Archive for August, 2011

Harold’s Provocative Questions (PQs)

August 25, 2011 at 9:54 am · Filed under Funding Opportunities, NIH Advice, Research News

At long last, the R01 and R21 RFAs seeking “Research Answers to NCI’s Provocative Questions” have been released. One would think Harold would be the Scientific/Research Contact, but it is Jerry Lee.

Unlike most FOAs, the PQ solicitation does not list “examples” of research topics … you will address one (and only one) PQ per application submitted:

Each application must address one and only one specific PQ, exactly as defined in this FOA. … They should NOT be construed as “examples” of specific topics. The scientific scope of each individual application must clearly and distinctly correspond to one (and only one) of the PQs listed above. Within an area defined by a given PQ, applicants may propose and pursue any topic they deem relevant as a “research answer” to that PQ. It is essential, however, that applicants visit “Provocative Question” web site (http://provocativequestions.nci.nih.gov/) for additional information for each PQ pertaining to context, background, feasibility, and expectations of needs to be accomplished for a successful solving of these problems.

Note: Applicants who fail to choose a specific PQ from this list, address more than one PQ within a single application, and/or re-write the PQ will have their applications rejected without review as non-responsive.

And without further ado, the questions are:

    PQ1. How does obesity contribute to cancer risk?

    PQ2. What environmental factors change the risk of various cancers when people move from one geographic region to another?

    PQ3. Are there ways to objectively ascertain exposure to cancer risk using modern measurement technologies?

    PQ4. Why don’t more people alter behaviors known to increase the risk of cancers?

    PQ5. Given the evidence that some drugs commonly and chronically used for other indications, such as an anti-inflammatory drug, can protect against cancer incidence and mortality, can we determine the mechanism by which any of these drugs work?

    PQ6. What are the molecular and cellular mechanisms by which patients with certain chronic diseases have increased or decreased risks for developing cancer, and can these connections be exploited to develop novel preventive or therapeutic strategies?

    PQ7. How does the life span of an organism affect the molecular mechanisms of cancer development and can we use our deepening knowledge of aging to enhance prevention or treatment of cancer?

    PQ8. Why do certain mutational events promote cancer phenotypes in some tissues and not in others?

    PQ9. As genomic sequencing methods continue to identify large numbers of novel cancer mutations, how can we identify the mutations in a given tumor that are most critical to the maintenance of its oncogenic phenotype?

    PQ10. As we improve methods to identify epigenetic changes that occur during tumor development, can we develop approaches to discriminate between “driver” and “passenger” epigenetic events?

    PQ11. How do changes in RNA processing contribute to tumor development?

    PQ12. Given the recent discovery of the link between a polyomavirus and Merkel cell cancer, what other cancers are caused by novel infectious agents and what are the mechanisms of tumor induction?

    PQ13. Can tumors be detected when they are two to three orders of magnitude smaller than those currently detected with in vivo imaging modalities?

    PQ14. Are there definable properties of a non-malignant lesion that predict the likelihood of progression to invasive or metastatic disease?

    PQ15. Why do second, independent cancers occur at higher rates in patients who have survived a primary cancer than in a cancer-naïve population?

    PQ16. How do we determine the clinical significance of finding cells from a primary tumor at another site?

    PQ17. Since current methods to assess potential cancer treatments are cumbersome, expensive, and often inaccurate, can we develop other methods to rapidly test interventions for cancer treatment or prevention?

    PQ18. Are there new technologies to inhibit traditionally “undruggable” target molecules, such as transcription factors, that are required for the oncogenic phenotype?

    PQ19. Why are some disseminated cancers cured by chemotherapy alone?

    PQ20. Given the recent successes in cancer immunotherapy, can biomarkers or signatures be identified that can serve as predictors or surrogates of therapeutic efficacy?

    PQ21. Given the appearance of resistance in response to cell killing therapies, can we extend survival by using approaches that keep tumors static?

    PQ22. Why do many cancer cells die when suddenly deprived of a protein encoded by an oncogene?

    PQ23. Can we determine why some tumors evolve to aggressive malignancy after years of indolence?

    PQ24. Given the difficulty of studying metastasis, can we develop new approaches, such as engineered tissue grafts, to investigate the biology of tumor spread?

One unspoken PQ: will the payline for these fall at the 7th percentile and/or at Harold’s discretion?

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Alving Departs NCRR … NCRR to Depart NIH?

August 20, 2011 at 7:35 pm · Filed under NIH Advice, Research News

Barbara Alving, MD, will resign from NCRR, which she has led since 2005, as of October 1, 2011. Perhaps not wanting to have his hand slapped by Congress for acting as though NCRR’s dissolution were a done deal, Collins quickly appointed Louise Ramm to serve as Acting Director as of Oct 1 (she is currently deputy director and director of extramural activities).

Regardless of whether Congress includes NCATS or NCRR in the CR to start FY12, it will be a thankless mess to manage come October 1, so godspeed to Dr. Alving as she moves on to something that can only be more fulfilling and less frustrating … and best wishes for sanity and serenity (now) to Dr. Ramm. Indeed, as Jocelyn Kaiser summarizes in an interview with Alving,

The uncertainty has left in limbo NCRR’s staff members, who have been told they’ll move with their programs to other institutes but haven’t received individual assignments. Alving’s farewell note advises them to “keep calm and carry on.”

Alving’s advice applies both to NCRR staff and the extramural community as we try to sort through this hastily executed effort to recreate NCRR as a new Center rather than expand and rebrand one of the most effective components of the NIH.

CTSAs (current and wannabe), the centerpiece of translational research at the NIH, have been a bit unsettled ever since Collins started pushing for his center with such urgency and immediacy. First, the current directors were caught off guard by the December SMRB meeting at which NCATS was abruptly approved (though no word at that time regarding NCRR’s fate). In May, the NIH canceled the October receipt date for new applications, saying the new RFA would be released later in 2011 for a June 2012 receipt date. Then in July, they postponed the RFA release to June 2012 with a December 2012 receipt date. Somehow, this does not seem to be “advancing” translational science.

The question remains whether the FY12 CR will include budget authority for NCRR or NCATS. Congress has a few other things on its plate, and the relevant subcommittee meetings that would consider a special change in the CR language to accommodate NCATS have not been scheduled, to my knowledge. To date, no one in the legislative branch has been publicly enthusiastic about Collins’ proposed changes, which remain in limbo under a cloud of voiced concerns. Stay tuned.

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Findings of Research Misconduct

August 9, 2011 at 9:10 am · Filed under Biomedical Research Ethics, Research News

Notice is hereby given that ORI has taken final action in the following case:

Based on the Respondent’s acceptance of ORI’s research misconduct findings, ORI found that Sheng Wang, PhD, who has been an Asst Prof, Dept of Medicine, Boston University School of Medicine Cancer Research Center, engaged in research misconduct in research supported by R01CA102940 and R01CA101992.

ORI found that the Respondent engaged in research misconduct by fabricating data that were included in 2 published papers:

1. Zhang, B., Faller, D.V., Wang, S. “HIC1 regulates tumor cell responses to endocrine therapies.’ Mol. Endocrinol. 23(12):2075-85, 2009; and

2. Zhang, B., Chambers, K.J., Leprince, D., Faller, D.V., Wang, S. “Requirement for chromatin-remodeling complex in novel tumor suppressor HIC1-mediated transcriptional repression and growth control.’ Oncogene 28(5):651-61, 2009.

Specifically, ORI found that Respondent:

Fabricated RT-PCR and ChIP experiments represented in Figures 1b, 2b, 3a,b, 4b,c, 6a,b, 7c in Mol. Endocrinol. 23(12):2075-85, 2009; RT-PCR and/or ChIP experiments were included in 6 of 7 figures in this publication; and

Fabricated RT-PCR and ChIP experiments represented in Figures 2a,b, 3a,b, 4a,c, 5a,b, 6b,c, 8a,b in Oncogene 28(5):651-61, 2009; RT-PCR and/or ChIP experiments were included in 6 of 8 figures in this publication.

Respondent has entered into a Voluntary Exclusion Agreement. Respondent and the U.S. PHS want to conclude this matter without further expenditure of time or other resources. Respondent accepts ORI’s findings of research misconduct as set forth above but neither admits nor denies committing research misconduct. The Agreement does not constitute an admission of liability on Respondent’s part. Respondent agrees not to appeal the jurisdiction of ORI or request a U.S. DHHS administrative hearing to review the findings as set forth in the Agreement.

As a condition of the Agreement, Respondent agrees that the Mol. Endocrinol. 23(12):2075-85, 2009, and Oncogene 28(5):651-61, 2009, publications be retracted.

In entering into the Agreement, Dr. Wang has voluntarily agreed for a period of 2 years, beginning on July 18, 2011:

(1) To exclude himself from any contracting or subcontracting with any agency of the United States Government and from eligibility or involvement in nonprocurement programs of the United States Government …; and

(2) To exclude himself from serving in any advisory capacity to PHS, including but not limited to service on any PHS advisory committee, board, and/or peer review committee, or as a consultant.

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