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

Gene Discovery in Rare Inherited Disorders

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.

Somatic Studies of the Epileptic Brain

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.

Genomics of Behavioral Health

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

Daniel C. Koboldt, M.S.
Principal Investigator

Mohammad Marhabaie, PhD
Postdoctoral Scientist 

Maeson Latsko, PhD
Postdoctoral Scientist (Wilson Lab)

Swetha Ramadesikan, PhD
Postdoctoral Scientist (Wilson Lab)

Olivia Grischow
Research Aide (Mardis and Miller Labs)