Neurobiology of Disease Chris Weihl Brad Schlaggar TA Yuetiva - - PowerPoint PPT Presentation

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Neurobiology of Disease Chris Weihl Brad Schlaggar TA Yuetiva - - PowerPoint PPT Presentation

Aug 19, 2022 378 likes •667 views

Bio5663 Neurobiology of Disease Chris Weihl Brad Schlaggar TA Yuetiva Deming Course Objectives Logistics Expectations Schedule/Website https://hopecenter.wustl.edu/ https://hopecenter.wustl.edu/?page_id=11922 Lessons from previous

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Bio5663 Neurobiology of Disease

Chris Weihl Brad Schlaggar TA Yuetiva Deming

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Course Objectives

  • Logistics
  • Expectations
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Schedule/Website

https://hopecenter.wustl.edu/ https://hopecenter.wustl.edu/?page_id=11922

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Lessons from previous years

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Comments on genetic studies

Hypothesis: ALS-FTD is a genetic disease and a heritable element can be identified at chromosome 9p21

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Hypothesis: Some muscle diseases have a genetic etiology, we hypothesize that exome sequencing will identify a genetic cause.

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Patient phenotyping

  • Clinical Neurology is a science in itself
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Two papers of same family

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Laser microdissection

Sequencing identifies known desmin mutations in this family

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Desmin is on chromosome 2q35 not 6q23

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Imaging techniques in neurologic disease

  • CT scan
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  • MRI
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MRI based Diffusion Tensor imaging

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PET/SPECT imaging

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PET base PIB imaging

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Functional MRI

  • BOLD contrast (blood-oxygen-level

dependent)

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Functional connectivity

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Functional connectivity

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Translational Neuroscience

  • Definitions
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Therapy development

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Where do drug companies get leads?

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  • Bayer HealthCare
  • Internal study with 23 labs and 67 projects
  • 70% Oncology
  • Outcomes of drug target discoveries
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Researchers at Amgen could only reproduce 6/53 published studies (11%)

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Academic labs can reproduce the studies

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Why discrepancies?

  • Unrelated to journal quality
  • Unrelated to previous claims regarding the

target

  • Unrelated to number of independent groups

that had validated

  • Other thoughts?