Yue Laboratory

Yue Laboratory

ZhenyuYue_

 

Molecular, Cellular, network, and Behavioral Mechanisms of Neurological Disorders and Therapeutic Development

The goal of the Yue Laboratory is to elucidate molecular, cellular, network, and behavioral mechanisms of neurological disorders. The Yue Laboratory employs a wide range of experimental and bioinformatic approaches, such as genetic, biochemical, molecular, cellular, transcriptomic (single cell RNAseq), 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. Our ultimate goal is to translate our knowledge from basic research to the development of molecular diagnostics and therapeutics.

Cell-type specific transcriptomics, molecular pathways and novel therapeutic target identification for Parkinson’s disease (PD)

Genetic linkage and genome wide association studies (GWAS) have begun to gain insight into the molecular mechanism of the PD. However, the vast majority of PD cases have no known genetic cause, and their etiology remains unclear. To dissect molecular mechanisms for dopamine (DA) neuron degeneration, post-GWAS research should investigate in what cell-type PD-linked genes or GWAS variants are actively expressed and how they are affected in vulnerable brain regions of PD. We aim to profile, validate, and characterize molecularly distinct neuron and glia types of PD by using three different biological systems: human postmortem tissues (e.g. SNpc and PFC), genetic mouse models, and induced human neurons (iPSC) 2D/3D midbrain cultures. We will conduct three highly integrated projects: (1) Validating and characterizing distinct DA neuron populations and their PD-associated vulnerability in mouse models through mouse genetics, transcriptomics, whole brain imaging and behavioral analysis; (2) Characterizing molecularly distinct DA neuron populations and their vulnerability in the SN of PD by multiplex RNA and protein spatial profiling, molecular anatomical analysis, and volumetric imaging; (3) Modeling and characterizing human DA neuron subpopulations and their PD-associated vulnerability identified from human SN by using hiPSC-based models.

Circuitry and inflammation mechanism in 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 a-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 a-synuclein; (2) LRRK2 acts as an interface for the signaling pathways that leads to PD and inflammatory bowel disease (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. Our study will provide insight into the PD biomarker development.

The role of microglial autophagy in preventing senescence and offering neuroprotection in Alzheimer’s disease animal models

Autophagy is evolutionarily conserved lysosomal degradation system of the cell. It is a critical pathway that controls cellular homeostasis and can be activated in response to cellular injury or stress. Autophagy is regulated distinctively in different cell types and strongly linked to the pathogenic pathways for neurodegenerative diseases. Our goals are to determine neuroprotective mechanism conferred by microglial autophagy and understand how dysfunctional autophagy in microglia contributes to the pathogenesis of Alzheimer’s disease (AD).  Our central hypothesis is that autophagy activation is required for disease associated microglia (DAM) metabolic fitness, prevention of senescence, and protection of neurons in the AD brains. We will investigate the role of microglial autophagy in controlling inflammation by selective degradation of inflammasomes via protein receptors that are neuroprotective in AD. In addition, we will develop therapeutic strategy to remove senescent microglia for neuroprotection during ageing and disease process.

Autophagy biology in the brain and its dysfunctions in neurons and glial cells in the pathogenesis of Alzheimer’s, Parkinson’s and Huntington’s disease

We propose to elucidate the landscape of autophagy process in the brains. We will investigate cell-type specific autophagy pathways (neuron vs. microglia) under physiological (young and old) and pathological conditions (AD, PD and HD). We will perform a systemic study that integrates multiple genetic mutant lines of mice, human induced neuron lines (hiN), quantitative proteomics, and molecular and cell biology to identify autophagy cargo and receptors in neurons and microglia. We will identify novel autophagy cargo and receptors in mediating autophagy functions in an age and neuron-type specific manner. We will also investigate the distinct mechanisms for the degradation of multiple disease-associated proteins such as tau, aSyn and huntingtin.  Our study will pave the way to identify novel therapeutic targets of autophagy in the treatment of Alzheimer’s, Parkinson’s and Huntington’s disease.

Autophagy Receptor AKAP11, PKA activity regulation in neurons, and psychiatric disease (schizophrenia and bipolar)

Recent human genetic study has identified AKAP11 as a significant risk gene for bipolar disorder shared with schizophrenia. Our study demonstrated AKAP11 is an autophagy receptor that mediates selective degradation of PKA inhibitory subunit R1a through autophagy. Our goal is to dissect the pathogenic mechanism whereby AKAP11 deficiency predispose to the psychiatric illness by characterizing genetic animal models and establish a novel bipolar animal model. We will test new therapeutic ideas by targeting autophagy receptor AKAP11 and PKA activity.

Zhenyu Yue, PhD

Aidekman Family Professorship
Professor of Neurology and Neuroscience
Director, Basic and Translational Research of Movement Disorders

Biography

Dr. Zhenyu Yue is the Aidekman Research Professor at Department of Neurology and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai. He is the Director of Basic Research of Movement Disorders and the Director for NINDS/NIH Exploratory Program for Parkinson’s disease Research. Dr. Yue’s laboratory investigates cellular and molecular mechanisms for neurological disorders including Parkinson’s disease (PD), Alzheimer’s diseases (AD), Huntington’s disease (HD), and schizophrenia/bipolar disorder. His laboratory employs multi-disciplinary approaches, such as systems biology (single-cell RNAseq, proteomics, spatial transcriptomics), molecular biology, protein/lipid biochemistry, optical imaging, immunohistochemistry, iPSC-induced neurons/glia, primary mouse neuron/glia cultures and genetic mouse models. Dr. Yue’s lab is currently focused on microglial functions and senescence in age-related neurodegenerative diseases, gut-brain axis in PD progression and transmission, dopamine neuron vulnerability/resilience in PD/Lew body dementia (LBD), cellular and molecular basis for selective autophagy underlying proteinopathies, synaptic trafficking and PKA-mediated neuronal activity regulation for synaptopathies, including psychiatric diseases. His lab is interested in translational research including biomarker and therapeutic development.  Dr. Yue has contributed more than 150 SCI publications including original research articles and reviews/commentaries.

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Tel: 212-824-8983 (Office)
Tel: 212-824-9144 to 9153 (Laboratory)
Fax: 212-241-3869
e-mail: zhenyu.yue@mssm.edu

Leon and Norma Hess Center for Science and Medicine
Room 9-106 (Office)
Room 9-201, 202 (Laboratory)
1470 Madison Avenue
New York, NY 10029

News

  • Sep 22th, 2022, Congratulations to Bik Tzu on having Trainee Professional Development Award from Society for Neuroscience (SfN)

  • Sep 9th, 2022, Insup Choi presented his study “Investigation of senescent microglia on Alzheimer’s disease” at 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 of 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 of 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. Bik Tzu has started her dissertation research in Yue lab
  • May 13rd, 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 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” on 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

LinkedIn 

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

Xiaoting Zhou

Associate Researcher

Research Topic: Human stem cell derived neuron, autophagy

ORCIDLinkedIn

Edward (Ted) Wickstead

Postdoctoral Fellow

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

ORCIDLinkedIn

Ravi Ghotra

Student/Research Technician

Research Topic: Microglia, Neurodegenerative disease

LinkedIn

Photos

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