Ertugrul M. Ozbudak, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-2607

Email ertugrul.ozbudak@cchmc.org

Segmentation of vertebral column; pattern formation; cell differentiation; systems biology; computational modeling

Visit the Ozbudak Lab

Ertugrul M. Ozbudak, PhD's, overriding interest is to achieve a quantitative understanding of complex biological systems by integrating systems-level biological experimentation with mathematical modeling. He has worked on different biological phenomena, such as: stochasticity and multistability in gene expression, cell polarization and symmetry breaking, entrainment of gene expression oscillations, gene regulatory networks and analysis of transcriptome during muscle differentiation and vertebral segmentation. He has utilized genome-wide techniques, single-cell microscopy measurements, time-resolved perturbation experiments, mathematical modeling and computational simulations to accomplish these projects.

Stochastic mechanisms are common in biological systems. His earlier PhD studies investigated the effects of these microscopic fluctuations (biochemical noise) on macroscopic variations in gene expression (phenotypic noise). His follow-up studies showed that cells could utilize positive feedback loops to exploit the stochastic gene expression to achieve bistability at the population level. These work were among the first multidisciplinary studies focused on stochastic gene expression and triggered the blossoming of the “stochastic gene expression” field.

Afterwards, Dr. Ozbudak investigated the systems-level properties of the vertebrate segmentation clock. He has performed computational modeling and time-resolved perturbation experiments to demonstrate that Notch signaling keeps the oscillations of neighboring cells synchronized. The period of the segmentation clock oscillations gets longer as cells are displaced along the posterior-to-anterior axis, which results in traveling waves of clock gene expression sweeping in the unsegmented tissue. By combining molecular-level computational modeling and quantitative experimentation, they showed that a gradient of gene expression time-delays along the axis underlies the traveling segmentation clock waves.

BS: Physics Department, Bogazici University, Istanbul, Turkey, 1999.

PhD: Physics Department, Massachusetts Institute of Technology Cambridge, MA, 2004.

Postdoctoral Research Fellow: Cancer Research UK (now Francis Crick Institute), London, UK, 2007.

Senior Research Associate: Stowers Institute for Medical Research, Kansas City, MO, 2009.

View PubMed Publications

Keskin S, Simsek MF, Vu HT, Yang C, Devoto SH, Ay A, Özbudak EM. Regulatory Network of the Scoliosis-Associated Genes Establishes Rostrocaudal Patterning of Somites in Zebrafish. iScience. 2019 Jan 21;12:247-259.

Simsek MF, Özbudak EM. Spatial Fold Change of FGF Signaling Encodes Positional Information for Segmental Determination in Zebrafish. Cell Rep. 2018 Jul 3;24(1):66-78.e8.

Keskin S, Devakanmalai GS, Kwon SB, Vu HT, Hong Q, Lee YY, Soltani M, Singh A, Ay A, Özbudak EM. Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling. Cell Rep. 2018 May 15;23(7):2175-2185.e4.

Ay A, Holland J, Sperlea A, Devakanmalai GS, Knierer S, Sangervasi S, Stevenson A, Ozbudak EM. Spatial gradients of protein-level time delays set the pace of the traveling segmentation clock waves. Development. 2014 Nov;141(21):4158-67.

Ay A, Knierer S, Sperlea A, Holland J, Özbudak EM. Short-lived Her proteins drive robust synchronized oscillations in the zebrafish segmentation clock. Development. 2013 Aug;140(15):3244-53.

Ozbudak EM, Tassy O, Pourquié O. Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4224-9.

Gomez C, Ozbudak EM, Wunderlich J, Baumann D, Lewis J, Pourquié O. Control of segment number in vertebrate embryos. Nature. 2008 Jul 17;454(7202):335-9.

Ozbudak EM, Lewis J. Notch signalling synchronizes the zebrafish segmentation clock but is not needed to create somite boundaries. PLoS Genet. 2008 Feb;4(2):e15.

Ozbudak EM, Thattai M, Lim HN, Shraiman BI, Van Oudenaarden A. Multistability in the lactose utilization network of Escherichia coli. Nature. 2004 Feb 19;427(6976):737-40.

Ozbudak EM, Thattai M, Kurtser I, Grossman AD, van Oudenaarden A. Regulation of noise in the expression of a single gene. Nat Genet. 2002 May;31(1):69-73. Epub 2002 Apr 22.

Regulatory Mechanisms Governing Vertebral Segmentation. Principal Investigator. National Institutes of Health. Sep 2014-Jun 2019. #R01 GM111987.

Elucidating the Mechanism of Precision in Vertebral Segmentation. Principal Investigator. National Institutes of Health. Apr 2017–Mar 2021. #R01 GM122956.