Dr. Ebbert studies neurodegenerative diseases using cutting-edge sequencing technologies and computational approaches (i.e., computational biology and bioinformatics), focusing primarily on Alzheimer’s disease and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). He ultimately aims to discover disease etiology, and develop pre-symptomatic diagnostics and effective therapeutics through targeted “multi-omic” studies that combine gene expression, methylation, and long-read and single-cell sequencing technologies. Discovering the underlying etiology for Alzheimer’s disease and ALS will ultimately require discovering the mechanism at which genetics, epigenetics, and downstream processes intersect to drive disease.

Long-read sequencing is of special interest to Dr. Ebbert, because it can identify large DNA mutations (i.e., structural mutations) causing disease. Many individuals suffering from neurodegenerative diseases, including both Alzheimer’s disease and ALS, do not have a known genetic cause despite extensive efforts from medical and research communities. Most studies, to date, focus on short-read sequencing, overlooking disease-causing structural mutations. Dr. Ebbert is using long-read sequencing technologies to identify disease-causing structural mutations in families and diseases with no known genetic cause.

Focus areas

• Discovering inherited and somatic disease-causing structural mutations in ALS and Alzheimer’s disease. The genetic cause for most individuals suffering from ALS and Alzheimer’s disease is unknown, despite major short-read sequencing efforts. Structural mutations are known to cause numerous neurodegenerative diseases, but few studies have specifically targeted these large mutations. Dr. Ebbert hopes to identify both genetic and somatic (mutations arising during development or later) structural mutations causing disease using long-read sequencing technologies, including PacBio and Oxford Nanopore Technologies.
• Combine gene expression, methylation, and cutting-edge sequencing technologies to reveal underlying disease etiology. Humans are complex on every level, and human diseases are no exception. To truly understand a disease’s underlying etiology, Dr. Ebbert is combining gene expression, methylation, and cutting-edge sequencing technologies (e.g., long-read and single-cell sequencing) to understand how the genetics and all downstream processes work together to cause or prevent ALS and Alzheimer’s disease.
• Develop pre-symptomatic disease diagnostics. To meaningfully improve an ALS or Alzheimer’s disease patient’s life and outcome requires an effective therapy; equally important, however, is a pre-symptomatic diagnostic. Neurodegenerative diseases require pre-symptomatic intervention, because recovering lost neurons is not possible once clinical symptoms onset. Dr. Ebbert is applying his extensive experience in developing disease diagnostics to ALS and Alzheimer’s disease to identify disease before it’s too late.

1. Ms. Sabrina M. Krause (Ph.D. student; May 2021-present)
2. Mr. Bernardo Aguzzoli-Heberle (Ph.D. student; May 2022-present)