Ertugrul Ozbudak

Ertugrul M Ozbudak

Associate Professor-Affiliate

Childrens Hospital Bldg R

COM Pediatrics Dev. Biology - 0054

Cincinnati Children's Hospital Medical Center
240 Albert Sabin way, Room: R3563, MLC 7007
Cincinnati, Ohio 45229

Professional Summary

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.

Education

Ph.D., Massachusetts Institute of Technology Cambridge, MA, USA, 2004 (Physics)

Research and Practice Interests

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

Research Support

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

Publications

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

Ay, Ahmet; Holland, Jack; Sperlea, Adriana; Devakanmalai, Gnanapackiam Sheela; Knierer, Stephan; Sangervasi, Sebastian; Stevenson, Angel; Ozbudak, Ertu?rul 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

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

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

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

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

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

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

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

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

Giudicelli, François; Ozbudak, Ertu?rul 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

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

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

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

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

Keskin, Sevdenur; Devakanmalai, Gnanapackiam S; Kwon, Soo Bin; Vu, Ha T; Hong, Qiyuan; Lee, Yin Yeng; Soltani, Mohammad; Singh, Abhyudai; Ay, Ahmet; Özbudak, Ertu?rul 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

Simsek, Muhammed; Ozbudak, Ertugrul M (2018. ) Spatial Fold Change of FGF Signaling Encodes Positional Information for Segmental Determination in Zebrafish.Cell Reports, , 24 (1 ) ,66–78

Post Graduate Training and Education

2004-2007 Postdoctoral Research Fellow, Cancer Research UK (now Francis Crick Institute), , London, UK

2007-2009 Senior Research Associate, Stowers Institute for Medical Research, , Kansas City, MO, USA

Contact 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