Mark Ebbert, Ph.D., studies neurodegenerative diseases using cutting-edge sequencing technologies and computational approaches such as computational biology and bioinformatics. Dr. Ebbert's research focuses primarily on Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease).
Ultimately, Dr. Ebbert aims to discover disease etiology and develop presymptomatic diagnostics and effective therapeutics through targeted multiomic studies that combine gene expression, methylation, and long-read and single-cell sequencing technologies. Discovering the underlying etiology for AD 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 (such as structural mutations) that cause disease. Many individuals who have neurodegenerative diseases such as AD and ALS do not have a known genetic cause, despite extensive efforts from medical and research communities. Most studies to date have focused 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.
- Discovering inherited and somatic disease-causing structural mutations in AD and ALS. The genetic cause for most individuals with AD and ALS 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 (long-read and single-cell sequencing) to understand how the genetics and all downstream processes work together to cause or prevent AD and ALS.
- Develop presymptomatic disease diagnostics. To meaningfully improve the life and outcomes of a patient with AD or ALS requires an effective therapy. Equally important, however, is a presymptomatic diagnostic. Neurodegenerative diseases require presymptomatic intervention, because recovering lost neurons is not possible once clinical symptoms onset. Dr. Ebbert is applying his extensive experience in developing disease diagnostics to AD and ALS to identify disease before symptoms occur.
Significance to patient care
To develop and apply disease-altering therapeutics, researchers need to understand what drives disease and be able to detect disease while the prescribed therapy can still intervene. Dr. Ebbert's research is solely focused on these efforts.
- New Vision Investigator, Charleston Conference on Alzheimer's Disease, 2017
- Editorial board member, Scientific Reports, 2016-present
- Recipient, Excellence in Science Award, American Association for the Advancement of Science, 2013