Donna Zhang

UA Pharmacy Professor Receives 2 NIH Grants of More than $3 Million to Study Arsenic

News Date: 
July 19, 2016 :00am

(UAHS News) Donna Zhang, PhD, professor in the Department of Pharmacology and Toxicology at the University of Arizona College of Pharmacy, is the principal investigator on two new R01 grants from the National Institutes of Health that will provide more than $3 million for her research.

UA Researcher Receives More Than $3 Million in Funding for Her Research

News Date: 
June 17, 2016 :00am

University of Arizona College of Pharmacy Researchers Discover Molecular Component of Cinnamon Prevents Colorectal Cancer in Mice

News Date: 
June 9, 2015 :00am

Research conducted at the University of Arizona College of Pharmacy and the UA Cancer Center indicates that a compound derived from cinnamon is a potent inhibitor of colorectal cancer.

ROS/Oxidative Stress

Relevance to Swehsc : 

The progressive nature of colorectal cancer (CRC) and poor prognosis associated with the metastatic phase of the disease create an urgent need for the development of more efficacious strategies targeting colorectal carcinogenesis.

Cluster of Efforts: 

The progressive nature of colorectal cancer (CRC) and poor prognosis associated with the metastatic phase of the disease create an urgent need for the development of more efficacious strategies targeting colorectal carcinogenesis. Cumulative evidence suggests that the redox-sensitive transcription factor Nrf2 (nuclear factor-E2-related factor 2), a master regulator of the cellular antioxidant defence, represents a promising molecular target for CRC chemoprevention. Recently, we have identified cinnamon, the ground bark of Cinnamomum aromaticum (cassia cinnamon) and Cinnamomum verum (Ceylon cinnamon), as a rich dietary source of the Nrf2 inducer cinnamaldehyde (CA) eliciting the Nrf2-regulated antioxidant response in human epithelial colon cells, conferring cytoprotection against electrophilic and genotoxic insult. Here, we have explored the molecular mechanism underlying CA-induced Nrf2 activation in colorectal epithelial cells and have examined the chemopreventive potential of CA in a murine CRC model comparing Nrf2+/+ and Nrf2-/- mice. In HCT116 cells, CA caused a Keap1-C151-dependent increase in Nrf2 protein half-life via blockage of ubiquitination with upregulation of cytoprotective Nrf2 target genes and elevation of cellular glutathione. After optimizing colorectal Nrf2 activation and target gene expression by dietary CA-supplementation regimens, we demonstrated that CA suppresses AOM/DSS-induced inflammatory colon carcinogenesis with modulation of molecular markers of colorectal carcinogenesis. Dietary suppression of CRC using CA supplementation was achieved in Nrf2+/+ but not in Nrf2-/- mice confirming the Nrf2-dependence of CA-induced chemopreventive effects. Taken together, our data suggest feasibility of CRC suppression by dietary CA, an FDA-approved food additive derived from the third most consumed spice in the world.

Milestones: 

Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. Long M, Tao S, Rojo de la Vega M, Jiang T, Wen Q, Park SL, Zhang DD*, Wondrak GT*. 2015. Cancer Prevention Res PMID: 25712056

NRF2-Mediated Cell Stress

Relevance to Swehsc : 

Hrd1 suppresses Nrf2-mediated cellular protection durling liver cirrhosis.

Cluster of Efforts: 

Increased endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) are the salient features of end-stage liver diseases. Using liver tissues from liver cirrhosis patients, we observed up-regulation of the XBP1-Hrd1 arm of the ER stress response pathway and down-regulation of the Nrf2-mediated antioxidant response pathway. We further confirmed this negative regulation of Nrf2 by Hrd1 using Hrd1 conditional knockout mice. Down-regulation of Nrf2 was a surprising result, since the high levels of ROS should have inactivated Keap1, the primary ubiquitin ligase regulating Nrf2 levels. Here, we identified Hrd1 as a novel E3 ubiquitin ligase responsible for compromised Nrf2 response during liver cirrhosis. In cirrhotic livers, activation of the XBP1-Hrd1 arm of ER stress transcriptionally up-regulated Hrd1, resulting in enhanced Nrf2 ubiquitylation and degradation and attenuation of the Nrf2 signaling pathway. Our study reveals not only the convergence of ER and oxidative stress response pathways but also the pathological importance of this cross-talk in liver cirrhosis. Finally, we showed the therapeutic importance of targeting Hrd1, rather than Keap1, to prevent Nrf2 loss and suppress liver cirrhosis.

UA Science Internship Pairs High School Students, Research Mentors

News Date: 
June 3, 2013 :00am

Each year many SWEHSC researchers host high school students in their laboratories. Facility managers assits them process their samples and understand their data. SWEHSC members teach them about toxicology and environmental health. The program was designed by the SWEHSC Outreach Core and is conducted in collaboration with the BIO5 Instutue. Read more about this year's program

Mechanisms of UV-induced photooxidative damage and skin cancer

Relevance to Swehsc : 

The unique environment of the southwest involves extraordinarily high levels of ultraviolet light exposure, leading to degenerative conditions in skin and to skin cancer. Center investigators are studying how environmental factors and micronutrients modulate UV damage.

Cluster of Efforts: 

Investigators/Funding: Bowden (RFG3), Jacobson E (RFG3), Jacobson M (RFG3), Wondrak (RFG3), Zhang (RFG3): NCI/CA43894, NCI/CA106677, NCI/CA122484, NCI/CA27502

Milestones: 
  • Folate is a nutrient essential for the appropriate control of cellular proliferation, synthesis of new DNA, repair of damaged DNA, and maintenance of epigenetic integrity, all of which are processes critical for skin homeostasis. The Jacobson laboratory is examining the effects of simulated solar light on skin cells as a function of folate status to assess folate as a potential chemoprevention agent.
  • Sirtuin expression in the skin is disregulated in response to UV radiation, and modulated by niacin (Jacobson). Multiple niacin dependent pathways have been identified that function to enhance terminal differentiation and the development and maintenance of the skin barrier and genomic stability. Such studies may lead to the identification of new agents to prevent photoaging and skin cancer.
  • UVB light promotes survival of initiated keratinocytes, in part, by the direct activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Dr. Bowden has identified quercetin as a novel chemopreventive agent targeting UVB-induced signaling pathways in an effort to reduce the incidence of non-melanoma skin cancer.
  • A series of potent cinnamoyl-derived Michael acceptor pharmacophores, including cinnamic aldehyde and methyl-1-cinnamoyl-5-oxo-2-pyrrolidine-carboxylate have been identified as potent inducers of the Nrf2/Keap1-controlled antioxidant response in skin cells (Wondrak and Zhang).

 

Research

The SWEHSC plays an important role in stimulating collaborative interactions among researchers. This is evidenced by a significant number of new, funded research projects, as well as a notable number of planned initiatives involving collaborations. The SWEHSC promotes and enhances collaborative research within and between the members through Research Focus Groups.

The themes of the three Research Focus Groups are seen below.

Donna Zhang, Ph.D.

Donna Zhang, PhD. was a Research Assistant Professor at the University of Missouri at Columbia and was recruited to UA in August 2005. Dr. Lau serves as her faculty mentor. Additionally, Donna is mentored by Drs. Jay Gandolfi and Terrence Monks and was successful in securing extramural funding, including the NIEHS ONES award and ACS grant within two years after arriving UA.

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