A cow utter

Our long term objectices are:

  • Improve milk production efficiency and animal health in dairy cows.

  • Prevent and treat breast cancer in humans.

Dr. Zhao received his BS degree in Animal Science from Anhui Agricultural University, China. He then moved to Nanjing Agricultural University of China to complete his MS degree in Animal Nutritional Physiology and Biochemistry under the mentorship of Hang Zhengkang.  After working as a Research Associate in Beijing Institute of Nutritional Resources for 4 years, He went the University of Alberta, Canada to complete his PhD in Molecular Nutritional Physiology, with John Kennelly as his advisor.  Dr. Zhao had his post-doctoral training at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, USA in Takami Oka’s laboratory before becoming a Research Scientist at American Registry of Pathology, Armed Forces Institute of Pathology, DC. In 2001, Dr. Zhao moved to Vermont as an Assistant Professor at the University of Vermont where he progressed through the ranks to become Professor.

The research in Dr. Zhao’s laboratory focuses on lactation physiology and metabolism. The current specific research areas include, but not limited to: i) antioxidation in the mammary gland, and ii) glucose uptake and utilization in bovine mammary gland. The pathology of breast cancer and mastitis is also a research interest in Dr. Zhao’s laboratory. The overall aims of Dr. Zhao’s research are to improve milk production efficiency and animal health in dairy cows and to prevent and treat breast cancer in humans.

Antioxidation in bovine mammary gland

Milk is an important source of nutrients in most human diets. Milk produced by dairy cows generates more than 35 billion dollars each year in sales (about 9% of U.S. agriculture earnings).  During milk production, cows are more likely to get an infection of the udder called mastitis. This triggers an immune response and causes white blood cells (WBC) to travel to the infected udders.  While the white blood cells work to destroy the infection, they release byproducts called oxygen radicals that also damage the cells that produce milk within the udder. Because of this damage, infected udders produce less milk. In this project we will explore ways that the milk producing cells try to protect themselves from this damage.  In particular, we will study the function of a special defense protein called Nrf2.  Nrf2 is known to play a key role in removing oxygen radicals that develop in other conditions like aging and cancer in humans. If Nrf2 plays a similar role in the milk producing cells, we will look for ways to boost natural Nrf2 activity to better protect the udders during mastitis.  Overall, this study will improve our ability to prevent or reduce the damage caused by mastitis, and will have real-world implications for improving the production of high-quality milk by our national herd of dairy cows.

Collaborators:

  • Dr. David Kerr, Department of Animal and Veterinary Sciences, University of Vermont, Burlington, VT, USA
  • Drs. Hongyun Liu and Jianxin liu, Institute of Dairy Science, Zhejiang University, Hangzhou, China

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Schematic diagram summarizing the potential antioxidation mechanisms of resveratrol in mammary epithelial cells

 

 

 

 

Schematic diagram summarizing the potential antioxidation mechanisms of resveratrol in mammary epithelial cells: Resveratrol reduces ROS production and induced expressions of several antioxidant-stress response genes (HO-1, Txnrd-1 and xCT) at Nrf2 dependent manner.Adapted from Jin et al. Oxidative Medicine and Cellular Longevity, Volume 2016, Article ID 2572175.

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Glucose uptake and metabolism in the mammary gland

Glucose is the major precursor of lactose, which is synthesized in Golgi vesicles of mammary secretory alveolar epithelial cells (MECs) during lactation. Glucose is also utilized as an energy source and a substrate for lipid and protein synthesis in MECs (see the figure on the right). Glucose is taken up by MECs through facilitative glucose transporters (GLUTs). The increased GLUT expression during lactogenesis is not stimulated by the accepted lactogenic hormones. New evidence indicates that a possible low oxygen tension resulting from increased metabolic rate and oxygen consumption may play a major role in stimulating glucose uptake and GLUT1 expression in MECs during lactogenesis.Our aim is to investigate the mechanisms of regulation of glucose uptake and utilization in MECs during physiological and pathological conditions. Because lactose synthesis dictates milk volume, regulation of glucose uptake and metabolism represents potentially fruitful areas for further research in dairy production. In addition, this research will have pathological implications for the treatment of breast cancer because glucose uptake and GLUT expression are up-regulated in breast cancer cells to accommodate the increased glucose need.

Collaborators:

  • Dr. Dwight Matthews, Department of Chemsitry, University of Vermont
  • Drs. Hongyun Liu and Jianxin liu, Institute of Dairy Science, Zhejiang University, Hangzhou, China

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Main pathways of glucose utilization in mammary alveolar epithelial cells.

 

 

 

Main pathways of glucose utilization in mammary alveolar epithelial cells. In mammary epithelial cells, glucose is mainly used in 1) lactose synthesis in the Golgi, 2) energy production via glycolysis and the tricarboxylic acid cycle (TCA), 3) NADPH production via the pentose phosphate shunt, and 4-6) providing substrates for lipid (glycerol and fatty acid, 4), protein (nonessential amino acid, 5) and nucleic acid (ribose, 6) syntheses. Adapted from Zhao F-Q, (2014) J Mammary Gland Biol Neoplasia 19:3¨C17

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Oct factors in breast cancer and regulation of milk gene expression

The octamer-binding transcription factors (Octs) were originally defined by their ability to bind to an 8-bp consensus DNA sequence [ATT(T/A)GCAT]. The expression of Oct-1 and -2 and their binding to the octamer motif in the mammary gland are developmentally and hormonally regulated, consistent with the expression of milk proteins. Both of these transcription factors constitutively bind to the proximal promoter of the milk protein gene beta-casein and might be involved in the inhibition or activation of promoter activity via interactions with other transcription factors or cofactors at different developmental stages. In particular, the lactogenic hormone prolactin and glucocorticoids induce Oct-1 and Oct-2 binding and interaction with both STAT5 and the glucocorticoid receptor on the beta-casein promoter to activate beta-casein expression (see the figure on the left). In addition, increasing evidence has shown the involvement of another Oct factor, Oct-3/4, in mammary tumorigenesis, making Oct-3/4 an emerging prognostic marker of breast cancer and a molecular target for the gene-directed therapeutic intervention, prevention and treatment of breast cancer.

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A working model illustrating the hormonal regulation of beta-casein gene transcription in mammary epithelial cells

 

 

 

A working model illustrating the hormonal regulation of beta-casein gene transcription in mammary epithelial cells. This model is modified from a model previously proposed by Rijnkels¡¯ et al. (2012). Adapted from Qian and Zhao, BBA 1859 (2016) 812¨C819

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Dr. Zhao holding a panda in a zoo

CV (PDF)

Join The Zhao Lab

Interested in being a graduate student in The Zhao Lab?

If you find your research interests align with our research goals, send Dr. Zhao an e-mail including:

  • A statement of your interests (including why you feel my lab is a good fit for you)
  • Your curriculum vitae (CV) or resume
  • Any pertinent scores such as your GPA, GRE and TOEFFL scores

Instructions outlining how to apply to the University of Vermont graduate program are on the UVM Graduate College website: UVM Graduate College or visit Application Instrictions

Educatoin

  • Post-Doctor Fellow, NIDDK, NIH, Bethesda, MD
  • Ph.D., University of Alberta, Alberta, Canada
  • M.S., Nanjing Agricultural University, Nanjing, China
  • B.S., Anhui Agricultural University, Hefei, Anhui Province, China

Professional Positions

Positions and employment:

  • 01 - Present: Assistant Professor; Associate Professor; and Professor, Deparment of Animal & Veterinary Sciences, University of Vermont, Burlington, VT
  • 98 - 01: Research Biologist, American Registry of Pathology, Armed Forces Institute of Pathology, DC

Professional Memberships

Work Address

211 Terrill, 570 Main St.
Burlington, VT 05405-0148
Tel: (802) 656-0786
Fax: (802) 656-8196
fzhao@uvm.edu