Elizabeth E Hull, Ph.D.
Program Director
Biomedical Sciences
Orcid identifier0000-0001-6100-9605 (opens in a new tab)
- Program DirectorBiomedical Sciences
- 623-572-3620
- Midwestern University, Biomedical Sciences Program, 19555 N 59th Avenue, Glendale, AZ, 85308, United States
RESEARCH INTERESTS
Current Research Projects
Changes in the cellular microenvironment can reprogram epigenetically plastic cells. In cancer, the resulting alterations in cellular phenotypes can have deleterious consequences including acquisition of tumorigenic and metastatic properties. Unfortunately, the acquisition of these epigenetic changes and the signaling events coordinating these responses remain poorly understood.
The human adrenocortical carcinoma SW13 line rapidly interconverts between a proliferative (epithelial-like) and a metastatic (mesenchymal-like) subtype. This naturally occurring epigenetic switch appears to be triggered by environmental cues (in both directions) and, in the pro-metastatic direction, by FDA-approved histone deacetylase inhibitors (HDACi). Current work in the lab is focused on deciphering the extracellular signals and intracellular responses which are involved in this subtype switch.
Project 1: SWI/SNF Chromatin Remodeling Complexes
The SWI/SNF chromatin remodeling complex plays a key role in regulating inducible gene expression in a tissue-specific manner. For example, the catalytic core exchanges accessory subunits during epithelial to mesenchymal transition (EMT), a transcriptional program activated during development and metastasis. Illustrative of its central role in gene expression, subunits of this complex are mutated in 20-30% of all cancers. Recent work in the lab suggests that altered SWI/SNF subunit composition may participate in the SW13 subtype switch between the proliferative (epithelial-like) and the metastatic (mesenchymal-like) subtypes. As SWI/SNF subunits may be targeted therapeutically, our current experiment aims seek to identify key epigenetic factors integral to tumor cell plasticity and correlate these to SWI/SNF complex activity.
Project 2: Extracellular Factors which Mediate the Subtype Switch
Recent data from the lab suggests that secreted components from one SW13 subtype appears to initiate the subtype acts to alters the behavior of the other subtype. Specifically, conditioned media from the metastatic (mesenchymal-like) subtype increases levels of Brm mRNA in the proliferative (epithelial-like) subtype within 24 hours. This is intriguing as BRM (SMARCA2) is the ATPase subunit of the SWI/SNF chromatin remodeling complex. Work in the lab is defining the components of the conditioned media which alters Brm mRNA and defining whether this reflects a complete subtype switch.
Lysosomal Function in Inflammation & Cancer
Epigenetic Regulation of Cancer
Chromatin Remodeling
Changes in the cellular microenvironment can reprogram epigenetically plastic cells. In cancer, the resulting alterations in cellular phenotypes can have deleterious consequences including acquisition of tumorigenic and metastatic properties. Unfortunately, the acquisition of these epigenetic changes and the signaling events coordinating these responses remain poorly understood.
The human adrenocortical carcinoma SW13 line rapidly interconverts between a proliferative (epithelial-like) and a metastatic (mesenchymal-like) subtype. This naturally occurring epigenetic switch appears to be triggered by environmental cues (in both directions) and, in the pro-metastatic direction, by FDA-approved histone deacetylase inhibitors (HDACi). Current work in the lab is focused on deciphering the extracellular signals and intracellular responses which are involved in this subtype switch.
Project 1: SWI/SNF Chromatin Remodeling Complexes
The SWI/SNF chromatin remodeling complex plays a key role in regulating inducible gene expression in a tissue-specific manner. For example, the catalytic core exchanges accessory subunits during epithelial to mesenchymal transition (EMT), a transcriptional program activated during development and metastasis. Illustrative of its central role in gene expression, subunits of this complex are mutated in 20-30% of all cancers. Recent work in the lab suggests that altered SWI/SNF subunit composition may participate in the SW13 subtype switch between the proliferative (epithelial-like) and the metastatic (mesenchymal-like) subtypes. As SWI/SNF subunits may be targeted therapeutically, our current experiment aims seek to identify key epigenetic factors integral to tumor cell plasticity and correlate these to SWI/SNF complex activity.
Project 2: Extracellular Factors which Mediate the Subtype Switch
Recent data from the lab suggests that secreted components from one SW13 subtype appears to initiate the subtype acts to alters the behavior of the other subtype. Specifically, conditioned media from the metastatic (mesenchymal-like) subtype increases levels of Brm mRNA in the proliferative (epithelial-like) subtype within 24 hours. This is intriguing as BRM (SMARCA2) is the ATPase subunit of the SWI/SNF chromatin remodeling complex. Work in the lab is defining the components of the conditioned media which alters Brm mRNA and defining whether this reflects a complete subtype switch.
Lysosomal Function in Inflammation & Cancer
Epigenetic Regulation of Cancer
Chromatin Remodeling
GRANTS
- EXTRAMURAL RESEARCH GRANTThe Role of Progranulin in the Inflammatory Response in Alzheimer DiseaseArizona Alzheimer's Consortium1 Jul 2024 - 30 Jun 2025People funded by this grant:
- Hull E
- EXTRAMURAL RESEARCH GRANTElucidating a Mechanistic Link Between Progranulin and Lysosomal Function in Alzheimer DiseaseArizona Alzheimer's Consortium1 Jul 2023 - 30 Jun 2024People funded by this grant:
- Hull E
- EXTRAMURAL RESEARCH GRANTProgranulin Transport and Processing: Implications for Development of New Alzheimer's TherapiesArizona Alzheimer's Consortium1 Jul 2023 - 30 Jun 2024People funded by this grant:
- Hull E
- EXTRAMURAL RESEARCH GRANTProgranulin and Lysosomal pH: Implications for Potential New Therapeutic Strategy for Neurodegenerative DiseasesArizona Alzheimer's Consortium1 Jul 2022 - 30 Jun 2023People funded by this grant:
- Hull E,
- Leyva K
- MWU INTRAMURAL GRANTIdentification of Epigenetic Factors in Tumor Cell Plasticity: SWI/SNF Chromatin Remodeling ActivityPeople funded by this grant:
- Hull E
- MWU INTRAMURAL GRANTmiRNA Regulation of GRN Expression in NeuroinflammationPeople funded by this grant:
- Hull E