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As Pan-Asian Proteomics Powerhouse Emerges, Focus is on Liver Cancer, SARS


It may be many time zones away from the headquarters of the big European and American companies, but Asia has become an emerging powerhouse in proteomics, with plenty of money to make and earn.

Asian proteomics scientists have formed their own club — Asia-Oceania Human Proteome Organization; their own interest groups, particularly for the study of liver disease and of SARS; and their own international collaborations. And as big instrument companies like Waters have recently been discovering , the Asian market for proteomics equipment is set to explode (see PM 7-25-03).

This past weekend, representatives from the eight member nations of AOHUPO held a teleconference to plan the group’s next meeting, which was postponed from its original September date due to SARS. Also, On Aug. 28, representatives from many countries in the region will meet in the North Asia Proteomics Conference, in Seoul, South Korea.

ProteoMonitor talked this week with some of the big players from five major Asian proteomics centers about their work and about the peculiarities of Asian proteomics.

Yonsei Proteome Research Center, Seoul, South Korea

Researchers at the Yonsei Proteome Research Center, led by Young-Ki Paik, president of the regional KHUPO and secretary-general of HUPO, are conducting five major proteomics projects: proteome profile changes in cholesterol metabolism; proteome analysis of hepatocellular cancer (part of HUPO’s liver proteome project); proteome expression comparison of lung cancer tumors; the construction of a database for the liver cancer proteome; and, most recently, the initiation of the Korean Human Plasma Proteome Project (part of HUPO’s HPPP).

At the moment, Paik is most excited about the KHPPP, for which his center just received an eight-year grant of $2.1 million per year from the Korean government. The project, which will receive guidance, protocols, and coordination from HUPO HPPP, began in July and represents a major breakthrough for proteomics funding in Korea, according to Paik. “This is the first time ever that the Korean government has put money on a global project like HPPP. The government usually puts money on something short term, like the development of drug targets, not on the construction of a reference map like this. This is a very meaningful start,” Paik said. The government is also currently funding “another wing” of proteomics projects focusing on drug development, to the tune of $4 million a year. In general, the Korean government is becoming more and more supportive of proteomics research, mostly as a way to balance out its already considerable generosity with genomics funding, according to Paik.

Like just about every other proteomics center in Asia, Paik’s research also focuses on liver disease — the second major cause of cancer death in Korea, and a huge problem throughout Asia, where hepatitis B and C still run rampant. “Liver disease is an awfully important disease among Asians, so we are trying to focus on those type of diseases together and cooperate in some additional organizations and collaborations,” Paik said.

Paik also is no stranger to the world of industrial collaborations. In addition to a partnership with a Korean private company that he did not name but said was providing his lab with $1 million over five years, Paik’s group also is managing a plethora of international industrial collaborations. Paik manages Korea’s Expasy mirror site for Swiss-Prot, and has worked extensively with GeneBio, creator of Melanie software (see PM 7-25-03). Paik claims to be the first person to train people to use Melanie 4.0, which was released in February as a beta product and will now be incorporated into Amersham’s 2D imaging software. He also said he is working with Nonlinear Dynamics to build up “a Progenesis type of database system.” In terms of instrument companies, Paik has built collaborations with Applied Biosystems and Agilent Technologies, and the latter will use Paik’s lab as a reference laboratory for its latest nano-ESI and tandem MS/MS products. Paik also has collaborations with Osaka University and Yamaguchi University in Japan.

Most of these collaborations pay off in the form of additional funds for YPRC. Still, “funding is never, never enough,” Paik said.

Paik will be the keynote speaker at the August conference in Seoul.

Yamaguchi University School of Medicine, Yamaguchi, Japan

Kazuyuki Nakamura, a founding member of HUPO, also founded JHUPO — the Japanese chapter of HUPO — with his colleague Akira Tsugita just last December. But he has been “working for the promotion of proteomics in Japan” for many years under the auspices of the Japanese Society of Biochemistry and the Japanese Electrophoresis Society. Nakamura’s main interests are his participation in the HLPP and HPPP, with an emphasis on using classic 2D gel and MALDI-TOF MS techniques to look for protein biomarkers for hepatocellular cancer, which kills 32,000 Japanese a year out of the 2 million currently living with hepatitis C in the country, Nakamura said.

Nakamura is also in the process of developing what he calls “chip electrophoresis,” in collaboration with Yoshinobu Baba at the University of Tokushima. This is a variation on capillary electrophoresis in which a nanoliter of protein sample is put in a narrow hollow from which the protein moves by electro-osmosis. Nakamura’s work, describing a 15-second separation of proteins by this method, was recently described in the August issue of Analytical Chemistry. The next step, he said, will be a direct integration of the method with mass spec, a project he is pursuing in collaboration with Agilent.

Like their Korean counterparts, Japanese proteomics scientists receive much of their funding from the government.” Nakamura said he gets about ¥10 million ($83,000) per year from government agencies. He also gets infrastructure support from Agilent and Shimadzu in collaborations that allow him to use the companies’ hybrid mass specs, such as Shimadzu’s Axima QIT hybrid Q-TOF ion trap developed with ABI.

Nakamura, along with Baba, is pursuing a possible partnership with Roche Diagnostics to develop a new machine for high-throughput protein expression of cDNA and protein crystallography. This project would serve as part of a larger venture called Protein 3000, which has been funded by the Japanese government for the past five years and has as its goal the analysis of the structure and function of 3,000 proteins. The government has already put 1 billion yen toward the project.

Nakamura also works closely with researchers at the Riken Institute in Saitama and Metropolitan University in Tokyo. He counts Paik as one of his “best friends,” and hopes that “in the near future we will share people for education and training for scientists in Asia to establish a big international collaboration group.”

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

Shui-Ten Chen is an AOHUPO council member, a founding member of THUPO (the Taiwan chapter of HUPO, established in March 2002) and a co-chair, with THUPO chairman and IBC colleague Andrew Wang, of the annual AOHUPO conference. Like those of his counterparts in Korea and Japan, one of Chen’s many current proteomics projects concerns the discovery of biomarkers in blood and urine for hepatocellular cancer. He also looks for biomarkers for breast and lung cancer. His biomarker determination method — which involves using multi-dimensional electrophoresis and SELDI-TOF to construct fingerprints indicative of cancer — is similar to that used in the early ovarian cancer biomarker studies conducted by Emanuel Petricoin and Lance Liotta at the US FDA and NCI (see PM 7-18-03, 2-18-02). However, Chen said he has been independently using these methods for at least a year and a half. The biomarker research is being conducted in collaboration with Max Chung of the National University of Singapore (see below) and will contribute to HLPP.

Chen is also working on developing nanotechnologies for immobilizing proteins on an array in such a way that the proteins do not decompose during storage. Chen said the proteins could be kept stable for up to six months using this method, although he wouldn’t explain how the method worked because the chip is still in the development phase.

Like many Taiwanese scientists, Chen recently added SARS to his list of interests. After receiving SARS coronavirus cDNA from the Taiwan Center for Disease Control, Chen cloned a SARS protease and spike protein, expressed them, and sent the proteins to a Taiwanese friend, Huang Jin Ming, at the University of Ala-bama Birmingham. Huang, an immunologist, is attempting to develop a SARS vaccine from the proteins.

The Taiwanese government far overtakes Korea and Japan with its generous support for proteomics research. Various agencies within the Taiwanese government put NT$20 billion ($600 million) toward “functional genomics” research and industrial development in 2002, of which about one third went to proteomics research, Chen said. That number is expected to increase by 5 to 6 percent each year. Chen, who receives a total of about $800,000 per year in funidng from various sources, with about 30 percent coming from the government funds, with the remainder coming mostly from Taiwanese biotech companies. He has also collaborated in the past on drug development with the Australian company Biotech Analytica.

Although Taiwanese researchers have historically cooperated closely with mainland China, in recent years that has changed. “Taiwan wants more independence and collaboration with other foreign countries now,” Chen said. “They don’t want too much of a relationship with mainland China, because of politics.”

National University of Singapore, Singapore

Max Chung, the Singapore representative for AOHUPO, runs the National University of Singapore’s Structural Biology and Proteomics Initiative, Singapore’s central proteomics resource center, along with Choy Leong Hew. But his reputation extends beyond the small island. It seems that everyone in Asia who knows proteomics is friends with Chung, who is better known as “Maxey.” “We all knew each other when we were in Australia together,” Chung explained.

Due mostly to the high cost of proteomics instrumentation, Singapore has consolidated much of its proteomics resources to a single site at NUS, where a variety of instruments — including tandem MS/MS, MALDI TOF, Q-TOF, and SELDI—are available to the community. “It’s a service to other universities and to small investigators who need MS or sequencing, and we can do it for a fee,” Chung said. In addition to being economical, having all the scientists who work with proteins in one place is also convenient, said Chung. “We can take you from target identification down to expression and functional studies and structural analysis — the whole pipeline process — right here,” Chung said.

Chung focuses most of his own energies on finding biomarkers for liver cancer using traditional 2D gels with Amersham’s CyDye technology and MS. He collaborates on this work with Chen, Paik, and several others throughout Asia. His partner, Hew, also looks at colorectal biomarkers, and the two recently received a new grant from the Singapore Cancer Syndicate for $SG300,000 per year ($171,000), to support their biomarker research.

At the moment, all of Chung’s funding comes from the Singapore government, although he hopes that industrial collaborations may take off in the next couple of years. In the meantime, Chung is mining his Asian colleagues for ideas and new technologies. “Different countries have different levels of expertise, and I think that’s what we need to discuss — we should see who has the best technology, for example, and then we can maybe send somebody to learn there rather than start from scratch,” Chung said.

Chung is convinced that the future of proteomics in Asia is limitless, but that much depends on the next generation. “Since we started five years ago, a lot of other countries, like Malaysia, have started projects too. But we need to train a new generation now and get them interested,” he said. “Then there will really be a big push toward proteomics in Singapore.”

Research Center for Proteome Analysis, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China

Qi-Chang Xia, a council member of HUPO and AOHUPO, was a founding member of China’s first proteomics center in the late 1990s. Since then, his group at Shanghai’s RCPA has been working on three major projects: finding liver cancer biomarkers and protein-protein linkages in work for the China branch of HLPP; searching for drugs and biomarkers for microbes, including SARS and leptospira interrogans — a bacterial infection that can cause meningitis; and the development of a central Chinese proteomics service center for “overall support for R&D related to proteomics in China,” Xia’s colleague Rong Zeng told ProteoMonitor in an e-mail.

China aims at being a “main player in the liver proteome project,” Zeng said in the e-mail interview. The RCPA is on its way to making this happen — Xia’s group has already confirmed several liver cancer biomarkers in clinical trials, and is currently applying for patents. It also has made “some significant progress in SARS proteomics.”

Like her colleagues in other Asian centers, Zeng would categorize the Chinese government as supportive of proteomics. The government currently funds various proteomics research to the tune of about $20 million over the past five years, Zeng said. She expects that number to increase “dramatically” over the next several years.

Zeng did not point to any international collaborations for Xia at the moment — beyond the informal ones with Chung and others—but said the group does work closely with fellow HUPO council member Fu-Chu He of the Beijing Raidation Institute and numerous other mainland Chinese researchers.


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