Timothy P. Sheets

Coordinated strategy for a model-based decision support tool for coronavirus disease, Utah, USA

Jacob C. Pettit, Timothy P. Sheets, M Good, Lindsay T. Keegan et autres

The coronavirus disease pandemic has highlighted the key role epidemiologic models play in supporting public health decision-making. In particular, these models provide estimates of outbreak potential when data are scarce and decision-making is critical and urgent. We document the integrated modeling response …

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Abstract 6594: 4-1BB: A double-edged sword for T cells

Liping Yang, Timothy P. Sheets, Yan Feng, Kuo-Sheng Hsu et autres

Abstract Background: The costimulatory receptor 4-1BB (CD137) is expressed on the surface of activated T cells, playing a pivotal role in enhancing T cell responses and emerging as a promising target for cancer immunotherapy. Its primary ligand, 4-1BBL (CD137L), is found on …

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Uncovering receptor-ligand interactions using a high-avidity CRISPR activation screening platform

Liping Yang, Timothy P. Sheets, Yang Feng, Guojun Yu et autres

The majority of clinically approved drugs target proteins that are secreted or cell surface bound. However, further advances in this area have been hindered by the challenging nature of receptor deorphanization, as there are still many secreted and cell-bound proteins with unknown …

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dbGuide: a database of functionally validated guide RNAs for genome editing in human and mouse cells

Alexander A Gooden, Christine N. Evans, Timothy P. Sheets, Michelle E. Clapp et autres

With the technology's accessibility and ease of use, CRISPR has been employed widely in many different organisms and experimental settings. As a result, thousands of publications have used CRISPR to make specific genetic perturbations, establishing in itself a resource of validated guide …

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dbGuide: A database of functionally validated guide RNAs for genome editing in human and mouse cells

Alexander A Gooden, Christine N. Evans, Timothy P. Sheets, Michelle E. Clapp et autres

ABSTRACT With the technology’s accessibility and ease of use, CRISPR has been employed widely in many different organisms and experimental settings. As a result, thousands of publications have used CRISPR to make specific genetic perturbations, establishing in itself a resource of validated …

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MODULATING KEY GENES INVOLVED IN PANCREAS FORMATION AND INSULIN SIGNALING USING CRISPR/CAS9 IN THE PIG

Timothy P. Sheets

Among the metabolic diseases, diabetes remains a “pressing problem” as recognized by World Health Organization, not only due to the impact on individuals’ lives, but also because of the rapid increase in newly diagnosed patients. To better understand the mechanisms of diabetes, …

Targeted Mutation of NGN3 Gene Disrupts Pancreatic Endocrine Cell Development in Pigs

Timothy P. Sheets, Ki‐Eun Park, Chi‐Hun Park, Steven M. Swift et autres

The domestic pig is an attractive model for biomedical research because of similarities in anatomy and physiology to humans. However, key gaps remain in our understanding of the role of developmental genes in pig, limiting its full potential. In this publication, the …

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Somatic Cell Nuclear Transfer Followed by CRIPSR/Cas9 Microinjection Results in Highly Efficient Genome Editing in Cloned Pigs

Timothy P. Sheets, Chi‐Hun Park, Ki‐Eun Park, Anne M. Powell et autres

The domestic pig is an ideal “dual purpose” animal model for agricultural and biomedical research. With the availability of genome editing tools such as clustered regularly interspaced short palindromic repeat (CRISPR) and associated nuclease Cas9 (CRISPR/Cas9), it is now possible to perform …

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Engineering large animal models of human disease

Bruce Whitelaw, Timothy P. Sheets, Simon Lillico, Bhanu P. Telugu

The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, …

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Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate

Danielle L. Gomez, Marci O’Driscoll, Timothy P. Sheets, Ralph H. Hruban et autres

Neurogenin 3 (NGN3) is necessary and sufficient for endocrine differentiation during pancreatic development and is expressed by a population of progenitor cells that give rise exclusively to hormone-secreting cells within islets. NGN3 protein can be detected in the adult rodent pancreas only …

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Evaluation of Delcath Systems’ Generation 2 (GEN 2) Melphalan Hemofiltration System in a Porcine Model of Percutaneous Hepatic Perfusion

Fred M Moeslein, Elizabeth McAndrew, William M. Appling, Nicole E. Hryniewich et autres

PURPOSE: A new melphalan hemoperfusion filter (GEN 2) was evaluated in a simulated-use porcine model of percutaneous hepatic perfusion (PHP). The current study evaluated melphalan filtration efficiency, the transfilter pressure gradient, and the removal of specific blood products. MATERIALS AND METHODS: A …

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Evaluation of melphalan, oxaliplatin, and paclitaxel in colon, liver, and gastric cancer cell lines in a short-term exposure model of chemosaturation therapy by percutaneous hepatic perfusion.

Rajneesh P. Uzgare, Timothy P. Sheets, Daniel St Johnston

BACKGROUND: The goal of this study was to determine whether liver, gastric, or colonic cancer may be suitable targets for chemosaturation therapy with percutaneous hepatic perfusion (CS-PHP) and to assess the feasibility of utilizing other cytotoxic agents besides melphalan in the CS-PHP …

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