CHERP – Pilot Research Projects

Dr. Robert Bristow - The Philip J. DiSaia Chair, Gynecologic Oncology & Professor, Obstetrics & Gynecology, UC Irvine

Dr. Alice Lee - Assistant Professor, Public Health, Cal State Fullerton

• Ovarian cancer is a highly fatal disease with a five-year relative survival of less than 50%. However, ovarian cancer survival is not the same for all women. Asian American ovarian cancer patients have the highest survival across all major racial groups, however the Asian American population is heterogeneous. Studies have shown that analyzing Asian Americans as a single group overlooks important ethnic-specific disparities, and this has been observed for ovarian cancer. Hence, this pilot project aims to better understand these disparities using data from the California Cancer Registry (CCR). The CCR is an ideal data source for this project given that it includes detailed demographic, socioeconomic, tumor, and treatment information by Asian subethnic group and covers the geographic region in the United States that is home to the largest number of Asian Americans.

  Our preliminary analyses of Asian American ovarian cancer patients using data in the CCR showed ethnic-specific percent differences for several survival-related characteristics. To clarify these differences, Aim 1 of this project will examine the association between Asian subethnic group and ovarian cancer tumor characteristics. Certain Asian subethnic groups may be more likely to present with ovarian cancers of a particular grade, stage, or histology, hence the ethnic-specific survival disparities may be attributed to the tumors themselves. Aim 2 of this project will examine whether receipt of National Comprehensive Cancer Network (NCCN) guideline adherent care and its association with ovarian cancer survival differ across Asian subethnic groups. NCCN guideline consensus statements reflect the most current and accepted standard for cancer treatment, hence the ethnic-specific survival disparities may be attributed to the treatment and care received. Certain Asian subethnic groups may be more likely to receive NCCN adherent care and receipt of that care may be differentially associated with survival.

  Given the fatality of ovarian cancer, understanding why some women die from ovarian cancer while others do not is a public health priority. Few ovarian cancer studies have focused on Asian Americans, hence this pilot project will not only shed light on an understudied segment of the population, but will do so in a way that recognizes the importance of the population’s heterogeneity so ethnic-specific disparities are not overlooked. Understanding how ovarian tumors and treatment care may differ by Asian subethnic group will inform the future work that is needed to understand the underlying factors contributing to ovarian cancer disparities and survival overall.

Dr. Olga Razorenova - Associate Professor, Molecular Biology and Biochemistry, UC Irvine

Dr. Nicholas Nikolaidis - Associate Professor, Biological Sciences, Cal State Fullerton 

• Cancer incidence, progression, drug-resistance, and mortality vary significantly by race and ethnicity. Triplenegative breast cancer (TNBC) subtype disproportionately affects African American (AA) women with high mortality rate due to metastasis. Recently, altered lipid metabolism (causing lipid composition changes in the tumor) was identified as a driver of TNBC metastasis, providing a rational for our central hypothesis that there are gene expression and/or genetic differences between AA and Caucasian White (CW) populations, causing lipid metabolism changes underlying TNBC initiation and progression. At the P20 pilot 1-year stage of the grant we will address a narrower hypothesis that there are differences in lipid composition in normal breast tissue, and cancer tissue between AA and CW populations. At the cellular level, cancer cells can alter lipid content endogenously (via metabolism) or exogenously (via lipid uptake from their microenvironment), yet knowledge about the contribution of each pathway to lipid metabolism dysregulation is lacking. At the human population level, several small nucleotide polymorphism (SNP) studies identified associations with lipid metabolism alterations in breast and other cancers, yet, the majority of these studies used patients of European origin. Thus, patient racial/ethnic differences remain to be uncovered. At the P20 pilot 1-year stage of the grant, our objectives are 1) to set up the pipeline for normal breast tissue, tumor and normal adjacent tissue (NAT) paired-sample acquisition and analysis and 2) to reveal the existence of lipid composition differences and lipid metabolism gene expression differences between paired NAT and cancer samples, as well as between AA and CW patient samples. These objectives will contribute to the overarching goal of this study (achieved at the R03 and R01 stages of this project): to establish causality between tumor lipid metabolism alterations and cancer initiation and progression in AA and CW populations. Here we will pursue the following Aims feasible within 1 year: 1) establish racial differences in lipid composition by lipidomic profiling of normal breast samples and tumor/NAT paired TNBC samples from AA and CW patients; and 2) establish racial differences in lipid metabolism gene expression by RNA sequencing of normal breast samples and/or tumor/NAT paired TNBC samples from AA and CW patients (using a limited number of samples due to the limited scope of the project). If successful, at the end of the P20 stage of the project we will generate preliminary data showing that there are differences in lipid composition between cancer and NAT as well as between AA and CW racial groups; with the first step made towards establishing underlying transcriptional changes. This will provide premise for an R03 application to link these lipid differences with cancer initiation and progression. Eventually, we will transition to a R01 application, which will include whole genome sequencing, and epigenetics (ChIP-seq) to find mechanistic details of the observed lipidomic and transcriptomic changes. Ultimately, this line of research will allow population-tailored prevention and therapies.

Cancer is the second cause of death overall with certain cancers showing disparate incidence and mortality patterns among specific groups. Despite decades of focused research and training efforts in cancer control, persistent health disparities remain for ethnic/racial populations, people with disabilities, those who live in rural areas, and/or who have lower education and economic resources. Currently, the health disparities workforce does not reflect the needed diversity in the United States and there are still critical gaps to address when it comes to accessing quality education and training to support the development of talented students/early career investigators in this field. 

Orange County is the third largest and second most densely populated county in California. The county mirrors the state’s vast ethnic/racial diversity which includes a sizeable proportion of non-Hispanic Whites, Hispanic/Latinos, Asian Americans, Blacks, and mixed/other. CSUF is an academic institution serving underserved populations and underrepresented students (ISUPS), and the UCI-CFCCC is an NCI-designated comprehensive cancer center at UC Irvine. CHERP is a collaborative cancer-specific partnership between these two institutions that aim to support highly interactive pilot cancer health disparities research that will not only advance cancer health disparities knowledge, but also serve as foundational training in this area of need for underrepresented undergraduate (CSUF) and master’s level (CSUF/UCI) students. The anticipated outcomes of each successful pilot project are to generate preliminary data that may be used in future competitive grant applications and provide student mentorship.

Disparity research: 

• Cancer health disparities are differences in the incidence, prevalence, mortality, and burden of cancer and related adverse health conditions that exist among specific population groups.
• These population groups may be characterized by gender, age, race, ethnicity, education, income, social class, disability, geographic location, or sexual orientation.

Under-represented student categories:

• Race/ethnicity: Blacks, Hispanics, American Indians/Alaska Natives, Native Hawaiians and Pacific Islanders, or other groups that can be demonstrated as underrepresented by the grantee institution
• Disability
• And/or from disadvantaged backgrounds, such as below established low-income thresholds

CHERP priority areas of interest: 

Cancer risk factor reduction (e.g., tobacco, obesity)

Cancer screening

Cancer epidemiology (including epigenetics)

Cancer survivorship

• CHERP will prioritize pilot projects that address disparity needs in the catchment area of Orange County.
• Topics can be in any area of cancer-related basic clinical, translational, prevention, control, behavioral and/or population research.
• Pilot projects must be highly interactive and involve at least one principal investigator from CSUF and UCI. 
• Projects that can generate critical preliminary data for a planned submission/resubmission of a peer-reviewed extramural NIH/CI or similar grant proposal will be considered, with special consideration given to applications supporting resubmissions that generate new data in response to prior critiques.
• A collaboration strategy and mentoring/training plan for early-stage investigators (if applicable) and under-represented students from each institution must be clearly described in the application.

All UC Irvine and CSUF faculty members are eligible to apply. An investigator from CSUF must partner with an investigator from UCI. The awarded UCI PI must join CFCCC membership prior to the project’s launch; the CSUF PI will be eligible to become an Associate Member of UCI-CFCCC. A collaboration between junior faculty and senior faculty co-leaders is not required but highly encouraged to provide mentorship opportunity. Though not required, it is also strongly encouraged that minority investigators from both institutions apply. 

●    Up to $100,000 direct costs ($50,000 per institution)
●    Projects are limited to one year of support
●    Expenditures on large equipment (e.g., >$5K) will require submitting justification for the equipment and approval. 
●    Co-funding is allowable and may be described in the application. However, co-funding is not a requirement.
●    Funds should be fully spent within the award period.  No-cost extensions will be granted in limited circumstances and are contingent on continued funding of the parent P20. All no-cost extensions must be requested in writing to CHERP administrators.

Click here to download the application form and guide. Submit the application as a single PDF file to cfcccadmin@hs.uci.edu by November 14, 2022 (11:59 pm PST). Required application components are outlined below. Incomplete applications will not be considered.

Format Requirements: Arial font, 11 pt., minimum 0.5 inch for all margins, no appendices.

CHERP Pilot Project Application Form Components:
1. Project Details
    A. Project Details Cover Sheet
    B. Scientific Abstract (0.75 page)
    C. Lay Audience Summary (0.25 page)
    D. Research and Mentoring Strategy (3 pages max.)
         D.1.  Background and Significance
         D.2. Specific Aims and Research Strategy
         D.3.  Student Recruitment and Mentoring Plan
         D.4.  Plans for Future Funding
    E. Multi-PI Leadership and Collaboration Plan (1 page max.)
    F. Bibliography/References Cited (no page limit)
    G. Detailed Budget (table) and Justification (1 page max.) from each institution
2. NIH-formatted Biosketches for MPIs and Key Personnel (no page limit)
3. Letters of Support (if applicable)

• Applications will be peer reviewed according to the 9-point NIH scientific review criteria with additional emphasis placed on the following criteria:
  • degree of collaboration between CSUF and UCI-CFCCC researchers;
  • focus on a cancer health disparity and priority areas;
  • potential for pilot data to inform future competitive NIH grant proposal;
  • ability to complete data collection within one year;
  • involvement of at least one underrepresented student (priority if recruited from the Cancer Research Education Program (CREP)
• Applicants will receive a copy of the review comments in an anonymous format.
• Applications whose projects use UCI-CFCCC Shared Resources or involve significant new collaborations are strongly encouraged.

Regulatory or institutional approvals required for the proposed study must be obtained by each institution as applicable. If sufficient progress in obtaining regulatory approvals has not been made within 6 months after award date, funding may be withdrawn. Prior to the release of funding:

• All projects involving human subjects must have IRB approval.*
• All projects involving animal subjects must have IACUC approvals.
• Projects requiring other regulatory or institutional use authorizations must obtain those approvals.
• Only one institution’s IRB will review. The location where the majority of the research procedures are administered will likely serve as the IRB on record.
• If a study is already approved at either institution, then the relying site (other institution) should be added via an amendment to the approved study. The CSUF IRB contact is Grace Amaya (gamaya@fullerton.edu), and the UCI IRB contact is Valerie Sanchez (Valerie.ms@uci.edu).

*Due to the collaborative nature of projects, the IRB’s at CSUF & UCI have established a reliance agreement for projects deemed to required expedited or higher levels of review.

1. Progress and Impact Reports: Due no later than 30 days after the end of the project period. Grantees will be asked to participate in mid-year check-ins as an opportunity for project and program leaders to identify areas that may need enhanced collaboration.
2. Financial Report: Due no later than 30 days after the end of the project period.
3. Impact Report: Additionally, co-PIs may be contacted annually for a period of 5 years after the project end date to track outcomes of each award, including trainee outcomes.
4. Grantees will present on the progress of their projects to the Internal Advisory Committee (IAC)  to help grantees problem solve any issues and/or  prepare for extramural research grant submissions. 

Publications resulting from this project must include the following acknowledgment:

“Research reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health under award number P20CA253254. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, California State University Fullerton, or the University of California, Irvine, Chao Family Comprehensive Cancer Center.”

If the project used a UCI CFCCC Shared Resource, please refer to this website for appropriate acknowledgement: https://cancer.uci.edu/research/research-resources/acknowledgement-guid…