Maxwell P. Lee, Ph.D.
Maxwell P. Lee, Ph.D.
Senior Associate Scientist
Head, High-Dimension Data Analysis Group

Center for Cancer Research
National Cancer Institute

Building 41, Room D702C
Bethesda, MD 20892
301-435-8956

Integrated genomic and epigenomic studies of breast cancer: an allelic-specific perspective My research involves applying my expertise in genomics and epigenomics to dissecting out the components of breast cancer. I have been focusing on elucidating allele-specific gene expression and allele-specific epigenetic modifications. We developed a specific adaptation of SNP array-based high throughput technology. We showed that differential expression from the two alleles of a given gene is common in normal tissue. We followed this by demonstrating that the genetic background influences the epigenetic state of chromatin.

Areas of Expertise
chromatin, breast cancer

Integrated genomic and epigenomic studies of breast cancer: an allelic-specific perspective My research involves applying my expertise in genomics and epigenomics to dissecting out the components of breast cancer. I have been focusing on elucidating allele-specific gene expression and allele-specific epigenetic modifications. We developed a specific adaptation of SNP array-based high throughput technology. We showed that differential expression from the two alleles of a given gene is common in normal tissue. We followed this by demonstrating that the genetic background influences the epigenetic state of chromatin. By investigating multiple epigenetic marks, we were able to show that histone H3 lysine 9/14 acetylation and lysine 4/9/27 methylation were influenced by their genetic background. My group further demonstrated that the chromatin state segregates as a Mendelian trait. This study was the first demonstration of the influence of the genomic background on the global epigenetic state in humans.

More recently, we have applied high-throughput genomic/epigenomic technologies, such as high-density SNP arrays, to identifying genes that present as plausible candidates for contributing to breast cancer development. The genomic investigation has led to the identification of two putative oncogenes, IRX2 and TBL1XR1. Our immunohistochemistry (IHC) studies showed that IRX2 and TBL1XR1 were frequently over-expressed in breast tumors. To date, our research has provided direct experimental evidence supporting an oncogenic effect for TBL1XR1. We used the shRNA approach to knock down the expression of TBL1XR1 in breast cancer cells and found that depletion of the TBL1XR1 protein in the cells reduced cell migration/invasion and suppressed tumor growth in mouse xenografts. Our epigenomic investigation has led to the identification of DNA methylation signatures that are selectively associated with clinical phenotypes such as lymph node involvement, histological grade, tumor size, and ER/PR/HER2 status. As an example, we observed a specific DNA methylation signature that distinguishes primary breast cancer samples diagnosed as high-grade from those diagnosed as low-mid-grade tumors.

My collaborators include Drs. Lalage Wakefield, Junya Fukuoka, Ken Buetow, Kent Hunter, Philip Taylor, Alisa Goldstein, and Dinah Singer.

Selected Publications
  1. Lee MP.
    Biochim. Biophys. Acta. 1819: 739-42, 2012. [ Journal Article ]
  2. Su H, Hu N, Yang HH, Wang C, Takikita M, Wang QH, Giffen C, Clifford R, Hewitt SM, Shou JZ, Goldstein AM, Lee MP, Taylor PR.
    Clin. Cancer Res.. 17: 2955-66, 2011. [ Journal Article ]
  3. Abnet CC, Freedman ND, Hu N, Wang Z, Yu K, Shu XO, Yuan JM, Zheng W, Dawsey SM, Dong LM, Lee MP, Ding T, Qiao YL, Gao YT, Koh WP, Xiang YB, Tang ZZ, Fan JH, Wang C, Wheeler W, Gail MH, Yeager M, Yuenger J, Hutchinson A, Jacobs KB, Giffen CA, Burdett L, Fraumeni JF, Tucker MA, Chow WH, Goldstein AM, Chanock SJ, Taylor PR.
    Nat. Genet.. 42: 764-7, 2010. [ Journal Article ]
  4. Kadota M, Yang HH, Gomez B, Sato M, Clifford RJ, Meerzaman D, Dunn BK, Wakefield LM, Lee MP.
    PLoS ONE. 5: e9201, 2010. [ Journal Article ]

Dr. Lee received his B.S. in biology from the University of Science and Technology of China in 1982 and his Ph.D. in biochemistry from Duke University in 1989. He carried out postdoctoral work at Duke from 1990 to 1994 and joined the National Institute on Aging (NIA) as a senior staff fellow in 1994. Dr. Lee became a junior faculty member at Johns Hopkins Medical School between 1995 and 1999, then joined IBM as a software engineer in 1999. He came to the NCI in 2000 as a tenure track investigator.

Name Position
Huaitian Liu Ph.D. Bioinformatics Specialist (Contr)
Howard H. Yang, Ph.D. Staff Scientist

Summary

Integrated genomic and epigenomic studies of breast cancer: an allelic-specific perspective My research involves applying my expertise in genomics and epigenomics to dissecting out the components of breast cancer. I have been focusing on elucidating allele-specific gene expression and allele-specific epigenetic modifications. We developed a specific adaptation of SNP array-based high throughput technology. We showed that differential expression from the two alleles of a given gene is common in normal tissue. We followed this by demonstrating that the genetic background influences the epigenetic state of chromatin.

Areas of Expertise
chromatin, breast cancer

Research

Integrated genomic and epigenomic studies of breast cancer: an allelic-specific perspective My research involves applying my expertise in genomics and epigenomics to dissecting out the components of breast cancer. I have been focusing on elucidating allele-specific gene expression and allele-specific epigenetic modifications. We developed a specific adaptation of SNP array-based high throughput technology. We showed that differential expression from the two alleles of a given gene is common in normal tissue. We followed this by demonstrating that the genetic background influences the epigenetic state of chromatin. By investigating multiple epigenetic marks, we were able to show that histone H3 lysine 9/14 acetylation and lysine 4/9/27 methylation were influenced by their genetic background. My group further demonstrated that the chromatin state segregates as a Mendelian trait. This study was the first demonstration of the influence of the genomic background on the global epigenetic state in humans.

More recently, we have applied high-throughput genomic/epigenomic technologies, such as high-density SNP arrays, to identifying genes that present as plausible candidates for contributing to breast cancer development. The genomic investigation has led to the identification of two putative oncogenes, IRX2 and TBL1XR1. Our immunohistochemistry (IHC) studies showed that IRX2 and TBL1XR1 were frequently over-expressed in breast tumors. To date, our research has provided direct experimental evidence supporting an oncogenic effect for TBL1XR1. We used the shRNA approach to knock down the expression of TBL1XR1 in breast cancer cells and found that depletion of the TBL1XR1 protein in the cells reduced cell migration/invasion and suppressed tumor growth in mouse xenografts. Our epigenomic investigation has led to the identification of DNA methylation signatures that are selectively associated with clinical phenotypes such as lymph node involvement, histological grade, tumor size, and ER/PR/HER2 status. As an example, we observed a specific DNA methylation signature that distinguishes primary breast cancer samples diagnosed as high-grade from those diagnosed as low-mid-grade tumors.

My collaborators include Drs. Lalage Wakefield, Junya Fukuoka, Ken Buetow, Kent Hunter, Philip Taylor, Alisa Goldstein, and Dinah Singer.

Publications

Selected Publications
  1. Lee MP.
    Biochim. Biophys. Acta. 1819: 739-42, 2012. [ Journal Article ]
  2. Su H, Hu N, Yang HH, Wang C, Takikita M, Wang QH, Giffen C, Clifford R, Hewitt SM, Shou JZ, Goldstein AM, Lee MP, Taylor PR.
    Clin. Cancer Res.. 17: 2955-66, 2011. [ Journal Article ]
  3. Abnet CC, Freedman ND, Hu N, Wang Z, Yu K, Shu XO, Yuan JM, Zheng W, Dawsey SM, Dong LM, Lee MP, Ding T, Qiao YL, Gao YT, Koh WP, Xiang YB, Tang ZZ, Fan JH, Wang C, Wheeler W, Gail MH, Yeager M, Yuenger J, Hutchinson A, Jacobs KB, Giffen CA, Burdett L, Fraumeni JF, Tucker MA, Chow WH, Goldstein AM, Chanock SJ, Taylor PR.
    Nat. Genet.. 42: 764-7, 2010. [ Journal Article ]
  4. Kadota M, Yang HH, Gomez B, Sato M, Clifford RJ, Meerzaman D, Dunn BK, Wakefield LM, Lee MP.
    PLoS ONE. 5: e9201, 2010. [ Journal Article ]

Biography

Dr. Lee received his B.S. in biology from the University of Science and Technology of China in 1982 and his Ph.D. in biochemistry from Duke University in 1989. He carried out postdoctoral work at Duke from 1990 to 1994 and joined the National Institute on Aging (NIA) as a senior staff fellow in 1994. Dr. Lee became a junior faculty member at Johns Hopkins Medical School between 1995 and 1999, then joined IBM as a software engineer in 1999. He came to the NCI in 2000 as a tenure track investigator.

Team

Name Position
Huaitian Liu Ph.D. Bioinformatics Specialist (Contr)
Howard H. Yang, Ph.D. Staff Scientist