Biology subjects

Gehman, A.

Publications and source records attributed to Gehman, A..

3 recordsLinked to original sources

bioRxiv2025

Managing populations after a disease outbreak: exploration of epidemiological consequences of managed host reintroduction following disease-driven host decline

Disease outbreaks in wild populations around the globe can lead to widespread mortality within populations, where recovery of individuals can be rare. An example of this population is the sunflower sea star Pyc-nopodia helianthioides in the Northeastern Pacific coast. The populations of this species, as well as many other sea star populations, have experienced massive mortality events due to an unidentified disease called Sea Star Wasting Disease (SSWD). Pycnopodia play a key role in providing top-down control of kelp grazers in rocky reefs across the Northeastern Pacific coast. This, combined with the massive declines in kelp coverage observed during the 2015-2016 marine heat wave observed in the Northeastern Pacific, has sparked an interest in reintroducing Pycnopodia individuals in the coast to potentially assist in recovery of the populations. However, the epidemiological implications of reintroducing healthy sea stars into the wild populations is an under-explored question. This work explores this question using a dynamical population model of Pycnopodia. We use this model to estimate the impacts of reintroducing healthy individuals into a wild sea star population. This analysis will provide valuable information for managers interested in restoring Pycnopodia populations.

ecology↗

bioRxiv2022

Lung Tumor Microphysiological System with 3D Endothelium to Evaluate Modulators of T-Cell Infiltration

Lung cancer is a leading cause of death worldwide, with only a fraction of patients responding to immunotherapy. The correlation between increased T-cell infiltration and positive patient outcomes has motivated the search for therapeutics promoting T-cell infiltration. While transwell and spheroid platforms have been employed, these models lack flow and endothelial barriers, and cannot faithfully model T-cell adhesion, extravasation and migration through 3D tissue. Presented here is a 3D chemotaxis assay, in a lung tumor on chip model with 3D endothelium (LToC-Endo), to address this need. The described assay consists of a vascular tubule cultured under rocking flow, through which T-cells are added; a collagenous stromal barrier, through which T-cells infiltrate; and a chemoattractant/tumor compartment. Here, activated T-cells extravasate and infiltrate in response to gradients of rhCXCL11 and rhCXCL12. Adopting a T-cell activation protocol with a rest period enables proliferative burst prior to introducing T-cells into chips, increases T-cell expression of CXCR3 and CXCR4 receptors, and enhances assay sensitivity. In addition, incorporating this rest recovers endothelial activation in response to rhCXCL12. As a final control, we show that blocking ICAM-1 interferes with T-cell adhesion and chemotaxis. This microphysiological system, which mimics in vivo stromal and vascular barriers, can be used to evaluate potentiation of immune chemotaxis into tumors while probing for vascular responses to potential therapeutics. Finally, we propose a translational strategy by which this assay could be linked to preclinical and clinical models to support human dose prediction, personalized medicine, and the reduction, refinement, and replacement of animal models.

bioengineering↗

bioRxiv2019

Effect of topical soluble epoxide hydrolase inhibition in a preclinical diabetic wound healing model.

The objective of this study was to test a topical formulation of EPHX2 inhibitor, GSK2256294, in a dermal wound diabetic (db/db) mouse model. Comparisons were made between groups treated with EPHX2 inhibitor, matching vehicle control and a currently approved treatment for diabetic ulcers, becaplermin/Regranex, as a positive control which is highly efficacious in this model. Leptin receptor-deficient (db/db) male mice were sequentially assigned to treatment groups (N=10 per group) based on blood glucose levels and body weight. Mice were given a single 8 mm diameter full thickness wound on the back. Wounds were photographed and traced, and fresh test materials applied periodically with fresh dressing. Of ten mice treated with GSK2256294, three had completely healed wounds at the study conclusion, and 8/10 mice reached at least 50% closure. In the vehicle group, no mice achieved complete closure, and only 6/10 reached at least 50% closure by the study conclusion. Nine of ten wounds achieved complete closure in the positive control group by 21 days. Although the EPHX2 inhibitor results were indicative of efficacy, the single-sided p-value criterion of 0.05 was not met in this study.

physiology↗