Elizabeth E. Hull, Ph.D.

Professor, Biomedical Sciences


Midwestern University
College of Health Sciences
Biomedical Sciences Program
Cactus Wren 310-B
19555 N 59th Avenue
Glendale, AZ 85308  

Contact me

EDUCATION

B.S. Molecular Biophysics & Biochemistry Yale University
Ph.D. Cell Biology& Biochemistry Rockefeller University

RESEARCH SUMMARY

My research focuses on the regulation of cellular behavior during wound healing and oncogenesis.  Although these two processes may not appear to have much in common, wound healing and oncogenesis share several features including epithelial to mesenchymal transition (EMT), inflammatory response, cell migration, and several signal transduction pathways.  Experiments use cell lines, transgenic zebrafish, and human tissue samples to these processes at the molecular level as detailed below.

Research projects

Project I: Epigenetic Control of Oncogenesis

The cellular microenvironment can reprogram epigenetically plastic cells. This may result in acquisition of oncogenic properties including metastatic or proliferative phenotypes.  Many cancer therapies fail to account for the contribution of the extracellular microenvironment to the disease process.  We utilize a unique epigenetically plastic cancer cell model to address the epigenetic control of tumorigenesis.  The human adrenocortical carcinoma line we study can switch between two subtypes via epigenetic mechanisms.  One subtype is a highly proliferative and epithelial-like while the other is slow growing and mesenchymal but has a greater metastatic capacity.  Our research is focused on understanding the molecular signals and environmental cues that contribute to the switch between these two phenotypes.  This work may lead to new combinatorial therapeutic approaches and more successful anticancer regimens.

Project II: Inflammatory Response in Wound Healing

In epithelial wound healing, inflammation plays an essential role in promotion of healing at early stages but may also be a key contributor to non-healing wounds and ulcers.  To study inflammation in epithelial wound healing, we utilize a zebrafish explant culture model in which epithelial tissue containing keratocytes, neutrophils and macrophages is removed from an anesthetized fish and placed in culture.  This process initiates changes in gene expression associated with wound healing, inflammation, and epithelial to mesenchymal transition (EMT) and is an established wound healing model.  Advantages of this system include the fact that cells within the tissue piece are not transformed and have not undergone the changes associated with passage of primary culture.  In addition, explant culture removes complications associated with in vivo wound healing assays and generates more interpretable results.  Furthermore, it allows us to focus on the reepithelization phase - a key phase in which an intact layer of skin is formed over the wound bed - and study how this stage is affected by the inflammatory response.  If explants are established from transgenic zebrafish expressing fluorescent proteins in their macrophages or neutrophils, the behavior of each cell type can be readily assayed in real-time motility assays.  Currently, we are studying how modulation of the inflammatory response affects EMT.  Future projects will focus on chronic inflammation and its effects on wound healing.  Results have broad implications including the promotion of rapid wound healing without scar formation.

 

Project III: Cutaneous Squamous Cell Carcinoma (SCC)

SCC is a common form of skin cancer with an estimated 700,000 cases diagnosed annually in the US. As most cases are successfully treated with complete excision, this cancer has not been heavily studied.  However, about 2% of patients will die from the disease.  As the incidence of SCC is increasing, the financial burden on the healthcare system and SCC associated mortality is rising.    Our work focuses on the role of exosomal miRNA and immune surveillance in the development of SCC and their possible use in diagnosis of metastatic SCC.  Exosomes are secreted, microscopic vesicles, the contents of which are involved in epigenetic reprogramming and intercellular communication.   Exosomes have been shown to promote oncogenesis by:

  1. suppressing immune surveillance mechanisms that target cancer cells
  2. promoting the dedifferentiation process known as epithelial to mesenchymal transition (EMT) which is an integral part of metastasis
  3. preparing distant sites for invasion by creating metastatic niches in target organs. 

Three factors make SCC an appropriate cancer in which to study the role of exosomes.  First, the cancer progresses slowly so that stages in the development of metastatic disease are more readily detected.  Second, we have access to a large number of properly processed patient samples which are linked to accurate clinicalhistory and quality pathology reports and the results of post-excision follow-up visits.  Third, exosomes from patient samples are readily correlated with results from characterized cell lines.  Although this work is focused on SCC, exosomes play a role in many other cancers and results are likely to have broad applicability to oncogenesis.  

Selected Publications 

Belden SE, Uppalapati CK, Pascual AS, Montgomery MR, Leyva KJ, Hull EE, Averitte RL (2017).  Establishment of a Clinic-Based Biorepository. Journal of Visualized Experiments, in press.      

Hull EE, Montgomery MR, Leyva KJ (2016).  HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases.  BioMed Research International 2016: 8797206.

Davis MR, Daggett JJ, Pascual AS, Lam JM, Leyva KJ, Cooper KE, Hull EE (2016). Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition.  BMC Cancer 16(1): 1.

Rapanan JL, Pascual AS, Uppalapati CK, Cooper KE, Leyva KJ, Hull EE (2015). Zebrafish Keratocyte Explants to Study Collective Cell Migration and Reepithelialization in Cutaneous Wound Healing.  Journal of Visualized Experiments (96), e52489, doi:10.3791/52489.      

Rapanan JL, Cooper KE, Leyva KJ, Hull EE (2014).  Collective cell migration of primary zebrafish keratocytes.  Experimental Cell Research 326(1): 155. 

McDonald T, Sumner A, Reyes J, Pascual A, Uppalapati C, Cooper K, Leyva K, Hull EE (2013).  Matrix Metalloproteinases & Collective Cell Migration in 24 hour Primary Zebrafish Explant Cultures: MMP13 Plays an Inhibitory Role & MMP14 May Respond to Stretch.  Cell Biology International Reports 20(2): 24.  

McDonald T, Pascual A, Uppalapati C, Cooper K, Leyva K, Hull EE (2013).  Zebrafish keratocyte explant cultures as a wound healing model system: differential gene expression & morphological changes support epithelial-mesenchymal transition. Experimental Cell Research 319(12): 1815.