Hillary Handler

Ph.D. 2022

Thesis Title

Disrupting Nuclear Localization of Expanded ATXN1 Mitigates SCA1 Phenotypes and Transcriptomic Perturbations

Current Position

Genetic Counselor at MHealth/Fairview

Undergraduate Institution and Major:

University of Puget Sound, B.S. in Molecular and Cellular Biology, 2013 
University of Minnesota, MS, Genetic Counseling, 2016

Graduate Advisor:

Harry T. Orr, Ph.D., Department of Laboratory Medicine and Pathology, Institute for Translational Neuroscience, Pathology Tulloch Professor of Genetics Director

Graduate Research:

Spinocerebellar ataxia type 1 (SCA1) is a dominant, fully penetrant, neurodegenerative disease characterized by progressive motor dysfunction and premature death. SCA1 pathology in the brainstem, underlying lethal aspects of the condition, is poorly understood. My research uses genetic, molecular, and computational approaches to elucidate molecular mechanisms of SCA1 in the brainstem.

Graduate Publications:

  • O'Callaghan B, Hofstra B, Handler HP, Kordasiewicz HB, Cole T, Duvick L, Friedrich J, Rainwater O, Yang P, Benneyworth M, Nichols-Meade T, Heal W, Ter Haar R, Henzler C, Orr HT. Antisense oligonucleotide therapeutic approach for suppression of ataxin-1 expression: A safety assessment. Mol Ther Nucleic Acids. 2020 Jul 25;21:1006-1016.
  • Friedrich J, Kordasiewicz HB, O’Callaghan B, Handler HP, Wagener C, Duvick L, Swayze E, Rainwater O, Hofstra B, Bennyworth M, Nichols-Meade T, Yang P, Chen Z, Pérez Ortiz JM, Clark HB, Öz G, Larson SN, Zoghbi H, Henzler C, Orr HT. Antisense oligonucleotide-mediated ataxin-1 reduction prolongs survival in SCA1 mice and reveals disease-associated transcriptome profiles. JCI Insight. 2018 Nov 2;3(21):e123193.

Thesis Committee Members:

Esther Krook-Magnuson, Ph.D., Department of Neuroscience (Chair)
Harry Orr, Ph.D., Department of Laboratory Medicine and Pathology
Rocio Gomez-Pastor, Ph.D., Department of Neuroscience
Ling Li, DVM Ph.D., Department of Experimental and Clinical Pharmacology
Patrick Rothwell, Ph.D., Department of Neuroscience

Research Categories:

  • Computational Neuroscience
  • Neurodegenerative Diseases and Neural Injury
  • Neurogenetics


Harry T. Orr, Ph.D., Department of Laboratory Medicine and Pathology
Timothy J. Ebner, MD, Ph.D., Department of Neuroscience
Patrick Rothwell, Ph.D., Department of Neruroscience