Yue Laboratory

ZhenyuYue_

 

Molecular and Cellular Mechanisms of Neurological Disorders and Therapeutic Development

The Yue Laboratory focuses on investigating the molecular, cellular, network, circuitry, and behavioral mechanisms underlying various neurological disorders and psychiatric conditions, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, bipolar disorder, and schizophrenia. The Yue lab employs a multidisciplinary approach, utilizing experimental and bioinformatic methods to gain insights into the pathogenesis of these disorders and to develop potential therapeutic strategies.

1. Disease Mechanisms: We focus on cellular processes such as autophagy-lysosome degradation, synaptic vesicle trafficking and activity, cellular metabolism, neuroinflammation, and protein/lipid kinase signaling.

2. Experimental Techniques: Mouse genetics, biochemical assays, molecular and cellular biology approaches, primary neuron/glia cultures, cellular imaging (both live and fixed), transcriptomics (including single-cell RNA sequencing and spatial transcriptomics), proteomics, bioinformatics, and animal pathology/behavioral studies.

3. Human-Relevant Models: Human-induced pluripotent stem cell (iPSC)-derived neurons and glia (2D and 3D), postmortem tissue analysis

4. Translational Research: Therapeutic target identification and validation, disease modification development focused on nanobody, gene therapy, and drug repositioning.

Pathogenic mechanism of neuron and glia interactions in Parkinson’s disease

We are undertaking the profiling and characterization of molecularly distinct subtypes of neurons and glia in the substantia nigra pars compacta (SNpc) from Parkinson’s disease (PD) brains. Our goal is to identify novel cell types and unravel the molecular mechanisms underlying the vulnerability and resilience of neurons in PD. We employ a multidisciplinary approach, integrating network modeling with experimental validation using human postmortem tissues, genetic mouse models, and induced human neurons (iPSC) in both 2D and 3D midbrain cultures. We aim to model and characterize human dopamine neuron subpopulations, pinpointing those associated with PD vulnerability within the SNpc, utilizing hiPSC-based models. See our PD Center website: https://icahn.mssm.edu/research/center-parkinsons-disease

Molecular mechanism of body-brain interactions during the progression of Parkinson’s disease

An increased incidence of PD in patients with inflammatory bowel disease (IBD), a chronic disease of the gut, has also been reported world-wide. With the finding of alpha-synuclein-associated Lewy body in peripheral tissues (e.g. gut) of PD patients, there is a growing appreciation for the hypothesis of gut-brain axis and chronic inflammation in the disease onset and progression for PD. The link between intestinal inflammation and PD is also enforced by elevated markers of intestinal inflammation. We aim to determine the subtypes of PD associated with prodromal gut chronic inflammation, dissect the pathogenic mechanism underpinning gut-brain axis, and identify molecular biomarkers and novel therapeutics for subtypes of PD.  We will test the hypothesis that (1) chronic inflammation in the gastrointestinal system contributes to a subset of PD, and this is mediated by pathogenic interaction between LRRK2 and alpha-synuclein; (2) LRRK2 acts as an interface for the signaling pathways that leads to PD and IBD, and investigation of LRRK2 targets (e.g. small GTPase Rab proteins) will help elucidate the molecular mechanisms for the gut-brain axis in the pathogenesis of PD.

Microglial autophagy and cellular senescence in Alzheimer’s disease and Parkinson’s disease

Autophagy represents an evolutionarily conserved lysosomal degradation system crucial for cellular homeostasis. Its regulation varies across cell types and is intricately linked to the pathogenic pathways of neurodegenerative diseases. Our research endeavors aim to elucidate the neuroprotective mechanisms conferred by autophagy in microglia and to comprehend how dysfunctional autophagy in microglia contributes to cellular senescence and the pathogenesis of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Our central hypothesis posits that cellular senescence is accelerated in microglia in the AD and PD brains. Through our investigations, we seek to delineate the role of microglial autophagy in modulating inflammation and curtailing senescence via selective degradation processes. Our ultimate goal is to devise therapeutic strategies geared towards the removal of senescent microglia to foster neuroprotection during both aging and the progression of neurodegenerative diseases.

Autophagy-lysosome dysfunctions in neurons and glial cells in the pathogenesis of neurodegenerative diseases

We propose to elucidate the cell-type-specific autophagy-lysosome pathways, focusing on neurons and microglia, under both physiological (young and old) and pathological conditions (Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease). Employing a systematic approach, we will incorporate multiple genetic mutant lines of mice, human-induced neuron lines (hiN), quantitative proteomics, and molecular and cell biology techniques to identify autophagy cargo and receptors in neurons and microglia. Furthermore, we will investigate the distinct mechanisms responsible for the degradation of multiple disease-associated proteins such as tau, alpha-synuclein (aSyn), and huntingtin. The findings of our study hold the potential to uncover novel biomarkers and therapeutic targets for autophagy-lysosomes in the treatment of Alzheimer’s, Parkinson’s, and Huntington’s diseases, thereby paving the way for innovative therapeutic interventions.

Dysfunctional AKAP11-PKA signaling underlying the pathogenic mechanism and in modeling psychiatric disease condition (schizophrenia and bipolar)

Recent human genetic study has identified AKAP11 as a definitive causal gene for bipolar disorder and enhanced risk factor for schizophrenia. Our study demonstrated AKAP11 is an autophagy receptor that mediates selective degradation of PKA-RI complex through autophagy. Our goal is to dissect the pathogenic mechanism whereby AKAP11 deficiency contributes to the psychiatric illness by characterizing genetic animal models and induced human neuron (iNeuron) models. We will test the new therapeutic ideas by targeting AKAP11-PKA signaling and activity.

Zhenyu Yue, PhD

*Professor of Neurology and Neuroscience
*Alex and Shirley Aidekman Family Professorship
*Director, Center for Parkinson’s disease Neurobiology
*Director, Basic and Translational Research of Movement Disorder

Friedman Brain Institute
Icahn School of Medicine at Mount Sinai

 

Biography

https://icahn.mssm.edu/profiles/zhenyu-yue

***

Address:
Leon and Norma Hess Center for Science and MedicineRoom 9-106 (office)
9-201,202 (laboratory)1470 Madison AvenueNew York, NY 10029
Tel: 212 824 8983 (office)
212 824 9144 to 9153 (Lab)

email:
zhenyu.yue@mssm.edu

 

News

  • November 10th~15th, 2023 Dr.Yue, Insup Choi, Xingjian Li, Bik Tzu Huang, Henry Kim, Marianna Liang, and Linh Chu presented their research at the SFN Conference https://www.sfn.org/meetings/neuroscience-2023/registration
  • November 15th, 2023, Congratulations to Linh Chu on receiving the Trainee Professional Development Award from the Society for Neuroscience (SfN)
  • November 2023 Congratulations on George Heaton’s grant from the New York Community Trust
  • October 2023 Congratulations to Linh on being selected as a recipient  of the 2023 Trainee Professional Development Award for SfN 2023
  • May 26th, 2023 Congratulations to Xiaoting on her successful Ph.D. thesis defense.
  • May 25th, 2023, Congratulations on Insup Choi’s paper published in Nature Cell Biology.https://www.nature.com/articles/s41556-023-01158-0
  • May 12th, 2023, Dr. Yue and a lab member participate in The Friedman Brain Institute @2023 Neuroscience Retreat https://friedmanbrain.icahn.mssm.edu/retreat-23/
  • May 1st, 2023, Congratulations on Insup Choi‘s K01 grant from (NIA/NIH)
  • Mar 7th, 2023, Welcome to Yue lab, Linh Chu. Linh has started her dissertation research in Yue lab
  • Dr. Yue, Insup Choi, You-Kyung Lee, and Xiaoting Zhou presented their research at the @Keystone Conference Autophagy and Neurodegeneration: Mechanisms to Therapies (March. 26~29, 2023)https://www.keystonesymposia.org/conferences/conference-listing/meeting?eventid=6812
  •  View our blog on the Parkinson’s Foundation Website! Link: Newest Parkinson’s Foundation Research Center Explores Dopamine Nerve Diversity in Parkinson’s | Parkinson’s Foundation
  • Bik Tzu and Marianna presented their research (poster session) at the SfN meeting.
  • Congratulations on Insup Choi’s recent review paper published in Science Advances.
  • Congratulations to Dr. Yue and his team for having a $2 Million Research Center Grant from the Parkinson’s Foundation (title: Profiling and Elucidating Molecular Mechanism of Neurodegeneration in Parkinson’s disease) https://bit.ly/3yjbG86
  • Sep 22nd, 2022, Congratulations to Bik Tzu Huang on receiving Trainee Professional Development Award from the Society for Neuroscience (SfN)
  • Sep 9th, 2022, Insup Choi presented his study “Investigation of senescent microglia on Alzheimer’s disease” at the REC seminar of ADRC
  • July 1st, 2022, Congratulations to Insup Choi. Insup has been promoted to Assistant Professor in Yue lab
  • July 1st, 2022, Congratulations to George Heaton on winning the best poster award in LRRK2 conference
  • June 27th, 2022, Welcome to Yue lab, Ted Wickstead. Ted has started his post-doctoral research in Yue lab
  • May 27th, 2022, Congratulations to Bik Tzu on becoming a T32 trainee by the Department of Pharmacological Science
  • May 13th, 2022, Congratulations to Insup Choi on winning the oral presentation award at the 14th FBI Neuroscience Retreat
  • Mar 7th, 2022, Welcome to Yue lab, Marianna Liang. Marianna has started her dissertation research in Yue lab
  • Jan 26th, 2022, Congratulations to Ravi Ghotra on his successful graduate thesis defense
  • Jan 10th, 2022, Congratulations to Dr. Insup Choi on winning the ADRC grant (Alzheimer Disease Research Center of Mount Sinai)
  • Nov 1st, 2021, Welcome to Yue lab, Heesoo Kim has joined Yue lab as Associate Researcher
  • Aug 23rd, 2021, Welcome to Yue lab, You-Kyung Lee has started her post-doctoral research in Yue lab
  • May 17th, 2021, Welcome to Yue lab, Bik Tzu Huang. Bik Tzu Huang has started her dissertation research in Yue lab
  • May 13th, 2021, Congratulations to Shiyi on the completion of his training in Yue lab and heading back to China for his thesis defense
  • May 10th, 2021, Congratulations to Steven Seegobin on his admission to LECOM medical school!!!
  • Apr 2nd, 2021, Researchers in Yue lab have found a novel therapeutic target for specific cancer treatment, here is the details
  • Jan 27th, 2021, Lab member Steven Seegobin gave a talk titled “Maintenance of Alpha-Synuclein Homeostasis by Microglia in Parkinson’s Disease” at the ADND/Loeb WIP seminar.
  • Jan 23rd, 2021, Congratulations to Dongxiao on her successful doctorate defense, you well deserved it, Dr. Liang.
  • Jul 1st, 2020, the latest update on Autophagy’s role by Prof. Yue, here are the details
  • Jun 2nd, 2020, Congratulations to Steven Seegobin, his PD animal review paper was accepted by Front Neuroscience, here are the details
  • Oct 1st, 2020, Congratulations to George Heaton!, Dr. Heaton has won first place in 2020 Poster Presentation Award at Morris K. Udall Centers of Excellence for Parkinson’s disease research.
  • Sep 1st, 2019, Congratulations to Insup Choi! Dr. Choi has won first place in 2019 Poster Presentation Award at Morris K. Udall Centers of Excellence for Parkinson’s disease research.
  • Nov 1st, 2011, Pioneering Research of Autophagy at Yue Lab
  • Mar 25th, 2011, Mount Sinai Researchers Uncover How a Gene Mutation Causes Parkinson’s Disease.

Open Positions

Post-Doctoral Fellow – Neurodegenerative Disease’s Mechanisms (PD, AD, and HD) (multiple positions)

The laboratory of Professor Zhenyu Yue is looking for highly motivated and collaborative postdoctoral fellows to join Friedman Brain Institute at Icahn School of Medicine at Mount Sinai in New York City.

Multiple positions are available for highly motivated and ambitious scientists to use a wide range of experimental and bioinformatic approaches to investigate the pathogenic mechanisms of neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s diseases. The lab employs mouse genetics, biochemical, molecular, cellular, transcriptomic (snRNAseq), proteomic, network, imaging (live and fixed), animal pathology/behavior, human iPSC neurons/glia and postmortem tissue analysis to dissect autophagy-lysosome, synaptic vesicle trafficking, cell metabolism, neuroinflammation, and protein/lipid kinase signaling in the neuropathogenesis.

Qualifications:

  • A recent Ph.D. graduate with demonstrated experience in any of the following fields: cell biology, molecular biology, mouse genetics, biochemistry, neuroscience, and/or systems biology.
  • The ideal candidates will have experience in any of the following research areas: molecular and cell biology in neuronal and/or glial culture models; confocal and/or stereological microscopy; protein biochemistry, proteomics; viral vector technology; development of genetic animal models; rodent neuropathology and behavior; bioinformatic, single cell/nuclei RNAseq, iPSC derived neurons/glia,

Please submit your online application with the following:

  • Cover letter outlining research experience and interests
  • Curriculum Vitae
  • Contact details for 3 references

Questions may be directed to Dr. Zhenyu Yue (zhenyu.yue@mssm.edu)

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Team

Zhenyu Yue, PhD

Aidekman Family Professorship
Professor of Neurology and Neuroscience

Faculty Profile

Xianting Li

Lab Manager

Research Topic: Neurodegenerative disease

ORCID | LinkedIn

Insup Choi

Assistant Professor

Research Topic: Microglia, Neurodegenerative disease

ORCIDLinkedIn

George Heaton

Postdoctoral Research Fellow

Research Topic: Parkinson’s Disease, Crohn’s Disease, Molecular Genetics

Google Scholar

Xingjian Li

Postdoctoral Fellow

Research Topic: Parkinson’s disease

You-Kyung Lee

Postdoctoral Fellow

Research Topic: Neurodevelopmental disorder, Neurodegenerative disease

ORCID

Yuanxi Zhang

Title: Associate Researcher

Research Topic: Neurodegenerative disease

ORCID

Bik Tzu Huang

PhD Student

Research Topic: Microglia, Neurodegenerative disease (Parkinson’s Disease and Alzheimer’s Disease)

ORCIDLinkedin

Marianna Liang

PhD Student

Research Topic: Neurodegenerative disease

ORCIDLinkedIn

Heesoo Kim

Associate Researcher

Henry Kim

Undergraduate research intern

Research Topic: Autophagy, neuronal autophagy

Yong Huang

Senior Scientist

Research Topic: Glia, Neurodegenerative diseases

ORCID LinkedIn

Edward (Ted) Wickstead

Postdoctoral Fellow

Research Topic: Alzheimer’s disease, Neuroinflammation, Cellular senescence

ORCIDLinkedIn

Linh Chu
 
PhD Student
 
Research Topic: Parkinson’s Disease, Network Modeling, Drug repurposing
 
Takahiro Shimizu
 
Postdoctoral Fellow
 
Research Topic: Neurodegenerative disease, Autophagy
 

Contact Us
We accept rotation students from Mount Sinai PhD, MD-PhD, MD, & MS programs

For postdoc position, please contact
zhenyu.yue@mssm.edu

Mail Address:
One Gustave L. Levy Place
New York, NY 10029

Lab Location
1470 Madison Avenue
Hess Center 9-201, 202 (lab), 9-106 (office)
New York, NY 10029