Mitzi Kuroda

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Mitzi Kuroda is a professor of genetics at Harvard Medical School and Brigham and Women's Hospital. [1] She was an HHMI Investigator at Brigham and Women's Hospital from 1993 to 2007. [2] She has identified many genes and enzymes involved in epigenetic regulation in the fruit fly. In addition, her research has shown the importance of epigenetics in cancer. Her laboratory has identified chromatin remodeling signals and processes that predispose cells to be transformed into cancer cells.

Contents

Early life and education

Mitzi Kuroda was born in 1958 in Fayetteville, Arkansas, where she attended elementary and junior high schools. [3]  She spent a year in Tokyo before returning to attend Fayetteville High School where she graduated as valedictorian in 1977. [3]

Mitzi Kuroda said, "When I learned about recombinant DNA in college, it captured my imagination. I had to toss aside all my plans to 'save the world' because the ability to make specific DNA molecules for molecular genetic experiments was just too enticing." [1] Kuroda received her BS in biology from Tulane University in 1981 [3] and her PhD in biological sciences at Stanford University, [3] working with mentor Charles Yanofsky. [1] Kuroda's work with Yanofsky involved collaboration with Iwona Stroynowski to reveal how a riboswitch mechanism called bacterial attenuation regulates operons for amino acid biosynthesis. [4]

Academic research career

After postdoctoral work at Stanford, Kuroda became a faculty member at Baylor College of Medicine. [1] She rose through the ranks at Baylor to full professor. [3] In 2003, she moved to Harvard Medical School. [1] Kuroda initially concentrated on regulation processes in the fruit fly. Her citation by the National Academy of Sciences upon her election said, "Her lab identified the MSL ribonucleoprotein complex, and discovered that it assembles and spreads from sites of non-coding roX RNA synthesis to regulate genes specifically on the fruit fly male X chromosome. Furthermore, they dissected the sex-specific regulation of this process, and the molecular mechanism by which the MSL complex influences transcriptional elongation." [5] She has developed an important technique in which epigenetic regulators and their targets are cross-linked, then analyzed via mass spectrometry. In 2017, her laboratory discovered a master regulatory complex for Drosophila development. [6]

Recently, she has begun studies of regulation in cancer cells. Kuroda's laboratory has shown that BRD4-NUT regulator leads to cancer via causing histone modification changes that produce a cascade of remodeling in which domains are opened to allow inappropriate expression of genes by transcription of their RNA. [7]

Honors and awards

https://www.searlescholars.net/person/253 [8]

Personal life

Kuroda is married to geneticist Stephen Elledge, and they have two grown children. [9]

Selected works

Related Research Articles

H3K27ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates acetylation of the lysine residue at N-terminal position 27 of the histone H3 protein.

H3K9me2 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the di-methylation at the 9th lysine residue of the histone H3 protein. H3K9me2 is strongly associated with transcriptional repression. H3K9me2 levels are higher at silent compared to active genes in a 10kb region surrounding the transcriptional start site. H3K9me2 represses gene expression both passively, by prohibiting acetylation and therefore binding of RNA polymerase or its regulatory factors, and actively, by recruiting transcriptional repressors. H3K9me2 has also been found in megabase blocks, termed Large Organised Chromatin K9 domains (LOCKS), which are primarily located within gene-sparse regions but also encompass genic and intergenic intervals. Its synthesis is catalyzed by G9a, G9a-like protein, and PRDM2. H3K9me2 can be removed by a wide range of histone lysine demethylases (KDMs) including KDM1, KDM3, KDM4 and KDM7 family members. H3K9me2 is important for various biological processes including cell lineage commitment, the reprogramming of somatic cells to induced pluripotent stem cells, regulation of the inflammatory response, and addiction to drug use.

H3K4me1 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the mono-methylation at the 4th lysine residue of the histone H3 protein and often associated with gene enhancers.

H3K36me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation at the 36th lysine residue of the histone H3 protein and often associated with gene bodies.

H2BK5ac is an epigenetic modification to the DNA packaging protein Histone H2B. It is a mark that indicates the acetylation at the 5th lysine residue of the histone H2B protein. H2BK5ac is involved in maintaining stem cells and colon cancer.

H4K20me is an epigenetic modification to the DNA packaging protein Histone H4. It is a mark that indicates the mono-methylation at the 20th lysine residue of the histone H4 protein. This mark can be di- and tri-methylated. It is critical for genome integrity including DNA damage repair, DNA replication and chromatin compaction.

H4K16ac is an epigenetic modification to the DNA packaging protein Histone H4. It is a mark that indicates the acetylation at the 16th lysine residue of the histone H4 protein.

H4K5ac is an epigenetic modification to the DNA packaging protein histone H4. It is a mark that indicates the acetylation at the 5th lysine residue of the histone H4 protein. H4K5 is the closest lysine residue to the N-terminal tail of histone H4. It is enriched at the transcription start site (TSS) and along gene bodies. Acetylation of histone H4K5 and H4K12ac is enriched at centromeres.

H4K8ac, representing an epigenetic modification to the DNA packaging protein histone H4, is a mark indicating the acetylation at the 8th lysine residue of the histone H4 protein. It has been implicated in the prevalence of malaria.

H4K12ac is an epigenetic modification to the DNA packaging protein histone H4. It is a mark that indicates the acetylation at the 12th lysine residue of the histone H4 protein. H4K12ac is involved in learning and memory. It is possible that restoring this modification could reduce age-related decline in memory.

H4K91ac is an epigenetic modification to the DNA packaging protein histone H4. It is a mark that indicates the acetylation at the 91st lysine residue of the histone H4 protein. No known diseases are attributed to this mark but it might be implicated in melanoma.

H3K23ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the acetylation at the 23rd lysine residue of the histone H3 protein.

H3K36ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the acetylation at the 36th lysine residue of the histone H3 protein.

H3K36me2 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the di-methylation at the 36th lysine residue of the histone H3 protein.

H3R42me is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the mono-methylation at the 42nd arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H3R17me2 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the di-methylation at the 17th arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H3R26me2 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the di-methylation at the 26th arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H3R8me2 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the di-methylation at the 8th arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H3R2me2 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the di-methylation at the 2nd arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H4R3me2 is an epigenetic modification to the DNA packaging protein histone H4. It is a mark that indicates the di-methylation at the 3rd arginine residue of the histone H4 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

References

  1. 1 2 3 4 5 6 "Scientist of the month: Mitzi Kuroda". ABCAM. Retrieved December 1, 2018.
  2. "Mitzi I Kuroda". HHMI. Retrieved December 1, 2018.
  3. 1 2 3 4 5 "Mitzi Kuroda, Hall of Honor Album" (PDF). Fayetteville AR. Retrieved December 3, 2018.
  4. Stroynowski, I.; Kuroda, M.; Yanofsky, C. (1983). "Transcription termination in vitro at the tryptophan operon attenuator is controlled by secondary structures in the leader transcript". Proc Natl Acad Sci U S A. 80 (8): 2206–2210. Bibcode:1983PNAS...80.2206S. doi: 10.1073/pnas.80.8.2206 . PMC   393787 . PMID   6340118.
  5. 1 2 "NAS Members: Mitzi Kuroda". National Academy of Sciences USA. Retrieved December 1, 2018.
  6. Kang, Hyuckjoon; Jung, Youngsook L.; McElroy, Kyle A.; Zee, Barry M.; Wallace, Heather A.; Woolnough, Jessica L.; Park, Peter J.; Kuroda, Mitzi I. (2017). "Bivalent complexes of PRC1 with orthologs of BRD4 and MOZ/MORF target developmental genes in Drosophila". Genes & Development. 31 (19): 1988–2002. doi:10.1101/gad.305987.117. PMC   5710143 . PMID   29070704.
  7. Alekseyenko, A.; Walsh, E.; Wang, X.; Grayson, A.; Hsi, P; Kharchenko, P; Kuroda, M.I.; French, C. A. (2015). "The oncogenic BRD4-NUT chromatin regulator drives aberrant transcription within large topological domains". Genes Dev. 29 (14): 1507–23. doi:10.1101/gad.267583.115. PMC   4526735 . PMID   26220994.
  8. "Mitzi Kuroda". Searle Scholars. Retrieved December 1, 2018.
  9. "Stephen Elledge". Yale Gruber Award. Retrieved December 1, 2018.