Prof. Benjamin Dekel

Biography

Prof. Dekel is the Head of the Pediatric Stem cell Research Institute and the Director of the Division of Pediatric Nephrology at the Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Israel.  He is a Professor of Pediatrics at the Sackler School of Medicine, Tel Aviv University and affiliated Faculty in the Department of Human Molecular Genetics and Biochemistry. He served as a Visiting Professor at the Institute of Stem Cell Biology, Stanford University. He received a bachelor's degree in Medical Sciences and an MD from the Technion (with distinction) and a doctorate (PhD) from the Weizmann Institute of Science (with distinction). Prof. Dekel completed a residency in Pediatrics at the Sheba Medical Center, a clinical fellowship in Pediatric Nephrology at the Schneider Children's Medical Center and a post-doctoral fellowship in stem cell biology at the Weizmann Institute of Science.

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.  Prof. Dekel initiated his work in this field as a graduate student and postdoctoral fellow at the Weizmann Institute of Science, which resulted in seminal studies demonstrating that kidney precursor tissues from humans or pigs could develop into fully functional nephrons when transplanted into adult mice, paving the way for the "growing kidneys" concept. Subsequently, as an independent investigator, he established his own laboratory for Regenerative and Developmental Nephrology and founded the Pediatric Stem Cell Research Institute at the Sheba Medical Center.  His laboratory takes a multi-disciplinary approach including genetics, genomics, molecular biology, biochemistry, and the development of preclinical murine models to cast light on fundamental problems of developmental biology, tissue regeneration, and cancer; while, at the same time, holding promise for novel disease therapies.  In the field of pediatric renal cancer and kidney development, Prof. Dekel 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. His team was the first was to prospectively isolate expandable human nephron progenitor cells from fetal kidneys and showed their beneficial effects in treating chronic renal injury. He 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 has sparked a multi-center clinical trial for relapsing pediatric cancer. His lab is now evaluating novel therapeutics aimed at eradicating cancer stem cell function in multiple aggressive tumors. In addition, Prof. Dekel has recently solved a fundamental question in renal biology as to how and to what extent the mammalian kidney maintains and regenerates its entire compartments at the single cell level by showing a mechanism of continuous regeneration and cellular renewal of kidney epithelia by fate-restricted and segment-specific clonal progeny that persists throughout adult life. Based on these basic discoveries Prof Dekel's group are utilizing human adult kidney tissue and novel methodologies to grow multiple lineage-restricted progenitors ex-vivo. These human adult kidney derived cells can generate different parts of the kidney after being transplanted into pre-clinical murine hosts and by that potentially serve as a novel form of renal regenerative medicine

Prof. Dekel's studies are summarized in over 100 publications in the leading medical journals; Nature Medicine, EMBO Molecular Medicine, N Engl J Med, PNAS, Cancer Research, Oncogene, Cell Reports, Stem Cell Reports, J Am Soc Nephrol, Nature Rev Nephrol. He is an elected member of the the American Society of Clinical Investigation (ASCI). Prof Dekel serves on the SAB of the UK Regenerative Medicine Initiative and has served on multiple review panels for journals and grant agencies including the ERC, MRC, and Kidney Research, UK.  Dr. Dekel serves as an inaugural Editorial Member of Stem Cells Translational Medicine and he is on the editorial board of other Stem cell/Tissue engineering journals.  His research has been supported by numerous sources including the Israel Scientific Foundation, Israel Cancer Research Fund, Israel Cancer Association, Israel Ministry of Health, Israel Ministry and Industry and Infrastructure, the European Research Committee (FP7), the NIH/NIDDK, Ziering and Brettler Foundations and collaborative grants with academic institutes including MD Anderson Cancer Center and Cedars-Sinai Hospital. As a PI, he has already trained a myriad of clinical and research physicians, investigators, and clinician-scientists and is constantly promoting the physician-scientist training on a national level. Prof. Dekel is a sought-after speaker receiving numerous and ongoing invitations to speak and chair sessions at leading national/international conferences in stem cell research, development and nephrology including keynote and plenary lectures. He and his students have been awarded several first place prizes for scientific presentations including the Society of Pediatric Research Award.  Dr. 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 and the prestigious Youdim Family Prize for Excellence in Cancer Research.

Research

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).

Selected Publications

Publications (last 5 years)

65. Pode-Shakked N, Harari-Steinberg O, Haberman-Ziv Y, Rom-Gross E, Bahar S, Omer D, Metsuyanim S, Buzhor E, Goldstein RS, Mark-Danieli M, Dekel B. Featured article: Resistance or sensitivity of Wilms’ tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target. Oncogene 2011;30(14):1664-80. B1

Highlighted in Global Medical Discovery:

http://globalmedicaldiscovery.com/key-scientific-articles/resistance-or-sensitivity-of-wilms-tumor-to-anti-fzd7-antibody-highlights-the-wnt-pathway-as-a-possible-therapeutic-target/

66. Pode-Shakked N, Dekel B, Wilms' tumor – a renal stem cell malignancy? Pediatr Nephrol. 2011 Sep;26(9):1535-43

67. Harari-Steinberg O, Pleniceanu O, Dekel B. Selecting the optimal cell for kidney regeneration: fetal, adult or reprogrammed stem cells. Organogenesis 2011 Apr 1;7(2).

68. Buzhor E, Harari-Steinberg O, Omer D, Mark-Danieli M, Noiman T, Goldstein RS, Dekel B. Kidney spheroids recapitulate tubular organoids leading to enhanced tubulogenic potency of human kidney-derived cells. Tissue Eng 2011;17(17-18):2305-19. B1

69. Noiman T*, Buzhor E*, Zangi L, Harari-Steinberg O, Dekel B, Goldstein RS. A rapid, economical and humane in-vivo assay system for analyzing organogenetic capacity of human kidney cells. Organogenesis 2011 Apr 1;7(2). * Equal first authors B1

70. Vivante A*,Lotan D*,Pode-Shakked N*, Landau D , Svec P, Nampoothiri S, Verma I, Abu-Libdeh A, Bockenhauer D, Dekel B**, and Anikster Y**. Familial Autosomal Recessive Renal Tubular Acidosis: Importance of Early Diagnosis. Nephron Physiol 2011;119(3):p31-p39.. ** Equal senior authors, corresponding author (Dekel B) B1

71. Machol K, Vivante A, Rubinsthein N, Dekel B, Paret G. Keeping the Heart in Mind when Managing Hemolytic Uremic Syndrome. Isr Med Assoc J. 2011;13(7):446-7. CASE REPORT

72. Kovalski Y, Cleper R, Krause I, Dekel B, Belenky A, Davidovits M. Hyponatremic hypertensive syndrome in pediatric patients: is it really so rare? Pediatr Nephrol. 2012 Jun;27(6):1037-40. B1

73. Has C, Spartà G, Kiritsi D, Weibel L, Moeller A, Vega-Warner V, Waters A, He Y, Anikster Y, Esser P, Straub BK, Hausser I, Bockenhauer D, Dekel B, Hildebrandt F, Bruckner-Tuderman L, Laube GF. Integrin α3 mutations with kidney, lung, and skin disease. N Engl J Med. 2012;366(16):1508-14. B1

74. Bussolati B, Dekel B, Azzarone B, Camussi G. Human renal cancer stem cells. Cancer Lett. 2013;338(1):141-6. REVIEW

75. Pode-Shakked N, Shukron R, Bahar S, Pri-Chen S, Tsvetkov P, Goldstein RS, Rom-Gross E, Mor Y, Fridman E, Goldmacher VS, Harari-Steinberg O, Mark-Danieli M, Dekel B. Isolation and characterization of renal cancer initiating cells in wilms tumor xenografts unveils new therapuetic targets. EMBO Mol Med, 2013;5(1):18-37. B1

Accompanying Focus Article: The Stem and Roots of Wilms Tumor, http://dx.doi.org/10.1002/emmm.201202173.

EMBO press release: http://www.embo.org/news-a-media-centre/press-releases/cancer-stem-cells-isolated-from-kidney-tumours.html

76. Vivante A, Mark-Danieli M, Davidovits M, Harari-Steinberg O, Omer D, Gnatek Y, Cleper R, Landau D, Kovalski Y, Weissman I, Eisenstein I, Soudack M, Wolf HR, Issler N, Lotan D, Anikster Y, Dekel B. Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling. J Am Soc Nephrol. 2013;24(4):550-8.  B1

Highlighted in Global Medical Discovery

77. Pleancianu O, Dekel B. Book chapter: Stem Cells in Fetal Tissue (The Kidney as a Model) in Human Fetal Tissue Transplantation, Bha​ttacharya Ed. Springer-Verlag London 2013. BOOK CHAPTER

78. Omer D, Harari-Steinberg O, Pleaniceanu O, Buzhor E, Metsuyanim S, Goldstein RS, Dekel B. Featured article: Chromatin-modifying agents reactivate embryonic renal stem/progenitor genes in human adult kidney epithelial cells but abrogate dedifferentiation and stemness. Omer D, Harari-Steinberg O, Buzhor E, Metsuyanim S, Pleniceanu O, Zundelevich A, Gal-Yam EN, Dekel B. Cell Reprogram. 2013;15(4):281-92. B1

79. Shukrun R, Pode Shakked N, Dekel B. Targeted therapy aimed at cancer stem cells: Wilms' tumor as an example. Pediatr Nephrol. 2013 Jun 13. [Epub ahead of print] REVIEW

80. Harari-Steinberg O* Metsuyanim S*, Omer D, Gnatek Y, Gershon R, Pri-Chen S, Ozdemir DD, Lerenthal Y,  Noiman T, Ben-Hur H, Vaknin Z, Schenider DF, Aronow BJ, Goldstein RS, Buzhor E, Hohenstein P, Dekel B. Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease. EMBO Mol Med 2013;5(10):1556-68. B1

81. Buzhor E, Omer D, Harari-Steinberg O, Vax E, Metsuyanim S, Noiman T, Goldstein RS, Dekel B. Re-activation of NCAM1 defines a sub-population of human adult kidney epithelial cells with clonogenic and stem/progenitor properties. Am J Pathol 2013;183(5):1621-33. B1

82. Pode B, Bunjanover Y, Dekel B, Anikster Y. The bitterness of Glucose/Galactose: Novel mutations in the SLC5A1 gene. J Pediatr Gastroenterol Nutr 2014;58(1):57-60. B1

83. Shukrun R, Vivante A, Pleniceanu O, Vax E, Anikster Y, Dekel B**, Lotan D**. A human integrin-α3 mutation confers major renal developmental defects. PLoS One. 2014 12;9(3):e90879. **Equal senior authors, corresponding author (Dekel B) B1

84. Rinkevich Y, Montoro DT, Contreras-Trujillo H, Harari-Steinberg O, Newman AM, Lim X, Van-Amerongen R, Bowman A,. Tsai JM, Nusse R, Longaker MT, *Weissman IL^, *Dekel B. In vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance and Regeneration. Cell Reports, 2014;7(4):1270-83 (*equal last authors). B1

85. Urbach A, Yermalovich A, Zhang J, Spina CS, Zhu H, Perez-Atayde AR, Shukrun R, Charlton J, Sebire N, Mifsud W, Dekel B, Pritchard-Jones K, Daley GQ. Lin28 sustains early renal progenitors and induces Wilms tumor. Genes and Development, 2014;28(9):971-82. B1

86. Shukrun R; Pode-Shakked N; Pleniceanu O, Omer D, Vax E, Pri-Chen S, Hu Q, Harari-Steinberg O, Huff V, Dekel B. Wilms' tumor blastemal stem cells dedifferentiate to propagate the tumor bulk. Stem Cell Reports. 2014;3(1):24-33. B1

87. Dziedzic K, Pleniceanu O, Dekel B. Kidney stem cells in development, regeneration and cancer. (Invited Review). Semin Cell Dev Biol. Semin Cell Dev Biol. 2014;36:57-65 REVIEW

88. Schlingmann KP, Ruminska J, Kaufmann M, Dursun I, Patti M, Kranz B, Pronicka E, Ciara E, Akcay T, Bulus D, Cornelissen EA, Gawlik A, Sikora P, Patzer L, Galiano M, Boyadzhiev V, Dumic M, Vivante A, Kleta R, Dekel B, Levtchenko E, Bindels RJ, Rust S, Forster IC, Hernando N, Jones G, Wagner CA, Konrad M. Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.

J Am Soc Nephrol. 2015 Jun 5. pii: ASN.2014101025. [Epub ahead of print]

89. Romagnani P, Rinkevich Y, Dekel B. Current lineage tracing methods to study kidney regeneration, their limitations and advantages. Nat Rev Nephrol. 2015;11(7):420-31REVIEW

90. Pleancianu O, Dekel B. Book chapter: Renal Stem Cells in Oxford Textbook of Clinical Nephrology (4^th edition, Chief Ed. Neil Turner). Oxford University Press 2015.

91. Pleancianu O, Dziedzic K, Dekel B. From embryonic rudiments to renal stem/progenitor cells in Kidney Development, Disease, Repair and Regeneration, 1st Edition (Ed. Little MH). Elsevier 2015.

92. Sanyal M, Morimoto M, Baradaran-Heravi A, Choi K, Kambham N, Jensen K, Dutt S, Dionis-Petersen KY, Liu LX, Felix K, Mayfield C, Dekel B, Bokenkamp A, Fryssira H, Guillen-Navarro E, Lama G, Brugnara M, Lücke T, Olney AH, Hunley TE, Polat AI, Yis U, Bogdanovic R, Mitrovic K, Berry S, Najera L, Najafian B, Gentile M, Nur Semerci C, Tsimaratos M, Lewis DB, Boerkoel CF. Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD). Clin Immunol. 2015 Oct 21;161(2):355-365. doi: 10.1016/j.clim.2015.10.005. [Epub ahead of print]

93.  Dekel B. The ever expanding kidney repair shop (Invited Editorial). J Am Soc Nephrol. 2015 Dec 7. pii: ASN.2015111207. [Epub ahead of print]

94. Pode-Shakked N, Pleniceanu O, Gershon R, Shukrun R, Kanter I, Bucris E, Pode-Shakked B, Tam G, Tam H, Caspi R, Pri-Chen S, Vax E, Katz G, Omer D, Harari-Steinberg O, Kalisky T, Dekel B. Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells. Sci Rep. 2016;6:23562.

95. Gilboa Y, Perlman S, Pode-Shakked N, Pode-Shakked B, Shrim A, Azaria-Lahav E, Dekel B, Yonath H, Berkenstadt M, Achiron R.Prenatal diagnosis of 17q12 deletion syndrome: from fetal hyperechogenic kidneys to high risk for autism. Prenat Diagn. 2016 Nov;36(11):1027-1032.

96. Perlman S, Lotan D, Dekel B, Kivilevitch Z, Hazan Y, Achiron R, Gilboa Y. Prenatal compensatory renal growth in unilateral renal agenesis. Prenat Diagn. 2016;36(11):1075-1080.

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. PPARg 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 Apr 5. pii: ASN.2016060694. doi: 10.1681/ASN.2016060694.

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 Jul 20. doi: 10.1158/1535-7163.MCT-17-0184. [Epub ahead of print]

(*equal last and corresponding authors.).

103. Pleniceanu O, Omer D, Azaria E, Dekel B. mTOR inhibition for sporadic angiomyolipoma. Kidney Int Reports (in press)

104. 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. Long term in vivo propagation of human malignant rhabdoid tumor as a platform to identify and target CIC/CSCs . (Under revision).

105. 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. (Submitted).