Ertugrul M Ozbudak , PhD

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.

Doctoral Degree: Massachusetts Institute of Technology Cambridge, MA, USA, 2004 (Physics)

Postdoctoral Fellowship: Francis Crick Institute London, UK, 2007

Senior Research Associate: Stowers Institute for Medical Research Stowers Institute for Medical Research, 2009

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

Grant: #R01 GM111987 Investigators:Ozbudak EM 2014 -2019 NIH Regulatory Mechanisms Governing Vertebral Segmentation. Principal Investigator. Role:PI Active Type:Grant

Grant: #R01 GM122956 Investigators:Ozbudak EM 2017 -2021 NIH Elucidating the Mechanism of Precision in Vertebral Segmentation. Role:PI Active Type:Grant

Peer Reviewed Publications

Racedo, Silvia E; Hasten, Erica; Lin, Mingyan; Devakanmalai, Gnanapackiam Sheela; Guo, Tingwei; Ozbudak, Ertugrul M; Cai, Chen-Leng; Zheng, Deyou; Morrow, Bernice E (2017. ) Reduced dosage of ?-catenin provides significant rescue of cardiac outflow tract anomalies in a Tbx1 conditional null mouse model of 22q11.2 deletion syndrome.PLoS genetics, , 13 (3 ) ,e1006687 More Information

Ay, Ahmet; Holland, Jack; Sperlea, Adriana; Devakanmalai, Gnanapackiam Sheela; Knierer, Stephan; Sangervasi, Sebastian; Stevenson, Angel; Ozbudak, Ertugrul M (2014. ) Spatial gradients of protein-level time delays set the pace of the traveling segmentation clock waves.Development (Cambridge, England), , 141 (21 ) ,4158-67 More Information

Ay, Ahmet; Knierer, Stephan; Sperlea, Adriana; Holland, Jack; Özbudak, Ertugrul M (2013. ) Short-lived Her proteins drive robust synchronized oscillations in the zebrafish segmentation clock.Development (Cambridge, England), , 140 (15 ) ,3244-53 More Information

Devakanmalai, Gnanapackiam Sheela; Zumrut, Hasan E; Ozbudak, Ertugrul M (2013. ) Cited3 activates Mef2c to control muscle cell differentiation and survival.Biology open, , 2 (5 ) ,505-14 More Information

Hanisch, Anja; Holder, Maxine V; Choorapoikayil, Suma; Gajewski, Martin; Özbudak, Ertugrul M; Lewis, Julian (2013. ) The elongation rate of RNA polymerase II in zebrafish and its significance in the somite segmentation clock.Development (Cambridge, England), , 140 (2 ) ,444-53 More Information

Ozbudak, Ertugrul M; Tassy, Olivier; Pourquié, Olivier (2010. ) Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation.Proceedings of the National Academy of Sciences of the United States of America, , 107 (9 ) ,4224-9 More Information

Ozbudak, Ertugrul M; Pourquié, Olivier (2008. ) The vertebrate segmentation clock: the tip of the iceberg.Current opinion in genetics & development, , 18 (4 ) ,317-23 More Information

Gomez, Céline; Ozbudak, Ertugrul M; Wunderlich, Joshua; Baumann, Diana; Lewis, Julian; Pourquié, Olivier (2008. ) Control of segment number in vertebrate embryos.Nature, , 454 (7202 ) ,335-9 More Information

Ozbudak, Ertugrul M; Lewis, Julian (2008. ) Notch signalling synchronizes the zebrafish segmentation clock but is not needed to create somite boundaries.PLoS genetics, , 4 (2 ) ,e15 More Information

Lewis, Julian; Ozbudak, Ertugrul M (2007. ) Deciphering the somite segmentation clock: beyond mutants and morphants.Developmental dynamics : an official publication of the American Association of Anatomists, , 236 (6 ) ,1410-5 More Information

Giudicelli, François; Ozbudak, Ertugrul M; Wright, Gavin J; Lewis, Julian (2007. ) Setting the tempo in development: an investigation of the zebrafish somite clock mechanism.PLoS biology, , 5 (6 ) ,e150 More Information

Mettetal, Jerome T; Muzzey, Dale; Pedraza, Juan M; Ozbudak, Ertugrul M; van Oudenaarden, Alexander (2006. ) Predicting stochastic gene expression dynamics in single cells.Proceedings of the National Academy of Sciences of the United States of America, , 103 (19 ) ,7304-9 More Information

Ozbudak, Ertugrul M; Becskei, Attila; van Oudenaarden, Alexander (2005. ) A system of counteracting feedback loops regulates Cdc42p activity during spontaneous cell polarization.Developmental cell, , 9 (4 ) ,565-71 More Information

Ozbudak, Ertugrul M; Thattai, Mukund; Lim, Han N; Shraiman, Boris I; Van Oudenaarden, Alexander (2004. ) Multistability in the lactose utilization network of Escherichia coli.Nature, , 427 (6976 ) ,737-40 More Information

Ozbudak, Ertugrul M; Thattai, Mukund; Kurtser, Iren; Grossman, Alan D; van Oudenaarden, Alexander (2002. ) Regulation of noise in the expression of a single gene.Nature genetics, , 31 (1 ) ,69-73 More Information

Keskin, Sevdenur; Devakanmalai, Gnanapackiam S; Kwon, Soo Bin; Vu, Ha T; Hong, Qiyuan; Lee, Yin Yeng; Soltani, Mohammad; Singh, Abhyudai; Ay, Ahmet; Özbudak, Ertugrul M (2018. ) Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling.Cell reports, , 23 (7 ) ,2175-2185.e4 More Information

Keskin, Sevdenur; Simsek, M Fethullah; Vu, Ha T; Yang, Carlton; Devoto, Stephen H; Ay, Ahmet; Özbudak, Ertugrul M (2019. ) Regulatory Network of the Scoliosis-Associated Genes Establishes Rostrocaudal Patterning of Somites in Zebrafish.iScience, , 12 ,247-259 More Information

Simsek, M Fethullah; Özbudak, Ertugrul M (2018. ) Spatial Fold Change of FGF Signaling Encodes Positional Information for Segmental Determination in Zebrafish.Cell reports, , 24 (1 ) ,66-78.e8 More Information

Zinani, Oriana Q H; Keseroglu, Kemal; Ay, Ahmet; Özbudak, Ertugrul M (2020. ) Pairing of segmentation clock genes drives robust pattern formation.Nature, , More Information

Cincinnati Children's Hospital Medical Center
240 Albert Sabin way, Room: R3563, MLC 7007
Cincinnati  Ohio, 45229
Phone: 513 803 2607
Ertugrul.Ozbudak@cchmc.org