• Drexel University College of Medicine, Elias Abrutyn Mentoring Award (2022)
• Drexel University College of Medicine, Faculty Launch Leadership Fellow (2018)
• Drexel University College of Medicine, Young Investigator Award (2009)
• Leukemia Research Foundation, New Investigator Award (2006)

Visit the Noguchi Lab.

Research Program: Genome Maintenance Mechanisms

Genomic instability is a hallmark of cancers and age-related diseases. Our long-term goal is to understand how cells maintain genomic integrity to regulate lifespan and avoid tumorigenesis. Emerging evidence suggests that a variety of environmental factors and toxins damage DNA, leading to an arrest of the DNA replication fork, the actual site of DNA synthesis. Arrested replication forks are prone to collapse, posing serious threats to genomic integrity, suggesting that DNA replication problems are critical drivers of genomic instability that promotes aging and tumorigenesis.

The Noguchi lab works with mammalian cells and fission yeast (Schizosaccharomyces pombe). Fission yeast is an exceptional model system for studying cell cycle control and genome maintenance mechanisms that are highly conserved amongst most eukaryotes, including humans. Our general approach defines principles and identifies important proteins in fission yeast and then determines whether human homologues of these proteins have related function using mammalian cell culture. 

Current Research Projects

• Identify and investigate the mechanisms of DNA replication at difficult-to-replicate chromosomal regions. There are numerous chromosomal regions that are prone to DNA damage. These regions are difficult to replicate, and are often associated with repetitive DNA sequences and high rates of transcription. We investigate the mechanisms that prevent genomic instability at these difficult-to-replicate regions, including telomeres and highly transcribed regions.
• Investigate the mechanisms of alcohol-mediated esophageal carcinogenesis. Alcohol consumption is a major cause of esophageal cancer. We investigate the role of acetaldehyde, the primary metabolite of alcohol, in genomic instability and esophageal cancer development. We also investigate DNA repair mechanisms that are responsible for the repair of alcohol/acetaldehyde-mediated DNA damage.
• Investigate the genetic mechanisms that govern lifespan extension by preserving genomic integrity. Aging begins at the molecular level: accumulation of damaged cellular constituents leads to cell dysfunction or cell senescence. Such damage also occurs on chromosomal DNA, leading to genomic instability. Therefore, our goal is to understand how cells maintain genomic integrity to regulate lifespan. We are also interested in the role of the TOR pathway in lifespan regulation under calorie-restricted conditions.  

Environmental factors or even our metabolism can cause DNA damage during DNA replication, leading to genomic instability, which is a hallmark of cancer and aging. Therefore, our research projects will provide a framework for guiding investigations that will greatly impact the biology of cancer and aging. 

For more information, please visit Noguchi Lab Official Site or Noguchi Lab Website.

Selected references:

“Fanconi anemia: Current insights regarding epidemiology, Cancer and DNA repair”
Peake JD, Noguchi E*
Human Genetics, doi: 10.1007/s00439-022-02462-9 (2022)

“The methyltransferase enzymes KMT2D, SETD1B, and ASH1L, are key mediators of both metabolic and epigenetic changes during cellular senescence”
Nacarelli T, Azar A, Potnis M, Johannes G, Mell J, Johnson FB, Brown-Borg H, Noguchi E, Sell C
Mol. Biol. Cell, 33(5):ar36. (2022)

“Alcohol metabolism enriches squamous cell carcinoma cancer stem cells that survive oxidative stress via autophagy”
Shimonosono M, Tanaka K, Flashner S, Takada S, Matsuura N, Tomita Y, Sachdeva UM, Noguchi E, Sangwan V, Ferri L, Momen-Heravi F, Yoon AJ, Klein-Szanto AJ, Diehl A, Nakagawa H
Biomolecules, 11(10): 1479. (2021)

“FANCD2 limits acetaldehyde-induced genomic instability during DNA replication in esophageal keratinocytes”
Peake JD, Noguchi C, Lin B, Theriault A, O'Connor M, Sheth S, Tanaka K, Nakagawa H, Noguchi E*
Mol Oncol. 15(11): 3109-3124. (2021)

“Maf1 limits RNA polymerase III-directed transcription to preserve genomic integrity and extend lifespan”
Noguchi C, Wang L, Shetty M, Mell JC, Sell C, Noguchi E*
Cell Cycle, 20(3):247-255. (2021)

“Autophagy mitigates ethanol-induced mitochondrial dysfunction and oxidative stress in esophageal keratinocytes”
Chandramouleeswaran PM, Guha M, Shimonosono M, Whelan KA, Maekawa H, Sachdeva UM, Ruthel G, Mukherjee S, Engel N, Gonzalez MV, Garifallou J, Ohashi S, Klei-Szanto AJ, Mesaros CA, Blair IA, Pellegrino da Silva R, Hakonarson H, Noguchi E, Baur JA, Nakagawa H
PLoS ONE, 15 (9):e0239625. (2020)

“Genetic investigation of formaldehyde-induced DNA damage response in Schizosaccharomyces pombe”
Anandrajan V, Noguchi C, Oleksak J, Grothusen G, Terlecky D, Noguchi E*
Current Genetics, 66(3): 593-605. (2020)

"Maf1-dependent transcriptional regulation of tRNAs prevents genomic instability and is associated with extended lifespan"
Shetty M, Noguchi C, Wilson S, Martinez E, Shiozaki K, Sell C, Mell JC, Noguchi E*
Aging Cell, 19(2): e13068. (2020)

"The NuA4 acetyltransferase and histone H4 acetylation promote replication recovery after topoisomerase I-poisoning"
Noguchi C, Singh T, Ziegler MA, Peake JD, Khair L, Aza A, Nakamura TM, Noguchi E*
Epigenetics & Chromatin, 12(1):24. (2019)

Books: DNA Replication Controls Volumes 1 and 2
Noguchi E (Editor)
Genes (Basel), MDPI. (2016-2017)

"Regulation of DNA replication through natural impediments in the eukaryotic genome”
Gadaleta MC, Noguchi E*
Genes (Basel), 8(3):98. (2017)

"Genetic controls of DNA damage avoidance in response to acetaldehyde in fission yeast"
Noguchi C, Grothusen G, Anandarajan V, Martínez-Lage García M, Terlecky D, Corzo K, Tanaka K, Nakagawa H, Noguchi E*
Cell Cycle, 16(1): 45-58. (2017)

"Timeless protection of telomeres"
Gadaleta MC, González-Medina A, Noguchi E*
Curr Genet, 62(4): 725-730. (2016)

"ALDH2 modulates autophagy flux to regulate acetaldehyde-mediated toxicity thresholds"
Tanaka K, Whelan KA, Chandramouleeswaran PM, Kagawa S, Rustgi SL, Noguchi C, Guha M, Srinivasan S, Amanuma Y, Ohashi S, Muto M, Klein-Szanto AJ, Noguchi E, Avadhani NG, Nakagawa H
Am J Cancer Res, 6(4): 781-796. (2016)

"Swi1/Timeless prevents repeat instability at fission yeast telomeres"
Gadaleta MC, Das MM, Tanizawa H, Chang Y, Noma K, Nakamura TM, Noguchi E*
PLOS Genetics, 12 (3): e1005943. doi:10.1371/journal.pgen.1005943 (2016)

"Chromatin immunoprecipitation to detect DNA replication and repair factors"
Gadaleta MC, Iwasaki O, Noguchi C, Noma K, Noguchi E*
Methods in Mol Biol, 1300: 169-186 (2015)

Book: Cell Cycle Control, Mechanisms and Protocols
Noguchi E, Gadaleta MC (Eds.)
Methods in Molecular Biology, Humana Press/Springer, Vol. 1170 (2014)

"Introductory review of computational cell cycle modeling"
Kriete A, Noguchi E, Sell C
Methods in Mol Biol, 1170: 267-265 (2014)

"Linking chromosome duplication to segregation via sister chromatid cohesion"
Leman AR, Noguchi E*
Methods in Mol Biol, 1170: 75-98 (2014)

"Chromatin immunoprecipitation to investigate origin association of replication factors in mammalian cells"
Leman AR, Noguchi E*
Methods in Mol Biol, 1170: 539-547 (2014)

"New Vectors for epitope tagging and gene disruption in Schizosaccharomyces pombe"
Gadaleta MC, Iwasaki O, Noguchi C, Noma K, Noguchi E*
BioTechniques, 55(5): 257-263. (2013)

"Proteasome-dependent degradation of replisome components regulates faithful DNA replication"
Roseaulin LC, Noguchi C, Noguchi E*
Cell Cycle, 12(16): 2564-2569. (2013)

"Roles of ChlR1 DNA helicase in replication recovery from DNA damage"
Shah N, Inoue A, Lee SW, Beishline K, Lahti JM, Noguchi E*
Exp. Cell Res, 319(14): 2244-2253. (2013)

"PP2A(Cdc55/B55), a possible therapeutic target in cyclin D1-dependent cancers"
Noguchi E*
Cell Cycle, 12(10): 1484-1485. (2013)

"The replication fork: Understanding the eukaryotic replication machinery and the challenges to genome duplication"
Leman AR, Noguchi E*
Genes (Basel), 4(1): 1-32. (2013)

"Coordinated degradation of replisome components ensures genome stability upon replication stress in the absence of the replication fork protection complex"
Roseaulin LC, Noguchi C, Martinez E, Ziegler MA, Toda T, Noguchi E*
PLoS Genetics, 9(1): e1003213. (2013)

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

"Local and global functions of Timeless and Tipin in replication fork protection"
Leman AR, Noguchi E*
Cell Cycle, 11 (21), 3945-3955. (2012)

"Swi1 associates with chromatin through the DDT domain and recruits Swi3 to preserve genomic integrity"
Noguchi C, Rapp JB, Skorobogatko YV, Bailey LD, Noguchi E*.
PLoS ONE, 7(8): e43988. (2012)

"Timeless preserves telomere length by promoting efficient DNA replication through human telomeres"
Leman AR, Dheekollu J, Deng Z, Lee SW, Das, MM, Lieberman PM, Noguchi E*
Cell Cycle, 11(12): 2337-2347. (2012).

"The double-bromodomain proteins Bdf1 and Bdf2 modulate chromatin structure to regulate S-phase stress response in Schizosaccharomyces pombe"
Garabedian MV, Noguchi C, Ziegler MA, Das MM, Singh T, Harper LJ, Leman AR, Khair L, Moser BA, Nakamura TM, Noguchi E*
Genetics, 190(2): 487-500. (2012).

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