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Tzung Fu Hsieh

Professor - Systems Biologist, Epigenetics

Plants for Human Health Institute


Dr. Tzung-Fu Hsieh joined the institute in August 2012 and coordinates a research program centered on the biological systems of flowering plants, including fruits and vegetables. Hsieh specializes in systems biology, a relatively new field of research that studies the interactions between the components of biological systems, and how those relationships impact the functions and behaviors of the systems. His area of focus is epigenetics, which aims to understand changes in gene behaviors that are caused by factors other than mutations in DNA.

Hsieh studies the development of endosperms, which play a critical role in human nutrition and health, accounting for more than 75 percent of the world’s food supply, according to the Food and Agriculture Organization of the United Nations (FAO). Cereal crops like corn, rice and wheat – some of the most widely produced crops in the world – are harvested for their grains, which are mostly endosperm. Hsieh is working to better understand endosperm development, including the role imprinted genes play.

Using systems biology approaches, Hsieh and colleagues have already identified certain epigenetics processes as critical regulators for plant reproduction and endosperm development. His studies will provide new opportunities for investigating how the environment can exert influences on plants through epigenetic changes. Ultimately, Hsieh would like to collaborate with N.C. Research Campus partners using the techniques he and colleagues have developed to decipher how plant epigenetics may impact human health. He also researches how epigenetics regulates the production of plant secondary metabolites.

Watch a video introduction of Dr. Hsieh and his research.

Lab Personnel:

Changqing Zhang, Senior Researcher

Mingzhuo Li, Postdoctoral Associate

Qirui (Cary) Cui, Graduate Student

View Publications on Google Scholar


Ph.D. Texas A and M University

B.S. National Tsing-Hua University, Taiwan

Area(s) of Expertise

Systems Biology, Epigenetics, Endosperm Development


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Date: 07/01/23 - 6/30/27
Amount: $650,000.00
Funding Agencies: USDA - National Institute of Food and Agriculture (NIFA)

The overall goal of this project is to develop effective management practices to minimize the biological risks associated with the newly developed genetically engineered (GE) tomato. Tomato is a predominantly self-fertilizing crop and also a facultative outcrossing species with a substantial pollen-mediated gene flow (PMGF) rate in the field. The adoption of genetic engineering significantly contributed to crop improvement. The inclusion of GE tomato into the agricultural landscape carries high risks related to the introduction of transgenes into related agricultural and wild relatives. Thus, effective biological containment technologies are needed to prevent PMGF from GE to non-GE tomato. We proposed to engineer tomato to produce CRISPR pollen which will degrade endosperm development in the non-GE plants but not the GE plants which will express a mutated endosperm lethality gene. It is expected that the engineered CRISPR pollen will not interfere with seed production in tomato. By doing this, the newly-developed GE tomato could be used as the background source for genetic engineering of any traits for sustainability. Our goals are intimately tied with the management practices to minimize environmental risks of the newly developed GE tomato, and fits squarely into the BRAG objectives. We expect our results will help develop regulatory and best management practices for future GE tomato plantings. We also expect we will develop an efficient biological containment strategy that is applicable to other GE crops currently or soon-to-be incorporated into non-GE agricultural settings.

Date: 07/01/22 - 6/30/24
Amount: $80,177.00
Funding Agencies: National Institutes of Health (NIH)

Epigenetic modifications play critical roles in gene regulation, development, and diseases. Understanding how epigenetic changes between species occur and how they affect gene regulation has potential to advance our knowledge of regulatory evolution. However, the details of epigenetic evolution are sparse, and how epigenetic evolution correlates with phenotype evolution is poorly understood. The proposed research will test a novel hypothesis that DNA methylation of distinctive cell types in human and non-human primate brains shows variation consistent with brain size evolution. Moreover, validation studies will be performed for specific candidate genes and genomic regions that show DNA methylation and gene expression difference related to brain region differences and species differences. This study will generate novel data to expand our understanding of epigenetic evolution of brains, and to infer functionally important positions of noncoding genomic regions. Furthermore, it will also provide knowledge on how epigenome changes during evolution and how epigenome evolution correlates with phenotype, which is a fundamental yet currently little understood topic.

Date: 08/01/17 - 7/31/22
Amount: $557,461.00
Funding Agencies: National Science Foundation (NSF)

DNA methylation is critical for processes including genomic imprinting, X-inactivation, transposonsilencing, and genome stability. Maintaining DNA methylation patterns is a result of active DNAmethylation and demethylation processes. Compared to pathways that promote and maintain DNAmethylation, much less is known about the function and regulation of DNA demethylation. In plants,genomic imprinting is established in the gametes by DEMETER (DME) mediated active DNAdemethylation, which is required for seed viability in Arabidopsis. The DME-like 5-methylcytosine(5mC) DNA glycosylases are active DNA demethylases that mediate the remove of 5-mC via baseexcision repair pathway. DME encodes a large polypeptide with multiple conserved domains, and exceptfor the well-characterized glycosylase domain, almost nothing is known about the functions of thesedomains. The proposed research focuses on understanding the function and regulation of the conserveddomains of DME. A novel bipartite model for structural and functional regulation for DME activity isproposed. Understanding how DME evolved to contain modular catalytic and regulatory domains, andelucidating how linker histone H1 assists DME active demethylation will significantly increase ourunderstanding of the active DNA demethylation pathway that has been adopted for reproductive successin plants. The knowledge learned in this application will provide vital information on how epigeneticinformation is established and maintained.

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