About

Jill R Murrell, PhD, is an Associate Professor of Clinical Pathology and Laboratory Medicine in the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine, University of Pennsylvania. She is affiliated with the Division of Genomic Diagnostics at The Children’s Hospital of Philadelphia. Her educational background includes a BA from Ball State University obtained in 1986 and a PhD from Indiana University completed in 1992. Her research focuses on genomic diagnostics, neurodevelopmental disorders, and genetic contributions to neurological and neurobehavioral conditions. She has contributed to understanding the genetic basis of epilepsy, tau filament structures in neurodegenerative diseases, and neurodevelopmental syndromes associated with genetic variants. Her work involves identifying genetic variants linked to developmental delay, autism, intellectual disability, and other neurodevelopmental phenotypes, advancing the understanding of the molecular mechanisms underlying these conditions.

Research topics

• Medicine
• Genetics
• Biology
• Internal medicine
• Pediatrics

Selected publications

• Tau filaments with the Alzheimer fold in human MAPT mutants V337M and R406W

  Nature Structural & Molecular Biology · 2025-03-05 · 15 citations

  articleOpen access

  Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are the most common forms of early-onset dementia. Unlike AD, FTD begins with behavioral changes before the development of cognitive impairment. Dominantly inherited mutations in MAPT, the microtubule-associated protein tau gene, give rise to cases of FTD and parkinsonism linked to chromosome 17. These individuals develop abundant filamentous tau inclusions in brain cells in the absence of β-amyloid deposits. Here, we used cryo-electron microscopy to determine the structures of tau filaments from the brains of human MAPT mutants V337M and R406W. Both amino acid substitutions gave rise to tau filaments with the Alzheimer fold, which consisted of paired helical filaments in all V337M and R406W cases and of straight filaments in two V337M cases. We also identified another assembly of the Alzheimer fold into triple tau filaments in a V337M case. Filaments assembled from recombinant tau (297-391) with substitution V337M had the Alzheimer fold and showed an increased rate of assembly.

  PublisherOA PDFDOI

• <i>USP25</i> in genetic generalized epilepsy: a gene under scrutiny

  Brain · 2025-10-25 · 1 citations

  article

  not available

  PublisherDOI

• Distinct tau filament folds in human MAPT mutants P301L and P301T

  Nature Structural & Molecular Biology · 2025-05-29 · 14 citations

  articleOpen access

  Mutations in MAPT, the tau gene, give rise to frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), with abundant filamentous tau inclusions in brain cells. Mutations that encode missense variants of residue P301 are the most common and result in the formation of filamentous inclusions made of mutant four-repeat tau. Here we report the cryo-electron microscopy structures of tau filaments from five individuals belonging to three different families with mutation P301L and from one individual from a family with mutation P301T. A distinct three-lobed tau fold resembling the two-layered fold of Pick's disease was present in the individuals with P301L tau. Two different tau folds were found in the individual with mutation P301T, the less abundant of which was a variant of the three-lobed fold. The major P301T tau fold was V-shaped, with partial similarity to the four-layered tau folds of corticobasal degeneration and argyrophilic grain disease.

  PublisherOA PDFDOI

• Tau filaments with the Alzheimer fold in cases with <i>MAPT</i> mutations V337M and R406W

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-04-30 · 12 citations

  preprintOpen access

  Frontotemporal dementia (FTD) and Alzheimer’s disease are the most common forms of early-onset dementia. Dominantly inherited mutations in MAPT , the microtubule-associated protein tau gene, cause FTD and parkinsonism linked to chromosome 17 (FTDP-17). Individuals with FTDP-17 develop abundant filamentous tau inclusions in brain cells. Here we used electron cryo-microscopy to determine the structures of tau filaments from the brains of individuals with MAPT mutations V337M and R406W. Both mutations gave rise to tau filaments with the Alzheimer fold, which consisted of paired helical filaments in all V337M and R406W cases and of straight filaments in two V337M cases. We also identified a new assembly of the Alzheimer fold into triple tau filaments in a V337M case. Filaments assembled from recombinant tau(297-391) with mutation V337M had the Alzheimer fold and showed an increased rate of assembly.

  PublisherOA PDFDOI

• Novel tau filament folds in individuals with <i>MAPT</i> mutations P301L and P301T

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-08-17 · 10 citations

  preprintOpen access

  Abstract Mutations in MAPT , the microtubule-associated protein tau gene, give rise to cases of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) with abundant filamentous tau inclusions in brain cells. Individuals with pathological MAPT variants exhibit behavioural changes, cognitive impairment and signs of parkinsonism. Missense mutations of residue P301, which are the most common MAPT mutations associated with FTDP-17, give rise to the assembly of mutant four-repeat tau into filamentous inclusions, in the absence of extracellular deposits. Here we report the cryo-EM structures of tau filaments from five individuals belonging to three unrelated families with mutation P301L and from one individual belonging to a family with mutation P301T. A novel three-lobed tau fold resembling the two-layered tau fold of Pick’s disease was present in all cases with the P301L tau mutation. Two different tau folds were found in the case with mutation P301T, the less abundant of which was a variant of the three-lobed fold. The major P301T tau fold was V-shaped, with partial similarity to the four-layered tau folds of corticobasal degeneration and argyrophilic grain disease. These findings suggest that FTDP-17 with mutations in P301 should be considered distinct inherited tauopathies and that model systems with these mutations should be used with caution in the study of sporadic tauopathies.

  PublisherOA PDFDOI

• Fetus with multiple congenital anomaly syndrome caused by novel variant in <i>ATP1A2</i>

  Prenatal Diagnosis · 2024-03-28 · 1 citations

  articleOpen access

  We report a 32-year-old G3P1 at 35 weeks 3 days with a dichorionic, diamniotic twin gestation who presented for evaluation secondary to ventriculomegaly (VM) in one twin. Fetal ultrasound and MRI demonstrated microcephaly, severe VM, compression of the corpus callosum, scalp and nuchal thickening, elongated ears, bilateral talipes, right-sided congenital diaphragmatic hernia (CDH), and loss of normal cerebral architecture, indicative of a prior insult in the affected twin. The co-twin was grossly normal. The family pursued a palliative care pathway for the affected twin and was delivered at 37 weeks and 6 days. The affected twin passed away within the first hour of life due to respiratory compromise. Postmortem trio exome sequencing identified a homozygous likely pathogenic variant in ATP1A2 (c.2439+1G>A). Although this variant is novel, it is predicted to affect the donor split site in intron 17, resulting in a frameshift and complete loss-of-function of the gene. Biallelic loss of function variants in this gene have been reported in seven individuals with multiple anomalies similar to those in the affected twin. However, only one other individual with a possible CDH has been previously reported. Our case suggests that CDH be included in the phenotypic spectrum of this disorder and reports the first frameshift mutation causing this autosomal recessive multiple congenital anomaly syndrome.

  PublisherOA PDFDOI

• PSMD11 loss-of-function variants correlate with a neurobehavioral phenotype, obesity, and increased interferon response

  The American Journal of Human Genetics · 2024-06-12 · 8 citations

  articleOpen access
  PublisherOA PDFDOI

• Heterozygous UBR5 variants result in a neurodevelopmental syndrome with developmental delay, autism, and intellectual disability

  The American Journal of Human Genetics · 2024-12-24 · 7 citations

  articleOpen access
  PublisherOA PDFDOI

• Monoallelic intragenic POU3F2 variants lead to neurodevelopmental delay and hyperphagic obesity, confirming the gene’s candidacy in 6q16.1 deletions

  The American Journal of Human Genetics · 2023-05-18 · 8 citations

  articleOpen access
  PublisherOA PDFDOI

• Mutation ∆K281 in MAPT causes Pick’s disease

  Acta Neuropathologica · 2023-06-23 · 18 citations

  articleOpen access

  Two siblings with deletion mutation ∆K281 in MAPT developed frontotemporal dementia. At autopsy, numerous inclusions of hyperphosphorylated 3R Tau were present in neurons and glial cells of neocortex and some subcortical regions, including hippocampus, caudate/putamen and globus pallidus. The inclusions were argyrophilic with Bodian silver, but not with Gallyas-Braak silver. They were not labelled by an antibody specific for tau phosphorylated at S262 and/or S356. The inclusions were stained by luminescent conjugated oligothiophene HS-84, but not by bTVBT4. Electron cryo-microscopy revealed that the core of tau filaments was made of residues K254-F378 of 3R Tau and was indistinguishable from that of Pick's disease. We conclude that MAPT mutation ∆K281 causes Pick's disease.

  PublisherOA PDFDOI

Recent grants

• NIH Grant RC2AG036650

  NIH · $2.7M · 2012

• NIH Grant R01NS037431

  NIH · $659k · 2002

Frequent coauthors

• Bernardino Ghetti

  Indiana University – Purdue University Indianapolis

  510 shared

• Hugh C. Hendrie

  309 shared

• Martin R. Farlow

  Indiana University School of Medicine

  274 shared

• Kathleen Hall

  274 shared

• Frederick W. Unverzagt

  Indiana University – Purdue University Indianapolis

  262 shared

• Sujuan Gao

  Indiana University School of Medicine

  236 shared

• Philip L. De Jager

  NewYork–Presbyterian Hospital

  190 shared

• Lisa L. Barnes

  Rush University Medical Center

  162 shared

Education

• Fellowship , Division of Genomic Diagnostics

  Children's Hospital of Philadelphia

  2018

• PhD, Medical and Molecular Genetics

  Indiana University

  1992