David Arnosti, PhD

David Arnosti

Contact Me

Professor of Biochemistry and Molecular Biology

Phone:
517-432-5504

Email:

dr dave

Education/Training

Ph.D. University of California, Berkeley
B.A. Lawrence University, Appleton, WI
Postdoctoral Research, University of Zurich and University of California, San Diego

Research Interest

Our laboratory's research is focused on understanding fundamental mechanisms of metazoan transcriptional regulation in the context of development. Our studies have employed the powerful genetic resources of Drosophila to discern how transcriptional regulatory elements drive tissue- and spatial-specific gene expression in the embryo. Combined biochemical and molecular genetic approaches have allowed us to determine chromatin-based mechanisms of conserved transcription factors such as the HES family protein Hairy on a genome-wide basis. Combined experimental and computational studies have elucidated biochemical properties of transcription factors operating on enhancer sequences, and revealed basic properties of �cis regulatory code�. In collaboration with the R. William Henry laboratory, we have probed the functional domains of the Retinoblastoma tumor suppressor protein, a conserved cell-cycle control factor important in human cancer and development. Our recent studies have exploited ChIP-seq and RNA-seq data to show that this transcriptional cofactor is widely deployed to regulate genes involved in diverse signaling and growth-control pathways, in addition to the better studied role in the cell cycle. Our recent work elucidating the cis-regulatory control of the insulin receptor gene showed for the first time that this supposed �housekeeping� gene is regulated by sophisticated sets of interlocking transcriptional inputs; variation in the complex enhancers of this gene likely underlie important population-level variation in human insulin signaling.

Research Topics

  • Developmental Biology
  • Gene Regulation
  • Embryogenesis
  • Cancer Biology
  • Systems Biology

Representative Publications

Anindita Mitra, Ana-Maria Raicu, Stephanie Hickey, Lori A. Pile, and David N. Arnosti (2021) Soft repression: subtle transcriptional regulation with global impact. BioEssays, 43: e2000231.

Steve Small and David N. Arnosti (2020) Transcriptional enhancers in Drosophila. Genetics. 216: 1-26.

Rima Mouawad, Pamela Himadewi, Dhruva Kadiyala, and David N. Arnosti (2020) Selective repression of the Drosophila cyclin B promoter by retinoblastoma and E2F proteins (2020) BBA Gene Reg Mech, 1863 (7): 1945-49.

Sandhya Payankaulam, Ana-Maria Raicu, and David N. Arnosti (2019) Transcriptional regulation of INSR, the insulin receptor gene. Genes (Basel), 10, 984.

Rima Mouawad, Jaideep Prasad, Dominic Thorley, Pamela Himadewi, Dhruva Kadiyala, Nate Wilson, Philipp Kapranov, and David N. Arnosti (2019) Diversification of Retinoblastoma Protein Function Associated with Cis and Trans Adaptations Mol. Biol. Evol. 36: 2790-2804

Yiliang Wei, Rewatee Gokhale, Anne Sonnenschein, Kelly Mone�t Montgomery, Andrew Ingersoll, and David N. Arnosti (2016) Complex cis-regulatory landscape of the insulin receptor gene underlies the broad expression of a central signaling regulator. Development, 143, 3591-3603.

Sandhya Payankaulam, Kelvin Yeung, Helen McNeill, R. William Henry, and David N. Arnosti (2016) Regulation of cell polarity determinants by the Retinoblastoma tumor suppressor protein, Scientific Reports (Nature), 6: 22879.

Rupinder Sayal, Jacqueline M. Dresch, Irina Pushel, Benjamin R. Taylor and David N. Arnosti, Quantitative perturbation analysis to predict a developmental cis-regulatory grammar (2016) eLife, 5:e08445.

Kurtulus Kok, Ahmet Ay, Li M. Li, and David N. Arnosti (2015) Genome-wide errant targeting by Hairy, eLife, 4 DOI: 10.7554.

Yiliang Wei, Shamba Mondal, Bartek Wilczy?ski, R. William Henry, and David N. Arnosti (2015) Genome-Wide Analysis of Drosophila Rbf2 Protein Highlights Diversity of RB Family Targets and Possible Role in Regulation of Ribosome Biosynthesis. G3 (Genetics Society of America), 5: 1503-1515.

Yiliang Wei and David N. Arnosti (2015) Enhancer trafficking: free throws and three-pointers, Developmental Cell, 32, 135-137.

NCBI bibliography

RDSTP

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