Ali Khoshnan, PhD

We study the molecular pathogenesis of Huntington’s disease (HD), a genetically inherited neurodegenerative disorder caused by expansion of a polyglutamine repeat in huntingtin protein (HTT). Mutant HTT is amyloidogenic and forms neurotoxic assemblies, which disrupt various signaling pathways and promote neurodegeneration. Patients develop debilitating motor, psychiatric, and cognitive symptoms.

Areas of interest

•Use human neurons, brain organoids, mice and Drosophila models to identify pathogenic assemblies of mutant HTT, study the mechanism of how assemblies spread and propagate in the nervous system, and characterize the neuronal pathways, which regulate neurodegeneration in HD.

•Produce and engineer antibodies and nanobodies targeting the pathogenic conformations of mutant HTT for diagnostic and therapeutic applications.

•Investigate the impact of microbiota-gut-brain pathways on the pathogenesis of HD in Drosophila and mouse models. In this project, we are characterizing the role of HTT in regulating microbial homeostasis in the gut, examining how mutant HTT disrupts these communications and triggers aberrant expression of genes implicated in brain development and physiology, and identifying the gut-brain circuits, which contribute to the onset of various HD symptoms.

•Develop gut-based therapies for HD.

• Developing novel nanobody-based biosensors and therapeutics for Huntington?s Disease
  NIH · R21NS137242 · Apr 15, 2024 – Mar 31, 2026 · Role: Principal Investigator
• Characterizing the Conformations and Neurotoxic Species of Huntingtin
  NIH · R01NS118859 · Jul 15, 2021 – Jun 30, 2026 · Role: Principal Investigator
• Validation of IKKbeta as a therapeutic target for HD
  NIH · R01NS074374 · Sep 30, 2011 – Jun 30, 2017 · Role: Principal Investigator

• Langen, Ralf
• Pandey, Nitin
• Siemer, Ansgar
• Wang, Rongfu
• Chen, Jeannie
• Klausner, Jeffrey