Browsing by Department "Veterinary Integrative Biosciences"

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COVID-19: RAPID: Collaborative Research: Optimizing non-pharmaceutical and pharmaceutical interventions for controlling COVID-19 at the community-level
Veterinary Integrative Biosciences; TAMU; https://hdl.handle.net/20.500.14641/446; National Science Foundation
During emerging infectious disease outbreaks, such as the current novel coronavirus (COVID-19) pandemic, mathematical models are important tools to help inform public health recommendations and best utilization of limited resources. This research will develop and analyze data-driven mathematical models to predict the spread and evaluate the success of various public health intervention strategies to control COVID-19 in the US and abroad. The models will account for the characteristics of the pathogen, the variation of transmission that occur within community and in hospital settings, and geographical difference in transmission. The broader impacts from these models will provide real-time information to assist public health officials and decision-makers in making critical decisions on COVID-19 control policies and resource allocation. Standard modeling approach such as compartmental population-based approach may not be suitable for modeling the spread of COVID-19, due to the high-level of heterogeneity of such systems, disease pathways, population makeup, host interactions on different levels of organization (household, workplace/school, social activities), and adaptive features of human behavior. The investigators will employ an individual-based modeling approach (IBM) that will accommodate such local heterogeneities. The investigators will use social, demographic, and epidemiological data of COVID-19 cases in the US and Korea, as well as hospital-level and city-level contact tracing data of COVID-19 in Wuhan, China, to parameterize their models. First, they will develop an IBM hospital-based model to explore different hospital-based interventions for mitigating the risk of nosocomial transmission of COVID-19 between patients and healthcare workers. Second, they will develop an IBM community-based model to evaluate and identify optimal non-pharmaceutical and potential pharmaceutical interventions for COVID-19 control in different local communities (city-county scale). The non-pharmaceutical interventions will include, amongst others: case isolation at home or hospitals, voluntary self-quarantine, stopping mass gathering, closure of schools, universities, or workplaces, and social distancing such as reduction of contacts, wearing of protective masks, and reduction of individuals' movements. Pharmaceutical interventions will include novel vaccines and antiviral therapies. This RAPID award is made by the Ecology and Evolution of Infectious Diseases Program in the Division of Environmental Biology, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
TEX-VAL: Texas A&M Tissue Chip Validation Consortium
Veterinary Integrative Biosciences; TAMU; https://hdl.handle.net/20.500.14641/357; DHHS-NIH-National Center for Advancing Translational Sciences
PROJECT SUMMARY TEX-VAL: Texas A&M Tissue Chip Validation Consortium This proposal is to facilitate the evolution of the Tissue Chip Validation Center at Texas A&M University (TEX- VAL) into TEX-VAL Consortium for validation of microphysiological systems (MPS). TEX-VAL Consortium's goal is to promote the use of tissue chips by the industry and regulatory bodies by creating a “safe harbor” public- private partnership that builds on an existing infrastructure and expertise of TEX-VAL, free of potential conflicts of interests in tissue chip development. In less than 2 years, between October 2016 and August 2018, TEX-VAL completed testing of 11 tissue chips developed by other NIH grantees. TEX-VAL established functionality, reproducibility, robustness and reliability of tissue chip models for a wide array of human tissues. These included the University of Washington proximal kidney tubule; Vanderbilt University neuro-vascular unit; Columbia University bone-tumor and skin; Johns Hopkins/Baylor College of Medicine gut enteroid; UC-Berkeley heart, liver and white fat; UC-Irvine vascularized tumor; Duke University skeletal muscle; and the University of Pittsburgh liver. Each tissue chip was tested using a standardized workflow consisting of material transfer (Tier -1), testing of the flow and drug binding to the devices (Tier 0), replication of the experiments performed by the developers (Tier 1), and testing of new drugs selected in partnership with NIH, iQ Consortium, and FDA (Tier 2). To enable comparative analyses with standard in vitro systems, all tissue chip experiments were conducted in parallel with relevant 2D cultures. Quality assurance project plans were developed and audited by a faculty member with experience in applicable guidelines. All experimental protocols and records adhered to the highest standards based on the Organisation for Economic Cooperation and Development guidance for describing non-guideline in vitro methods, and appropriate guidance on validation of alternatives to animal methods from the FDA and the National Toxicology Program. All data and protocols were shared with respective developers and deposited into the University of Pittsburgh Microphysiology Systems Database (MPS-Db). In the next phase of funding, the TEX-VAL Consortium will utilize Texas A&M University's existing infrastructure for phenotyping and imaging at the Institute of Biosciences and Technology (Houston, TX) and College of Veterinary Medicine (College Station, TX), analytical chemistry at the Geosciences and Environmental Research Group (College Station, TX), and microfluidics at the NanoBio Systems Laboratory (College Station, TX). TEX-VAL Center already secured commitments for testing of 19 new tissue chips from NIH-funded developers. There are also a number of commitments from key members of the iQ Consortium and government agencies to negotiate transition from NIH-funded model for tissue chip testing to one funded and administered as a public-private partnership. Finally, TEX-VAL has an extensive network of partnerships with relevant regulatory agencies in the USA and Europe, which will continue to serve as an important channel for engagement with diverse stakeholders to communicate the scientific promise, technical robustness, as well as any limitations of the tested tissue chips.
UTX: A Novel Regulator of Decidualization?
Veterinary Integrative Biosciences; https://hdl.handle.net/20.500.14641/1084; DHHS-NIH-Eunice Kennedy Shriver National Institute of Child Health & Human Development
During pregnancy, endometrial stromal cells transdifferentiate into decidual cells, a process known as decidualization, to support the implanting embryos. The development of decidua with full functionality requires coordinated cell proliferation, differentiation, and apoptosis. Despite a series of elegant studies that have made breakthroughs in progesterone receptor signaling, transcription factors, and growth factor signaling in uterine decidualization, the role of epigenetic regulators remains poorly defined. Defective decidualization leads to pregnancy complications such as miscarriage, intrauterine growth restriction, and pregnancy loss. Therefore, identification of molecular mechanisms underpinning decidualization is of fundamental importance. Built on novel preliminary findings using conditional knockout mouse model of UTX in the uterus, this proposal will identify the function of a lysine demethylase, UTX, in the development of an integral decidua and decipher how UTX regulates endometrial stromal cell differentiation. A multipronged approach incorporating genetic, cellular, and molecular tools has been proposed. The findings are anticipated to establish a new paradigm in understanding the role of epigenetic regulators in uterine biology. Thus, completion of the proposed studies will have a substantial impact, with potential translational implications in the treatment of endometrial dysfunction and pregnancy loss associated with decidualization defects.