Daniel G. TENEN

Professor Tenen is a leader in gene regulation in both normal differentiation and cancer, with a focus on leukemia, lung cancer, and liver cancer. Current efforts include basic studies understanding gene regulation in normal and leukemic hematopoietic stem cells, with an aim to develop novel ways of manipulating gene expression in stem cells as well as exploiting differences between normal and leukemic stem cells as a basis for targeted leukemia stem cell therapy, and the role of stem cell oncofetal proteins in leukemia and solid tumors, especially liver cancer. Recent studies have focused on noncoding RNAs, and include published findings on antisense RNAs, RNA editing, and noncoding RNAs in gene regulation, methylation, and cancer. Our most recent studies demonstrated that RNA can regulate DNA methylation, and that RNA can be utilized to induce demethylation in a gene-specific manner. We are working on methods of activating tumor suppressors silenced in cancer.

Selected Publications:

  1. Ye M, Zhang H, Yang H, Koche R, Staber PB, Cusan M, Levantini E, Welner RS, Bach CS, Zhang J, Krivtsov A, Armstrong SA, Tenen DG. Hematopoietic differentiation is required for initiation of acute myeloid leukemia. 2015. Cell Stem Cell 17:611-623.
  2. Welner RS, Amabile G, Bararia D, Czibere A, Yang H, Zhang H, Pontes LF, Ye M, Levantini E, Di Ruscio A, Martinelli G, Tenen DG. Treatment of chronic myelogenous leukemia by blocking cytokine alterations found in normal stem and progenitor cells. 2015. Cancer Cell 27:671-681.
  3. Amabile G*, Di Ruscio A*, Müller F*, Welner RS, Yang H, Ebralidze AK, Zhang H, Levantini E, Qi L, Martinelli G, Brummelkamp T, Le Beau MM, Figueroa ME, Bock C, Tenen DG. Dissecting the role of aberrant DNA methylation in human leukemia. 2015. Nat Commun. 6:709. *co-first authors.
  4. Staber PB, Zhang P, Ye M, Welner RS, Levantini E, Di Ruscio, Ebralidze AK, Bach C, Zhang H, Zhang J, Vanura K, Delwel, Yang H, Huang G, Tenen DG. The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells. 2014. Blood 124:2391-2399. PMCID in process.
  5. Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA, Terragni J, Figueroa ME, De Figureido Pontes LL, Alberich-Jorda M, Zhang P, Wu M, D’Alò F, Melnick A, Leone G, Ebralidze KK, Pradhan S, Rinn JL, Tenen DG. DNMT1-interacting RNAs block gene specific DNA methylation. 2013. Nature 503:371-376. PubMed Central PMCID: PMC3870304.
  6. Yong KJ, Gao C, Lim JSJ, Yan B, Yang H, Dimitrov T, Kawasaki A, Ong CW, Wong KF, Lee S, Ravikumar S, Srivastava S, Tian X, Poon RT, Fan ST, Luk JM, Dan YY, Salto-Tellez M, Chai L, Tenen DG. Oncofetal Gene SALL4 Defines an Aggressive Hepatocellular Carcinoma Subtype. 2013. N Engl J Med 368:2266-76. PMCID: PMC3781214.
  7. Ye M, Zhang H, Amabile G, Yang H, Staber PB, Zhang P, Levantini E, Alberich-Jordà M, Zhang J, Kawasaki A, Tenen DG. C/EBPa controls acquisition and maintenance of adult hematopoietic stem cell quiescence. 2013. Nature Cell Biol. 15:385-94. PMCID: PMC3781213.
  8. Staber PB, Zhang P, Ye M, Welner R, Nombela-Arrieta C, Bach C; Kerenyi M, Bartholdy BA, Zhang H; Alberich-Jorda M, Lee S, Yang H, Ng F, Zhang J, Leddin M, Silberstein LE, Hoefler G, Gottgens B, Rosenbauer F, Huang G, Tenen DG. Sustained PU.1 Levels Balance Cell Cycle Regulators to Prevent Exhaustion of Adult Hematopoietic Stem Cells. 2013. Molecular Cell 49:934-46.
  9. Amabile G, Welner RS, Nombela-Arrieta C, D’Alise AM, Di Ruscio A, Ebralidze AK, Kraytsberg Y, Ye M, Kocher O, Neuberg DS, Khrapko K, Silberstein LE, Tenen DG. In Vivo Generation of Transplantable Human Hematopoietic Cells from Induced Pluripotent Stem Cells. 2013. Blood 121:1255-64.
  10. Pabst T, Mueller BU, Zhang P, Radomska HS, Narravula S, Schnittger S, Behre G, Hiddemann W, Tenen DG. Dominant-negative mutations of CEBPA, encoding CCAAT/Enhancer Binding Protein- (C/EBP) in acute myeloid leukemia. 2001: Nature Genetics 27:263-270
Name Daniel G. TENEN
Affiliations Director, Cancer Science Institute of Singapore, NUS
Programme Leader and Senior Principal Investigator, Cancer Science Institute of Singapore, NUS
Distinguished Professor in Medicine, NUS
Email daniel.tenen[at]nus.edu.sg

Education

Institute Degree (if applicable) Year(s)
University of California, Los Angeles CA B.A. 1971
Harvard Medical School, Boston MA M.D. 1975

Professional Experience

Director, Cancer Science Institute of Singapore, National University of Singapore 2008 – Present
Programme Leader and Senior Principal Investigator, Cancer Science Institute of Singapore, National University of Singapore 2008 – Present
Distinguished Professor in Medicine, National University of Singapore 2008 – Present
Director, Blood Program, Harvard Stem Cell Institute, Harvard Medical School 2005 – Present
Professor of Medicine, Harvard Medical School 1999 – Present
Associate Professor of Medicine, Harvard Medical School 1994 – 1999
Assistant Professor of Medicine, Harvard Medical School 1986 – 1993
Instructor in Medicine, Harvard Medical School 1978 – 1986
Research Fellow in Medicine, Harvard Medical School & Dana-Farber Cancer Institute (Laboratory of David M. Livingston) 1975 – 1984

Tim Hon Man CHAN

PhD
Research Scientist

Identification and characterisation of novel oncogenes and tumor suppressor genes involved in liver cancer.

Akihiko NUMATA

MD, PhD
Adjunct Research Scientist

Development of new therapy for leukemia.

Vladimir Espinosa ANGARICA

PhD
Research Fellow

Bioinformatics study of the regulation of DNA methylation and gene expression mediated by DNMT1-ncRNA interactions.
Bioinformatics study of non-coding RNA interaction networks.

Pramila Baban GHODE

PhD
Research Fellow

Structural insights into DNMT1-RNA interactions that regulate gene methylation.

DGT - Li Feng

LI Feng

PhD
Research Fellow

Interrogate the RNA binding partners of transcription factors to understand the RNA biology and therapeutics in haematopoiesis and leukaemia.

LIU Bee Hui

LIU Bee Hui

PhD
Research Fellow

Small molecule screening to target SALL4-NuRD interaction.

Sridhar RADHAKRISHNAN

PhD
Research Fellow

Design and synthesis of small molecules targeting SALL4-NuRD interaction.

Justin TAN

PhD
Research Fellow

Discovery and characterisation of novel therapeutics for SALL4-dependent liver cancer.

TEO Wei Wen

PhD
Research Fellow

Noncoding RNA and Polycomb complex.

WU Chan Shuo

PhD
Research Fellow

Development of bioinformatics pipelines. Providing bioinformatics support.

YONG Kol Jia

Research Fellow

Identification of the roles of stem cell factor SALL4 in solid tumors.

TANG Jing Ping

Senior Laboratory Executive

Lab management and work on crystallography and SALL4 drug screening project.

TAN Zi Hui

Laboratory Executive

The Role of DNMT3B in Trilineage Differentiation of Human Embryonic Stem Cells.

YEO Zhen Zhen Joanna

Laboratory Executive

Chemical screening and characterisation of novel therapeutics targeting SALL4-dependent hepatocellular carcinoma.

CAO Xinang

PhD student

PRC2-RNA interaction.                                                                                                                               .

Kalpana KUMARI

PhD student

RNA specific regulation of DNMT1.

Junsu KWON

PhD student

Identification and characterization of novel ncRNA involved in SALL4 regulation in HCC.

LIU Yanjing

PhD student

RNA approach for gene specific demethylation.

TAN Hong Kee

PhD student

RNA binding of DNMT3 and chromatin interaction in AML.

ZHOU Qiling

PhD student

Transcriptional regulation of myeloid transcription factors.