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Post Doc in neurodegenerative disease

Employer
Johns Hopkins University
Location
Johns Hopkins Hospital, Baltimore
Salary
$55,000 with benefits
Closing date
Oct 18, 2021
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Job Details

We are looking for highly motivated postdoctoral candidates to participate in studies of the pathophysiology of nuclear transport and the nuclear pore complex in neurodegenerative disorders including in ALS and dementias in the laboratory of Jeffrey Rothstein MD, PhD at Johns Hopkins University.

Work in the laboratory is focussed on understanding the underlying defect(s) of the nuclear pore complex (NPC) and its regulation as a disease initiating event in amyotrophic lateral sclerosis, Alzheimer’s disease and other dementias along with the development of therapies to mitigate NPC damage.  For the last decade we have employed human and rodent models to explore the role of the NPC in neurodegeneration pathophysiology.  The model systems include a very large population of highly characterized induced pluripotent cel lines for ALS , FTD and AD along with transgenic rodent models of these diseases.   Most recently we identified a specific set of nucleoporins that initiate a cascade of NPC failure and have now identified an underlying initiating event, including ESCRT3 pathway and gene therapies to mitigate damage/disease.  Projects include:

  1. Nuclear Biology in Neurodegeneration: to address fundamental questions on implicating nuclear pore complex and nuclear transport in dementia and ALS (Donnelley et al, Neuron, 2013; Zhang et al Nature 2015; Grima et al, Neuron 2017; Eftekharzadeh, Neuron 2018; Zhang et al, Cell, 2018, Coyne et al, Neuron 2020) and other related neurodegenerative diseases.
  2. Development of therapies targeting the regulation of nuclear pore and nuclear transport in neurodegeneration. These studies may involve collaboration with biotechnology companies interested in this new therapeutic target and its potential widespread disease engagement.
  3. Development of new iPS and rodent transgenic models of nuclear pore and nuclear pore regulation defects present in familial and sporadic ALS/dementia.

Experimental approaches, including biochemistry, genetics, molecular imaging and cell biology, from human and in vivo/in vitro rodent to mammalian systems are employed. New techniques applied in the lab include iPSC, genome editing, single cell analysis, whole genome analytics and metabolic studies. Access to the largest library of human iPS cell lines (~750) for ALS and dementia along with full omics data thru our ANSWER ALS Program (https://dataportal.answerals.org/home). Candidates with a strong background in molecular biology, advanced imaging (confocal, structured illumination microscopy/Cryo EM), cellular biology, and/or biochemistry are encouraged to apply.

Position Information: Candidates should have a doctoral degree and strong research background. Please send a statement of research experience and career goals, a copy of Curriculum Vitae, and contact information of at least one or two references to Dr. Jeffrey D. Rothstein at jrothstein@jhmi.edu. The post doc position is for at least 2 years or more and is fully funded.  Candidates can start at any time.  

The Johns Hopkins Medical Institutions provide a stimulating and collaborative environment for biomedical research. Our lab is located in the Brain Science Institute and affiliated with the Depts of Neurology and Neuroscience at the School of Medicine. The Baltimore/Washington D.C. area also offers rich professional and living (county hiking and water activities) opportunities

Selected Recent Relevant Publications:

  • Coyne et al. Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS. Science Trans Med, 2021, in press.
  • Coyne AN, et al. G4C2 Repeat RNA Initiates a POM121-Mediated Reduction in Specific Nucleoporins in C9orf72 ALS/FTD. Neuron. 2020;107(6):1124-40 
  • Eftekharzadeh B, et al. Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer's Disease. Neuron. 2019;101(2):349.: 
  • Zhang K.  Stress granule formation disrupts nucleocytoplasmic transport. Cell. 2018;173(4):958-71
  • Zhang K et al. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature. 2015;525(7567):56-61. 

Company

Jeffrey D. Rothstein, M.D., Ph.D. is the John W. Griffin Director for the Brain Science Institute, as well as a Professor of Neurology and Neuroscience, and the Founding Director of the Robert Packard Center for ALS Research at Johns Hopkins University School of Medicine. He received his BA in Neuroscience from Colgate University (1977), along with an MA in Neurochemistry-Biopsychology from the University of Chicago (1979). He received his PhD in Physiology and Biophysics-Neurochemistry (1984), and MD (1985) at the University of Illinois College of Medicine and Health Sciences Center. He completed a medical University of North Carolina , Chapel Hill and his neurology residency (1989) and neuromuscular fellowship (1991) at Johns Hopkins University. In 1991, Dr. Rothstein accepted a position as Assistant Professor in the Department of Neurology. In 2000, in addition to being promoted to his current position as Professor of Neurology and Neuroscience, Dr. Rothstein became the Director and Founder of the Robert Packard Center for ALS Research, which has raised approximately $130 million to date. In 2011, he became the Director of the Johns Hopkins Brain Science Institute; a University Wide Translational Neuroscience institute founded on a $100mil gift. A respected and internationally renowned neuroscientist, Dr. Rothstein is credited as being one of the world’s top clinical and basic ALS researcher and has over 30 years as a clinician scientist studying ALS pathophysiology, astrocyte/oliogodendroglial biology and therapy discovery; it was his research on ALS pathogenesis that lead to the first successful, FDA-approved drug to alter neurodegeneration in ALS. More recently his group has defined the basic cellular defect in nuclear transport/pores that underlie a large percentage of ALS, Huntington’s disease and Alzheimer’s dementia patients. He holds patents for candidate therapeutics and started a biotech company to help develop drugs and PET ligands for neurodegeneration. In addition to running an ALS clinic at Johns Hopkins which evaluates and manages over 400 ALS patients every year, he also runs a Brain Science Institute drug discovery group to identify novel therapeutics for neurological and psychiatric disease. Dr. Rothstein has received numerous awards for his work in the field of ALS and basic-to-clinical science, such as the Sheila Essay Award recognizing his worldwide contribution to ALS research, and the Diamond Award for ALS research, as well as the Lois Pope Foundation award for medical research, the Swiss Hartmann Muller Prize and more.
Find Us
Telephone
410-614-3846
Location
855 N. WOlfe St
Rangos 270
Baltimore
MD
21205
US
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