Mark R. Cookson is a senior investigator at the National Institute on Aging (NIA), part of the National Institutes of Health (NIH). He leads the Cell Biology and Gene Expression Unit and is a leading authority on the genetics and molecular biology of Parkinson's disease[1]. With over two decades of research focused on understanding the molecular mechanisms underlying Parkinson's disease, Dr. Cookson has made seminal contributions to our understanding of how genetic factors contribute to disease risk and progression.
Dr. Cookson received his PhD in molecular genetics and completed postdoctoral training in neuroscience before joining the NIH. At the National Institute on Aging, he established the Cell Biology and Gene Expression Unit, where his research focuses on understanding the molecular mechanisms underlying Parkinson's disease.
His laboratory combines molecular biology, cell biology, and genetic approaches to investigate how known Parkinson's disease genes function in neurons and how mutations in these genes lead to disease. Before joining the NIA, Dr. Cookson established his research program to investigate the function of proteins implicated in neurodegenerative diseases, with a particular focus on Parkinson's disease.
Dr. Cookson's research program investigates the cellular and molecular mechanisms underlying Parkinson's disease, with a particular emphasis on:
LRRK2 Pathogenesis: Dr. Cookson's lab has been instrumental in understanding how LRRK2 mutations lead to neuronal dysfunction[2]. Their work has shown that LRRK2 phosphorylates Rab proteins, linking LRRK2 activity to membrane trafficking pathways.
Genetic Risk Factors: Contributed to genome-wide association studies identifying common genetic variants that increase PD risk. His work has helped identify numerous susceptibility loci for sporadic Parkinson's disease.
Rab Proteins: Discovered connections between LRRK2 and Rab protein families in membrane trafficking. This breakthrough revealed a key pathway through which LRRK2 mutations cause neuronal dysfunction.
Protein Quality Control: Elucidated how mutations in PD genes affect cellular protein clearance mechanisms, including autophagy and the ubiquitin-proteasome system.
Alpha-Synuclein Aggregation: Investigated the mechanisms by which alpha-synuclein forms toxic aggregates and how this process is influenced by genetic and environmental factors.
Dr. Cookson's research has been pivotal in understanding LRRK2 (leucine-rich repeat kinase 2), one of the most common genetic causes of Parkinson's disease. His lab demonstrated that LRRK2 phosphorylates Rab proteins, which are key regulators of membrane trafficking in cells. This discovery provided a molecular link between LRRK2 function and cellular transport pathways that may be disrupted in PD[3].
The Cookson laboratory has characterized:
Through genome-wide association studies and other genetic approaches, Dr. Cookson has contributed to identifying numerous genetic risk factors for sporadic Parkinson's disease. His work has helped reveal that Parkinson's disease is genetically complex, with multiple genes and variants contributing to disease risk. Key findings include:
A significant focus of Dr. Cookson's work involves understanding how cells handle misfolded proteins. His research has explored the autophagy-lysosome and ubiquitin-proteasome systems, which are responsible for clearing damaged proteins that can accumulate in neurodegenerative diseases. This work has implications for understanding:
Dr. Cookson's research has revealed important connections between PD genes and synaptic function. His work on LRRK2 and Rab proteins has shown how mutations affect:
Dr. Cookson has authored over 200 publications on Parkinson's disease and neurodegeneration:
Cookson MR. LRRK2 as a therapeutic target in Parkinson's disease. Nat Rev Neurol. 2022
Cookson MR, Bandmann O. Parkinson's disease: insights from the genome. Nat Rev Genet. 2010
Cookson MR. The role of LRRK2 in Parkinson's disease. Nat Rev Neurosci. 2020
Dixon CL, et al. LRRK2 mediates tethering of Golgi vesicles and lysosomes. Nat Neurosci. 2022
Berger Z, et al. LRRK2: from pathogenesis to therapy. Nat Rev Neurol. 2020
Dr. Cookson serves as Editor-in-Chief of npj Parkinson's Disease, a peer-reviewed journal publishing research on all aspects of Parkinson's disease. He is also involved in training the next generation of neuroscience researchers through his laboratory and mentorship programs at the NIH. His leadership roles include:
Dr. Cookson's contributions to Parkinson's disease research have been recognized through:
Dr. Cookson has trained numerous postdoctoral fellows and graduate students who have gone on to successful careers in academia, industry, and government research. His laboratory has produced many independent investigators who continue to advance our understanding of neurodegenerative diseases.
Dr. Cookson maintains active collaborations with researchers at:
Current research in the Cookson laboratory focuses on:
National Institute on Aging. Mark R. Cookson - Laboratory of Cell Biology and Gene Expression. https://www.nia.nih.gov ↩︎
Cookson MR. LRRK2 as a therapeutic target in Parkinson's disease. Nat Rev Neurol. 2022. ↩︎
Steger M, Tonelli F, Cookson MR, et al. Phosphoproteomics of LRRK2 reveals a link to Rab regulation. Nat Neurosci. 2016. ↩︎