Science Portrait: Dr. Xiqun Chen

**Dr. Xiqun Chen, MD, Associate Professor of Neurology, Massachusetts General Hospital, Harvard Medical School**

This is a summary of the curriculum vitae (CV) of Dr. Xiqun Chen, MD, PhD, Associate Professor and Principal Investigator at the Department of Neurology at Massachusetts General Hospital, Harvard Medical School, Boston, USA. The overall goal of Dr. Chen’s work is to develop improved therapies for Parkinson’s disease (PD) and related neurodegenerative disorders. She will give a presentation at Fujita Health University.

Dr. Chen and her group specialize in PD, especially in relation to cancer. PD is characterized by the degeneration of dopamine neurons, many of which make a dark pigment called “neuromelanin,” and on that topic she has been collaborating with Prof. Kazumasa Wakamatsu and Prof. Shosuke Ito of Fujita Health University (e.g., Cai et al. 2023).

Dr. Chen has published in multiple top-journals, including Annals of Neurology (2011, 2017, 2019), PNAS (2013, 2017), EBioMedicine (2018a, 2018b), Molecular Neurodegeneration (2022), and Progress in Neurobiology (2023).

Her ability to research the cross-fields between PD and cancer was greatly recognized in 2020 by her receiving, as the leading PI, a multi-million grant from Aligning Science Across Parkinson’s (ASAP) to study the genetic connections between PD and cancer (link).

A notable finding in her career was that red hair (again, the connection with pigmentation) is associated with an increased risk for PD (Chen et al. 2017). This finding which was even elaborately mentioned in major common press newspapers like The Sun.

Dr. Chen received her medical and PhD degrees and residency training from Shanghai Medical College, Fudan University. Fudan University is renowned and positioned 44^th in the THE World university ranking 2024 (e.g., Kyoto University is ranked 55^th).

After graduation with medical and PhD degrees from Shanghai Medical College, Fudan University in 2001, Dr. Chen pursued her postdoctoral fellowships at the University of Rochester and Columbia University in the USA to study signaling pathways relevant to dopaminergic neuron survival and degeneration. She joined Massachusetts General Hospital, Harvard Medical School, in 2009. There, she later established her research program focusing on Parkinson’s – cancer associations as a basis for better understanding Parkinson’s disease through multiple disciplinary collaborations. Her lab investigates common genetic and environmental factors connecting Parkinson’s disease and cancer, as well as related fundamental cellular processes that lead to degeneration in neurons and overgrowth in dividing cells. With her team, Dr. Chen is seeking to translate her research findings to clinical therapies, reflecting her continuing commitment to improving care for patients with Parkinson’s and related diseases.

CURRICULUM VITAE

EDUCATION

2001 Doctor of Medicine/Doctor of Philosophy (Ph.D.), Clinical Integrated Medicine/Neurology, Fudan University (Shanghai, China)

Supervisor: Professor Dingfang Cai

Thesis: Effects of long-term L-dopa on the nigrostriatal system in rat models of Parkinson’s

disease: evidence for cell death in the striatum but not in the substantia nigra

2001 Guanghua Award, Outstanding doctoral student, Fudan University, Shanghai, China

POSITIONS

Postdoctoral Training

08/1998 – 12/2000 Resident Clinical Integrated, Medicine/Neurology, Huanshan Hospital, Fudan University, Shanghai, China

08/2001 – 07/2003 Clinical Fellow Neurology Ruijing Hospital, Shanghai Jiaotong University, Shanghai, China

12/2001 – 11/2004 Fellow (Exchange scholar), Pharmacology & Physiology, The University of Rochester, Rochester, NY, USA

12/2004 – 06/2009 Fellow Neurology College of Physicians and Surgeons, Columbia University, New York, NY, USA

07/2009 – 07/2010 Postdoctoral Research Fellow, Neurology Harvard Medical School, Boston, MA, USA

Faculty Academic Appointments

07/2010 – 01/2014 Instructor, Neurology, Harvard Medical School, Boston, MA, USA

02/2014 – 02/2023 Assistant Professor, Neurology, Harvard Medical School, Boston, MA, USA

02/2023 – present Associate Professor Neurology Harvard Medical School, Boston, MA, USA

PUBLICATIONS

RESEARCH PUBLICATIONS

1. Sun B, Chen X, Lu X, Sterling C, Tank AW. Chronic nicotine treatment induces tyrosine hydroxylase gene expression in locus coeruleus: evidence that this induction is mediated by both transcriptional and post-transcriptional mechanisms. Molecular Pharmacology 2004; 66(4): 1011-21.

2. Xu L, Chen X, Sun B, Sterling C, Tank AW. Evidence for regulation of tyrosine hydroxylase mRNA translation by stress in rat adrenal medulla. Brain Research 2007; 1158:1-10.

3. Chen X, Rzhetskaya M, Kareva T, Bland R, During MJ, Tank AW, Kholodilov N, Burke RE. Antiapoptotic and trophic effects of dominant-negative forms of dual leucine zipper kinase in dopamine neurons of the substantia nigra in vivo. Journal of Neuroscience 2008; 28(3): 672-80.

4. Chen X*, Xu L*, Radcliffe P, Sun B, Tank AW. Activation of tyrosine hydroxylase mRNA translation by cAMP in midbrain dopaminergic neurons. Molecular Pharmacology 2008; 73(6): 1816-28 (*denotes co-first authors).

5. Tank AW, Xu L, Chen X, Radcliffe P, Sterling CR. Post-transcriptional regulation of tyrosine hydroxylase expression in adrenal medulla and brain. Annals of New York Academy of Sciences 2008; 1148:238-48.

6. Kim SR, Chen X, Oo TF, Kareva T, Yarygina O, Wang C, During M, Kholodilov N, Burke RE. Dopaminergic pathway reconstruction by Akt/Rheb-induced axon regeneration. Annals of Neurology 2011; 70(1): 110-20.

7. Chen X, Tagliaferro P, Kareva T, Kholodilov N, Burke RE. Neurotrophic effects of serum- and glucocorticoid-inducible kinase on adult murine mesencephalic dopamine neurons. Journal of Neuroscience 2012; 32(33): 11299-308.

8. Burdett T, Desjardins CA, Logan R, McFarland NR, Chen X (corresponding author), Schwarzschild MA. Efficient determination of purine metabolites in brain tissue and serum by high-performance liquid chromatography with electrochemical and UV detection. Biomedical Chromatography 2013; 27(1): 122-9.

9. Chen X (corresponding author), Burdett T, Desjardins C, Logan R, Xu Y, Cipriani S, Schwarzschild MA. Disrupted and transgenic urate oxidase alter urate and neurodegeneration in a mouse model of Parkinson’s disease. Proceedings of the National Academy of Sciences 2013; 110(1): 300-5.

10. Chen X*, Wales P, Quinti L, Zuo F, Moniot S, Herisson F, Rauf NA, Hua Wang4, Silverman RB, Ayata C, Maxwell MM, Steegborn C, Schwarzschild MA, Outeiro TF, Kazantsev AG*. The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson’s disease but not amyotrophic lateral sclerosis and cerebral ischemia. PLOS One 2015; Jan 21;10(1):e0116919 (*denotes co-senior authors).

11. Bakshi R, Zhang H, Logan R, Joshi I, Xu Y, Chen X, Schwarzschild MA. Neuroprotective effects of urate are mediated by augmenting astrocytic glutathione synthesis and release. Neurobiological Diseases 2015 Oct;82:574-579.

12. Chen X (corresponding author), Chen H, Cai W, Maguire M, Ya B, Zuo F, Logan R, Li H, Robinson K, Vanderburg CR, Yu Y, Wang Y, Fisher DE, Schwarzschild MA. The melanoma-linked “redhead” MC1R influences dopaminergic neuron survival. Annals of Neurology 2017; 81(3):395-406.

13. Kastanenka KV, Hou SS, Shakerdge N, Logan R, Feng D, Wegmann S, Hawkes JM, Chen X, and Bacskai BJ. Optogenetic restoration of disrupted slow waves halts amyloid deposition and restores calcium homeostasis in Alzheimer’s disease. PLoS One 2017; 12(1):e0170275.

14. Chen X*, Feng D, Schwarzschild M, Gao X*. Red hair, MC1R variants, and risk for Parkinson’s disease – a meta-analysis. Annuals of Clinical and translational Neurology 2017; 4(3):212-216. (*denotes co-senior author).

15. Quinti L*, Dayalan Naidu S*, Träger U*, Chen X*, Kegel-Gleason K, Llères D, Connolly C, Chopra V, Low C, Moniot S, Sapp E, Tousley AR, Vodicka P, Van Kanegan MJ, Kaltenbach LS, Crawford LA, Fuszard M, Higgins M, Miller JRC, Farmer RE, Potluri V, Samajdar S, Meisel L, Zhang N, Snyder A, Stein R, Hersch SM, Ellerby LM, Weerapana E, Schwarzschild MA, Steegborn C, Leavitt BR, Degterev A, Tabrizi SJ, Lo DC, DiFiglia M, Thompson LM, Dinkova-Kostova AT, Kazantsev AG. KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington’s disease patients. Proceedings of the National Academy of Sciences 2017; 114(23):E4676-E4685. (*denotes co-first authors).

16. Cai W**, Feng D, Schwarzschild MA, McLean PJ, Chen X. Bimolecular Fluorescence Complementation of Alpha-synuclein Demonstrates its Oligomerization with Dopaminergic Phenotype in Mice. EBioMedicine 2018; 29:13-22 (**denote mentee).

Commentary: Richter F. Lighting Up Alpha-synuclein Oligomers. EBioMedicine 2018 pii: S2352-3964(18)30070-7.

17. Bakshi R, Xu Y, Mueller KA, Chen X, Granucci E, Paganoni S, Sadri-Vakili G, Schwarzschild MA. Urate mitigates oxidative stress and motor neuron toxicity of astrocytes derived from ALS-linked SOD1G93A mutant mice. Molecular and Cellular Neuroscience 2018; 92:12-16.

18. Chen X (corresponding author), Umeh CC, Tainsh RE, Feng DD, Maguire M, Zuo F, Rahimian M, Logan R, Wang X, Ascherio A, Macklin EA, Buys ES, Schwarzschild MA; Parkinson Study Group (PSG) The Safety of Urate Elevation in Parkinson’s Disease (SURE-PD) investigators. Dissociation between urate and blood pressure in mice and in people with early Parkinson’s disease. EBioMedicine 2018; 37:259-268.

Commentary: Petruzzo M, Moccia M. Time to reconsider urate: Neuroprotective potential may prevail on cardiovascular risk in animal models and clinical trials. EBioMedicine 2018 pii: S2352-3964(18)30484-5.

19. Bakshi R, Macklin EA, Logan R, Zorlu MM, Xia N, Crotty GF, Zhang E, Chen X, Ascherio A, Schwarzschild MA. Higher urate in LRRK2 mutation carriers resistant to Parkinson disease. Annals of Neurology 2019; 85(4):593-599.

20. Kastanenka KV, Calvo-Rodriguez M, Hou SS, Zhou H, Takeda S, Arbel-Ornath M, Lariviere A, Lee YF, Kim A, Hawkes JM, Logan R, Feng D, Chen X, Gomperts SN, Bacskai BJ. Frequency-dependent exacerbation of Alzheimer’s disease neuropathophysiology. Scientific Reports 2019; 9(1):8964.

21. Hasimoglu YG, Chen X, Bakshi R, Schwarzschild MA, Macklin EA. Does serum urate change as Parkinson’s disease progresses? Journal of Parkinson’s Disease 2020; 10(4): 1571–1576.

22. Crotty GF, Maciuca R, Macklin EA, Wang J, Montalban M, Davis SS, Alkabsh JI, Bakshi R, Chen X, Ascherio A, Astarita G, Huntwork-Rodriguez S, Schwarzschild MA. Association of caffeine and related analytes with resistance to Parkinson’s disease among LRRK2 mutation carriers: A metabolomic study. Neurology 2020; 10.1212.

23. Zhang Y, Guarin D**, Chen X*, Gao X*. Parkinson’s disease and cancer – meta-analysis and systemic review (*denotes co-senior authors; **denote co-first author and mentee). BMJ Open 2021; 11(7):e046329.

24. Cai W**, Feng D, Vanderburg CR, Frosch MP, Fisher DE, Jackson IJ, Mclean P, Schwarzschild MA, Chen X. Melanocortin 1 Receptor activation protects against alpha-synuclein in models of Parkinson’s disease (**denote mentee). Molecular Neurodegeneration 2022; 17(1):16.

25. Ye Q**, Al-Kuwari N, Pranay Srivastava P, Chen X. Oncogenic BRAFV600E induces microglial proliferation through extracellular signal-regulated kinase and neuronal death through c-Jun N-terminal kinase. Neural Regeneration Research 2023; 18(7):1613-1622. (**denote mentee)

26. Cai W*, **, Wakamatsu K*, Zucca FA*, Wang Q, Yang K, Mohamadzadehonarvar N, Srivastava P, Casella L, Ito S, Zecca L, Chen X. Dopa pheomelanin is increased in nigral neuromelanin of Parkinson’s disease. Progress in Neurobiology 2023; 223:102414. (*denote co-first authors; **denote mentee)

27. Srivast P**, Nishiyama S, Lin SH, Srivast A, Su C, Peng W, Levy M, Schwarzschild M, Xu Y, Chen X. Peripheral MC1R activation modulates immune responses and is neuroprotective in a mouse model of Parkinson’s disease. Res Sq [Preprint]. 2023 Jun 12:rs.3.rs-3042571. Revision. (**denote mentee)