Koboldt Lab
Next-generation sequencing technologies have fundamentally changed the study of human genetics. Thousands of disease genes have been catalogued since the completion of the draft human genome sequencing in 2001. Genetic testing has been widely adopted as a key diagnostic tool, particularly for developmental disorders and rare genetic diseases. Despite these critical advances, our knowledge of the relationship between genotype and phenotype remains incomplete. This is evident from the fact that clinical genetic testing provides a molecular diagnosis for just 25-30% of patients referred for it.
The incredible throughput and numerous applications of high-throughput sequencing instruments holds enormous potential but also brings considerable challenges. The sheer volume of data calls for a new class of bioinformatics tools to process genomic data, as well as to identify and assess the millions of genetic variants present in all individuals to identify which ones may contribute to disease.
The Koboldt Lab analyzes genomic data from several translational research studies at the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital to study the genetic basis of conditions that affect children, particularly rare diseases, epilepsy and pediatric cancers. Using modern techniques for genomic interrogation and analysis, the lab team searches for likely-causal genetic variants patients affected by these diseases, with an emphasis on the discovery and characterization of new disease genes. The Koboldt Lab also develops bioinformatics tools and approaches to facilitate genomic analysis and variant interpretation.
Areas of Research
Despite the considerable advances in gene discovery and genetic testing, most patients who undergo comprehensive genetic testing (e.g. clinical exome sequencing) fail to obtain a molecular diagnosis. Such patients often continue on a diagnostic odyssey of medical testing that can last months or years without finding an answer.
Using state-of-the-art genomic approaches — whole-genome sequencing, transcriptome analysis and long-read sequencing — and innovative bioinformatics approaches, the Koboldt Lab identifies novel candidate genes and gene-phenotype associations in hopes of assisting patients and families in search of a diagnosis.
Epilepsy is one of the most common conditions associated with neurological disorders, affecting as many as 1 in 26 individuals in the United States alone. While 20-30% of cases are caused by acquired conditions (e.g. stroke, head injury or tumor), the majority are believed to have an underlying genetic etiology.
Nationwide Children’s Hospital’s Level 4 Epilepsy Center offers advanced epilepsy surgery services, including evaluation using intracranial electrodes to identify epileptogenic zones and surgical excision of affected tissue. The Kobolt Lab obtains excised tissue and matched normal (blood) samples from epilepsy patients for genomic study, which usually involves exome sequencing (tissue and normal samples) and RNA-seq (tissue samples), with the goal of identifying somatic variants in brain tissue that underlie disease etiology.
While the factors predisposing children to mood disorders such as depression and bipolar disorders and developmental behavior disorders like autism spectrum disorder are undoubtedly complex and varied, the Kobolt Lab believes that state-of-the-art genome sequencing of affected families may help elucidate genetic predisposition factors.
In partnership with Behavioral Health researchers at Nationwide Children’s, the Kobolt Lab is examining genomic factors influencing behavioral health.
Meet Our Team
Principal Investigator
Dan Koboldt is a Principal Investigator at the Institute for Genomic Medicine at Nationwide Children's Hospital, and a Research Assistant Professor of Pediatrics at The Ohio State University.
Previously, he worked as a staff scientist for the Genome Institute at Washington University, where he contributed to high-profile projects including the first cancer genome (AML1), the Cancer Genome Atlas, the 1,000 Genomes Project, and the Alzheimer's Disease Sequencing Project.
He is the developer of VarScan, a widely-used somatic mutation caller for next-generation sequencing data, and MendelScan, a variant prioritization and disease gene mapping tool for family-based sequencing studies of inherited disease.
At Nationwide Children’s, his group specializes in developing tools for the analysis and interpretation of next-generation sequencing data, particularly as applied to study rare genetic diseases in children.
Mohammad Marhabaie, PhD
Postdoctoral Scientist
Mohammad Marhabaie is a Senior Bioinformatics Scientist in Koboldt lab. His primary interests and responsibilities in the team are developing tools and pipelines to analyze human genetics and genomics data. He earned his B.S. in biology from the University of Isfahan in Iran, M.S. in biological science from the University of Akron in Ohio, and Ph.D. in molecular genetics from the Ohio State University. Concurrent with his undergraduate studies, he completed a three-year IT program in computer science and programming at the Aptech Computer Education Institute. With a strong background in computer science and a deep passion for biology, he is a skilled bioinformatician who has published research studies on a broad spectrum of biological topics, including spider taxonomy, spider silk biomechanics and evolution, developmental biology, RNA-binding proteins and RNA biology, rare diseases, genomics, and human genetics.
Olivia Roof
Research Intern
Olivia Roof works with Dan Koboldt’s team as a research intern learning more about human genetics and genome analysis. She is currently attending Otterbein University and plans to graduate with a Biology major and Chemistry minor. She hopes to pursue a career in genetics and continue to learn more about the field during her time at Nationwide Children's.
Swetha Ramadesikan, PhD
Postdoctoral Scientist (Wilson Lab)