Chen Lab: Xiqun Chen, MD, PhD

Overview

The Chen Laboratory at the MassGeneral Institute for Neurodegenerative Disease (MIND), under the direction of Xiqun Chen, MD, PhD, investigates common genetic and environmental factors connecting Parkinson’s disease (PD) and cancer, as well as related fundamental cellular processes that lead to degeneration in neurons and overgrowth in dividing cells. We bring together a team of experts in the fields of Parkinson’s disease and cancer to borrow sophisticated approaches from cancer research to collaboratively test a hypothesis that immune dysregulation is the reason why alterations in LRRK2 and Parkin can cause both Parkinson’s disease and cancer, with a focus on Parkinson’s disease in this proposed work.

We will use dopamine-producing neurons derived from Parkinson’s disease patient stem cells, and mouse models with genetically modified LRRK2 and Parkin to modulate and characterize their immune signatures in both the periphery and the brain. In addition, we will perform immune profiling in samples from patients with Parkinson’s disease or cancer. Most recently, the lab identified a critical role of the melanoma-related red hair gene in models of PD.

The lab seeks to translate research findings to clinical therapies through multiple disciplinary collaborations with other teams under the Aligning Science Across Parkinson’s (ASAP) initiative, reflecting a continuing commitment to improving care for patients with Parkinson's and related diseases.

Research Projects

LRRK2/Parkin α-Syn vaccination models

Built upon existing knowledge of CD40/CD40L in immune regulation, this project seeks to understand the role of CD40 signaling in LRRK2 mutation-associated immune dysregulation.

PD immune models

This project oversees the characterization and profiling of immune cells and other biofluids from PD patients with or without LRRK2 mutations, in addition to detecting and determining autoantibodies with a novel optimized platform.

Research Positions

Read about and apply for residency, fellowship and observership programs in neurology.

All applicants should search for current opportunities on the Massachusetts General Hospital careers page.

Selected Publications

Cai, W., Wakamatsu, K., Zucca, F. A., Wang, Q., Yang, K., Mohamadzadehonarvar, N., Srivastava, P., Tanaka, H., Holly, G., Casella, L., Ito, S., Zecca, L., & Chen, X. (2023). DOPA pheomelanin is increased in nigral neuromelanin of Parkinson's disease. Progress in neurobiology, 223, 102414. https://doi.org/10.1016/j.pneurobio.2023.102414

Ye, Q., Srivastava, P., Al-Kuwari, N., & Chen, X. (2023). Oncogenic BRAFV600E induces microglial proliferation through extracellular signal-regulated kinase and neuronal death through c-Jun N-terminal kinase. Neural regeneration research, 18(7), 1613–1622. https://doi.org/10.4103/1673-5374.361516

Cai, W., Srivastava, P., Feng, D., Lin, Y., Vanderburg, C. R., Xu, Y., Mclean, P., Frosch, M. P., Fisher, D. E., Schwarzschild, M. A., & Chen, X. (2022). Melanocortin 1 receptor activation protects against alpha-synuclein pathologies in models of Parkinson's disease. Molecular neurodegeneration, 17(1), 16. https://doi.org/10.1186/s13024-022-00520-4

Cai, W., Feng, D., Schwarzschild, M. A., McLean, P. J., & Chen, X. (2018). Bimolecular Fluorescence Complementation of Alpha-synuclein Demonstrates its Oligomerization with Dopaminergic Phenotype in Mice. EBioMedicine, 29, 13–22. https://doi.org/10.1016/j.ebiom.2018.01.035

Chen, X., Chen, H., Cai, W., Maguire, M., Ya, B., Zuo, F., Logan, R., Li, H., Robinson, K., Vanderburg, C. R., Yu, Y., Wang, Y., Fisher, D. E., & Schwarzschild, M. A. (2017). The melanoma-linked "redhead" MC1R influences dopaminergic neuron survival. Annals of neurology, 81(3), 395–406. https://doi.org/10.1002/ana.24852

Full NCBI PubMed publications list.