H. Phillip KOEFFLER

The major focus of Prof Koeffler’s lab is identifying key DNA abnormalities in cancers and translating these findings into novel classifications and diagnoses. In addition, his team has begun looking for new therapeutic approaches based on the DNA changes that occur in these tumours. They have learned that not only do tumours have common unifying DNA changes, each have unique DNA changes. Therefore successful therapy will require the ability to survey rapidly the entire genome for alterations so that they can tailor therapy for the alterations within each individual’s cancer. Another major focus is testing drugs and other agents for their therapeutic efficacy in cancers.

We study the cellular and molecular biology of cancer – from genes to humans. Our basic research begins with whole exon deep sequencing of selected cancer subtypes. In particular, we are focused on samples from patients that have a recurrence of the cancer or the cancer is resistant to standard therapies. This affords the opportunity to identify genes associated with cancer progression. After identifying mutant genes, we study the functional consequences of these mutations by standard molecular and cellular biology techniques such as over-expression and silencing of the genes, and looking at the biological consequences both in vitro, as well as, in vivo in murine model systems. Where appropriate, we make germline alterations in mice to recapitulate the disease. We study the importance of these altered genes in human cancers, taking advantage of large collection of human tumor samples. Using these collections, we analyze for aberrant gene expression both at the RNA and protein levels (quantitive RT-PCR, Western blot, and immunohistochemistry including the use of large tissue arrays). The major cancers that we explore include: nasopharyngeal, lung, breast, and pancreatic cancers, glioblastoma multimultiforme (brain tumor), various sarcomas and hematopoietic malignancies.

Selected Publications:

  1. Lin D, Xu L, Ding L, Sharma A, Liu LZ, Yang H, Tan P, Vadgama J, Karlan B, Lester J Urban N, Schummer M, Doan N, Said JW, Sun H, Walsh M, Thomas CJ, Patel P, Yin D, Chan D, Koeffler HP. Genomic and functional characterizations of phosphodiesterase 4D in human cancers. PNAS. Mar 27 2013. [Epub ahead of print].
  2. Lin D, Yin T, Koren-Michowitz M, Ding L, Gueller S, Gery S, Tabayashi T, Bergholz U, Kazi JU,  Ronnstrand L, Stocking C, Koeffler HP. Adaptor protein LNK binds to and inhibits normal and leukemic FLT3. Blood, Oct18; 120(16): 3310-7, 2012. PMID 22942183.
  3. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo a, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi t, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, shih LY, Haferlach T, Chiba S, Nakauchi H, Miyano S, Ogawa S. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature, Sep11;478(7367):64-9, 2011.
  4. Duy C, Hurtz C, Shojaee S, Cerchietti L, Geng H, Swaminathan S, Klemm L, Kweon SM, Nahar R, Braig M, Park E, Kim YM, Hofmann WK, Herzong S, Jumaa H, Koeffler HP, Yu JJ, Heisterkamp N, Graeber TG, Wu H, Ye BH, Melnick A, Muschen M. BCL6 enables Ph+ acute lymphoblastic leukemia cells to survive BCR-ABL1 kinase inhibition. Nature 473(7347):384-8, 2011. PMID 21593872
  5. Sherborne AL, Hosking FJ, Prasad RB, Kumar R, Koehler R, Vijayakrishnan J, Papaemmanuil E, Bartram CR, Stanulla M, Schrappe M, Gast A, Dobbins SE, Ma Y, Sheridan E, Taylor M, Kinsey SE, Lightfoot T, Roman E, Irving JA, Allan JM, Moorman AV, Harrison CJ, Tomlinson IP, Richards S, Zimmermann M, Szalai C, Semsei AF, Erdelyi DJ, Krajinovic M, Sinnett D, Healy J, Neira AG, Kawamata N, Ogawa S, Koeffler HP, Hemminki K, Greaves M, Houlston RS. Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk. Nat Genet. 2010, 42(6):492-4.
  6. Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, Tamura A, Honda H, Sakata-Yanagimoto M, Kumano K, Oda H, Yamagata T, Takita J, Gotoh N, Nakazaki K, Kawamata N, Onodera M, Nobuyoshi M, Hayashi Y, Harada H, Kurokawa M, Chiba S, Mori H, Ozawa K, Omine M, Hirai H, Nakauchi H, Koeffler HP, Ogawa S. Gain-of-function of mutated c-Cbl tumor suppressor associated with myeloid neoplasms with 11q UPD. Nature, 2009, 460(7257):904-8.
  7. Kawamata N, Ogawa S, Zimmermann M, Niebuhr B, Stocking C, Sanada M, Hemminki K, Yamatomo G, Nannya Y, Koehler R, Flohr T, Millr C, Harbott J, Ludwig W, Stanulla M, Schrappe M, Bartram C, Koeffler HP. Cloning of genes involved in chromosomal translocations by high resolution single nucleotide polymprphism genomic microarray.  PNAS. 105(33):11921-6, 2008.
  8. Gery S, Komatsu N, Baldjyan L, Yu A, Koo D, Koeffler HP.  The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells.  Mol. Cell. 22(3):375-82, 2006.
  9. Chumakov AM, Grillier I, Chumakova E, Chih D, Slater J and Koeffler HP.  Cloning of the Novel Human Myeloid-Cell-Specific C/EBPε- Transcription Factor.  Mol. Cell. Biol., 17(3) 1375-1386,1997.
  10. Masuda H, Miller C, Koeffler HP, Battifora H, Cline MJ.  Rearrangement of the p53 gene in human osteogenic sarcoma.  PNAS, 84:7716-7719, 1987.
Name H. Phillip KOEFFLER
Affiliations Senior Principal Investigator, Cancer Science Institute of Singapore, NUS
Professor, Department of Medicine, Yong Loo Lin School of Medicine, NUS
Deputy Director (Research), National University Cancer Institute of Singapore, NUHS
Email mdchpk[at]nus.edu.sg

Education

Institute Degree (if applicable) Year(s)
University of Wisconsin, Madison, WI B.A.: Zoology 1968
Baylor College of Medicine, Houston, TX- M.D.: Medicine 1972
Internship and Residency, Los Angeles County USC Medical Center Los Angeles, California 1975
Fellowship, UCLA, Division of Hematology/Oncology Department of Medicine, (Martin J. Cline, Chief) 1978

Professional Experience

Senior Principal Investigator, Cancer Science Institute of Singapore, National University of Singapore 2009 – Present
Professor, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore 2009 – Present
Deputy Director of Cancer Research, National University of Singapore 2009 – Present
Professor of Medicine, Cedars-Sinai Professorial Series 2009 – Present
Professor of Bioengineering, University of California Los Angeles, Los Angeles, CA 2008 – Present
Holder of The Mark Goodson Chair in Oncology Research Cedars-Sinai Medical Center 01/1997 – 2010
Director, Division of Hematology/Oncology, Cedars-Sinai Medical CenterProfessor of Medicine, UCLA School of Medicine, Los Angeles, CA 04/1990 – 2010
Present Professor of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, California 07/1986
Associate Professor of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, California 07/1982 – 07/1986
Visiting Scientist, Department of Molecular Biology, California Institute of Technology, Pasadena, California, (Dr. Thomas Maniatis) 07/1979 – 09/1979
Assistant Professor of Medicine, UCLA, Division of Hematology/Oncolog, Department of Medicine, Los Angeles, California 06/1978 – 07/1982
Visiting Scientist, University of Chicago, Department of Biochemistry (Eugene Goldwasser, Ph.D.) 07/1978 – 08/1978
Dr LIN Dechen

LIN Dechen

PhD Visiting Senior Research Scientist

I am studying genetic abnormalities in human cancers including copy number variations as well as single nucleotides changes.

Dr Vikas MADAN

Vikas MADAN

PhD Senior Research Scientist

Functional studies on splicing factors frequently mutated in Myelodysplastic Syndrome and identification of somatic mutations associated with emergence and progression of acute myeloid leukemia to understand disease genetics and evolution.

CHEN Ye

PhD Research Fellow

Transcriptional addiction and cancer models

DING Ling Wen

PhD Research Fellow

Functional study of adaptor protein Lnk (SH2B3) and to identify novel driver mutation of ALL (Acute Lymphoblastic Leukemia) by whole exon sequencing.

Maya JEITANY

PhD Research Fellow

 

JIANG Yanyi

PhD Research Fellow

My research focuses on the identification of super-enhancers and novel long-non coding RNA in human cancers.

Dr Deepika KANOJIA

Deepika KANOJIA

PhD Research Fellow

Study of genomic alterations and rearrangements in Liposarcomas using next generation sequencing technology to discover new therapeutic targets.

JIANG Yuan

PhD Research Fellow

Investigate genomic abnormalitites of nasopharyngeal carcinoma

Pavithra SHYAMSUNDER

PhD Research Fellow

XU Liang

XU Liang

PhD Research Fellow

Study of epigenetic alterations and addictions in human malignancies.

SUN Qiaoyang

PhD Research Fellow

Functional study of histone methyltransferase SETDB1. Identify novel driver mutation of AML (MLL-PTD subtype) by whole exon sequencing.

XIAO Jinfen

Research Fellow

My research focus is studying the oncogene in breast cancer initiation and the mechanism underlining its tumorigenesis potential.

LOH Xin Yi

Research Assistant

My research is on role of RNA-binding protein in degrading oncogenic transcripts in breast carcinogenesis.

Anand M.T

Research Assistant

I mainly analyse data generated from Next Generation Sequencing and Microarrays. I also assist postdocs and graduate students in bioinformatic work.

LIN Yu-Tong, Ruby

Laboratory Executive

Responsible for lab management and assisting in research works.

TEOH Weoi Woon

Laboratory Executive

Responsible for lab management and assisting in research works.

HAN Lin

PhD student

The role of ARID1A in normal and malignant hematopoiesis.