshtein A and Landsman L. Islet Pericytes are Required for ß-Cell Maturity. DIABETES (2016) 65, 3008–3014
Grants
2023 - 2028 Israel Science Foundation (ISF)
2023 - 2028 European Research Council (ERC)
2018 - 2023 Israel Science Foundation (ISF)
2018 - 2021 Future and Emerging Technologies (FET) Open, Horizon 2020, EU
2017 - 2019 European Foundation for the Study of Diabetes (EFSD)
2016 - 2018 German-Israeli Foundation (GIF), with Dr. Francesca Spagnoli
2014 - 2017 State of Israel Ministry of Health Research Grant
2013 - 2018 European Research Council (ERC)
2013 - 2017 Marie Curie Career Integration Grant (CIG)
Awards
2020 The Hans Lindner Prize for excellent scientific achievements, the Israel Endocrine Society