Yale University | 0 | B.S.
Work in my laboratory utlizes biochemical and molecular techniques to study the behavior of cells. A common theme running through much of our recent work is epithelial to mesenchymal transition (EMT), a transcriptional program activated in embryonic development (type 1), wound healing (type 2), and cancer metastasis (type 3). We have explored the EMT process in a variety of context utilizing an epithelial wound healing in zebrafish to study type 2 EMT and cutaneous squamous cell carcinoma clinical samples to focus on type 3 EMT. Our current focus is the initiation of the type 3 EMT transcriptional program in an epigenetically plastic cancer cell line which transitions from an epithelial-like, highly proliferative subtype to a mesenchymal-like, metastatic subtype. Specifically, we focus on the extracellular signals which initiate the intercoversion of the these subtypes and the involvement of the SWI/SNF (BAF) chromatin remodeling complex in the execution of this type 3 EMT-like transcriptional program.
My laboratory is focused on training a variety of students at many stages of their training in research. Productivity of the research program relies on students from the Master of Biomedical Sciences Pragrams, Arizona College of Osteopathic Medicine, College of Veterinary Medicine, and PGY1-3 traninees participating in Midwestern sponsored residency programs. To effectively mentor students and trainees, I have deliberately developed a collaborative culture in the laboratory which is both student-friendly and supportive. This includes crafting research projects which contribute to the overall goals of the laboratory that are technically feasible and can be accomplished in the short period of time the students have to spend devoted to research. The success of the research program can be seen in the fact that most students trained in the laboratory have presented their work at national meetings and are co-authors on published papers with many being first-authors. After training in my laboratory, students have typically been successful in gaining admissions to professional school programs and several have indicated that their research experience in the lab was positive and that they intend to integrate research into their professional careers.
College of Graduate Studies - AZ
College of Veterinary Medicine
Biomedical Sciences (M.A.)
Biomedical Sciences (M.B.S.)
Yale University | 0 | B.S.
Biochemistry and Immunology in the Biomedical Sciences program (BMMAG 550, BMMSG 550, BMMAG 524, BMMSG 524)
Immunology in the AZCOM / AZ Podiatry curriculum (MICRG 1531, MICRG 1532)
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.
Publications since 2013. Student / trainee authors in italics, corresponding author indicated by #.
A.S. Pascual, J.L. Rapanan, C.K. Uppalapati, K.E. Cooper, K.J. Leyva, E.E. Hull#, Dual inhibition of TGFβR and ROCK reverses the epithelial to mesenchymal transition in collectively migrating zebrafish keratocytes, Cell Biol Int (2021). [PMID 33710707].
Seaton K, Mullens D, Barr J, Hull E#, Averitte R (2021). “Amniotic Tissue Derived Allografts in Post-Mohs Micrographic Surgery: Preliminary Study Assessing Wound Closure Rate.” Wounds (in press).
Montgomery MR and Hull EE# (2019). Alterations in the Glycome after HDAC Inhibition Impact Oncogenic Potential in Epigenetically Plastic SW13 Cells. BMC Cancer, 19(1):79. [PMID 30651077]
Manway M, Blackburn S, Barr J, Hull E#, Averitte R, and Ahn Y (2018). Effects of Acupuncture on Chronic Idiopathic Pruritus: An Uncontrolled Pilot Study Evaluating Inflammatory Changes with Treatment. Journal of Complementary and Integrative Medicine, Nov 3;16(3) [PMID 30391935].
Hull EE#, Montgomery MR, and Leyva KJ (2017). Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers. International Journal of Molecular Sciences, 2017 June 26;18(7) [PMID 28672878].
Belden SE, Uppalapati CK, Pascual AS, Montgomery MR, Leyva KJ, Hull EE#, and Averitte RL (2017). Establishment of a Clinic-Based Biorepository. Journal of Visualized Experiments. JoVE 2017 May 29;(123):55583. [PMID 28605380].
Hull EE#, Davis MR, and Leyva KJ (2016). HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy & Inflammatory Diseases. Biomed Res Int, 2016: p. 8797206. [PMID 27556043].
Davis, MR, Daggett JJ, Lam J, Pascual, AS, Cooper KE, Leyva KJ, and Hull EE# (2016). “Epigenetically maintained sw13+ and sw13- subtypes have different oncogenic potential and convert with HDAC1 inhibition.” BMC Cancer. 2016;16:1-13 [PMID 27556043].
Rapanan JL, Pascual AS, Uppalapati CK, Cooper KE, Leyva KJ, and Hull EE# (2015). “Zebrafish Keratocyte Explants to Study Collective Cell Migration and Reeepithelization in Cutaneous Wound Healing”. Journal of Visualized Experiments, Feb 25;(96). doi: 10.3791/52489. [PMID 25742068].
Rapanan JL, Cooper KE, Leyva KJ, and Hull EE# (2014). “Collective cell migration of primary zebrafish keratocytes”. Experimental Cell Research 326(1): 155. [PMID 24973510].
McDonald T, Pascual A, Uppalapati C, Cooper K, Leyva K, and Hull EE# (2013). Zebrafish keratocyte explant cultures as a wound healing model system: differential gene expression & morphological changes support epithelial-mesenchymal transition.Experimental Cell Research319(12): 1815. [PMID 23588205].
American Society for Cell Biology
American Association for Cancer Research
America Association for the Advancement of Science
Intramural Funding from MWU
Selected Previous Awards & Fellowships
Teacher of the Year Award, Biomedical Sciences Program, MWU
Excellence in Service Award, Nominated by MA & DO students, MWU
Faculty Merit Award, California State University
Henry & Camille Dreyfus Teaching & Research Fellowship
NIH Individual NRSA Postdoctoral Fellowship