Faculty & Research
- Contact Information
- Contact Brian Calvi by bcalvi [at] indiana [dot] edu
- By telephone: 812-855-5450
- JH 361B
- Molecular, Cellular & Developmental Biology
- Research Areas
- Chromatin, Chromosomes, and Genome Integrity
- Developmental Mechanisms and Regulation in Eukaryotic Systems
- Eukaryotic Cell Biology, Cytoskeleton and Signaling
Ph.D., Harvard University, 1993
Postdoctoral Fellow, Carnegie Insitution of Washington, 1993-1998
American Cancer Society Research Scholar
It is critical to discover the mechanisms of normal cell cycle regulation if we are to fully understand what goes awry in cancer cells. We focus on how cells coordinate the duplication of their genome with cell division. This is an important question because defects in this coordination cause genome instability and are common early events in carcinogenesis.
We use the genetic, molecular, and cell biological tools available in the fruitfly, Drosophila melanogaster, to study cell cycle regulation and to define DNA damage and the checkpoint responses in a developmental context. For example, we are asking how the eukaryotic cell tightly regulates the activity of origins of DNA replication so that the genome is duplicated exactly once per cell cycle.
We are intensely interested in how epigenetic regulation of chromatin influences the activity of origins of DNA replication in different cell types. Recently, we have extended some of our findings by testing in human cells the principles we have learned in Drosophila. Our recent findings may be relevant to how cancer cells escape apoptosis during genotoxic stress, and the potential of re-replication to cause genome instability and cancer in different cell types.
- Epigenetic regulation of origins of DNA replication.
- The checkpoint response to re-replication and its effect on genome stability.
- Integration of cell cycle regulation with development.
Calvi, B.R. (2013) Making Big Cells: One size does not fit all. Proceedings of the National Academy of Sciences, 110 (24) 9621-9622 (invited commentary).
- McConnell, K., Dixon, M., and Calvi, B.R. (2012) The histone acetyltransferases CBP and Chameau integrate developmental and DNA replication programs in Drosophila ovarian follicle cells. Development, 139: 3880-3890. PMD 22951641. (featured by an "In this issue" article)
- Liu, J., McConnell, K., Dixon, M. and Calvi, B.R. (2011) Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the pre-RC. Mol. Biol. Cell. 23(1): 200-212 PMID:22049023
- Maqbool SB, Mehrotra S, Kolpakas A, Durden C, Zhang B, Zhong H, Calvi BR. (2010) Dampened activity of E2F1-DP and Myb-MuvB transcription factors in Drosophila endocycling cells. J Cell Sci. 123: 4095-4106. PMID: 21045111
- Mehrotra, S., S. B. Maqbool, A. Kolpakas, K. Murnen and B.R. Calvi. (2008) Endocycling cells do not apoptose in response to DNA re-replication genotoxic stress. Genes & Development 22:3158-3171. [cover article]
- Clark et al. (2007). Evolution of genes and genomes on the Drosophila phylogeny. Nature, 450:203-218.
- Calvi, BR, Byrnes, BA, and Kolpakas, AJ. (2007) Conservation of epigenetic regulation, ORC binding, and developmental timing of DNA replication origins in the genus Drosophila. Genetics 177:1291-1301.
- White, A.E., Leslie, M.E., Calvi, B.R., Marzluff, W.F., and Duronio,R.J. (2007) Cyclin E/CDK2 regulation of the Drosophila melanogaster histone locus body. Molecular Biology of the Cell 18(7), 2491-2502.
- Review: B.R. Calvi. (2006) Developmental Gene Amplification. In: DNA Replication and Human Disease. Cold Spring Harbor Laboratory Press. Melvin DePamphilis (ed.), pp 233-255.
- May, N.R., Thomer, M., Murnen, K.F., and Calvi, B.R. 2005 The origin binding protein Double parked, and its inhibitor Geminin, increase in response to replication stress. Journ. Cell Sci. 118:4207-4217.
- Bandura JL, Beall E., Bell M, Silver H, Botchan, M, and Calvi, BR (2005) humpty dumpty is required for developmental DNA amplification and cell proliferation in Drosophila. Current Biology 15: 755-759.
- Aggarwal, B.D. and Calvi, B.R. (2004). Chromatin regulates origin activity in Drosophila follicle cells. Nature 430: 372-376.
- Thomer, M., May, N.R., Aggarwal, B.D., Kwok, G., and Calvi, B.R. (2004). Drosophila double-parked is sufficient for re-replication during development and is regulated by Cyclin E / CDK2. Development 131(19): 4807-4818.
- Schwed GM, May NR, Pechersky Y, Calvi BR. (2002). Drosophila MCM6 is required for chorion gene amplification and genomic replication. Mol. Biol. of the Cell 13(2): 607-620.