Harold (H. Phillip) Phillip Koeffler, MD

Dr. Phillip Koeffler studies the cellular and molecular biology of cancer focusing on glioblastoma multiforme, breast and lung cancers and leukemias/lymphomas. He has performed a SNP Chip analysis on more than 2000 cancers of different varieties and used these data to develop new diagnostic and prognostic indicators of various cancers, as well as to identify novel alterations in these cancers. He is doing exon sequencing and paired Ð end tagged sequencing of selective leukemia and cancer samples at the time of diagnosis, remission and relapse in order to define the complete genomic changes at diagnosis and relapse. In addition, he actively studies the anti-cancer activity of novel compounds including those from various medicinal plants, nuclear hormone receptor ligands and fusions of monoclonal antibodies conjugated to various agents. He is also associating in vitro and in vivo efficacy of a novel compound with the genomic signature of the cancer.

Additional research within Koeffler's lab include:

1. Studies of an adaptor protein LNK that interacts with activated tyrosine kinase receptors and inhibits the activity of these activated receptors.
2. Studies of the dysregulation of circadian rhythm genes in cancer particularly focusing on PER-1 and PER-2.
3. Studies of transcription factors particularly their anti-microbial stimulatory activities in hypoxic conditions.

Thoennissen NH, Krug UO, Lee DH, Kawamata N, Iwanski GB, Lasho T, Weiss T, Nowak D, Koren-Michowitz M, Kato M, Sanada M, Shih LY, Nagler A, Raynaud SD, Muller-Tidow C, Mesa R, Haferlach T, Gilliland DG, Tefferi A, Ogawa S, Koeffler HP. Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms. Blood. 2010 Apr 8;115(14):2882-90. Epub 2010 Jan 12.

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, Gonzalez Neira A, 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 Jun;42(6):492-4. Epub 2010 May 9.

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 tumour suppressor in myeloid neoplasms. Nature. 2009 Aug 13;460(7257):904-8. Epub 2009 Jul 20.

Kawamata N, Ogawa S, Zimmermann M, Niebuhr B, Stocking C, Sanada M, Hemminki K, Yamatomo G, Nannya Y, Koehler R, Flohr T, Miller CW, Harbott J, Ludwig WD, Stanulla M, Schrappe M, Bartram CR, Koeffler HP. Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11921-6. Epub 2008 Aug 12.

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. 2006; 22(3): 375-82.