onat-lab

 

Name of the lab (area of work/subject depiction)

Onat lab (Human Genetics, Genomics, Rare and Common Disorders, Bioinformatics, Disease Gene Identification Metabolic Disorders, Neurodegenerative Disorders, Psychiatric Disorders, Behavioral Phenotypes, Cytogenetics, Disease Epidemiology, Population Genetics)

PI: Asst. Prof. Dr. Onur Emre Onat

Introduction of the PI.

Dr. Onat graduated from Boğaziçi University, Department of Molecular Biology and Genetics in 2004. Between 2004 and 2012, he researched the causes of rare diseases during his master's and doctoral studies at Bilkent University, Department of Molecular Biology and Genetics. The main research area in this process was on the discovery of disease-causing genes of a cerebellar hypoplasia (CAMRQ) that is notable for walking on all fours in humans. After his doctorate education, he focused on unraveling the molecular mechanism of the "hunger/satiety" feeling regulated by neurons in the hypothalamus region of the brain in a collaborative project between Rockefeller and Bilkent Universities co-directed by Drs. Jeffrey Friedman, the discoverer of the hormone leptin and the winner of the Lasker award and Tayfun Özçelik, TUBITAK science award winner. During this period, he focused on diseases with complex inheritance and took part in establishing a comprehensive DNA bank and genome database. In this context, he continued his studies on the discovery of genes for metabolic diseases such as familial obesity, extreme leanness, and polycystic ovarian syndrome, neurodegenerative diseases such as essential tremor and Parkinson's, and psychiatric and behavioral phenotypes associated with circadian rhythm such as delayed sleep phase and attention deficit and hyperactivity disorder. He is a leading expert in the field of omics data analysis, and his research has been published in top scientific journals such as Cell, Nature Genetics, JCI, Genome Research, PNAS, and EJHG. Dr. Onat is a passionate advocate for the use of omics data to improve human health, and he is committed to training the next generation of omics scientists.

A brief description of the ongoing work

The main focus of Onat Lab is to contribute to the genetic etiologies of human diseases and the enhancing precision medicine by developing new analysis methods and algorithms to investigate disease-causing mutations and genes by comparing next-generation sequencing genomic data of patients with control individuals or unaffected family members. For this, the Lab apply and combine computational biology approaches such as bioinformatics, statistical genomics, biological databases, network modellings, machine learning, population genetics, with molecular cytogenetic approaches such as homozygosity mapping, linkage analysis, SNP genotyping, and with various molecular biology approaches.

Key strengths

By integrating omics data with clinical and population health information, the Lab aims to bridge the gap between basic research and clinical practice by leveraging cutting-edge techniques and methodologies to analyze large-scale biological datasets, generate meaningful insights, and translate scientific discoveries into practical applications that benefit healthcare and society.

Vision as a team leader.

Dr. Onur Emre Onat aims to advance the fields of human genetics and genomics by integrating genetic data with bioinformatics and advanced analytical methods to uncover disease mechanisms and promote personalized medicine. His priorities include understanding the genetic etiology of rare and common diseases, developing innovative algorithms, and translating this knowledge into clinical applications. He is committed to contributing to Turkey's emergence as a global center for genetic research and fostering the next generation of scientists.

Qualifications

PhD    Ihsan Dogramaci Bilkent University

MSc    Ihsan Dogramaci Bilkent University

BSc     Boğazici University

Field of expertise

Human Genetics, Bioinformatics, Disease Epidemiology, Population Genetics.

Affiliations

Department of Biotechnology, Institute of Health Sciences, Bezmialem Vakif University, Turkey 

Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Turkey 

List of publications

1. Onat OE*, Akbostanci C, Doganyigit-Revino KE, Sen M, Akbostanci CM. “Effects of essential tremor on longevity and mortality rates in families." Manuscript is under review by PlosOne*
2. Onat OE*. Exploring CRY1 Protein Residue Associations with Diurnal and Nocturnal Behaviors Across Vertebrate Species. PBS. 2024; 14(1): 58-106.
3. Sedillo J, Badduke C, Schrodi S, Scaria V, Onat OE, Alfadhel M, Ober C, Wentworth-Sheilds W, Steiner RD, Saba JD. Prevalence estimates of sphingosine phosphate lyase insufficiency syndrome in worldwide and select populations.  Genetics in Medicine Open 2024; 2; 100840.
4. Congur I, Koni E, Onat OE, Tokcaer Keskin Z. Meta-analysis of commonly mutated genes in leptomeningeal carcinomatosis. PeerJ. 2023; 19; 11: e15250.
5. Kars ME, Başak AN, Onat OE, Bilguvar K, Choi J, Itan Y, Çağlar C, Palvadeau R, Casanova JL, Cooper DN, Stenson PD, Yavuz A, Buluş H, Günel M, Friedman JM, Özçelik T. “The genetic structure of the Turkish population reveals high levels of variation and admixture." Proc Natl Acad Sci U S A. 2021; 118(36):e2026076118.
6. Akar OS, Gunes S, Abur U, Altundag E, Asci R, Onat OE, Ozcelik T, Ogur G. “Multiscale analysis of SRY-positive 46,XX testicular disorder of sex development: Presentation of nine cases." Andrologia. 2020; 11: e13739. PMID: 3288206.
7. Onat OE, Kars ME, Gül Ş, Bilguvar K, Wu Y, Özhan A, Aydın C, Başak AN, Trusso MA, Goracci A, Fallerini C, Renieri A, Casanova JL, Itan Y, Atbaşoğlu CE, Saka MC, Kavaklı İH, Özçelik T. “Human CRY1 variants associate with attention deficit/hyperactivity disorder." J Clin Invest. 2020; 130: 3885-3900.
8. Demirayak P, Onat OE, Gevrekci AÖ, Gülsüner S, Uysal H, Bilgen RS, Doerschner K, Özçelik TS, Boyacı H. “Abnormal subcortical activity in congenital mirror movement disorder with RAD51 mutation." Diagn Interv Radiol. 2018; 24: 392-401.
9. Patke A, Murphy PJ, Onat OE, Krieger AC, Özçelik T, Campbell SS, Young MW. “Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder." Cell. 2017; 169: 203-215.
10. Özçelik T, Onat OE. “Genomic landscape of the Greater Middle East." Nat Genet. 2016; 48: 978-979.
11. Kanaan SB, Onat OE, Balandraud N, Martin GV, Nelson JL, Azzouz DF, Auger I, Arnoux F, Martin M, Roudier J, Ozcelik T, Lambert NC. “Evaluation of X Chromosome Inactivation with Respect to HLA Genetic Susceptibility in Rheumatoid Arthritis and Systemic Sclerosis." PLoS One.  2016; 11: e0158550.
12. Unal Gulsuner H, Gulsuner S, Mercan FN, Onat OE, Walsh T, Shahin H, Lee MK, Dogu O, Kansu T, Topaloglu H, Elibol B, Akbostanci C, King MC, Ozcelik T, Tekinay AB. “Reply to Tzoulis et al.: Genetic and clinical heterogeneity of essential tremor.“Proc Natl Acad Sci USA. 2015; 112: E2269.
13. Unal Gulsuner H, Gulsuner S, Mercan FN, Onat OE, Walsh T, Shahin H, Lee MK, Dogu O, Kansu T, Topaloglu H, Elibol B, Akbostanci C, King MC, Ozcelik T, Tekinay AB. “Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease." Proc Natl Acad Sci USA. 2014; 111: 18285-18290.
14. Dal GM, Ergüner B, Sağıroğlu MS, Yüksel B, Onat OE, Alkan C, Özçelik T. “Early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair." J Med Genet. 2014; 51: 455-459.
15. Okten G, Gunes S, Onat OE, Tukun A, Ozcelik T, Kocak I. “Disruption of HDX gene in premature ovarian failure." Syst Biol Reprod Med. 2013; 59: 218-222.
16. Onat OE, Gulsuner S, Bilguvar K, Nazli Basak A, Topaloglu H, Tan M, Tan U, Gunel M, Ozcelik T. “Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion." Eur J Hum Genet. 2013; 21: 281-285.
17. Gunes S, Asci R, Okten G, Atac F, Onat OE, Ogur G, Aydin O, Ozcelik T, Bagci H. “Two males with SRY-positive 46,XX testicular disorder of sex development.“Syst Biol Reprod Med. 2013; 59: 42-47.
18. Gulsuner S, Tekinay AB, Doerschner K, Boyaci H, Bilguvar K, Unal H, Ors A, Onat OE, Atalar E, Basak AN, Topaloglu H, Kansu T, Tan M, Tan U, Gunel M, Ozcelik T. “Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred" Genome Res. 2011; 21: 1995-2003.
19. Ozcelik T, Akarsu N, Uz E, Caglayan S, Gulsuner S, Onat OE, Tan M, Tan U. “Reply to Herz et al. and Humphrey et al.: Genetic heterogeneity of cerebellar hypoplasia with quadrupedal locomotion.“Proc Natl Acad Sci USA. 2008; 105: E32-33.
20. Ozcelik T, Akarsu N, Uz E, Caglayan S, Gulsuner S, Onat OE, Tan M, Tan U. “Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans." Proc Natl Acad Sci USA. 2008; 105: 4232-4236.
21. Onat OE, Tez M, Ozçelik T, Törüner GA. “MDM2 T309G polymorphism is associated with bladder cancer." Anticancer Res. 2006; 26: 3473-3475.

Ongoing Grants

1. Investigation and molecular characterization of the roles of obesity-associated STEAP1B, KCNQ5 and UCP1 genes in disease pathogenesis, TUBITAK 1001.
2. Uyku bozuklukları ile ilişkili genlerin keşfi, moleküler karakterizasyonu ve hastalık patogenezindeki rollerinin araştırılması, TÜSEB. 

Completed grants/projects

1. The genetics of PCOS (PolyCystic Ovarian Syndrome) in Turkish Families: Identification of causal gene mutations in PCOS, Rockefeller University Center for Clinical and Translational Science (RUCCTS) 
2. The Genetics of Obesity in Turkish Families: Identification of causal gene mutations in obesity, Rockefeller University Center for Clinical and Translational Science (RUCCTS) 

Achievements as a lab/team.

Our research focuses on understanding the impact of genes on traits by developing robust genome sequencing data analysis methods. In this context, we have developed the "Genomics Analysis and Annotation Pipeline," which integrates bioinformatics, statistical genomics, and population genetics. Our goals include discovering rare mutations using machine learning techniques and network simulations, developing diagnostic tools for Mendelian disorders, and understanding the genetic factors underlying complex diseases.

Our studies focus on rare and complex diseases, such as metabolic, neurodegenerative, and behavioral disorders. We aim to uncover disease mechanisms, identify disease genes, and develop therapeutic strategies through multi-omics data analysis and advanced technologies. Notably, our research includes the investigation and molecular characterization of the roles of obesity-associated STEAP1B, KCNQ5, and UCP1 genes in disease pathogenesis, funded by the TÜBİTAK 1001 program, and the discovery and molecular characterization of genes associated with sleep disorders, as well as their roles in disease pathogenesis, funded by TÜSEB.

At the ONAT Lab, we aim to improve human health by leveraging expertise in genetics and bioinformatics to develop innovative approaches. We collaborate with leading scientists worldwide, including Nobel laureates, taking an interdisciplinary approach to solving the pathogenesis of diseases and developing new therapeutic methods. Collaboration is at the core of our research. Our team employs innovative strategies and reproducible "Genomics Pipelines" to explore the determinants and pathogenesis of human diseases. The work conducted at the ONAT Lab holds significant potential for better understanding diseases and developing new treatments for various disorders.

Approach

As a PI, my goal is to educate the next generation of scientists and build a strong scientific community in Turkey. My work focuses on researching the genetic etiologies of human diseases and developing new analytical methods to identify disease-causing mutations and genes. I encourage my team to approach their research with curiosity and precision.

BILSAB's advanced infrastructure and visionary mission provide great support in achieving these goals. The institute allows us to conduct comprehensive research by combining computational biology approaches such as bioinformatics, statistical genomics, machine learning, and population genetics with molecular cytogenetics methods and biological databases. By comparing patient genomic data with unaffected family members, we are able to make solid discoveries.

BILSAB not only addresses fundamental scientific questions but also fosters the development of innovative tools in healthcare through its interdisciplinary collaborative environment and resources. Students and researchers will learn these multidisciplinary approaches and be equipped to tackle future scientific challenges, contributing effectively to the field. In this way, BILSAB contributes to Turkey's leadership in biotechnology on a global scale.

Conclusion

My scientific journey is centered on unraveling the genetic causes of human diseases, especially rare and complex conditions, and advancing precision medicine. By combining computational biology, bioinformatics, and molecular genetics, I aim to identify disease-causing mutations and genes, with the goal of improving human health. My work bridges the gap between basic research and clinical applications, contributing to both scientific understanding and practical healthcare solutions. Through my research, I strive to inspire future generations of scientists, equipping them with the tools and knowledge to tackle the world's most pressing health challenges and make meaningful contributions to the field of genetics and genomics.

About the Team

Our team consists of PI, a PhD Candidate, four PhD Students.

Number of team members/students in lab

5

Names and designations.

1. Faruk Üstünel  PhD Candidate / Research Assistant                Bezmialem Vakıf University
2. Levise Tenay     PhD Student/ Lab Technician                             Bezmialem Vakıf University
3. Büşra Nur Çetin           PhD Student / Tübitak Scholar                           Bezmialem Vakıf University
4. Sümeyye Cilmeli          PhD Student/ Tübitak Scholar                            Bezmialem Vakıf University
5. Vildan Saraç      MSc/ Research Assistant / TÜSEB Researcher           Bezmialem Vakıf University

Introduction to the Team members:

Faruk Üstünel

Faruk Üstünel is a bioinformatician and PhD candidate in drug discovery and development, focusing on identifying therapeutic targets for circadian rhythm disorders using omics data and machine learning. He holds a bachelor's degree in Molecular Biology and Genetics from Istanbul University and a master's degree in Biotechnology from Bezmialem Vakıf University.

Currently a Research Assistant at the Beykoz Institute of Life Sciences and Biotechnology, he investigates rare variant associations and applies computational tools to explore the genetic basis of disease. In addition to his academic work, he is an entrepreneur in agricultural genomics, leveraging genomic technologies to enhance crop resilience and sustainability.

He is dedicated to advancing bioinformatics and biotechnology through innovative research and practical applications in healthcare and agriculture.

Levise Tenay

Levise Tenay is a Bioinformatician and PhD candidate in Biotechnology, specializing in structural bioinformatics and small molecule drug targeting. She holds a Bachelor's degree in Biomedical Engineering from Biruni University. Following her undergraduate studies, Levise gained invaluable experience as a volunteer researcher in the Bioinformatics Department at Saarland University, Germany, where she contributed to several bioinformatics projects with a strong focus on computational modeling, data analysis, and algorithm development.

Her research primarily focuses on leveraging structural bioinformatics to explore protein structure-function relationships and design small molecules capable of selectively modulating these interactions for therapeutic purposes. At the Beykoz Institute of Life Sciences and Biotechnology, where she currently works as a Lab Technician, Levise applies advanced computational techniques—such as molecular docking, molecular dynamics simulations, and protein-protein interaction network analysis—to study the structural and functional dynamics of proteins involved in disease pathways. Her work includes investigating the impact of rare genetic variants on protein stability, folding, and function, with the aim of uncovering novel molecular mechanisms that can inform the development of targeted drug candidates. This research is poised to contribute significantly to the understanding of complex diseases at the molecular level, potentially leading to more effective and personalized therapeutic approaches.

Büşra Nur Çetin

Büşra Nur ÇETİN is a Molecular Biologist investigating the molecular basis of rare diseases and contributing to the drug discovery process. After completing her undergraduate degree in Molecular Biology and Genetics at Istanbul University and her master's degree in Biotechnology, she focused on examining the effects of antifungal agents at the genomic and proteomic levels, particularly on cellular stress and apoptosis mechanisms.

Following her master's degree, she gained experience in both academic and industrial settings, working under GLP and non-GMP conditions in protein production, purification, and characterization processes.

Currently, she is pursuing a PhD in Biotechnology at the Beykoz Institute of Life Sciences and Biotechnology. Her research focuses on identifying disease-associated variants using omics data and performing functional analyses. Her ultimate goal is to develop biotechnological solutions for discovering new therapeutic targets for the diagnosis and treatment of rare diseases.

Sümeyye Cilmeli

Sümeyye Cilmeli is a Molecular Biologist and Geneticist, currently a PhD candidate in the Biotechnology Department at Bezmialem Vakıf University, researching the molecular characterization of obesity. She completed her undergraduate studies in Molecular Biology and Genetics at Uludağ University in Bursa and went on to earn a Master's degree in Molecular Biology and Genetics from Ondokuz Mayıs University in Samsun.

Her research background spans a wide range of areas in biotechnology and genetic analysis. She has been actively involved in managing clinical studies and R&D projects, gaining experience in protein purification, optimization of biotechnological products, and genetic analyses. As a Clinical Site Coordinator at ETHIC CRO, she participated in Phase 3 clinical trials supported by companies such as Johnson & Johnson and Bayer. Additionally, she worked as an R&D Specialist at VERA GÜBRE, where she contributed to projects involving polyhydroxybutyrate production and the development of biotechnological products. She also served as a teaching assistant at Ondokuz Mayıs University, teaching chromatographic techniques and molecular biology courses. Currently, she is a PhD candidate at Bezmialem Vakıf University's Life Science and Biotechnology Institute, conducting research under the TÜBİTAK 1001 project on the molecular characterization of obesity at ONAT Lab.

Vildan Saraç

Vildan Saraç is a Molecular Biologist specializing in the mechanisms of transcription factors and the identification of genes associated with sleep disorders. She earned her bachelor's and master's degrees in Molecular Biology and Genetics from Yıldız Technical University. During her master's studies, she conducted experimental and bioinformatics research on transcription factor mechanisms using cell culture models. 

Currently, she is a Research Assistant at the Bezmialem Vakıf University Life Sciences and Biotechnology Institute. Her research focuses on the discovery of genes related to sleep disorders, their molecular characterization, and their roles in disease pathogenesis. Her goal is to enhance the understanding of human genetics and elucidate the impact of genetic mutations on disease mechanisms.

Onat Lab Projects

1. Onur Emre Onat         Obezite İle İlişkilendirilmiş Steap1b, Kcnq5 ve Ucp1 Genlerinin Hastalık Patogenezindeki Rollerin Araştırılması ve Moleküler Karakterizasyon        Completed
2. Onur Emre Onat         Yurtiçi Bilimsel Etkinlik Düzenleme Desteği(17.Uluslararası Sağlık Bilişimi ve Biyoinformatik Sempeozyumu)         Completed
3. Onur Emre Onat         STEAP1B Varyantlarının Obezite Patogenezindeki Rolünün In Vitro ve In Vivo Modellerle Analizi      In Revision
4. Onur Emre Onat         Büyük Ölçekli Genom Analizlerinde Hastalık Geni ve İlaç Hedefi Keşfi için HPC Tabanlı Modüler Biyoinformatik İş Akışı Geliştirilmesi         In Revision
5. Onur Emre Onat         Obezite İle İlişkilendirilmiş Steap1b, Kcnq5 ve Ucp1 Genlerinin Hastalık Patogenezindeki Rollerin Araştırılması ve Moleküler Karakterizasyon        Ongoing
6. Onur Emre Onat         Uyku bozuklukları ile ilişkili genlerin keşfi, moleküler karakterizasyonu ve hastalık patogenezindeki rollerinin araştırılması      Ongoing
7. Onur Emre Onat         Uyku Fazı Bozukluklarının Genetik Temellerinde Evrimsel Korunmuşluğun Rolü: Cactus447way Tüm Genom Hizalamalarından Elde Edilen Diurnal ve Nocturnal Spesifik Varyantların UK Biobank Uyku Kohortunda İncelenmesi  Ongoing

Lab alumni, their current status.

1. Nisa Esen                                 Bioinformatics Specialist Acibadem Healthcare Group
2. Eliz Öz                           PhD Student                        Acıbadem University
3. İrem Çongur               PhD Research Fellow                    Technische Universität Dresden
4. Ekin Köni                                  Molecular Biologist                       NPG Aquarius
5. Nazlı Sultan Şahin                 Dietitian                               Klinik Obezite
6. Aleyna Çelebi              Researcher                          UC Davis
7. Nisa Çelebi                  Researcher                          UC Davis

Testimonies by Alumni.

ONAT Lab has provided its graduates with invaluable opportunities to develop expertise in genetics, bioinformatics, and molecular biology. The lab's innovative and interdisciplinary approach has equipped them with the skills to excel in various fields, such as biotechnology, cancer research, and clinical applications. The resources, training, and collaborative environment offered by the lab have enabled graduates to explore complex disease mechanisms, enhance their research capabilities, and develop essential problem-solving skills. Thanks to the foundation provided by ONAT Lab, graduates have been able to build successful careers and contribute to meaningful scientific advancements.