The research of Yongjie Zhang, Ph.D., is focused on investigating disease mechanisms associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), two fatal diseases that are pathologically and genetically related. Dr. Zhang has significant expertise in functional and molecular biology, as well as animal modeling.
Using an array of complementary tools, Dr. Zhang's laboratory is specifically interested in investigating the pathogenic pathways by which aggregation-prone proteins (such as TDP-43, C9orf72 dipeptide repeat protein) cause cellular functional defects and neurodegeneration, resulting in novel therapeutic strategies to mitigate toxicities associated with these abnormal protein deposits.
- C9orf72 mutation in FTD and ALS. Neuronal inclusions of C9orf72 dipeptide repeat (DPR) proteins are a pathological hallmark of C9orf72-associated FTD (c9FTD) and ALS. Dr. Zhang developed novel mouse models expressing individual DPR proteins. His research focuses on investigating how individual DPR proteins specifically affect cellular pathways, neurodegeneration and behavioral deficits.
- DPR proteins and TDP-43. TDP-43 inclusions are another pathological hallmark of c9FTD and ALS. Dr. Zhang observed that DPR proteins and TDP-43 co-aggregate in stress granules, the cytosolic dense aggregations composed of proteins and RNAs. His research focuses on investigating how DPR proteins and the associated stress granule pathway induce TDP-43 proteinopathy.
- Therapeutic strategy to treat c9FTD and ALS. Dr. Zhang seeks to identify and test novel genetic modifiers and antisense oligonucleotides (ASOs) as therapeutic approaches to mitigate C9orf72-associated pathology and neurodegeneration in culture cells and mouse models.
Significance to patient care
The ultimate goal of Dr. Zhang's research is to identify novel therapeutic targets and design target-specific therapies to successfully treat FTD and ALS.
- Recipient, Target ALS Foundation Grant Program, 2017-2019, 2020-2022
- Recipient, ALS Association Research Grant, 2014-2017, 2015-2018
- Recipient, Alzheimer's Association New Investigator Research Program, 2014-2016
- Recipient, AFAR Affiliate Research Grant Program, 2009-2010