Wilfried O. Rossoll, Ph.D., and colleagues study molecular mechanisms and cellular pathways of neurodegeneration in diseases characterized either by reduced assembly of RNA and proteins, such as spinal muscular atrophy (SMA), or by increased protein aggregation, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease.
Dr. Rossoll's research team uses model systems such as cell culture, mouse models and stem cell-derived neurons from human patients to understand how dysfunction in RNA processing and protein homeostasis can cause neurodegenerative diseases. As researchers learn more about disease mechanisms, the focus is shifting to translational research to develop new therapeutic approaches for treatment and prevention.
- Disease mechanisms in SMA. Spinal muscular atrophy (SMA) is the most common genetic cause of death for infants. Dr. Rossoll's team is using advanced cellular and animal models to study the molecular functions of the disease protein SMA, how reduced levels of this protein cause a deficiency of RNA-protein assembly, and the degeneration of motor neurons in SMA.
- Mechanisms of protein aggregation in neurological disease. Research in Dr. Rossoll's lab is focused on aggregation-prone proteins such as TDP-43 and tau, which are critically involved in the pathogenesis of ALS, FTD and Alzheimer's disease. Studies in the lab seek to gain a detailed understanding of the aggregate-associated proteome, mechanisms that promote the aggregation, and how to prevent the pathology from occurring and spreading across the central nervous system.
- Modifiers and novel therapeutic targets of disease progression. Dr. Rossoll's team recently discovered a potent modifier of pathological TDP-43 aggregation, which is a hallmark of FTD, ALS and other neurodegenerative diseases. His team is utilizing cutting-edge techniques in the areas of biochemistry, molecular and cell biology, and fluorescence microscopy to identify ways to prevent the formation of pathological protein aggregates in various cell models including patient-derived cells and in vivo models.
Significance to patient care
The unmet need for effective therapies to treat the growing number of patients with neurodegenerative diseases is creating a mounting personal and financial burden on society. Among the most common hallmarks of these diseases are defects in RNA processing and the pathological aggregation of proteins. Research in Dr. Rossoll's lab is dedicated to providing a better understanding of these processes, which is an essential step in the development of effective novel therapeutic strategies for patients with neurodegenerative disorders.
- Faculty member, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 2016-present
- Program faculty member, Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 2015-present
- Associate director, Laboratory of Translational Cell Biology (LTCB) Stem Cell Lab, Emory University School of Medicine, 2012-2017
- Faculty member, Center for Neurodegenerative Disease, Emory University, 2007-2017