פרופ' בנימין דקל

Prof. Benjamin Dekel is an Endowed Professor of Pediatrics, Incumbent of the Klayman Chair in Nephro-Urology, a member of the Department of Human Molecular Genetics & Biochemistry, Vice-Dean for Research and Innovation and Director of the Sagol Center for Regenerative Medicine at the School of Medicine, Tel Aviv University. Prof. Dekel is Head of the Pediatric Stem Cell Research Institute and Chief of Pediatric Nephrology at Sheba Medical Center, Tel Hashomer. He served as a Visiting Professor at the Institute of Stem Cell Biology, Stanford University. Prof. Dekel received a bachelor's degree in Medical Sciences and an MD from the Technion and a PhD and post-Doc from the Weizmann Institute of Science, all with honors. His research focuses on human kidney stem cell biology and regenerative medicine, to cast light on fundamental problems of developmental biology, tissue regeneration, and cancer, holding promise for novel disease therapies.

 
Prof. Dekel is known internationally as one of the most innovative and highly recognized investigators in the field of human renal stem cell biology and regenerative medicine. He has pioneered the identification of human stem/progenitor cells and their use in tissue repair and regeneration as well as targeted therapy in pediatric cancer.   
Prof. Dekel established laboratory for Regenerative and Developmental Nephrology and founded the Pediatric Stem Cell Research Institute at the Sheba Medical Center.  His team was the first to prospectively isolate expandable human nephron progenitor cells from fetal kidneys and showed their beneficial effects in treating chronic renal injury. Moreover, his research group discovered the mechanism of action responsible for cell renewal and local regeneration in the adult mammalian kidney. This discovery led to development of novel methodologies allowing for 3D growth of multiple lineage-restricted renal progenitors as human kidney spheroids and organoids, which generate different parts of the kidney after being transplanted into pre-clinical murine hosts. Accordingly, the Dekel lab invented a novel form of renal regenerative therapy.
In addition, Prof.  Dekel was the first to link normal and malignant human nephron stem cells and identify and isolate the Wilms' tumor stem cells. His group achieved complete eradication of tumor xenografts by targeting these cancer stem cells with an antibody drug immunoconjugate. Prof. Dekel's anti-cancer stem cell therapeutic approach ignited a multi-center clinical trial for relapsing pediatric kidney cancer. His lab evaluates novel therapeutics cancer stem cell function in multiple aggressive tumors. 
 

Currently, Prof. Dekel serves as Director of Sagol Center for Regenerative Medicine (SCRM) and as President of the Israeli Stem Cell Society (ISCS). He is an elected member of the American Society of Clinical Investigation (ASCI), the Society of Pediatric Research (APS/SPR) and a member of the UK Regenerative Medicine Initiative SAB committee. Prof Dekel is an inaugural member of the Israeli National Academy for Science in Medicine by the Israel Medical Association.

Prof. Dekel's studies are summarized in over 120 publications in the leading bio-medical journals, and he is a sought-after speaker; As a PI, he has trained a myriad of clinical and research physicians, investigators, and clinician-scientists and is constantly promoting the physician-scientist training on a national level.

His research has been supported by numerous sources including the ISF, BSF, ICRF, ICA, IPMP, Google X, Israel Ministry of Health, Israel Ministry of Science, Israel Ministry of Industry and Infrastructure (Kamin, Nofar programs), the ERC (FP7), NIH/NIDDK, Ziering and Brettler Foundations and collaborative grants including MD Anderson Cancer Center and Cedars-Sinai Hospital.

 
Prof. Dekel has received the Chaim Boichis Award for Pediatric Research, the APF Kass Fund Award for medical research, the Bat Sheva de Rothschild Physician-Scientist Award, the Daniel Moran Award for excellent pediatric research at TAU (x3), the prestigious Youdim Family Prize for Excellence in Cancer Research and the Israel Medical Association Prize for Medical-Scientific contribution.   

The questions we ask in the lab fall under three main categories:

1. Do human kidneys harbor stem/progenitor cells and if so can we use these cells to regenerate kidney organs for people suffering from renal disease? Also what would be the most efficient method to robustly isolate and expand them? Cell sorting with antibodies aimed at their surface markers; direct reprogramming from other cell sources; differentiation of pluripotent stem cells and induction of renal lineage?   

2. Do human kidney cancers and other pediatric solid tumors harbor cancer stem cells/tumor initiating cells/tumor propagating cells and if so can we target these cells in a manner that would lead to tumor eradication? What are the molecular signals that govern these cells specifically and can they be targeted? Do other pediatric solid tumors share similar cell types and can we identify cancer stem cells in these tumors?

3. Why are children born with malformed kidneys? What is the genetic basis for malformed kidneys in the pediatric population and can aberrant products of these genes lead to failure of early kidney stem cell differentiation and to human disease in which nephrons are improperly formed?

We use multiple technologies to try and answer these questions including cell culture, cell sorting, gene cloning, quantitative RT-PCR, immunofluorescence, confocal microscopy, genomics, proteomics, bioinformatics, and animal models of disease

Human kidney progenitor cells derived from adult kidneys are grown as floating spheres in culture. Picture of spheres two-month in culture (left panel). Genetically labeling cells with mCherry shows that clonal expansion – a stem/progenitor trait - takes place in the spheres (right panel).

Publications (last 5 years)

97. Pleniceanu O, Shukrun R, Omer D, Vax E, Kanter I, Dziedzic K, Pode-Shakked N, Mark-Daniei M, Pri-Chen S, Gnatek Y, Alfandary H, Varda-Bloom N, Bar-Lev DD, Bollag N, Shtainfeld R, Armon L, Urbach A, Kalisky T, Nagler A, Harari-Steinberg O, Arbiser JL, Dekel B. PPAR is central to initiation and propagation of human angiomyolipoma suggesting its potential as a therapeutic target. EMBO Mol Med. 2017 Apr;9(4):508-530.
98. Vivante A, Mann N, Yonath H,‡ Weiss AC, Getwan M,| Kaminski M, Bohnenpoll T, Teyssier C, Chen J, Shril S, van der Ven AT, Ityel H, Schmidt JM,  Widmeier E, Bauer SB, Sanna-Cherchi S, Gharavi AG, Lu W, Magen D, Shukrun R, Lifton R Tasic V, Stanescu HC, Cavaillès V, Robert Kleta, Anikster Y, Dekel B, Kispert A, Lienkamp SS,  Hildebrandt H. 
A Dominant Mutation in Nuclear Receptor Interacting Protein 1 Causes Urinary Tract Malformations via Dysregulation of Retinoic Acid Signaling J Am Soc Nephrol 2017;28(8):2364-2376
99. Pillar N, Pleniceanu O, Fang M, Ziv L, Botchan S, Cheng L, Dekel B*, Shomron N* A novel variant in the FHL1 gene associated with X-linked recessive hypoparathyroidism. Hum Genetics 2017 Jul;136(7):835-845. (*equal last and corresponding authors.).
100. Zajicek M, Perlman S, Dekel B, Lahav E, Lotan D, Lotan D, Achiron R, Gilboa Y.
Crossed ectopic kidney: prenatal diagnosis and postnatal follow-up. Prenat Diagn. 2017 May 15. doi: 10.1002/pd.5070.     
101. Pode-Shakked N, Gershon R, Tam G, Omer D, Gnatek Y, Kanter I, Oriel S, Katz G, Harari-Steinberg O, Kalisky T, Dekel B.  Evidence for in vitro preservation of human nephrogeneis at the single cell level. Stem Cell Reports 2017 May 25. pii: S2213-6711(17)30180-7.    
102. Markovsky E, Vax E, Ben-Shushan D, Eldar-Boock A, Shukrun R , Yeini E, Barshack I, Caspi R, Harari-Steinberg O, Pode-Shakked N, Dekel B*, Satchi-Fainaro R*. Wilms tumor NCAM-expressing cancer stem cells as potential therapeutic target for polymeric nanomedicine
Mol Cancer Ther. 2017 10.1158/1535-7163.MCT-17-0184. (*equal last and corresponding authors.). 
103. Pleniceanu O, Omer D, Dekel B. mTOR inhibition for sporadic angiomyolipoma. Kidney Int Rep. 2017;3(1):155-159.
104. Perlman S, Roitman L, Lotan D, Kivilevitch Z, Pode-Shakked N, Pode-Shakked B, Achiron R, Dekel B, Gilboa Y. Severe fetal hydronephrosis: the added value of associated congenital anomalies of the kidneys and urinary tract (CAKUT) in the prediction of postnatal outcome.
Prenat Diagn. 2018 Jan 5. doi: 10.1002/pd.5206. [Epub ahead of print]
105. Trink A, Kanter I, Pode-Shakked N, Urbach A, Dekel B, Kalisky T. Geometry of Gene Expression Space of Wilms' Tumors From Human Patients. Neoplasia. 2018 Aug;20(8):871-881. 
106. Golan H, Shukrun R, Mark-Daniely M, Pode-Shakked N; Pleniceanu O, Omer D, Vax E, Pri-Chen S, Harari-Steinberg O, Toren A, Dekel B. In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example. Stem Cell Reports 2018;11(3):795-810.  
107. Raved D, Tokatly-Latzer I, Anafi L, Harari-Steinberg O, Barshack I*, Dekel B*, Pode-Shakked N. * Blastemal NCAM+ALDH1+ Wilms' tumor cancer stem cells correlate with disease progression and poor clinical outcome: A pilot study. Pathol Res Pract. 2019;215(8):152491* (equal last authors)
108. Sagiv D, Harari-Steinberg O, Wolf M, Dekel B*, Omer D*. The Feasibility to Isolate and Expand Tympanic Membrane Squamous Epithelium Stem Cells from Scarred Perforation Margins. Otol Neurotol. 2019;40(10):e1030-e1036. (*equal last and sole corresponding author). 
109. Shukrun R, Golan H, Caspi R, Pode-Shakked N, Pleniceanu O, Vax E, Bar-Lev DD, Pri-Chen S, Jacob-Hirsch J, Schiby G, Harari-Steinberg O, Mark-Danieli M, Dekel B*, Toren A*.
NCAM1/FGF module serves as a putative pleuropulmonary blastoma therapeutic target.
Oncogenesis. 2019 2;8(9):48. (*sole corresponding author and equal last author).  
110. Perlman S, Borovitz Y, Ben-Meir D, Hazan Y, Nagar R, Bardin R, Brusilov M, Dekel B, Achiron R, Gilboa Y. Prenatal diagnosis and post-natal outcome of anterior urethral anomalies.
Prenat Diagn. 2020;40(2):191-196
111. Huizing M, Yardeni T, Fuentes F, Malicdan MCV, Leoyklang P, Volkov A, Dekel B, Brede E, Blake J, Powell A, Chatrathi H, Anikster Y, Carrillo N, Gahl WA, Kopp JB.. Rationale and Design for a Phase 1 Study of N-Acetylmannosamine for Primary Glomerular Diseases. Kidney Int Rep. 2019;4(10):1454-1462.
112. Weissman I, Rawlins E, Jensen K, Barker R, Beltrao-Braga P, Dekel B, Frisen J, Surani A, Fehlings M. Voices: The importance of Fetal Tissue Research. Cell Stem Cell 2019; 24: 357-359. 
113. Harari-Steinberg O, Omer D, Gnatek Y, Pleniceanu O, Goldberg S, Cohen-Zontag O, Pri-Chen S, Kanter I, Ben Haim N, Becker E, Ankawa R, Fuchs Y, Kalisky T, Dotan Z, Dekel B. Ex Vivo Expanded 3D Human Kidney Spheres Engraft Long Term and Repair Chronic Renal Injury in Mice. 
Cell Rep 2020 Jan 21;30(3):852-869.
114. Perlman S, Borovitz Y, Bar-Adon S, Dekel B, Achiron R, Gilboa Y. Fetal Pancake Kidney: Prenatal Diagnosis and Postnatal Follow-up. J Ultrasound Med. 2020 Feb 27.
115. Wineberg Y,  Bar-Lev T, Futorian A, Ben-Haim N,  Armon L, Ickowicz D, Oriel S, Bucris, E, Yehuda, Y, Pode-Shakked N, Gilad S, Benjamin S, Hohenstein P, Dekel B*, Urbach A*, Kalisky T*. 
Single-Cell RNA Sequencing Reveals mRNA Splice Isoform Switching during Kidney Development. J Am Soc Nephrol 2020;31(10):2278-2291.* (last senior authors)
116. Pleniceanu O, Harari-Steinberg O, Omer D, Gnatek I, Lachmi BE , Cohen-Zontag O , Manevitz-Mendelson E , Barzilai A, Rosenzweig B, Eisner A, Dotan Z. Fine LG, Dekel B* Greenberger S, Successful introduction of human renovascular units into the mammalian kidney. J Am Soc Nephrol 2020;31(12):2757-2772. (*sole corresponding author and equal last author).
Editorial:  Schmidt-Ott KM., Mix for Regeneration: Nephron Replacement by Transplanted Cells. J Am Soc Nephrol. 2020;31(12):2743-2745.
117. Cohen-Zontag O, Gershon R, Harari-Steinberg O, Kanter I, Omer D, Pleniceanu O, Tam G, Oriel S, Ben Hur H, Katz G, Dotan Z, Kalisky T, Dekel B*, Pode-Shakked N. Human kidney clonal proliferation disclose lineage-restricted precursor characteristics. (*sole corresponding author and equal last author). Sci Rep. 2021;11(1):6970
118. Namestnikov M, Pleniceanu O, Dekel B. Mixing Cells for Vascularized Kidney Regeneration. Cells. 2021;10(5):1119 (invited review)
119. Omer D, Pleniceanu O, Gnatek Y, Eden-Friedman Y, Namestnikov M , Cohen-Zontag O , Goldberg S , Friedman N, Mandelboim M , Vitner EB , Achdout H, Avraham R, Zahavy E , Israely T , Mayan H , Dekel B. Human Kidney Spheroids and monolayers provide insights into SARS-CoV-2 Renal Interactions. J Am Soc Nephrol, 2021 Jun 10:ASN.2020111546. doi: 10.1681/ASN.2020111546. (Covered globally in all major media outlets).
120. Omer D, Harari-Steinberg O, Buzhor E, Metsuyanim S, Gal-Yam, Dekel B. Reprogramming human adult kidney epithelia into long-term self-renewing proximal tubule progenitors via ectopic Oct4 expression. (Mol Ther, Revision).
121. Wineberg Y*, Kanter I*, Ben-Haim N*, Pode-Shakked N*, Bucris E, Bar-Lev TH, Oriel S, Yehuda Y, Gershon R, Shukrun R, Bar-Lev DD, Urbach A, Dekel B**, Kalisky T**, “Characterization of splice isoform switching during human kidney development” (*Co-first authorship) (**Co-senior authorship), bioRxiv. doi: https://doi.org/10.1101/816371. (Scientific Reports, in press)
122. Namestnikov M, and Dekel B. Moving to a new dimension: 3D kidney cultures for kidney regeneration. Current opinion in biomedical engineering. 2022; https://doi.org/10.1016/j.cobme.2022.100379