Lipid Technology

We are interested in developing new technologies (including novel techniques, methodologies, models, or devices) that can be used to enhance lipid research and improve human nutrition as well as diagnosis, prevention and treatment of human diseases. Over the past few years, we have made several breakthroughs in technology development. Our current projects, in collaboration with researchers in different disciplines, aim to create revolutionary technologies or products for research and clinical practice.


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fat-1 transgenic technology

As the health benefits of long chain omega-3 fatty acids, found mainly in fish oils, have been well recognized, the demand for these fatty acids has been growing in recent years. A great effort has been made in food industry to incorporate omega-3 fatty acids into the food supply, especially meat products, which normally contain little omega-3 fatty acids but large amounts of omega-6 fatty acids. Because the essential omega-3 fatty acids cannot be de novo synthesized nor be derived from other fatty acids in mammals and other food animals, they must be obtained from the diet. Thus, the only possible way so far to enrich animal tissues with omega-3 fatty acids has been dietary supplementation (i.e. feeding animals with omega-3 fats derived from flax seed, fishmeal or other marine products), which is unsustainable because not only is it costly and time consuming, but the source of marine products is also limited and contaminated.

To solve these problems, we have invented a sustainable way to provide land-based dietary sources of omega-3 fatty acids by genetically modifying animals to produce their own omega-3 fatty acids without the need of dietary supplementation. Our strategy is to convert omega-6 to omega-3 fatty acids by introducing a double bond into the omga-6 hydrocarbon chain using a gene (namely  fat-1 ) encoding an omega-3 fatty acid desaturse from the roundworm C. elegans. We proved this concept in cultured cells (by adenovirus-mediated gene transfer) in 2001 (PNAS 2001;98:4050) and successfully generated the world’s first “omega-3-producing” mammal (mouse) (by the method of microinjection) in 2004 (Nature 2004;427:504) as well as the first omega-3 livestock (pig) (by nuclear transfer cloning) in 2006 (Nature Biotechnology 2006;24:435).  This discovery has changed reality--- the transgenic animals are now capable of producing omega-3 from omega-6 fatty acids and have high levels of omega-3 fats in all of their organs and tissues, with no need of dietary supplementation.

This technology offers a new strategy for producing omega-3 fatty acid-rich animal food products (e.g. meat, milk and eggs). This would allow people to continue to eat the foods they enjoy and still obtain the beneficial omega-3 fatty acids they need for their health without stringent dietary changes. The dependence on the limited supply and costly consumption of fish would become unnecessary. Thus, this discovery may have a great impact on both agriculture and human nutrition.

We are currently collaborating with other scientists to generate "omega-3-producing" cows, chickens, and fish. We are also interested in developing other nutrients-enhanced foods. Our long-term goal is to create healthy food (especially animal food products with optimal lipid composition), through genetic engineering.


Selected Publications:

  1. Kang ZB, Ge Y, Chen ZH, Brown J, Laposata M, Leaf A, Kang JX. Adenoviral gene transfer of C. elegans n-3 fatty acid desaturase optimizes fatty acid composition in mammalian cells. Proc. Natl. Acad. Sci. U S A. 2001;98:4050-4054.
  2. Kang JX, Wang J, Wu L, Kang ZB.Fat-1 transgenic mice convert n-6 to n-3 fatty acids. Nature 2004; 427;504.
  3. *Lai L, *Kang JX, Witt W, Wang J, Yong HY, Hao Y, Wax DM, Li R, Evans R, Starzl TE, Prather RS, Dai Y. Cloned fat-1 transgenic pigs rich in omega-3 fatty acids. Nature Biotechnology 2006;24:435-436
    (*Contributed equally).
  4. Kang JX, Leaf A.  Why the omega-3 piggy should go to market. Nature Biotechnology 2007; 25(5):505-506.

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  Lipid Analysis

While many technologies/tools have been developed for genomics and proteomics to study cellular function, technologies for lipidomics are still underdeveloped and the advanced tools available for lipid research are very limited currently. Lipidomics presents unique challenges for sample collection and extraction and for determining molecule structure, concentration and activity. Technologies/ methods currently in use for lipidomics have significant limitations in efficiency, cost and throughput. We are interested in developing lipid-related technologies for use in both laboratory and clinical settings. We have produced a simple method for lipid extraction and methylation, which improves the conventional protocol greatly. We are currently developing a device for auto-process of lipid samples for GC analysis and a test kit for measuring n-6/n-3 ratio without the need of GC. Our work, in collaboration with experts in chemistry and engineering, arms to improve the process of sample separation and processing, and create new methods, reagents or instrumentation for identifying and measuring lipid molecules. The new technologies, if successful, will have the potential to be used as high-throughput applications and help advance the science of lipids.

Selected Publications:

  1. Kang JX, Wang J.  A simplified method for analysis of fatty acid composition.  BMC Biochemistry 2005; 6(1):5. (Highly accessed paper)
  2. Araujo P, Nguyen TT, Frøyland L, Wang J, Kang JX. Evaluation of a rapid method for the quantitative analysis of fatty acids in various matrices. J Chromatogr A. 2008;1212(1-2):106-113.

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Chemical Imaging

In collaboration with Prof. Sunney Xie of Harvard University, we are developing live cell and label-free imaging methods to allow direct visualization and quantitative analysis of cellular lipids. An area of special interest to us is the detection of polyunsaturated fatty acids, especially omega-3 fatty acids in living cells. Normally, fluorescent labels are used for tacking lipid molecules but their introduction can alter the original structure of lipid molecules and may have some side effects. The non-imaging analytical techniques such as gas chromatography and mass spectrometer are destructive and do not give sub-cellular resolution. We have recently developed a new multi-photon vibrational imaging technique using stimulated Raman scattering microscopy. With this technique, we are now able to observe distribution and interactions of cellular lipids such as omega-3 fatty acids in living cells with no destruction to cells and no need of labeling. This technology has a great potential as a new tool for lipid research. We are currently optimizing the technology and exploring its potential applications. We are also developing other imaging techniques, arming at mapping of the spatio-temporal dynamics of lipids and their interactions with other molecules in living cells.

Selected Publications:

  1. Freudiger CW, Min  W, Saar BG, Lu S, Holtom GR, He C, Tsai JC, Kang JX, Xie XS. Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy. Science 2008:322(5909):1857-1861.

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