Cathryn L. Haigh, Ph.D.

Cathryn L. Haigh, Ph.D.

Credit: NIAID
Chief, Prion Cell Biology Unit

Major Areas of Research

  • Prion diseases
  • Prion redox biology
  • Prion protein processing and function
  • Cerebral organoid models of prion infection and disease

Program Description

The Prion Cell Biology Unit is focused on elucidating the underlying cellular pathways causing neuronal death and dysfunction during prion diseases, as well as understanding the basic cellular functions of the prion protein. We are specifically interested in investigating: the role of the prion protein in cellular redox homeostasis; how perturbations in redox balance influence disease progression and toxicity; the influence of the prion protein on neural stem cell self-renewal and differentiation; and the functional outcomes of prion protein post-translational modifications. 

The Unit is also dedicated to advancing the tools and techniques available for studying prion diseases. We recently developed a human cerebral organoid model of prion infection that recapitulates certain features of human disease (see figure). The cerebral organoid model is being utilized to investigate the cellular and sub-cellular responses induced by infection with different sporadic Creutzfeldt-Jakob Disease (CJD) sub-types. We are additionally applying this technology to understanding the role of hereditary PRNP mutation in the causation of prion diseases.





Three side-by-side photos of 1. a young human cerebral organoid, 2. a prion seeding assay of organoids, and 3. western blotting for protease-resistant prion protein

Figure shows a young (< 10 days old) human cerebral organoid forming organized regions of brain tissue (left). Middle; A prion seeding assay (real-time Quaking-Induced Conversion) of organoids that were infected with brain homogenates from one of two CJD subtypes, MV1 or MV2, and allowed to develop prion infection. Increased ThT fluorescence readings are indicative of increased prion seeds or infectious units. Normal brain homogenate (NBH) organoids are controls that remained un-infected. Right; Western blotting for protease-resistant prion protein (PrP), a biochemical indicator of the mis-folded prions that accumulate during human disease. In these examples differences are observed between the MV1 and MV2 CJD sub-type inoculums. Adapted from Groveman et al., 2019, Acta Neuropath Comms 7, 90.

Credit
NIAID

Figure shows a young (< 10 days old) human cerebral organoid forming organized regions of brain tissue (left). Middle; A prion seeding assay (real-time Quaking-Induced Conversion) of organoids that were infected with brain homogenates from one of two CJD subtypes, MV1 or MV2, and allowed to develop prion infection. Increased ThT fluorescence readings are indicative of increased prion seeds or infectious units. Normal brain homogenate (NBH) organoids are controls that remained un-infected. Right; Western blotting for protease-resistant prion protein (PrP), a biochemical indicator of the mis-folded prions that accumulate during human disease. In these examples differences are observed between the MV1 and MV2 CJD sub-type inoculums. Adapted from Groveman et al., 2019, Acta Neuropath Comms 7, 90.

Credit:
NIAID

Biography

Dr. Haigh received her Ph.D. in Biochemistry from the University of Bath (UK). Her thesis focused on the cellular function of the prion protein and genetic control of its expression.

In July 2006, she relocated to The University of Melbourne (Australia) to continue working on the cellular function and post-translational modifications of the prion protein as a senior research officer. Following securing further Australian funding, Dr. Haigh’s research branched into several new areas; redox imbalance throughout the course of prion infection, the development of stem cell models of prion disease and the role of the prion protein in controlling stem cell functions. 

In 2017, Dr. Haigh accepted a tenure track position at the Rocky Mountain Laboratories to further her research into redox homeostasis and prion biology.

Research Group

 





Bradley Groveman, Ryan Walters, Cathryn Haigh, and Simote Foliaki pose for a photo

From left to right: Bradley Groveman, Ryan Walters, Cathryn Haigh, and Simote Foliaki.

Credit
NIAID

From left to right: Bradley Groveman, Ryan Walters, Cathryn Haigh, and Simote Foliaki.

Credit:
NIAID

Dr. Bradley Groveman

Dr. Simote Foliaki

Dr. Ryan Walters

Katie Williams

Anna Smith

Selected Publications

Groveman BR, Ferreira NC, Foliaki ST, Walters RO, Winkler CW, Race B, Hughson AG, Zanusso G, Haigh CL. Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt-Jakob disease. Sci Rep. 2021 Mar 9;11(1):5165. doi: 10.1038/s41598-021-84689-6.

Foliaki ST, Groveman BR, Yuan J, Walters R, Zhang S, Tesar P, Zou W, Haigh CL.  Pathogenic Prion Protein Isoforms Are Not Present in Cerebral Organoids Generated from Asymptomatic Donors Carrying the E200K Mutation Associated with Familial Prion Disease.  Pathogens. 2020 Jun 18;9(6):482. doi: 10.3390/pathogens9060482.

Carroll JA, Groveman BR, Williams K, Moore R, Race B, Haigh CL.  Prion protein N1 cleavage peptides stimulate microglial interaction with surrounding cells.  Sci Rep. 2020 Apr 20;10(1):6654. doi: 10.1038/s41598-020-63472-z.

Groveman, BR, Foliaki, S, Orru, CD, Zanusso, G, Carroll, JA, Race, B, Haigh, CL. Sporadic Creutzfeldt-Jacob Disease infection of human cerebral organoids. Acta Neuropathologica Communications. 2019 7:90.

Collins SJ, Tumpach C, Groveman BR, Drew SC, Haigh CL. Prion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression. Cell Mol Life Sci. 2018 Mar 24. doi: 10.1007/s00018-018-2790-3.

Collins SJ, Haigh CL. Simplified Murine 3D Neuronal Cultures for Investigating Neuronal Activity and Neurodegeneration. Cell Biochem Biophys. 2017 Mar;75(1):3-13. doi: 10.1007/s12013-016-0768-z.

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