Progress 07/01/17 to 06/30/22
Outputs
Target Audience:The target audiences are: 1) scientists and health care professionals working in the area of childhood obesity, 2) undergraduate and graduate students and postdoctoral researchers in life science, and 3) public health officials. Changes/Problems:No problems were encountered. What opportunities for training and professional development has the project provided?This project has provided training opportunities for one PhD student (Nick Robl), one veterinary school student (Joseph Goldhardt), two postdoctoral researchers (Rong Li and Yanan Liu) and twelve undergraduate students (Riley Hunter, Felicity Koenig, Ben Cyr, Kyra Bramwell, Robert Schmid, Juman Al-Haddad, Bekah Stewart, Aubrey Ukena, McKaily Adams, Chloe Quin, Isabella DeJesus, and Thomas Smith). These trainees had training opportunities in critical scientific thinking, proposing hypothesis driven experiments/projects, molecular and cellular biology techniques, as well as developing genetic animal model development by genetic engineering in non-murine species. How have the results been disseminated to communities of interest?The animal models have been distributed to other institutions who are using them to study childhood obesity or/and dyslipidemia. I also incorporated the research discoveries from this project into my class ADVS 6060, Genetics of Metabolic Syndromes, a class that I am teaching for the Master of Public Health (MPH) Program. We are planning to disseminate the scientific discoveries through publications in peer-reviewed scientific journals and presenting them in scientific conferences and research symposium. What do you plan to do during the next reporting period to accomplish the goals?We are planning to expand the breeding colonies and use the animals to study obesity and dyslipidemia. We are also planning to create addition genetically engineered animal models. One of the examples of the new genetically engineered animal models is the human-NTCP (sodium taurocholate cotransporting polypeptide) transgenic hamster model (NTCP is the cellular receptor for hepatitis B virus infection). It has been established that NTCP activity is involved in the development of obesity (https://pubmed.ncbi.nlm.nih.gov/31237863/) and that chronic HBV infection and diabetes/obesity are significant risk factors for hepatocellular carcinoma (HCC; https://pubmed.ncbi.nlm.nih.gov/33305479/). Therefore, developing NTCP transgenic hamster model is a natural continuation of this project.
Impacts
What was accomplished under these goals?
Multiple genetically engineered Syrian hamster models for childhood obesity and dyslipidemia have been established, including CETP KO, HBB KO, SR-B1 KO, GLP-1R KO, and GLP-2R KO. These novel hamster models are being used by the Wang lab and other laboratories to study metabolic diseases.
Publications
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Progress 10/01/20 to 09/30/21
Outputs
Target Audience:The target audiences are: 1) scientists and health care professionals working in the area of childhood obesity, 2) undergraduate and graduate students and postdoctoral researchers in life science, and 3) public health officials. Changes/Problems:No changes needed and no problems encountered. What opportunities for training and professional development has the project provided?This project has provided training opportunities for one PhD student (Nick Robl), one veterinary school student (Joseph Goldhardt), two postdoctoral researchers (Rong Li and Yanan Liu). These trainees had training opportunities in critical scientific thinking, proposing hypothesis driven experiments/projects, molecular and cellular biology techniques, as well as developing genetic animal model development by genetic engineering in non-murine species. How have the results been disseminated to communities of interest?We are planning to disseminate the scientific discoveries through publications in peer-reviewed scientific journals and presenting them in scientific conferences and research symposium. What do you plan to do during the next reporting period to accomplish the goals?We are planning to expand the breeding colonies and use the animals to study obesity and dyslipidemia.
Impacts
What was accomplished under these goals?
Multiple genetically engineered Syrian hamster models for childhood obesity and dyslipidemia have been established, including CETP KO, HBB KO, SR-B1 KO, GLP-1R KO, and GLP-2R KO. These novel hamster models are being used by the Wang lab and other laboratories to study metabolic diseases.
Publications
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Progress 10/01/19 to 09/30/20
Outputs
Target Audience:The target audiences are: 1) scientists and health care professionals working in the area of childhood obesity, 2) undergraduate and graduate students and postdoctoral researchers in life science, and 3) public health officials. Changes/Problems:No changes needed and no problems encountered. What opportunities for training and professional development has the project provided?This project has provided training opportunities for one PhD student (Nick Robl), one veterinary school student (Joseph Goldhardt), two postdoctoral researchers (Rong Li and Yanan Liu). These trainees had training opportunities in critical scientific thinking, proposing hypothesis driven experiments/projects, molecular and cellular biology techniques, as well as developing genetic animal model development by genetic engineering in non-murine species. How have the results been disseminated to communities of interest?Oral and poster presentations at graduate research symposia at USU. What do you plan to do during the next reporting period to accomplish the goals?We plan to carry out the following research activities with the hamster models we developed. (1) with the CETP KO model, we will be carrying out studies to investigate the effects of diets on lipid profile as a function of CETP. We will also investigate the activity of CETP on the development of atherosclerosis. (2) with the HBB KO model, we will use it to model beta thalassemia and inflammation.
Impacts
What was accomplished under these goals?
During this period of project covered by this report, we continued our research to characterize the lipid profiles in the CETP knockout hamsters fed with high lipid diets and normal rodent diets. We demonstrated that loss of function of CETP significantly reduce the level of triglycerides. Our studies indicate that inhibition of CETP function could be an effective way to reduce triglycerides, a potent trigger for chronic inflammation. We also established and partially characterized an HBB knockout hamster model to study beta thalassemia, a blood disorder caused by HBB mutations that also affects blood lipoprotein profiles. Our studies have helped the submission of 4 external grant proposals.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Brocato, R. L., Principe, L. M., Kim, R. K., Zeng, X., Williams, J. A., Liu, Y., Li, R., Smith, J. M., Golden, J. W., Gangemi, D., Youssef, S., Wang, Z., Glanville, J., & Hooper, J. W. (2020, October 27). Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2-Infected Syrian Hamsters. Journal of virology, 94(22).
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Miao, J. X., Wang, J.-H., Li, H. Z., Guo, H. R., Dunmall LSC, Zhang, Z., Cheng, Z. G., Gao, D. L., Dong, J. Z., Wang, Z., & Wang, Y. H. (2020, August 28). Promising xenograft animal model recapitulating the features of human pancreatic cancer. World journal of gastroenterology, 26(32), 4802-4816.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Ranadheera, C., Valcourt, E. J., Warner, B. M., Poliquin, G., Rosenke, K., Frost, K., Tierney, K., Saturday, G., Miao, J., Westover, J. B., Gowen, B., Booth, S., Feldmann, H., Wang, Z., & Safronetz, D. (2020, July 23). Characterization of a novel STAT 2 knock-out hamster model of Crimean-Congo hemorrhagic fever virus pathogenesis. Scientific reports, 10(1), 12378.
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Progress 10/01/18 to 09/30/19
Outputs
Target Audience:1) academic researchers and research institutions, 2) government agencies, such as the NIH, CDC, and USDA, 3) pharmaceutical companies that are interested in developing therapeutics for metabolic syndromes, such as obesity, dyslipidemia, cardiac vascular diseases, atherosclerosis and related conditions. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This project has provided training for two postdocs, a PhD graduate student and two undergraduate students by one-on-one working with the PI. It has also provided a training opportunity for all of the researchers attending the 2017 International Society of Transgenic Technology (ISTT) conference. How have the results been disseminated to communities of interest?We presented 3 posters at the 2017 ISTT and gave one oral presentation at the 1st International Symposium of Hamster Models in 2018. A PhD student, Nick Robl, who works on this project gave an invited oral presentation at the 1st International Symposium of Hamster Models in October, 2018, in China. Nick Robl will also be presenting the research discoveries at the Keystone Symposium on Metabolism and Immunity, April 3-7, 2020, Keystone, Colorado. What do you plan to do during the next reporting period to accomplish the goals?Continue to characterize the CETP KO model. We also initiated a new project to study CETP KO on Pichinde virus infection. We plan to develop more genetically engineered hamsters models of atherosclerosis and carry out in depth studies on these models.
Impacts
What was accomplished under these goals?
After the successful establishment of the CETP KO hamsters model by CRISPR/Cas9-mediatred gene targeting technology, we have been conducting studies on the blood lipid profile of the hamsters, fed with normal diets and Western diet (high fat and high fructose), to investigate the effects of CETP deficiency. Preliminary data show that CETP deficiency affects the profiles of lipoprotein particles and elevates triglycerides regardless diets. We recently also initiate a new project to investigate the role of lipid metabolism in Pichinde virus infection and whether CETP activity affects disease outcomes.
Publications
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Progress 10/01/17 to 09/30/18
Outputs
Target Audience:1) academic researchers and research institutions, 2) government agencies, such as the NIH, CDC, and USDA, 3) pharmaceutical companies that are interested in developing therapeutics for metabolic syndromes, such as obesity, dyslipidemia, cardiac vascular diseases, atherosclerosis and related conditions. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This project has provided training for a postdoc, a graduate student and two undergraduate students by one-on-one working with the PI. It has also provided a training opportunity for all of the researchers attending the 2017 International Society of Transgenic Technology (ISTT) conference. A PhD student, Nick Robl, who works on this project gave an invited oral presentation at the 1st International Symposium of Hamster Models in October, 2018, in China. How have the results been disseminated to communities of interest?We presented 3 posters at the 2017 ISTT and gave one oral presentation at the 1st International Symposium of Hamster Models in 2018. What do you plan to do during the next reporting period to accomplish the goals?Continue to characterize the CETP KO model and develop more genetically engineered hamster models of atherosclerosis and carry out in depth studies on these models.
Impacts
What was accomplished under these goals?
In addition to the SMPD1 KO hamster model, we have also successfully established a strain of CETP KO hamsters as a model of atherosclerosis. These CETP KO hamsters have been successfully produced in the lab by CRISPR/Cas9-mediatred gene targeting technology. We have been feeding the CETP KO and wild type hamsters (controls) with normal diets and Western diet (high fat and high fructose) and have been conducting studies on the blood lipid profile of the hamsters to investigate the effects of CETP deficiency. Our recent data suggest that a second in-frame ATG site in the hamster SMPD1 gene is used, the deletion upstream of this AGT site that was introduced by gene targeting only affects partially the function of SMPD1. Because of this, we are focusing on the CETP KO hamster model in which the CETP function is fully abolished.
Publications
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Progress 07/01/17 to 09/30/17
Outputs
Target Audience:1) academic researchers and research institutions, 2) government agencies, such as the NIH, CDC, and USDA, 3) pharmaceutical companies that are interested in developing therapeutics for metabolic syndromes, such as obesity, dyslipidemia, cardiac vascular diseases, atherosclerosis and related conditions. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This project has provided training for a postdoc, a graduate student and two undergraduate students by one-on-one working with the PI. It has also provided a training opportunity for all of the researchers attending the 2017 International Society of Transgenic Technology (ISTT) conference. How have the results been disseminated to communities of interest?We presented 3 posters at the 2017 ISTT. What do you plan to do during the next reporting period to accomplish the goals?Develop more genetically engineered hamsters models of atherosclerosis and carry out in depth studies on these models.
Impacts
What was accomplished under these goals?
We have successfully established a strain of SMPD1 knockout hamsters as a model of atherosclerosis. We have conducted preliminary studies on the blood lipid profile of the SMPD1 KO hamsters.
Publications
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