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Independent Labs Reach Same Conclusion Regarding the Role of Skp2
Posted March 13, 2009
This week, two papers were published in the March 8 Advance On-line issue of the scientific journal Nature Cell Biology. The senior authors of both papers are BIDMC scientists. Both are researchers in BIDMC’s Cancer Center, working to develop new cancer drugs. Their laboratories are located one floor apart in the Center for Life Sciences (CLS) building.
But the coincidences don’t end there. It turns out that two and a half years ago, Pier Paolo Pandolfi, MD, PhD, and Wenyi Wei, PhD, discovered by sheer chance that they were investigating the very same novel mechanism responsible for the overexpression of the Skp2 gene in many types of cancer.
You might say that great minds think alike.
“It was quite a twist of fate that these two papers were published in the same journal on the exact same day,” says Pandolfi, who is now Director of Research in BIDMC’s Cancer Center. “Wenyi and I arrived at our hypotheses completely independent of one another – in separate labs at separate institutions in different cities. Furthermore, our work was challenging much of the accepted thinking [in this area of cancer cell biology] governing how the AKT oncoprotein regulates the activity and function of the Skp2 E3 ubiquitin ligase protein.”
In the sometimes fiercely competitive world of biomedicine, the dual publication of these papers is also the outcome of true scientific “sportsmanship.”
It all started in July 2006, when Pandolfi and Wei were seated next to one another at a dinner in Boston. A member of the faculty at Memorial Sloan-Kettering Cancer Institute in New York City at the time, Pandolfi asked Wei what he was working on. The young investigator, who had just been recruited to join BIDMC’s Department of Pathology, began to describe his research interests and his cancer genetics experiments, including his discovery of a process by which phosphorylation of Skp2 by AKT disrupts the ability of another set of genes – Apc/Cdh1 – to degrade Skp2 – and might contribute to overexpression of the Skp2 gene in cancers.
“Stop right there,” Pandolfi remembers telling Wei. “Don’t tell me anymore.”
It was neither lack of interest nor bad manners that led to Pandolfi’s putting an end to the conversation. Rather, it was scientific courtesy. For, as it turned out, in a surprising coincidence, Pandolfi’s laboratory had spent the previous two years investigating a very similar hypothesis, and had already written their results and submitted their paper to the journal Nature.
“I was very excited to know that another independent lab had drawn a similar conclusion, especially when it was one of the best labs in the world,” says Wei. “I also understood how important this project was to me, as it was an extension of a paper I’d published in Nature in 2004. But because the Pandolfi lab was so far ahead of the game, I didn’t think I should continue to work on this project. As a starting junior faculty member, my lab wasn’t in a position to compete, even though we had accumulated substantial experimental evidence.”
But, as it turned out, the story didn’t end there.
“Many months later, Dr. Pandolfi sent me an e-mail, informing me that their Nature paper had been delayed, and asking whether we would like to finish our investigation,” remembers Wei. “Because our two labs were trying to answer the same question from two distinct points of view, Dr. Pandolfi thought that we could complement and strengthen one another’s work.”
And, so their experiments continued. Both labs independently submitted their papers to the journal Nature Cell Biology, and went through the journal’s rigorous review and editing process. And both learned last week that each of the papers would be published on-line March 8.
As a leading expert among cancer researchers studying the PTEN/AKT genes, Pandolfi’s research has led to major breakthroughs in understanding how mutations in oncogenes and tumor suppressor genes result in leukemias, lymphomas and solid tumors.
“It is a great honor for me to work with Dr. Panolfi,” says Wei, who is a recent recipient of young investigator grants from the Kimmel Foundation and the V Foundation, both leading supporters of groundbreaking cancer research. “As a starting junior faculty member, I benefit a lot from this complementary partnership. Dr. Pandolfi has been extremely generous in helping me to apply for NIH grants and in furthering my lab’s advances.”
Moving forward, Pandolfi and Wei plan to formally collaborate on future investigations. “This is proving to be an extremely worthwhile avenue to follow in the pursuit of cancer therapies, and the fact that Wenyi and I have our labs just a staircase apart from one another will greatly benefit our progress,” says Pandolfi.
“Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APC-Cdh1-mediated Skp2 destruction,” by Daming Gao, Hiroyuki Inuzuka, Alan Tseng, Rebecca Chin, Alex Toker and Wenyi Wei, all of BIDMC’s Department of Pathology.
“Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB” by Hui-Kuan Lin, Guocan Wang, Zhenbang Chen, Julie Teruya-Feldstein, Yan Liu, Chia-Hsin Chan, Wei-Lei Yang, Hediye Erdjument-Bromage, Keiichi Nakayama, Stephen Nimer, Paul Tempst and Pier Paolo Pandolfi. (Wang and Chen of BIDMC’s Cancer Center, Departments of Medicine and Pathology.)
Click here to learn more about work in the Pandolfi laboratory.
Click here to learn more about work in the Wei laboratory.
