University of Virginia’s Hui Li and Stand Up to Cancer

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Hui Li, PhD, Assistant Professor of Pathology, University of Virginia Cancer Center. Photo: SU2C.

If you’re looking for a postdoctoral fellowship in cancer – or even a sabbatical – check out the latest list of Stand Up to Cancer (SU2C) Innovative Research Grant (IRG) awardees. At last month’s annual meeting of the American Association for Cancer Research, I attended a reception where I was able to meet many of these newly-bestowed grantees.

The scientist I was most fortunate to speak with at length was Dr. Hui Li from the University of Virginia (lab web site). Dr. Li’s fascinating work on “trans-splicing” of RNAs in cancers that create novel chimeric proteins stands to not only help us understand an underappreciated process in cancer development but also reveal new targets for cancer therapy.

For example, the best known example of a cancer-causing DNA rearrangement (or translocation) event is the “Philadelphia chromosome.” This translocation leads to the production of the oncogenic Bcr-Abl fusion protein in chronic myelogenous leukemia (and also occurs in some erythroleukemias). Targeting the kinase activity of this protein has led to the relatively new therapeutic, Gleevec/Glivec (imatinib), which was then later discovered to inhibit another kinase, c-kit, in gastrointestinal stromal tumors.

ResearchBlogging.orgFittingly, the cytogeneticist who first identified the Philadelphia chromosome, Dr. Janet Rowley, co-authored the commentary on Dr. Li’s 2008 Science paper that first described a hormone- and hypoxia-regulated oncogenic RNA splicing product in endometrial cancer. This work, begun during his postdoctoral fellowship and research scientist years with Dr. Jeffrey Sklar at Yale University, was further shown in this 2009 paper in Cell Cycle to be selective to endometrial cancer relative to hyperplastic nodules.

Fusion RNAs. Either chromosome translocation or RNA trans-splicing can give rise to fusion mRNAs and proteins. Some chromosomal translocations produce two hybrid genes that may produce mRNAs containing the 5′ end of one gene and the 3′ end of the other. Both may encode fusion proteins. Alternatively, normal mRNAs corresponding to both genes can recombine by trans-splicing that may produce equivalent fusion mRNAs and proteins. Only one of the possible fusion mRNAs and proteins is examined by Li et al. CREDIT: ADAPTED BY P. HUEY/SCIENCE

Dr. Li was one of 13 early-career investigators to receive three-year, $250,000/year grants to study a research area that might be deemed too risky to be funded by “traditional mechanisms.” Much of the awards reception made murky reference to these “traditional” sources but I found it ironic that the IRG acronym for these innovative awards is the same one used by NIH for Initial Review Groups, or study sections.

Some background is in order: Stand Up to Cancer is a cancer charity that seemingly came out of nowhere to raise $80 million in a Fall 2008 telethon. The advocacy and research support group was co-founded by a team of highly-accomplished women – nary a man to be seen on the founders page – each of whom has been touched by cancer (such as the well-known example of Katie Couric) to harness the reach of the entertainment community to catalyze progress against cancers that strike across society. Their brief mission statement is:

Stand Up To Cancer is a new initiative created to accelerate groundbreaking cancer research that will get new therapies to patients quickly and save lives. SU2C’s goal is to bring together the best and the brightest in the cancer community, encouraging collaboration instead of competition. By galvanizing the entertainment industry, SU2C creates awareness and builds broad public support for this effort.

Dr. Jerome Groopman provides perhaps the best description of the SU2C approach to cancer funding, citing angiogenesis pioneer, Dr. Judah Folkman, as the initial driver for this effort, one that encourages that support of high-risk research with potentially high rewards. Groopman, originally a skeptic of this new effort, noted that the SU2C founders chose to avoid creating “a large and self-perpetuating bureaucracy” but still guided by a world-class team of scientific advisors.

Like smart investors, the organizers of SU2C recognize uncertainty and eschew arrogance, crafting a balanced portfolio rather than placing all the assets on one project or approach. There are safeguards against conflict of interest, so that scientists do not “feed themselves” or their friends. Collaboration and communication underlie each “Dream Team.” The predominant culture of failing to share data among researchers will not be tolerated.

Their original round of grants went to so-called “Dream Teams” of scientists that are engaged in collaborative, translational science across institutions to “work collaboratively, rather than competitively, to develop new treatments quickly in order to save lives now.” Five Dream Teams were funded to study the PI3K pathway in women’s cancer, cancer cell metabolism in pancreatic cancer, the epigenetics of cancer, circulating tumor cells, and strategies to overcome anticancer drug resistance in breast cancers. A total of $73.6 million was awarded to the five teams for the execution of three-year projects.

But where did this leave junior investigators? Certainly some early-career researchers are supported in the Dream Teams. But for independent, high-risk, high-reward projects, SU2C set aside about $9 million each for two rounds (2009, 2011) of early-career awards like those Dr. Li received. SU2C partnered with the AACR to solicit and review these grants with the multidisciplinary SU2C Scientific Advisory Committee. (AACR then administers the grants as described at the SU2C site.)

I like the review process as it was described to me by Dr. Li: after an initial round of review, a couple dozen finalists were flown to Philadelphia where they were given 10 minutes to present their ideas to the advisory panel followed by questions. Nerve-wracking, indeed, but anything that wasn’t clear in the application could be corrected right then and there.

Each finalist was then asked to record an interview about their projects and motivations for the study of cancer. I’m not sure if this aspect was part of the review process, but I expect that an ability to be a good ambassador for the program would be consistent with an organization aligned with the Entertainment Industry Foundation (although an editor for a major scientific journal remarked to me that the camera work was pretty wobbily for a professional production – see Dr. Li’s video or the following “Meet the IRG Recipients video – I suspect that was done on purpose, a derivation of the “‘utterly bankrupt’ shaky cam” technique.).

I chose only to feature one scientist here, primarily because I was so fascinated by Dr. Li’s work that I didn’t get around much more to hob-nob with the other 12 recipients (although I must give a shout-out to UNC-Chapel Hill recipient, Dr. Angelique W. Whitehurst, who I figured I could catch up with at home.) But Dr. Li did mention one thing to me that is very important and very unusual: he is at the point where funding is not an issue but the recruitment of personnel is. Therefore, if you are scientist interested in working in Dr. Li’s laboratory at the University of Virginia, do yourself a favor and contact him.

The Hui Li Laboratory Website

Hui Li Main Department of Pathology Listing

Hui Li Laboratory Clinical Research Opportunities

Disclosure: Food and an open-bar were offered at the Stand Up To Cancer press conference and awards ceremony that I attended on April 4, 2011, at the Annual Meeting of the American Association for Cancer Research in Orlando FL

References:

Li, H., Wang, J., Mor, G., & Sklar, J. (2008). A Neoplastic Gene Fusion Mimics Trans-Splicing of RNAs in Normal Human Cells Science, 321 (5894), 1357-1361 DOI: 10.1126/science.1156725

Li H, Wang J, Ma X, & Sklar J (2009). Gene fusions and RNA trans-splicing in normal and neoplastic human cells. Cell Cycle, 8 (2), 218-22 PMID: 19158498

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