Postdoctoral Associates in Neurodegenerative Diseases: University of Minnesota-Twin Cities.

Postdoctoral Associates in Neurodegenerative Diseases:

University of Minnesota-Twin Cities.

Multiple funded openings are available for postdoctoral scientists to study the pathogenic mechanisms of Alzheimer's disease (AD) and/or Parkinson's disease (PD).

For AD, we are studying the mechanisms of AD associated neurodegeneration and evaluation of therapeutic targets for disease modifying therapies.

Mechanism based therapy development: The projects include evaluation of BACH1, Glo-1, and other antioxidant defense systems in the AD pathogenesis. For example, we found that pharmacological stimulation of Glo-1 leads to neuroprotection in AD models and genetic repression of Glo-1 promotes neuroinflammation and progressive neurodegeneration in transgenic mouse model of AD.

Adoptive Immunity in neurodegeneration: We are also working in collaboration with Dr. Michael Farrar (Center for Immunology, UofM) to study the role of regulatory T (Treg) cells in AD. While CNS inflammation, particularly microglial activation, is a key component of AD pathogenesis, peripheral adoptive immunity, largely mediated by T-cells, is emerging as a significant pathologic component in AD. Among the T cells, Tregs functions to attenuate too much inflammatory activation via suppression of effector T-cells and microglia. Initial human studies indicate to reduced Treg function in AD and in mouse models of AD.

Role of aS in AD: We are also studying interaction between tau pathology in alpha-synuclein expression. We found that the loss of aS expression significantly attenuates onset of memory and motor deficits in a transgenic mouse model of tauopathy. In contrast, expression of human WT aS causes reduced lifespan in tauopathy model. We are currently exploring the mechanistic basis for our observations. Related, we are exploring pathological relationship between amyloid pathology and incidence of alpha-synuclein pathology. We are particularly interested in neuronal hyperactivity and mTOR dysregulation.

For PD, we are interested the how alpha-synuclein (aS) pathology occurs in PD and what the neurobiological impact of alpha-synuclein pathology.

Dementia in alpha-synucleinopathies: Dementia in PD and DLB occur without significant neurodegeneration in cortical-limbic system. We found that aS abnormalities cause neuro-network hyperactivity, postsynaptic deficits and synaptic plasticity in a tau-dependent manner. We are currently exploring the mechanistic pathways as well as defining the role of other circuit dysfunctions associated with alpha-synucleinopathy.

Role of Cellular Quality Control Pathways: We are studying the basis of lysosomal deficits and chronic endoplasmic reticulum stress (ERS) in neurons with aS pathology. For example, we made the first observation that aS can enter ER and aggregate, causing chronic ERS. Manipulation of ERS pathways can differentially impact onset and progression of aS pathology and neurodegeneration.

Senescence in PD and related diseases: Aging is the greatest risk factors for neurodegenerative diseases, including PD. We are studying the role of cellular senescence as a driving factor in Age-related vulnerability to PD. We found that aS pathology, in mouse and human, induces neuronal senescence and decreasing senescence burden attenuates aS pathology. We are currently studying the molecular mechanisms involved in our findings.

The projects will utilize animal and cellular models, human tissues, mouse genetics, immunological/cell biological/biochemical approaches, transcriptomic analysis (RNAseq, snRNAseq, Spatial transcriptomics), high-content immunohistochemical analysis, quantitative neuropathology, behavioral analysis, and neurophysiological analysis.

The laboratory is funded by multiple grants from Federal/Private sources and involve extensive national/international collaborations with a diverse group of investigators. We are part of international consortium called ASAP-Collaborative Research Network (https://parkinsonsroadmap.org/research-network/#). The laboratory is located within the Wallin Medical Biosciences Building at University of Minnesota, housing the Center for Neurodegenerative Diseases, Institute for Translational Neuroscience, and Center for Immunology. Candidate will join a highly collaborative, vibrant, and supportive laboratory environment currently consisting of multiple postdoctoral scientists, students and supporting staff. Candidates must have a Ph.D. and/or M.D. degree with strong background in relevant Biomedical Sciences. Fluency in English, both verbal and written, is essential. We will prioritize individuals who have background or interest in the following approaches: quantitative analysis of neuropathology and neurodegeneration, neuroimmunology, studies of protein quality control, and/or single cell/spatial transcriptomics.

Appointment level and salary will be commensurate with the relevant experience. Candidates should email C.V. (including citizenship/VISA information), brief statement of prior research and future goals (1 page), and contact information for at least 2 referees to Michael K. Lee, Ph.D. (mklee@umn.edu).

Twin Cities (Minneapolis-St Paul) is 16th largest metro area in USA and considered one of the best cities for young professionals in USA. (https://www.niche.com/places-to-live/minneapolis-hennepin-mn/)