Laboratory for Lipid Medicine & Technology

Overview

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Lipids (fats and oils) often have a direct effect on human health.  The modern prevalent and life-threatening illnesses, such as heart disease, cancer, Alzheimer's and diabetes, are all linked to fats or lipids contained in our diets.  The Laboratory for Lipid Medicine and Technology (LLMT), under the direction of Jing X. Kang, MD, PhD, studies lipid biology and nutrition and develops technologies and products for the prevention and treatment of fat-related diseases.

Specifically, we study the health effects of omega-3 fatty acids (fish oil fatty acids, found mainly in fish and fish oils), how they work and how genetic technologies can be used to further their benefits.  We are particularly interested in the beneficial effects of omega-3 fatty acids on cardiovascular disease, cancer, inflammatory disorders and neurodegenerative diseases.  Studies are performed at the molecular, cellular, animal and human levels.  Techniques employed are those of molecular biology, cell biology, biochemistry and biophysics,  including the methods of genetics, nutrigenomics, proteomics, lipidomics and genetically modified animal models.

Over the past few years, our laboratory has made several groundbreaking discoveries including:

• Demonstration of the anti-arrhythmic properties of polyunsaturated fatty acids and retinoic acid, as well as development of lipid formulations for the prevention and treatment of cardiac arrhythmias and sudden cardiac death
• Invention of a biotechnology that could be used to produce omega-3 fats and modify essential fatty acid composition in mammalian cells without fatty acid supplementation
• Creation of the first transgenic mammal (mouse) and livestock (pig) capable of converting omega-6 to omega-3 fatty acids
• Establishment of the fat-1 mouse model as a new tool for omega-3 fatty acid research, which eliminated the confounding factors of diet, and demonstration of the importance of omega-3 tissue content as well as the n-6/n-3 fatty acid ratio in disease prevention
• Establishment of simple methods for analysis of fatty acid composition
• Development of cutting edge technology for chemical imaging of polyunsaturated fatty acids (e.g. omega-3 fatty acids) in living cells without labeling

Our laboratory is also proud of its contribution to the training of more than 40 pre- and post-doctoral trainees from different countries during the last five years.

Group Members

Dr. Kang

Dr. Jing Xuan Kang graduated from the Guangdong Medical College in 1984, received his PhD in medical biochemistry (nutrition and metabolism) from the University of Alberta in 1993 and undertook his postdoctoral training with Dr. Alexander Leaf in the Department of Medicine at the Massachusetts General Hospital and Harvard Medical School. Dr. Kang is currently a Principal Investigator and Director of the Laboratory for Lipid Medicine and Technology at Mass General.

Dr. Kang is one of the leading scientists in the field of omega-3 research. He studies the health effects of omega-3 fatty acids, how they work and how genetic technologies can be used to further their benefits. His work has contributed substantially to the advance of science and technology in his field. His innovations and breakthroughs have been recognized internationally.

Dr. Kang’s scientific contribution during the early stage of his career in Harvard is reflected by his pioneering work in demonstrating the anti-arrhythmic effect of omega-3 fatty acids. By using cutting-edge techniques and integrated methods, Dr. Kang (together with Dr. Leaf and collaborators) conducted a coherent series of seminal studies to systematically examine the anti-arrhythmic effect of omega-3 fatty acids at different levels, including molecular biology, electrophysiology, cell biology, animal model and clinical trials. His studies were the first to demonstrate that the anti-arrhythmic action of the fatty acids results mainly from stabilization of the electrical activity of the heart cells. His studies have also resulted in two patented formulas for the prevention and treatment of cardiac arrhythmia and sudden death. Several of his publications on these subject matters are the landmark papers of the field and have been cited more than 100 times so far. His work has contributed to the establishment of the American Heart Association’s Scientific Statement on increased intake of omega-3 for cardiovascular health.

The most important scientific contribution Dr. Kang has made is the development of fat-1 biotechnology to produce omega-3 fatty acids in animals.  Normally, the essential omega-3 fatty acids cannot be de novo synthesized nor be derived from other fatty acids in mammals and many other animals as well (including those used for food, e.g. livestock), and must be obtained from the diet.  Dr. Kang was the first to tackle this problem by using a genetic strategy-engineering genetically modified animals capable of making omega-3 on their own. His idea was to introduce a gene encoding a fatty acid converting enzyme, found only in low life such as the round worm C. elegans, into mammalian cells and animals, and thus enable them to convert omega-6 fatty acids, a type of fat far too excessive in the diets and tissues of animals and humans, to the beneficial omega-3 fatty acids, which are scarce in the diet and tissues and mainly found in fish. He proved the 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, a mouse, by the method of microinjection in 2004 (Nature 2004;427:504) as well as the first omega-3 livestock, a pig, by nuclear transfer cloning in 2006 (Nature Biotechnology 2006;24:435). His discovery has changed reality. Now the transgenic animals are capable of producing omega-3 from omega-6 fatty acids and have high levels of omega-3 in all of their organs and tissues, with no need of dietary supplementation. This is a revolutionary technology and has a potential impact on agriculture, human nutrition as well as omega-3 research. A U.S. patent (# 7,238,851) has been granted for this invention.

Dr. Kang’s discovery provides a new strategy for producing omega-3 fatty acid-rich foodstuff (e.g. meat, milk and eggs) by generating large transgenic animals/livestock (e.g. cow, pig, sheep and chicken). The current practice to enrich animal foods with omega-3 fatty acids is to feed animals with exogenous n-3 fatty acids (e.g. fish meal or other marine products), which is a costly and unsustainable means, as over-fishing and seafood contamination have become serious concerns today. Dr. Kang’s transgenic technology will provide a land-based, cost-effective and sustainable source of omega-3 to meet the increasing demand for omega-3 in the future. With such an innovation, the public could get the right amount of beneficial omega-3 fish oil fatty acids from non-fish sources, without having to make stringent changes in their diets. People will instead continue eating the foods they enjoy while still receiving the health benefits of omega-3, such as a 40 percent reduction in the risk of cardiac sudden death. Because of the potential impact, his discovery has drawn extraordinary attention from both the public and the scientific community and was widely reported by almost all the major media in the world (in 2004 about his fat-1 mice and in 2006 about the omega-3 pigs). Dr. Kang’s discovery was chosen as one of Top 100 Science Stories of 2006 by Discover magazine as well as one of the Top 10 Significant Boston Research of 2006 by Nature Network.

Dr. Kang’s discovery also provides a new tool for omega-3 research, as the transgenic mice he created can serve as a model of increased tissue content of omega-3 fatty acids for studying the benefits of omega-3s in the body without changing diets. The use of the "omega-3" transgenic mice can eliminate the need of feeding animals omega-3 fatty acids-supplemented diet and thereby avoid the potential confounding effects derived from dietary supplementation. This makes it possible to evaluate the health benefits of omega-3 fatty acids and elucidate the molecular mechanism of their action in a well-controlled experimental condition. Dr. Kang has so far received more than 100 requests for his transgenic mice and for research collaboration from biomedical scientists worldwide. His lab is currently collaborating with dozens of laboratories in different countries to study the health effects of n-3 fatty acids using his transgenic mice. Many papers derived from these studies have been published and highlighted by high impact journals. Several workshops on the transgenic mouse model have also been held so far. His work with the transgenic mice was selected as one of the Most Significant Dietary Supplement Research Advances of 2006 by the National Institutes of Health and named again by Discover magazine as one of the Top 100 Science Stories of 2007. His studies using the transgenic mice have provided new knowledge, obtained for the fist time from a system without confounding factors of diet, for our understanding of the role of tissue status of omega-3 fatty acids as well as n-6/n-3 fatty acid ratio in disease prevention, and how these fatty acids work at a molecular level.

Dr. Kang is also interested in the development of innovative methods or devices for lipid analysis. Most recently, his team helped develop a cutting-edge technology for chemical imaging, which allows observing distribution and interactions of cellular lipid molecules, such as omega-3 fatty acids, in living cells with no destruction to cells and no need of labeling. In addition, a method developed by Dr. Kang’s lab to simplify the procedures of fatty acid analysis has been widely adopted by researchers in the field.

Dr. Kang’s seminal work has opened up new fields of investigation in nutritional medicine. His research has resulted in more than 100 scientific papers and books and several US patents. Much of his work was published in the top tier journals in the field of biomedical science, including Nature, Science, Nature Biotechnology, Nature Medicine, PNAS, Lancet, JCI, etc. Dr. Kang was the first to publish an original report about omega-3 in Nature. His high-impact publications have increased the public's as well as the scientific community’s awareness of omega-3. In fact, more and more scientists from other disciplines are becoming interested in omega-3 and collaborating with Dr. Kang. He has been invited to speak at more than 80 national and international conferences/seminars, including the Mass General Medical Grand Round, during the last few years. He was named one of The Best and Brightest 2007 by Esquire magazine.

Dr. Kang has also contributed significantly to education. He actively participated in teaching and training, and has mentored more than 40 pre- and post-doctoral trainees from different countries during the last five years.

Director, Laboratory for Lipid Medicine and Technology -Jing X. Kang, MD, PhD

Research Assistant - Shannon Bates

Lab Manager - Jingdong Wang

Instructor in Medicine - Karsten Weylandt

Postdoctoral Fellows - Chengwei He, Yu Zhang, Jianbo Wang, Jing Liu

Predoctoral Students - Xiying Qu, Rong Rong

Visiting Scholar - Ronghua Dia

Research Projects

We work on the forefront of omega-3 fatty acid research, developing and applying new experimental models and techniques to study the health effects of the essential fatty acids, how they work and how they can be applied to optimize human health.

• Development of nutri-biotechnology for production of healthy food by modification of food nutrient contents (e.g. fat composition) using genetic engineering
• Nutrigenetics and nutrigenomics focusing on lipid-gene interaction using animal models or human specimens combined with techniques of lipidomics and genomics/proteomics to elucidate the molecular mechanisms of omega-3 essential fatty acids
• Lipidomics identification and quantification of bioactive small lipid molecules, particularly those derived from omega-3 polyunsaturated fatty acids by using GC-MS and LC-MS/MS
• Development of new analytical methods/devices for quick assay or high-through-put analysis of fatty acids and chemical imaging of lipids in living cells
• Translational research focusing on nutritional supplementation for health promotion and complimentary therapy of certain diseases

Fat-1 Mouse Model

The fat-1 transgenic mice, generated in our lab, can do what no other mammal can: create their own endogenous omega-3 fatty acids. They carry a transgene, namely fat-1, from the round worm C. elegans, which is capable of converting omega-6 fatty acids to omega-3 fatty acids. Due to this novel capability, fat-1 mice have an increased content of omega-3 fatty acids and a balanced ratio of omega-6 to omega-3 fatty acids in all tissues and organs, independent of diet. The fat-1 mouse can be a new tool for omega-3 fatty acid research.

Research Positions

LLMT has established international programs to foster collaborations in lipid research and promote educational training by working with leading academic and medical institutions.

Research collaboration

We promote international cross-discipline collaboration to integrate the unique research resources and expertise available in different institutions/countries.

Training program for visiting scholars, postdoctoral fellows and pre-doctoral students

Foreign researchers are welcome to join our team. Positions with Mass General and/or Harvard appointment will be offered to qualified trainees to conduct research here for either a short (six months) or a long term (less than one year).

Summer internship program

Outstanding college students or senior high school students with interest and motivation in biomedical research will be accepted to work here for two to three months during the summer to learn knowledge about fats/lipids and health and some basic laboratory techniques. Opportunity of conducting a small project of interest is also offered.

Publications

Kang JX, Wang J, Wu L, Kang ZB. Fat-1 transgenic mice convert n-6 to n-3 fatty acids. Nature 2004; 427;504.

This work successfully generated the world’s first transgenic “Omega-3-producing” mammal (mouse) that is capable of converting omega-6 into omega-3 fatty acids and has high levels of omega-3 in all organs and tissues, with no need of dietary supplementation.

*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).

This study moved to generate larger transgenic animals (livestock) capable of producing omega-3 fatty acids. The fat-1 pig was the first “Omega-3-producing” livestock. This success indicates a new strategy for producing omega-3 fatty acid-rich foods (e.g. meat, milk and eggs).

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.

This study developed a novel technology that allows researchers to observe distribution and interactions of cellular lipids, such as fatty acids, in living cells with no destruction to cells and no need of labeling. This technology provides a new tool for biomedical research.

Hudert C, Weylandt KH, Wang J, Lu Y, Song H, Dignass A, Serhan CN, Kang JX. Fat-1 transgenic mice are protected from experimental colitis. Proc. Natl. Acad. Sci. USA 2006;103(30):11276-11281.

This was the first study using the fat-1 transgenic mouse model to examine the effect of increased omega-3 fatty acids levels in tissues on disease susceptibility. The results of this study not only demonstrate the usefulness of the fat-1 transgenic mouse as a new experimental model, but also indicate that the formation of resolvins and protectins is a key molecular mechanism in the anti-inflammatory effect of omega-3 fatty acids.

Xia SH, Wang J, Lu Y, Song H, Serhan CN, Kang JX. The growth of melanoma is reduced in Fat-1 transgenic mice: Impact of n-6/n-3 essential fatty acids. Proc. Natl. Acad. Sci. USA 2006; 103(33):12499-12504.

This study utilized the newly generated fat-1 transgenic mouse and their wild type littermates to look at the role of n-6/n-3 fatty acid tissue ratio in tumor formation. The results suggest that the ratio of n-6/n-3 fatty acids in tissue play an important role in the formation of lipid mediators, cancer-related gene expression and tumor growth and that omega-3 fatty acids could have an anti-cancer effect due to the reduced tumor formation in fat-1 mice.

He CW, Cui L, Wang J, Kang JX. Improved spatial learning performance of fat-mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid. Proc. Natl. Acad. Sci. U S A. 2009 June 22. [Epub ahead of print]

This study generated comprehensive evidence from both in vitro and in vivo experiments demonstrating that the level of omega-3 fatty acid DHA in the brain influences neural structure and function.

Visit PubMed for a complete list of publications.