Ken-ichi Noma, Ph.D.

Assistant Professor, Gene Expression and Regulation Program
215-898-3933, Office

Introduction

The laboratory of Ken-ichi Noma, Ph.D., focuses on the mechanisms that regulate three-dimensional higher-order genome structure, influencing various biological processes.  Defective organization of higher-order genome structure is known to be involved in human diseases, including many cancers.  By uncovering the molecular mechanisms governing higher-order genome structure and its biological significance, the laboratory aims to establish a mechanistic framework for understanding the molecular etiology for human diseases related to nuclear organization.

Research Summary

The eukaryotic genome is extensively but precisely folded in the nucleus. For instance, the human genome is composed of ~ 1.8 m of DNA fiber packaged into a ~ 6 µm diameter nuclear compartment. Such genome packaging is not only brought about by condensing genetic material, but spatial positioning of distinct chromosomal loci, referred to higher-order genome organization, and also has critical roles in various DNA regulatory activities such as transcription and DNA replication.

We have recently discovered that the evolutionarily conserved TFIIIC complex, a well-known transcription factor for RNA polymerase III transcribing small non-coding RNAs including tRNAs, participates in organizing higher-order genome structure in fission yeast. We have also shown that TFIIIC binding to specific DNA sequences is critical for boundary function demarcating chromosomal domains. Our laboratory is currently seeking to better understand the TFIIIC-dependent three-dimensional organization of the genome. We are also exploring a number of other currently uncharacterized mechanisms governing higher-order genome structure.

The overall goal of our laboratory is to determine the in vivo three-dimensional genome structure and to elucidate its influence on DNA regulatory activities. In order to achieve this goal, our group employs genomic assays, fluorescent microscopy, molecular biology, and biochemical approaches, in addition to exploiting the power of yeast genetics. Ultimately, we will extend our research regarding nuclear organization in fission yeast into mammalian systems to characterize the molecular pathology of human diseases, including cancers.

Selected Publications

1 - Sonoda R, Naomoto Y, Shirakawa Y, Fujiwara Y, Yamatsuji T, Noma K, Tanabe S, et al., Preferential up-regulation of heparanase and cyclooxygenase-2 in carcinogenesis of Barrett's Oesophagus and intestinal-type gastric carcinoma., Histopathology. 2010 Jul;57(1):90-100., 20653782

2 - Noma K, Kamakaka RT., The human Pol III transcriptome and gene information flow., Nature Structural & Molecular Biology. 2010 May;17(5):539-41. , 20442738

3 - Iwasaki O, Tanaka A, Tanizawa H, Grewal SI, Noma KI., Centromeric localization of dispersed Pol III genes in fission yeast., Molecular Biology of the Cell. 2010 Jan;21(2):254-65. [Epub 2009 Nov 12], 19910488

4 - Wang Y, Reddy B, Thompson J, Wang H, Noma K, Yates JR 3rd, Jia S., Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein., Molecular Cell. 2009 Feb 27;33(4):428-37., 19250904

5 - Lioni M, Noma K, Snyder A, Klein-Szanto A, Diehl JA, Rustgi AK, Herlyn M,Smalley KS., Bortezomib induces apoptosis in esophageal squamous cell carcinoma cells through activation of the p38 mitogen-activated protein kinase pathway., Molecular Cancer Therapeutics. 2008 Sep;7(9):2866-75., 18790767

6 - Noma K, Smalley KS, Lioni M, Naomoto Y, Tanaka N, El-Deiry W, King AJ, Nakagawa H, Herlyn M., The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis., Gastroenterology. 2008 Jun;134(7):1981-93. [Epub 2008 Mar 4], 18439605

7 - Cam HP, Noma K, Ebina H, Levin HL, Grewal SI., Host genome surveillance for retrotransposons by transposon-derived proteins., Nature. 2008 Jan 24;451(7177):431-6. Comment in: Nature. 2008 Jan 24;451(7177):412-3. , 18094683

8 - Sugiyama T. Cam HP. Sugiyama R. Noma K. Zofall M. Kobayashi R. Grewal SI., SHREC, an effector complex for heterochromatic transcriptional silencing., Cell. 128(3):491-504, 2007 Feb 9., 17289569

9 - Noma K. Cam HP. Maraia RJ. Grewal SI., A role for TFIIIC transcription factor complex in genome organization., Cell. 125(5):859-72, 2006 Jun 2., 16751097

10 - Morris SA, Shibata Y, Noma K, Tsukamoto Y, Warren E, Temple B, Grewal SI, Strahl BD., Histone H3 K36 methylation is associated with transcription elongation in Schizosaccharomyces pombe., Eukaryotic Cell. 2005 August; 4(8):1446-54. , 16087749