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Holly A. F. Stessman
Creighton University
AutismBortezomibProteasome inhibitorGeneticsBiology
48Publications
19H-index
2,717Citations
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Publications 48
Newest
#1Hanyin Cheng (BCM: Baylor College of Medicine)H-Index: 3
#2Leah Gottlieb (UPenn: University of Pennsylvania)H-Index: 2
Last. Gholson J. Lyon (CSHL: Cold Spring Harbor Laboratory)H-Index: 37
view all 29 authors...
N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and HYPK, respectively. Through a genotype-first approach with exome sequencing, we identified and phenotypically characterized 30 individuals from 30 unrelated families wit...
3 CitationsSource
#1Ravyn M. DuncanH-Index: 1
#2Leticia ReyesH-Index: 5
Last. Nathan G. DolloffH-Index: 2
view all 6 authors...
The clinical potential of epigenetic cancer therapy has not been fully realized. Histone deacetylase inhibitors (HDACi), for example, only benefit a minor fraction of all cancer patients despite thousands of preclinical studies demonstrating their antitumor effects. In this study we show that a new structural class of protein disulfide isomerase (PDI) that was discovered by our lab dramatically enhances the antitumor effects of HDACi and select other epigenetic modifiers. We set out to identify ...
Source
Neurogenesis is an elegantly coordinated developmental process that must maintain a careful balance of proliferation and differentiation programs to be compatible with life. Due to the fine-tuning required for these processes, epigenetic mechanisms (e.g., DNA methylation and histone modifications) are employed, in addition to changes in mRNA transcription, to regulate gene expression. The purpose of this review is to highlight what we currently know about histone 4 lysine 20 (H4K20) methylation ...
Source
#1Benjamin Cogné (University of Nantes)H-Index: 4
#2Sophie Ehresmann (Centre Hospitalier Universitaire Sainte-Justine)H-Index: 3
Last. Philippe M. Campeau (UdeM: Université de Montréal)H-Index: 29
view all 115 authors...
Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collabora...
3 CitationsSource
#1Bradley P. Coe (UW: University of Washington)H-Index: 39
#2Holly A. F. Stessman (Creighton University)H-Index: 19
Last. Evan E. Eichler (UW: University of Washington)H-Index: 141
view all 11 authors...
We combined de novo mutation (DNM) data from 10,927 individuals with developmental delay and autism to identify 253 candidate neurodevelopmental disease genes with an excess of missense and/or likely gene-disruptive (LGD) mutations. Of these genes, 124 reach exome-wide significance (P < 5 × 10−7) for DNM. Intersecting these results with copy number variation (CNV) morbidity data shows an enrichment for genomic disorder regions (30/253, likelihood ratio (LR) +1.85, P = 0.0017). We identify genes ...
14 CitationsSource
#1Hanyin Cheng (Baylor University)H-Index: 3
#2Avinash V. Dharmadhikari (Baylor University)H-Index: 11
Last. Gholson J. Lyon (CSHL: Cold Spring Harbor Laboratory)H-Index: 37
view all 72 authors...
N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10. Through a genotype-first approach with ...
7 CitationsSource
#1Caitlin M. Hudac (UW: University of Washington)H-Index: 12
#2Holly A. F. Stessman (UW: University of Washington)H-Index: 19
Last. Raphael Bernier (UW: University of Washington)H-Index: 44
view all 9 authors...
Background Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder. Promising initiatives utilizing interdisciplinary characterization of ASD suggest phenotypic subtypes related to specific likely gene-disrupting mutations (LGDMs). However, the role of functionally associated LGDMs in the neural social phenotype is unknown.
6 CitationsSource
#1Sébastien KüryH-Index: 20
#2Geeske M. van Woerden (Erasmus University Medical Center)H-Index: 13
Last. Sandra MercierH-Index: 16
view all 104 authors...
Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 f...
20 CitationsSource
#1Bradley P. Coe (UW: University of Washington)H-Index: 39
#2Holly A. F. Stessman (Creighton University)H-Index: 19
Last. Evan E. Eichler (UW: University of Washington)H-Index: 141
view all 6 authors...
We combined de novo mutation (DNM) data from 10,927 cases of developmental delay and autism to identify 301 candidate neurodevelopmental disease genes showing an excess of missense and/or likely gene-disruptive (LGD) mutations. 164 genes were predicted by two different DNM models, including 116 genes with an excess of LGD mutations. Among the 301 genes, 76% show DNM in both autism and intellectual disability/developmental delay cohorts where they occur in 10.3% and 28.4% of the cases, respective...
2 CitationsSource
#1Madeleine R. Geisheker (UW: University of Washington)H-Index: 3
#2Gabriel Heymann (UW: University of Washington)H-Index: 2
Last. Evan E. Eichler (UW: University of Washington)H-Index: 141
view all 40 authors...
This study characterizes the properties of disease-causing mutations that produce sporadic amino acid replacements in proteins of people with autism and developmental delay. The mutations tend to cluster and reoccur at specific regions important to protein function, highlighting for future follow-up ∼200 candidate genes, many involved in neuronal signaling.
44 CitationsSource
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