Fisher Cherry
Research Assistant II
Positions
- Research Assistant II
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Symptom Research CAO
Internal Medicine
UT MD Anderson Cancer Center
Houston, Texas, United States
Education
- BS from Texas A&M University
- 05/2019 - College Station, Texas, United States
- PhD from ÌÇÐÄÊÓƵ of Medicine
- Houston, Texas, United States
Professional Statement
Austim spectrum disorders (ASD) are a heterogeneous subset of neurodevelopmental disorders characterized by restricted, repetitive behaviors and language deficits. Males are four-times more likely to be diagnosed with ASD than females. This historic sex-bias highlights the significance of the X chromosome in ASD pathogenesis. Many genes associated with ASD are critical for neruonal function and dose-sensitive. Therefore, methyl-CpG-binding protein 2 (MeCP2) is a compelling gene to model and study ASD.
Mutations in MeCP2 can lead to drastic neurodevelopmental disorders. Null mutations in MeCP2 cause Rett Syndrome, a disorder that mainly affects females. These patients experience intellectual disability, language deficits, and motor deficits. Males with Rett typically die during infancy. Duplications in MeCP2 cause MeCP2 Duplication Syndrome (MDS), a disorder that mainly affects males. These males experience seizures, intellectual disability, and motor deficits. Females with MDS typically do not have a phenotype, because they have an extreme skewing of their X chromosome inactivation in favor of the healthy allele.
Milder mutations in MeCP2 recapitulate a subset of phenotypes observed in Rett Syndrome or MDS. When MeCP2 levels were decreased by ~50%, mice displayed Rett-like phenotypes. However, when MeCP2 levels were decreased by only ~30%, mice displayed autism-related phenotypes. This was observed in an overexpression model as well. When MeCP2 levels were increased to 200% compared to wild-type, mice displayed MDS-like phenotypes. When MeCP2 levels were increased to only ~150% compared to wild-type, mice displayed autism-related phenotypes.
Mild mutations, like point mutations, in MeCP2 have been observed in patients with less severe neurodevelopmental disorders like schizophrenia or autism. These patients are commonly male. I hypothesize that similar mutations in non-coding regions, like the promoter, will increase or decrease MeCP2 levels in a manner that less severe than what is observed in patients with Rett Syndrome or MDS, and this mild alteration in MeCP2 levels will confer autism-related phenotypes. Since MeCP2 is an X-linked gene, I also hypothesize that males are more vulnerable to these mild, non-coding mutations.
Mutations in MeCP2 can lead to drastic neurodevelopmental disorders. Null mutations in MeCP2 cause Rett Syndrome, a disorder that mainly affects females. These patients experience intellectual disability, language deficits, and motor deficits. Males with Rett typically die during infancy. Duplications in MeCP2 cause MeCP2 Duplication Syndrome (MDS), a disorder that mainly affects males. These males experience seizures, intellectual disability, and motor deficits. Females with MDS typically do not have a phenotype, because they have an extreme skewing of their X chromosome inactivation in favor of the healthy allele.
Milder mutations in MeCP2 recapitulate a subset of phenotypes observed in Rett Syndrome or MDS. When MeCP2 levels were decreased by ~50%, mice displayed Rett-like phenotypes. However, when MeCP2 levels were decreased by only ~30%, mice displayed autism-related phenotypes. This was observed in an overexpression model as well. When MeCP2 levels were increased to 200% compared to wild-type, mice displayed MDS-like phenotypes. When MeCP2 levels were increased to only ~150% compared to wild-type, mice displayed autism-related phenotypes.
Mild mutations, like point mutations, in MeCP2 have been observed in patients with less severe neurodevelopmental disorders like schizophrenia or autism. These patients are commonly male. I hypothesize that similar mutations in non-coding regions, like the promoter, will increase or decrease MeCP2 levels in a manner that less severe than what is observed in patients with Rett Syndrome or MDS, and this mild alteration in MeCP2 levels will confer autism-related phenotypes. Since MeCP2 is an X-linked gene, I also hypothesize that males are more vulnerable to these mild, non-coding mutations.
Selected Publications
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AC Das, JM Nichols, CV Crelli, L Liu,, R Vichare, HV Pham, CM Gaffney, FR Cherry, PM Grace, AJ Shepherd, JM Janjic. " " Sci Rep. 2024 Aug 16;
Pubmed PMID: .
Funding
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Graduate School of Biomedical Sciences Busch-80 Scholarship
- ÌÇÐÄÊÓƵ of Medicine
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T32 139534-03
- (07/31/2023 - 07/30/2025)
- National Institutes of Health
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