The West Laboratory
Duke Center for Neurodegeneration
& Neurotherapeutic Research DCNN
Message from the Director: The West lab is a training hub focusing on identifying critical pathogenic mechanisms underlying neurological diseases like Parkinson’s disease and dementia with the goal of developing new therapeutics to block disease progression. The West lab is housed in the new Duke Center for Neurodegeneration and Neurotherapeutics at Duke University. Our group fosters an inclusive and supportive environnment that values and prioritizes diversity, and the celebration of different lived experiences. We focus on maintaining the highest levels of rigor in science, implementation of AI and unbiased methodologies to guide our work, and training in related statistical approaches. Please contact us for more information!
Andrew West, PhD
Director, Duke Center for Neurodegeneration and Neurotherapeutics (DCNN)
Professor, Departments of Pharmacology, Cell Biology, Neurobiology, Neurology
3 Genome Court, MSRBIII, Durham, NC 27710
Email: parkinson.lab@duke.edu
Browse our publications:
Would you like to learn more about joining our team? email: parkinson.lab@duke.edu
New in 2024! AVAILABLE POSITIONS IN THE LAB
May, 2024- An Edward N. and Della Thome Foundation Parkinson's Fellowship is available for eligible post-doctoral scholars to find new therapeutic approaches to counteract neuroinflammation associated with APOE4 alleles and pathological tau deposition. Individuals potentially interested in careers in Industry are especially encouraged to apply.
March, 2024- A 2-year Post-Bac fellowship supported by the Michael J. Fox Foundation is available to work with mouse models in the gut to brain signaling axis relevant to different microbiome exposures in Parkinson's disease. Individuals potentially interested in biomedical sciences and applying to competitive graduate programs are especially encouraged to apply.
Feb, 2024- An NINDS-supported post-doctoral fellowship is available to study pattern recognition receptor activation in the progression of cognitive decline associated with dementia and Parkinson's disease. Individuals interested in pursing careers in inflammation in academia or industry settings are especially encouraged to apply.
West Lab 2022 Annual Picnic
Top Row L to R: Dr. Andy West, Dr. Yuan Yuan, Dr. Nicole Bryant, Velda Wang, Deney Li, Eugene Cho, Amber Fu, Samuel Strader, Kash Sreeram
Bottom Row L to R: Dr. Zhiyong Liu, Josh Li, John Lin, Jon Lin, Julia Ziaa, Nicole Malpeli, Arpi Sokratian
Suggested Activities at lab events: eating bbq (vegan options available!), swinging on ropes, feeding the lab mascot goats, and getting to know your teammates better!
West lab alumni spolight We are incredibly proud of our trainees and the prestigous positions they have moved onto in recent years. Click to visit the West Lab alumni spolight page
Click to learn about the Current All-Star Members of the West laboratory!
Priority Research Questions
Does Parkinson's disease start in the gut?
<A post-doctoral position is now open to study mechanisms of gut-brain interactions in PD!*>
*email parkinson.lab@duke.edu to apply!
Why do many, or even most, PD patients report changes in their gastrointestinal function years or even a decade before motor deficits associated with disease? Perhaps the answer lies within minute molecular changes in gut cells in disease that have so far been overlooked.
Conformational changes in the protein known as (alpha) α-synuclein are thought of as the beating heart of Parkinson's disease and many cases of dementia. But where does the protein misfolding first occur? If we had a better idea of where the earliest changes happen, the 'flame of disease' could be stamped out before the fire spreads to other areas across the brain.
Working wtih expert gastroenterologists here at Duke, as well as out collaborative team at Emory and Univ. of Florida, we have identified a type of 'neuron-like' cell in the gut called enteroendocrine cells that might be the nidus for initial α-synuclein changes. Enteroendocrine cells are unique in that they express α-synuclein protein and make direct contact with toxins from the environment, pathogens, and other disease-associated microbiome changes in the lumen of the gut, as well as make direct contact (on the other side of the cells) with neurons that form the vagus nerve and might serve as a conduit to the brain. Perhaps, through this conduit, misfolded α-synuclein escapes to infect the brain.
We are actively exploring this novel circuit using advanced models and patient-derived α-synuclein conformers associated with disease progression.
Our recent published work is featured on the front page of JCI Insight!
Do nanoplastics contribute to dementia risk and progression?
The abberrant accumulation of the protein α-synuclein occurs in most cases of Alzheimer's disease, and defines pathology in dementia with Lewy bodies and Parkinson's disease. We know that the majority of riskfor these diseases is not genetically inherited, but comes from environmental factors along with aging. However, what these environmental factors consist of that interact in the aging process is mostly an open question.
Through a series of screens, we identified environmentally-relevant concentrations of nanoplastics that are able to soak into neurons and interact with α-synuclein at the lysosome. The interaction between nanoplastics and α-synuclein does not appear to be benign: nanoplastics re-arrange the molecular structure of α-synuclein into a conformation that looks like the type of folding associated with pathological spread in different dementias and Parkinson's disease.
Questions remain about gut and brain exposures to nanoplastics in dementia risk, why types of nanoplastic particles pose the greatest risk, and what we can do to counteract these interactions once they have begun.
Do different α-synuclein prion-like strains dictate phenotypes in disease?
Genetic factors, what is inherited in DNA, are well known to influence the risk of developing Parkinson's disease and dementia. But genetics poorly explains the marked heterogenity in progression, and cognitivie decline, that are at the heart of these devestating diseases.
Perhaps, what may drive disease phenotypes, buried deep within the atomic structures of α-synuclein aggregation occuring in disease, may be minute differences in protein folding that can dramatically affect the disease course.
For the first time, we have the techology using cryo-electron microscopy (CryoEM) to peer into these α-synuclein structures and correlate their differences with phenotypes in model systems and patient cells.
If we had a better knowledge of structures occuring in disease, and the disease phenotypes they might produce in patients, we might be able to develop better models of disease that identify patient-tailored ligands that interupt the aggregation and inflammation process associated with α-synuclein.
How does neuroinflammation contribute to the progression of Parkinson's disease and dementia
<A post-doctoral position is now open to study neuroinflammation mechanisms in PD!*>
*email parkinson.lab@duke.edu to apply!
Mutations in the gene that encodes the protein known as LRRK2 are among the most common known genetic causes of neurodegeneration and Parkinson's disease. Mutations that cause neurodegeneration appear to increase LRRK2 activity. Usually genetic variation linked with neurodegeneration results in loss of function, but the gain of function in LRRK2 presents a rare oppurtunity to peer into the inner workings of this novel enzymatic cascade.
Through recent single-cell sequencing datasets, we now understand that some of the highest LRRK2 expression levels are in peripheral immune cells in the innate immune system.
In our long-standing program initiated over a decade ago, we continue to closely examine LRRK2 function in immune cells. We utilize a series of different biochemical approaches to probe the inner catalytic core of LRRK2 enzymatic cycling in macrophages cells where LRRK2 expression is very high. disease-relevant cells. In a novel hypothesis we are testing experimentally, we propose that LRRK2-expressing immune cells that invade the brain from the periphery critically mediate the overt loss of neurons in the course of disease, contributing to disease phenotypes in a non-cell autonomous manner.
If we can better understand the nature of how LRRK2 activity can cause Parkinson's disease, we might be better able to develop new therapies that block the disease from moving forward.