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.

mdchpk[at]nus.edu.sg

Biosketch

Senior Principal Investigator, Cancer Science Institute of Singapore, National University of Singapore
Distinguished Visiting Professor, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
Senior Consultant, Department of Haematology-Oncology, National University Hospital
Professor of Medicine, Cedars-Sinai Medical Center/UCLA

1978 – Present National Society of Clinical Investigation
1997 – Present Holder of the Mark Goodson Chair in Oncology Research (CSMC)
2009 – 2019 STAR Investigator Award
2013 – Present American Association of Physicians

Research

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.

Lab Members

Selected Publications

1. Xu L, Chen Y, Huang Y, Sandanaraj E, Yu JS, Lin RY, Dakle P, Ke X, Chong YK, Koh L, Mayakonda A, Nacro K, Hill J, Huang M, Gery S, Lim SW, Huang Z, Xy Y, Chen J, Bai L, Wang S, Wakimioto H, Yeo TT, Ang BT, Muschen M, Tang C, Tan TZ, Koeffler HP (2021). Topography of transcriptionally active chromatin in glioblastoma. Sci Adv. 7(18):eabd4676.

2. Chen L, Huang M, Plummer J, Pan J, Jiang YY, Yang Q, Silva TC, Gull N, Chen S, Ding LW, An O, Yang H, Cheng Y, Said JW, Doan N, Dinjens WN, Waters KM, Tuli R, Gayther SA, Klempner SJ, Berman BP, Meltzer SJ, Lin DC and Koeffler HP (2020). Master transcription factors form interconnected circuitry and orchestrate transcriptional networks in oesophageal adenocarcinoma. Gut. 69(4):630-640.

3. Ding LW, Sun QY, Edwards JJ, Fernandez LT, Ran XB, Zhou SQ, Scolyer RA, Wilmott JS, Thompson JF, Doan N, Said JW, Venkatachalam N, Xiao JF, Loh XY, Pein M, Xu L, Mullins DW, Yang H, Lin DC and Koeffler HP (2019). LNK suppresses interferon signaling in melanoma. Nat Commun 10(1): 2230

4. Shyamsunder P, Shanmugasundaram M, Mayakonda A, Dakle P, Teoh WW, Han L, Kanojia D, Lim MC, Fullwood M, An O, Yang H, Shi J, Hossain MZ, Madan V and Koeffler HP (2019). Identification of a novel enhancer of CEBPE essential for granulocytic differentiation. Blood 133(23): 2507-2517.

5. Chen Y, Xu L, Mayakonda A, Huang ML, Kanojia D, Tan TZ, Dakle P, Lin RY, Ke XY, Said JW, Chen J, Gery S, Ding LW, Jiang YY, Pang A, Puhaindran ME, Goh BC and Koeffler HP (2019). Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma. Nat Commun 10(1): 1353.

6. Jiang Y, Jiang YY, Xie JJ, Mayakonda A, Hazawa M, Chen L, Xiao JF, Li CQ, Huang ML, Ding LW, Sun QY, Xu L, Kanojia D, Jeitany M, Deng JW, Liao LD, Soukiasian HJ, Berman BP, Hao JJ, Xu LY, Li EM, Wang MR, Bi XG, Lin DC and Koeffler HP (2018). Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression. Nat Commun 9(1): 3619

7. Xie JJ, Jiang YY, Jiang Y, Li CQ, Lim MC, An O, Mayakonda A, Ding LW, Long L, Sun C, Lin LH, Chen L, Wu JY, Wu ZY, Cao Q, Fang WK, Yang W, Soukiasian H, Meltzer SJ, Yang H, Fullwood M, Xu LY, Li EM, Lin DC and Koeffler HP (2018). Super-Enhancer-Driven Long Non-Coding RNA LINC01503, Regulated by TP63, Is Over-Expressed and Oncogenic in Squamous Cell Carcinoma. Gastroenterology 154(8): 2137-2151. e1.

8. Lin DC, Dinh HQ, Xie JJ, Mayakonda A, Silva TC, Jiang YY, Ding LW, He JZ, Xu XE, Hao JJ, Wang MR, Li C, Xu LY, Li EM, Berman BP and Phillip Koeffler H (2018). Identification of distinct mutational patterns and new driver genes in oesophageal squamous cell carcinomas and adenocarcinomas. Gut 67(10):1769-1779

9. Madan V, Kanojia D, Li J, Okamoto R, Sato-Otsubo A, Kohlmann A, Sanada M, Grossmann V, Sundaresan J, Shiraishi Y, Miyano S, Thol F, Ganser A, Yang H, Haferlach T, Ogawa S and Koeffler HP (2015). Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome. Nat Commun 6: 6042

10. Lin DC, Hao JJ, Nagata Y, Xu L, Shang L, Meng X, Sato Y, Okuno Y, Varela AM, Ding LW, Garg M, Liu LZ, Yang H, Yin D, Shi ZZ, Jiang YY, Gu WY, Gong T, Zhang Y, Xu X, Kalid O, Shacham S, Ogawa S, Wang MR and Koeffler HP (2014). Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat Genet 46(5): 467-473