An awardees account of the DaCCoTA

Sanku Mallik

Professor, Department of Pharmaceutical Sciences

North Dakota State University

Fargo, ND 58105

Sanku.Mallik@ndsu.edu

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Declarations

• Presenter does not have any conflict of interest.

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• This conference is supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number U54GM128729.

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• The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Outcomes and content

• Leverage NIH grant applications with DaCCoTA support

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Strategies to increase competitiveness of NIH grant applications

Requirements of “Preliminary Results”

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Common mistakes in grant applications

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Background (Purpose)

• My R01 award (1R01 GM114080; 2015 – 2019) was due for the renewal. However, without demonstrating the efficacy of the targeted nanoparticles in mice tumors, the chances of a “fundable score” was low.

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• So, I decided to defer the renewal application by an year, requested a no-cost extension from NIH, and decided to apply for a DaCCoTA grant for the animal experiments.

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• Feasibility application “Nanoparticles for drug delivery to triple-negative breast cancer.”
• DaCCoTA funded the application in 2019.

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Impact of the DaCCoTA award (Method)

• With the award, we determined the efficacy of targeted nanoparticles in reducing triple-negative breast cancer in a mouse model.

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• We established a collaboration with an oncologic surgeon (Dr. Daniel M. Tuvin) at the Sanford Broadway Clinic, Fargo, North Dakota.

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• We received six patient samples of triple-negative breast cancer to generate patient-derived xenografts (PDX) for testing the nanoparticles.

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Results from the DaCCoTA award

• The award led to three peer-reviewed publications in American Chemical Society journals.
• The published results formed the critical component of “Progress Report and Preliminary Studies” for successful NIH R01 award renewal in 2020 (2 R01 GM114080).
• The R01 grant allowed me to continue to serve as the PI for a COBRE Phase 2 application (2 P20 GM109024; Center for Diagnostic and Therapeutic Strategies for Pancreatic Cancer). I also “drafted” Dr. Venkatachalem to serve as the Co-Director for the COBRE Center.
• We submitted the COBRE renewal application on September 27, 2021. We received the Impact Score in February 2022. It was “certainly within the striking distance.”
• NIGMS COBRE Grants Management Specialist asked us to submit the “JIT Information” on April 25, 2022. We submitted the documents on May 02, 2022.
• We received another request from NIGMS COBRE Grants Management Specialist on June 02 to submit IACUC approval pages for the three projects. We submitted the documents on June 17.
• We received an email from the Grants Management Specialist on July 06 saying “we are aiming for July 15^th for the NoA to be posted.” Current status of the application in eRA Commons is “award prepared.”

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Results from another DaCCoTA award

• I wanted to develop a new R01 proposal to NIH, probing the mechanisms of gender variation in the severity of Covid-19 infection.

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• To obtain the “Preliminary Results,” I applied and received a DaCCoTA Pilot Project award on Covid infection severity in patients with lung metastatic breast cancer.

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• The Pilot Project expanded the triple-negative breast cancer PDX models into a biobank containing 250 frozen tumor tissues and 40 primary cell cultures.

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• We are using the biobank to study if hypoxia overexpresses the two proteins responsible for the cellular internalization of the SARS-Cov-2 virus. However, we have not published the results yet.

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• Hence, we submitted an NIH R03 application (1 R03 CA277207-01; Expressions of ACE2 receptor in male and female lung cancer patients under hypoxia) to obtain additional results for an R01 application.

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Overall impact of the DaCCoTA awards (Conclusions)

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• The two DaCCoTA awards helped me tremendously to continue to conduct nationally-competitive research and fulfill my career goals.

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• The same opportunity is available to all awardees.

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Methods to increase competitiveness of NIH proposals

• Select the appropriate collaborator with complementary expertise directly related to the project.

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• Plan ahead; think critically. Do I have sufficient published preliminary results? If not, postpone the proposal submission and apply for the appropriate DaCCoTA support.

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• The peer reviews of the DaCCoTA proposal will allow you to improve the NIH application. The support will provide the necessary preliminary results.

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• Clinical collaborators and the use of PDX cancer models are viewed favorably by the NIH Study Sections (translational aspects of foundational projects).

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• If the DaCCoTA project is progressing slowly, apply for a no-cost extension. Instead of an R01 application, consider R03 or R21 proposals.

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Requirements of Preliminary Results

• For R01 applications, published preliminary results are mandatory. Use DaCCoTA support and publish to demonstrate the feasibility of each Specific Aim.

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• Publish papers with the clinical collaborator to demonstrate to the reviewer that you have an established clinical collaboration.

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Common mistakes in NIH grant applications

• The Specific Aims are sequential; success of Aim 2 depends on completion of Aim 1.

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• No clinical collaborator or PDX models of cancer to show future translational aspects of the project.

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• Insufficient preliminary results to demonstrate feasibility of the proposed studies or the results lack scientific rigor.

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Acknowledgments

• DaCCoTA (NIGMS, U54GM128729)
• Pilot Projects Program: Dr. Sathish Venkatachalem – discussion on the feasibility of the idea, relevance to DaCCoTA, animal experiments, translational aspects.

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• Clinical Research Resources and Facilities Core: Tabatha Lemke, Miranda Ruiter – IRB application, patient sample procurement.

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• Confocal fluorescence microscope: Pharmaceutical Sciences Department, purchased with DaCCoTA funds.

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• NIH (NIGMS) 2R01 GM114080

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• NIH COBRE Animal Studies Core Facility (1 P20 GM109024)

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• Dr. Satish Venkatachalem, NDSU

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• Dr. Jiyan Mohammad

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• Dr. Narendra Kale

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• Shubhashri Ambhore
• Connor Edvall
• Babak Mamnoon
• Parinaz Ghanbari

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