A photo of M. Ertugrul Ozbudak.

Associate Professor, UC Department of Pediatrics

513-803-2607

Biography & Affiliation

Biography

My research interests delve into developing a quantitative understanding of complex biological systems by joining systems-level biological investigation with mathematical modeling. During my career, I have researched a multitude of different biological events, including:

  • Cell polarization and symmetry breaking
  • Entrainment of gene expression oscillations
  • Gene regulatory networks
  • Stochasticity and multi-stability in gene expression
  • Temporal analysis of transcriptome during muscle differentiation and vertebral segmentation

To complete these research projects, I utilized a variety of tools and approaches, such as single-cell microscopy measurements, genome-wide procedures, computational simulations, time-resolved perturbation tests and mathematical modeling. Additionally, I have extensive expertise in systems-level analysis of biological systems. In my lab, I work collaboratively with an interdisciplinary team from various backgrounds, including biology, physics and engineering.

My research team and I aim to identify the systems-level machinery governing vertebral segmentation, which is a groundbreaking case of spatial pattern formation during embryonic development. We have an overarching goal of determining how gene expression noise is cushioned by gene regulatory networks to attain robustness in developmental pattern formation.

Stochastic processes occur regularly in biological systems. For instance, among genetically identical bacteria, gene expression levels can be significantly different between individual bacteria within the population. The cause of this difference is due to the random nature of biochemical reactions. During my graduate work, I researched the impact of these fluctuations, known as biochemical noise, on macroscopic variations in gene expression. Our stochastic computational model found consistent results showing the proteins are developed in random, sharp bursts. These findings provide the first results for the microscopic biochemical source of phenotypic noise.

In my research lab, my team and I have incorporated these methods to study the scale and sources of expression noise in the levels of the vertebrate segmentation clock genes. We exhibited that segmentation clock transcription levels have low amplitude and high heterogeneity. We found that variability in the clock gene expression is blocked by Notch signaling and a negative feedback loop. We also uncovered that chromosome linkage reduces uncorrelated transcriptional variability and delivers phenotypic robustness for a developmental pattern formation.

I received the Merck/Massachusetts Institute of Technology computational biology fellowship in 2000. I then pursued a Cancer Research UK, Marie Curie and European Molecular Biology Organization (EMBO) postdoctoral fellowships from 2005 to 2007. I have more than 15 years of experience in the developmental biology field and began my work at the Cincinnati Children’s Hospital Medical Center in 2017. My research has been published in various journals, including Nature Genetics, Cell Reports and Nature.

Research Interests

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

Academic Affiliation

Associate Professor, UC Department of Pediatrics

Research Divisions

Developmental Biology



Blog Posts

Spine Development: It Takes Gene Pairs to Get it Right

Genomics and Development

Spine Development: It Takes Gene Pairs to Get it Right

Ertugrul M. Ozbudak, PhD12/23/2020

Education

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.

Publications

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

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

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

Reduced dosage of β-catenin provides significant rescue of cardiac outflow tract anomalies in a Tbx1 conditional null mouse model of 22q11.2 deletion syndrome. Racedo, SE; Hasten, E; Lin, M; Devakanmalai, GS; Guo, T; Ozbudak, EM; Cai, CL; Zheng, D; Morrow, BE. PLoS Genetics. 2017; 13:e1006687-e1006687.