Our Science

Ken-ichi Noma, Ph.D.

Ken-ichi Noma, Ph.D.

  • Associate Professor, Gene Expression and Regulation Program

  • 215-898-3933, Office
Summary

Ken-ichi Noma is interested in the mechanisms that regulate the three-dimensional genome structure, which influences various nuclear processes such as transcription, DNA replication, repair, and chromosome segregation. By uncovering the molecular mechanisms governing the three-dimensional genome structure and its biological significance, the Noma laboratory seeks to establish a clear mechanistic framework for understanding the molecular underpinnings for human cancers related to the disorganization of the cell nucleus.

As an undergraduate, Noma studied electronics and computer engineering, developing skills that he puts to good use even now in the fields of genomics and biomedicine. A growing interest in the improvement of human life led Noma to enroll in a biotechnology program where he successfully engineered a strain of carrot that could grow in the desert. His work on carrots involved spontaneous mutations generated during cell culture from whence he developed an interest in how genomes accumulate various mutations and, in particular, the role of mobile genetic elements referred to as transposons.

As a graduate student at the University of Tokyo, he identified novel retrotransposons and characterized the transposition mechanism in terms of epigenetic regulation. His interest in epigenetics led him to a postdoctoral fellowship at the Cold Spring Harbor Laboratory, where he pioneered a technique to map specific epigenetic changes over a large chromosomal region of the fission yeast genome. In 2003, he was awarded the American Association for the Advancement of Science’s prestigious Newcomb Cleveland Prize for his work on how RNA interference (RNAi) machinery mediates transcriptional silencing. In 2004, Noma became a staff scientist at the National Cancer Institute.

After joining The Wistar Institute as an assistant professor in 2007, he received the 2008 NIH Director’s New Innovators Award, which is recognized as the most prestigious award for young scientists. The Noma laboratory is also supported by grants from the G. Harold & Leila Y. Mathers Foundation (2011), V Foundation for Cancer Research (2010), and Edward Mallinckrodt, Jr. Foundation (2010).

In the Noma laboratory, recent technological advancements have given rise to the modeling of complex 3-D genome structures in the nucleus of the model organism fission yeast using a genomic approach that combines the molecular biology procedure, called chromosome conformation capture, with massively parallel DNA sequencing. This unique approach to genome modeling is the first to successfully fuse two completely independent disciplines—microscopy and genomics—and it has allowed Noma to show that distinct chromosomal territories exist in fission yeast. By showing that fission yeast has a functional genome organization similar to that found in mammalian transcription factories, this work proves that fission yeast represents the perfect model organism to understand functional organization of eukaryotic genome in higher eukaryotes including human. The Noma laboratory has been hard pressed to understand genome disorganization and chromosome instability in human cancers, but has made much progress in this difficult field of study.

Selected Publications

1.    Kim KD, Tanizawa H, Iwasaki O, Corcoran CJ, Capizzi JR, Hayden JE, Noma K. Centromeric motion facilitates the mobility of interphase genomic regions in fission yeast. J Cell Sci August 28, 2013. doi:10.1242/jcs.133678 PMID: 23986481

2.    Tanaka A, Tanizawa H, Sriswasdi S, Iwasaki O, Chatterjee AG, Speicher DW, Levin HL, Noguchi E, Noma K. Epigenetic regulation of condensin-mediated genome organization during the cell cycle and upon DNA damage through histone H3 lysine 56 acetylation. Mol Cell 48, 532-546, 2012. PMID: 23084836

3.    Tanizawa H, Noma K. Unravelling global genome organizations by 3C-seq. Semin Cell Dev Biol 23, 213-221, 2012 PMID:22120510

4.    Iwasaki O, Noma K. Global genome organization mediated by RNA polymerase III-transcribed genes in fission yeast. Gene. 2010 Dec 29. [Epub ahead of print]  PMID: 21195141

5.    Tanizawa H, Iwasaki O, Tanaka A, Capizzi JR, Wickramasinghe P, Lee M, Fu Z, Noma K. Mapping of long-range associations throughout the fission yeast genome reveals global genome organization linked to transcriptional regulation.  Nucleic Acids Research 38, 8164-8177, 2010. PMID: 21030438

6.    Iwasaki O, Tanaka A, Tanizawa H, Grewal SIS, Noma K. Centromeric localization of dispersed Pol III genes in fission yeast. Mol Biol Cell 21, 254-265, 2010. PMID: 19910488

7.    Noma K, Kamakaka RT. The human Pol III transcriptome and gene information flow. Nat Struct Mol Biol 17, 539-541, 2010. PMID:  20442738

8.    Noma K, Cam HP, Maraia RJ, Grewal SIS. A role for TFIIIC transcription factor complex in genome organization. Cell 125, 859-872, 2006. PMID: 16751097

9.    Noma K, Sugiyama T, Cam H, Verdel A, Jia S, Zofall M, Jia S, Moazed D, Grewal SIS. RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing. Nature Genetics 36, 1174-1180, 2004. PMID: 15475954

10.   Noma K, Grewal SIS. Histone H3 lysine 4 methylation is mediated by Set1 and promotes maintenance of active chromatin states in fission yeast. Proc. Natl. Acad. Sci. USA 99, 16438-16445, 2002. PMID: 12193658

11.   Hall IM,* Shankaranarayana GD,* Noma K,* Ayoub N, Cohen A, Grewal SIS. Establishment and maintenance of a heterochromatin domain. Science 297, 2232-2237, 2002 * Equally contributed. PMID:  12215653

12.   Noma K, Allis CD, Grewal SIS. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 293, 1150-1155, 2001. PMID: 11498594