Jeffrey Everitt

Positions:

Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

D.V.M. 1977

Cornell University

Adjunct Professor of Pathology, College of Veterinary Medicine,, Department Of Pathology

North Carolina State University

Grants:

Molecular Genetics of BBS

Administered By
Institutes and Centers
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Advanced Technologies for Reducing Decompression Obligation and Risk

Administered By
Anesthesiology, General, Vascular, High Risk Transplant & Critical Care
Awarded By
Creare, Inc.
Role
Co Investigator
Start Date
End Date

Combatting Bladder Cancer by Inducing Epithelial Turnover

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Stable therapy in Pompe disease through genome editing

Administered By
Pediatrics, Medical Genetics
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Publications:

Optimizing ethyl cellulose-ethanol delivery towards enabling ablation of cervical dysplasia.

In low-income countries, up to 80% of women diagnosed with cervical dysplasia do not return for follow-up care, primarily due to treatment being inaccessible. Here, we describe development of a low-cost, portable treatment suitable for such settings. It is based on injection of ethyl cellulose (EC)-ethanol to ablate the transformation zone around the os, the site most impacted by dysplasia. EC is a polymer that sequesters the ethanol within a prescribed volume when injected into tissue, and this is modulated by the injected volume and delivery parameters (needle gauge, bevel orientation, insertion rate, depth, and infusion rate). Salient injection-based delivery parameters were varied in excised swine cervices. The resulting injection distribution volume was imaged with a wide-field fluorescence imaging device or computed tomography. A 27G needle and insertion rate of 10 mm/s achieved the desired insertion depth in tissue. Orienting the needle bevel towards the outer edge of the cervix and keeping infusion volumes ≤ 500 µL minimized leakage into off-target tissue. These results guided development of a custom hand-held injector, which was used to locate and ablate the upper quadrant of a swine cervix in vivo with no adverse events or changes in host temperature or heart rate. After 24 h, a distinct region of necrosis was detected that covered a majority (> 75%) of the upper quadrant of the cervix, indicating four injections could effectively cover the full cervix. The work here informs follow up large animal in vivo studies, e.g. in swine, to further assess safety and efficacy of EC-ethanol ablation in the cervix.
Authors
Mueller, JL; Morhard, R; DeSoto, M; Chelales, E; Yang, J; Nief, C; Crouch, B; Everitt, J; Previs, R; Katz, D; Ramanujam, N
MLA Citation
Mueller, Jenna L., et al. “Optimizing ethyl cellulose-ethanol delivery towards enabling ablation of cervical dysplasia.Sci Rep, vol. 11, no. 1, Aug. 2021, p. 16869. Pubmed, doi:10.1038/s41598-021-96223-9.
URI
https://scholars.duke.edu/individual/pub1494616
PMID
34413378
Source
pubmed
Published In
Scientific Reports
Volume
11
Published Date
Start Page
16869
DOI
10.1038/s41598-021-96223-9

ARHGEF26 enhances Salmonella invasion and inflammation in cells and mice.

Salmonella hijack host machinery in order to invade cells and establish infection. While considerable work has described the role of host proteins in invasion, much less is known regarding how natural variation in these invasion-associated host proteins affects Salmonella pathogenesis. Here we leveraged a candidate cellular GWAS screen to identify natural genetic variation in the ARHGEF26 (Rho Guanine Nucleotide Exchange Factor 26) gene that renders lymphoblastoid cells susceptible to Salmonella Typhi and Typhimurium invasion. Experimental follow-up redefined ARHGEF26's role in Salmonella epithelial cell infection. Specifically, we identified complex serovar-by-host interactions whereby ARHGEF26 stimulation of S. Typhi and S. Typhimurium invasion into host cells varied in magnitude and effector-dependence based on host cell type. While ARHGEF26 regulated SopB- and SopE-mediated S. Typhi (but not S. Typhimurium) infection of HeLa cells, the largest effect of ARHGEF26 was observed with S. Typhimurium in polarized MDCK cells through a SopB- and SopE2-independent mechanism. In both cell types, knockdown of the ARHGEF26-associated protein DLG1 resulted in a similar phenotype and serovar specificity. Importantly, we show that ARHGEF26 plays a critical role in S. Typhimurium pathogenesis by contributing to bacterial burden in the enteric fever murine model, as well as inflammation in the colitis infection model. In the enteric fever model, SopB and SopE2 are required for the effects of Arhgef26 deletion on bacterial burden, and the impact of sopB and sopE2 deletion in turn required ARHGEF26. In contrast, SopB and SopE2 were not required for the impacts of Arhgef26 deletion on colitis. A role for ARHGEF26 on inflammation was also seen in cells, as knockdown reduced IL-8 production in HeLa cells. Together, these data reveal pleiotropic roles for ARHGEF26 during infection and highlight that many of the interactions that occur during infection that are thought to be well understood likely have underappreciated complexity.
Authors
Bourgeois, JS; Wang, L; Rabino, AF; Everitt, J; Alvarez, MI; Awadia, S; Wittchen, ES; Garcia-Mata, R; Ko, DC
MLA Citation
Bourgeois, Jeffrey S., et al. “ARHGEF26 enhances Salmonella invasion and inflammation in cells and mice.Plos Pathog, vol. 17, no. 7, July 2021, p. e1009713. Pubmed, doi:10.1371/journal.ppat.1009713.
URI
https://scholars.duke.edu/individual/pub1487685
PMID
34242364
Source
pubmed
Published In
Plos Pathog
Volume
17
Published Date
Start Page
e1009713
DOI
10.1371/journal.ppat.1009713

Infectious diseases of the upper respiratory tract: implications for toxicology studies.

Authors
Everitt, JI; Richter, CB
MLA Citation
Everitt, J. I., and C. B. Richter. “Infectious diseases of the upper respiratory tract: implications for toxicology studies.Environmental Health Perspectives, vol. 85, Environmental Health Perspectives, Apr. 1990, pp. 239–47. Crossref, doi:10.1289/ehp.85-1568352.
URI
https://scholars.duke.edu/individual/pub1483719
Source
crossref
Published In
Environmental Health Perspectives
Volume
85
Published Date
Start Page
239
End Page
247
DOI
10.1289/ehp.85-1568352

Ex Vivo MR Histology and Cytometric Feature Mapping Connect Three-dimensional in Vivo MR Images to Two-dimensional Histopathologic Images of Murine Sarcomas.

Purpose To establish a platform for quantitative tissue-based interpretation of cytoarchitecture features from tumor MRI measurements. Materials and Methods In a pilot preclinical study, multicontrast in vivo MRI of murine soft-tissue sarcomas in 10 mice, followed by ex vivo MRI of fixed tissues (termed MR histology), was performed. Paraffin-embedded limb cross-sections were stained with hematoxylin-eosin, digitized, and registered with MRI. Registration was assessed by using binarized tumor maps and Dice similarity coefficients (DSCs). Quantitative cytometric feature maps from histologic slides were derived by using nuclear segmentation and compared with registered MRI, including apparent diffusion coefficients and transverse relaxation times as affected by magnetic field heterogeneity (T2* maps). Cytometric features were compared with each MR image individually by using simple linear regression analysis to identify the features of interest, and the goodness of fit was assessed on the basis of R2 values. Results Registration of MR images to histopathologic slide images resulted in mean DSCs of 0.912 for ex vivo MR histology and 0.881 for in vivo MRI. Triplicate repeats showed high registration repeatability (mean DSC, >0.9). Whole-slide nuclear segmentations were automated to detect nuclei on histopathologic slides (DSC = 0.8), and feature maps were generated for correlative analysis with MR images. Notable trends were observed between cell density and in vivo apparent diffusion coefficients (best line fit: R2 = 0.96, P < .001). Multiple cytoarchitectural features exhibited linear relationships with in vivo T2* maps, including nuclear circularity (best line fit: R2 = 0.99, P < .001) and variance in nuclear circularity (best line fit: R2 = 0.98, P < .001). Conclusion An infrastructure for registering and quantitatively comparing in vivo tumor MRI with traditional histologic analysis was successfully implemented in a preclinical pilot study of soft-tissue sarcomas. Keywords: MRI, Pathology, Animal Studies, Tissue Characterization Supplemental material is available for this article. © RSNA, 2021.
Authors
Blocker, SJ; Cook, J; Mowery, YM; Everitt, JI; Qi, Y; Hornburg, KJ; Cofer, GP; Zapata, F; Bassil, AM; Badea, CT; Kirsch, DG; Johnson, GA
MLA Citation
Blocker, Stephanie J., et al. “Ex Vivo MR Histology and Cytometric Feature Mapping Connect Three-dimensional in Vivo MR Images to Two-dimensional Histopathologic Images of Murine Sarcomas.Radiol Imaging Cancer, vol. 3, no. 3, May 2021, p. e200103. Pubmed, doi:10.1148/rycan.2021200103.
URI
https://scholars.duke.edu/individual/pub1483145
PMID
34018846
Source
pubmed
Published In
Radiol Imaging Cancer
Volume
3
Published Date
Start Page
e200103
DOI
10.1148/rycan.2021200103

Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model.

Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution with in vivo imaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 μL dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 μL doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors.
Authors
Nief, C; Morhard, R; Chelales, E; Adrianzen Alvarez, D; Bourla Bs, I; Lam, CT; Sag, AA; Crouch, BT; Mueller, JL; Katz, D; Dewhirst, MW; Everitt, JI; Ramanujam, N
MLA Citation
Nief, Corrine, et al. “Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model.Plos One, vol. 16, no. 1, 2021, p. e0234535. Pubmed, doi:10.1371/journal.pone.0234535.
URI
https://scholars.duke.edu/individual/pub1472908
PMID
33507942
Source
pubmed
Published In
Plos One
Volume
16
Published Date
Start Page
e0234535
DOI
10.1371/journal.pone.0234535