Dr. Singh obtained his Ph.D. in Biochemistry and Biomedical Sciences from McMaster University in Canada.  His research focuses on leveraging human genetics to build resources amenable to unraveling the earliest consequences of the mutations that cause late-onset human neurological disorders, and the impact of their modifiers.  Through integrative functional assays mediated cellular state profiling, this holistic approach to dissecting the underlying disease process seeks to translate findings at the lab bench into effective clinical applications.

Questions being addressed in the lab

  1. What are the earliest consequences of HTT CAG repeat expansion at the cellular level?
  2. How can we increase the sensitivity of functional readouts to fully capture the phenotypic complexity?
  3. How can we leverage natural expression variation to gain functional insights?

Projects underway to answer these questions

  1. Human Genetics Driven Neurological Disease Modeling

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  3. Harnessing the Power of Morphological Profiling for Characterizing Genotype-Phenotype Relationship

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  5. Leveraging Natural Expression Variation for Functional Analysis

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Answers Found

  1. Induced pluripotent stem cells from patients with Huntington’s disease show CAG repeat expansion associated phenotypes

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  3. Developmental alterations in Huntington’s disease neural cells. CHIP-seq in iPSC-derived neurons shows that epigenetic profiles in non-disease cells are correlated with transcriptional changes in HD.

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  5. Polyglutamine-expanded huntingtin exacerbates age-related disruption of nuclear integrity and nucleocytoplasmic transport. Expanded polyQ huntingtin disrupts neuronal nuclear envelope morphology in a dose- and age-dependent manner

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