Howard H. Yang, Ph.D.
Staff Scientist

Dr. Yang integrates genomics and epigenomics data using statistics and machine learning method to discover genes and epigenetic markers important for understanding human cancers and to study their functions in the normal and cancer cells. He conducts genome-wide analysis of genotype, copy number, expression and methylation data in the esophageal cancer and gastric cancer study to find SNPs, genes and methylation markers related to the cancer risk and patient survival. Similarly, he also analyzes expression and methylation profiles in breast cancer, colon cancer and liver cancer studies to detect markers related to the patient survival, metastasis-free survival and relapse-free survival.

Areas of Expertise
biostatistics, bioinformatics, genetics and genomics, computational biology, systems biology

Contact Info

Howard H. Yang, Ph.D.
Center for Cancer Research
National Cancer Institute
2115 E. Jefferson Street, Room 6059
Rockville, MD 20852
301-435-1534
yanghow@mail.nih.gov

My research is to integrate genetics, genome, biostatistics and bioinformatics to discover genes and epigenetic markers important for human cancers and to study their functions in the normal and cancer cells. Our allele-specific chromatin immunoprecipitation studies have shown genetic influence on chromatin state in the human genome. We analyzed chromatin states in 12 lymphoblastoid cells derived from two CEPH families using an allele specific chromatin immunoprecipitation (ChIP-on-chip) assay with Affymetrix 10K SNP chip. We performed the allele specific ChIP-on-chip assays for the 12 cell lines using antibodies targeting at RNA polymerase II and five post-translation modified forms of the histone H3 protein. This allowed us to evaluate variation of chromatin states across pedigrees.

These studies demonstrated that chromatin state clustered by family. Our results support the idea that genetic inheritance can determine the epigenetic state of the chromatin as shown previously in model organisms. To our knowledge, this is the first demonstration in humans that genetics may be an important factor that influences global chromatin state mediated by histone modification. The results were published in PLoS Genetics in 2007. To study the influence of Genetic Background and Tissue Types on Global DNA Methylation Patterns. We performed DNA methylation analysis using the Affymetrix 500K SNP array on tumor, adjacent normal tissue, and blood DNAfrom 30 patients with esophageal squamous cell carcinoma (ESCC). The use of multiple tissues from 30 individuals allowed us to evaluate variation of DNA methylation states across tissues and individuals.

Our results demonstrate that blood and esophageal tissues shared similar DNA methylation patterns within the same individual, suggesting an influence of genetic background on DNA methylation. Our results were published in PLoS One in 2010. We studied the Novel Gene Amplifications in Breast Cancer and Coexistence of Gene Amplification with an Activating Mutation of PIK3CA. We have identified the 17 loci focally amplified in primary breast tumors, 6 of which contain potential novel oncogenes. Based on the selected genes, we made the profile of the gene amplification in 161 primary breast tumors and did survival analysis using the selected genes and some gene expression data sets in public domain. Our findings were published in Cancer Research in 2009.

Selected Publications
  1. Sato M, Kadota M, Tang B, Yang HH, Yang YA, Shan M, Weng J, Welsh MA, Flanders KC, Nagano Y, Michalowski AM, Clifford RJ, Lee MP, Wakefield LM.
    Breast Cancer Res.. 16: R57, 2014. [ Journal Article ]
  2. Wang G, Hu N, Yang HH, Wang L, Su H, Wang C, Clifford R, Dawsey EM, Li JM, Ding T, Han XY, Giffen C, Goldstein AM, Taylor PR, Lee MP.
    PLoS ONE. 8: e63826, 2013. [ Journal Article ]
  3. Di LJ, Byun JS, Wong MM, Wakano C, Taylor T, Bilke S, Baek S, Hunter K, Yang H, Lee M, Zvosec C, Khramtsova G, Cheng F, Perou CM, Miller CR, Raab R, Olopade OI, Gardner K.
    Nat Commun. 4: 1449, 2013. [ Journal Article ]
  4. 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 ]
  5. Yang HH, Hu N, Wang C, Ding T, Dunn BK, Goldstein AM, Taylor PR, Lee MP.
    PLoS ONE. 5: e9355, 2010. [ Journal Article ]

Research

My research is to integrate genetics, genome, biostatistics and bioinformatics to discover genes and epigenetic markers important for human cancers and to study their functions in the normal and cancer cells. Our allele-specific chromatin immunoprecipitation studies have shown genetic influence on chromatin state in the human genome. We analyzed chromatin states in 12 lymphoblastoid cells derived from two CEPH families using an allele specific chromatin immunoprecipitation (ChIP-on-chip) assay with Affymetrix 10K SNP chip. We performed the allele specific ChIP-on-chip assays for the 12 cell lines using antibodies targeting at RNA polymerase II and five post-translation modified forms of the histone H3 protein. This allowed us to evaluate variation of chromatin states across pedigrees.

These studies demonstrated that chromatin state clustered by family. Our results support the idea that genetic inheritance can determine the epigenetic state of the chromatin as shown previously in model organisms. To our knowledge, this is the first demonstration in humans that genetics may be an important factor that influences global chromatin state mediated by histone modification. The results were published in PLoS Genetics in 2007. To study the influence of Genetic Background and Tissue Types on Global DNA Methylation Patterns. We performed DNA methylation analysis using the Affymetrix 500K SNP array on tumor, adjacent normal tissue, and blood DNAfrom 30 patients with esophageal squamous cell carcinoma (ESCC). The use of multiple tissues from 30 individuals allowed us to evaluate variation of DNA methylation states across tissues and individuals.

Our results demonstrate that blood and esophageal tissues shared similar DNA methylation patterns within the same individual, suggesting an influence of genetic background on DNA methylation. Our results were published in PLoS One in 2010. We studied the Novel Gene Amplifications in Breast Cancer and Coexistence of Gene Amplification with an Activating Mutation of PIK3CA. We have identified the 17 loci focally amplified in primary breast tumors, 6 of which contain potential novel oncogenes. Based on the selected genes, we made the profile of the gene amplification in 161 primary breast tumors and did survival analysis using the selected genes and some gene expression data sets in public domain. Our findings were published in Cancer Research in 2009.

Publications

Selected Publications
  1. Sato M, Kadota M, Tang B, Yang HH, Yang YA, Shan M, Weng J, Welsh MA, Flanders KC, Nagano Y, Michalowski AM, Clifford RJ, Lee MP, Wakefield LM.
    Breast Cancer Res.. 16: R57, 2014. [ Journal Article ]
  2. Wang G, Hu N, Yang HH, Wang L, Su H, Wang C, Clifford R, Dawsey EM, Li JM, Ding T, Han XY, Giffen C, Goldstein AM, Taylor PR, Lee MP.
    PLoS ONE. 8: e63826, 2013. [ Journal Article ]
  3. Di LJ, Byun JS, Wong MM, Wakano C, Taylor T, Bilke S, Baek S, Hunter K, Yang H, Lee M, Zvosec C, Khramtsova G, Cheng F, Perou CM, Miller CR, Raab R, Olopade OI, Gardner K.
    Nat Commun. 4: 1449, 2013. [ Journal Article ]
  4. 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 ]
  5. Yang HH, Hu N, Wang C, Ding T, Dunn BK, Goldstein AM, Taylor PR, Lee MP.
    PLoS ONE. 5: e9355, 2010. [ Journal Article ]