Gregory Shanower, PhD
Greg Shanower, PhD, is assistant professor of molecular biology in the Department of Basic Sciences. Dr. Shanower holds a PhD in biomedical sciences from Wright State University, Dayton, OH. Greg performed his postdoctoral work at both Princeton and Rutgers University in New Jersey. His research interests include epigenetic maintenance of gene expression in Drosophila melanogaster, repair of DNA double strands breaks in the fly and developmental regulation of fly hematopoiesis.
Dr. Shanower’s research will investigate what role histone modifications play in stem cell maintenance and development in various tissues of Drosophila melanogaster. Recently it has been shown that histone modifications play a central role in maintaining stem cell identity. Since Drosophila is one of the premier model systems for studying stem cell biology, Dr. Shanower would like to examine how histone modifying enzymes regulate stem cell dynamics during fly development. In particular, he intends to examine how mutations in grappa (gpp), a gene encoding a methyltransferase which modifies the lysine 79 residue of Histone H3, exhibit phenotypes indicative of a failure to maintain stem cell populations in the fly. Dr. Shanower intends to use a genetic approach to examine how gpp influences stem cell dynamics. gpp mosaic clones will be generated in somatic and germline tissues using the FLP/FRT recombination method. Using this methodology, he hopes to determine how gpp influences: A) stem cell development and B) maintenance of the stem cell niche.
Student research opportunities
Investigating the role of histone modifications in stem cell maintenance and development is the current focus of Dr. Shanower’s research. grappa (gpp) is the Drosophila melanogaster ortholog of Dot1L, a human gene encoding an enzyme that methylates lysine residues on Histone H3. Methylation of Histone H3 on lysine 79 via Dot1L is directly linked to active gene transcription, maintenance of telomeric silencing, and regulation of cell cycle progression. However, to date very few studies have examined the role this histone methyltransferase plays in developmental processes. Our evidence suggests that gpp regulates a major signal transduction pathway involved in cell cycle regulation in the fly. This signaling pathway is involved in multiple aspects of carcinogenesis in human cells. However, the transcriptional regulation of this signaling pathway is not well defined in either flies or humans. Therefore, we aim to examine gpp’s role as a transcription factor regulating this pathway using Drosophila melanogaster as a model system. Further, our lab is investigating how chromatin modifying enzymes regulate: 1) signal transduction pathways in epithelial cells, 2) cellular polarity of epithelial cells, and 3) stem cell and stem cell niche biology.
- Atamna H, Brahmbhatt M, Atamna W, Shanower G, Dhahbi J. ApoHRP-based Assay to Measure Intracellular Regulatory Heme. Metallomics, Dec 2014. DOI: 10.1039/C4MT00246F
- Schwartz YB, Linder-Basso D, Kharchenko PV, Tolstorukov MY, Kim M, Li HB, Gorchakov AA, Minoda A, Shanower GA, et.al Nature and function of insulator protein binding sites in the Drosophila genome. Genome Res. (Sep. 2012). PMID:22767387. Full Text
- Gohl D, Aoki T, Blanton J, Shanower G, Kappes G, Schedl P. 2011. Mechanism of Chromosomal Boundary Action: Roadblock, Sink or Loop? Genetics. Jan 26. [Epub ahead of print]PMID: 21196526. Full Text
- Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC, Ernst J, Sabo PJ, Larschan E, Gorchakov AA, Gu T, Linder-Basso D, Plachetka A, Shanower G, Tolstorukov MY, Luquette LJ, Xi R, Jung YL, Park RW, Bishop EP, Canfield TP, Sandstrom R, Thurman RE, Macalpine DM, Stamatoyannopoulos JA, Kellis M, Elgin SC, Kuroda MI, Pirrotta V, Karpen GH, Park PJ. 2010. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature. 2010 Dec 22. [Epub ahead of print]PMID: 21179089. Full Text
- modENCODE Consortium et al., 2010. Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science, 330(6012):1787-97. Full Text
- Riddle NC, Minoda A, Kharchenko PV, Alekseyenko AA, Schwartz YB, Tolstorukov MY, Gorchakov AA, Jaffe JD, Kennedy C, Linder-Basso D, Peach SE, Shanower G, Zheng H, Kuroda MI, Pirrotta V, Park PJ, Elgin SC, Karpen GH. 2010. Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin. Genome Res. Dec 22. [Epub ahead of print]PMID: 21177972. Full Text
- An assessment of histone-modification antibody quality. Egelhofer TA, Minoda A, Klugman S, Lee K, Kolasinska-Zwierz P, Alekseyenko AA, Cheung MS, Day DS, Gadel S, Gorchakov AA, Gu T, Kharchenko PV, Kuan S, Latorre I, Linder-Basso D, Luu Y, Ngo Q, Perry M, Rechtsteiner A, Riddle NC, Schwartz YB, Shanower GA, Vielle A, Ahringer J, Elgin SCR, Kuroda MI, Pirrotta V, Ren B, Strome S, Park PP, Karpen GH, Hawkins RD, Lieb JD. . Nature Structural & Molecular Biology. Epub 2010 Dec 5.
- Characterization of the grappa gene, the Drosophila histone H3 lysine 79 methyltransferase. Shanower GA, Muller M, Blanton JL, Honti V, Gyurkovics H, Schedl P.Genetics. 2005 Jan;169(1):173-84. Epub 2004 Sep 15. PMID: 15371351. Full Text
- The Fab-8 boundary defines the distal limit of the bithorax complex iab-7 domain and insulates iab-7 from initiation elements and a PRE in the adjacent iab-8 domain. Barges S, Mihaly J, Galloni M, Hagstrom K, Müller M, Shanower G, Schedl P, Gyurkovics H, Karch F. Development. 2000 Feb;127(4):779-90. PMID: 10648236. Full Text
- A difference in the pattern of repair in a large genomic region in UV-irradiated normal human and Cockayne syndrome cells. Shanower GA, Kantor GJ. Mutat Res. 1997 Nov;385(2):127-37. PMID: 9447234. Full Text
- A re-examination of the intragenome distribution of repaired sites in proliferating xeroderma pigmentosum complementation group C fibroblasts. Kantor GJ, Shanower GA. Mutat Res. 1992 Nov;293(1):55-64. PMID: 1383811. Full Text
PhD – Wright State University, Dayton, Ohio
Postdoctoral – Princeton University, Princeton, NJ
Postdoctoral – Rutgers University, New Brunswick, NJ