Project Grant F31CA294932
- This Project Grant award from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) provides $527,159 in funding to Brigham & Women's Hospital, a subsidiary of Partners Healthcare System, to conduct research on the role of DNA damage and cell fate plasticity in the initiation of BRCA1-related basal-like breast cancer. The key objectives of the research are to: 1) study whether BRCA1-deficient luminal mammary cells acquire a fetal mammary stem cell-like gene expression program...
- This Project Grant award of $543,221.00 from the National Cancer Institute (NCI) under the Cancer Biology Research program (CFDA 93.396) is supporting research at the Albert Einstein College of Medicine to better understand the cellular and molecular mechanisms driving lineage plasticity in basal-like breast cancer (BLBC). The key objectives are to: 1) Define the critical de-differentiated cell states involved in BLBC progression and explore strategies to target these cells for cancer...
- This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) provides $388,750 to The Washington University to conduct research on the role of senescent cancer-associated fibroblasts (senCAFs) in breast cancer progression. The key objectives are to: 1) Determine the organ-specific effects of senCAFs on metastatic breast cancer progression; 2) Examine how senCAFs impact extracellular matrix dynamics and tumor cell migration; and 3) Assess the impact of senCAFs on...
- This federal Project Grant award in the amount of $155,605 was provided by the National Cancer Institute (CFDA 93.398 Cancer Research Manpower) to Brigham & Women's Hospital Inc., a subsidiary of Partners Healthcare System, to conduct research on the association between contraception use and ovarian/breast cancers through metabolic profiling. The overarching goal of this 1-year project is to comprehensively quantify changes in metabolites and pathways associated with oral contraception...
- This Project Grant award from the National Cancer Institute (CFDA 93.398 Cancer Research Manpower) provides $176,040.00 to The General Hospital Corporation (doing business as Massachusetts General Hospital) to conduct research on the effects of aging on CDC1 function and CD8 T cell immunity in tumors. The research aims to gain a better understanding of how age-related declines in immune function can impact the effectiveness of CD8+ T cell immunity and immunotherapy response in older cancer...
- This federal Project Grant award of $153,768 from the National Cancer Institute under the Cancer Research Manpower program (CFDA 93.398) aims to elucidate the impact of peroxisome biogenesis on adaptive immune responses, particularly within the tumor microenvironment and anti-tumor immunity. The principal investigator at The Medical University of South Carolina will conduct research to delineate the mechanisms by which peroxisome capacity influences T cell exhaustion, lipid accumulation, and...
- This Project Grant award from the National Cancer Institute (CFDA 93.393 - Cancer Cause and Prevention Research) provides $187,000.00 to Northwestern University to conduct research investigating the role of lipid metabolism in epigenetic reprogramming and its potential contribution to the development of estrogen receptor-negative breast cancer. The research aims to discover local factors within the breast environment that may increase risk for this breast cancer subtype, which has fewer known...
- This Project Grant award from the National Institute of Child Health and Human Development (NICHD), under the Child Health and Human Development Extramural Research program (CFDA 93.865), is focused on engineering in vitro models of pregnancy-induced liver changes. The goal is to develop and utilize liver microtissues containing primary mouse liver cells to elucidate the role of paracrine factors and in vivo preconditioning on phenotypic changes in the liver during pregnancy. The $440,908 award,...
- The National Cancer Institute (NCI) awarded a $425,573 Project Grant under the Cancer Treatment Research program (CFDA 93.395) to the Magee-Womens Research Institute and Foundation in Pennsylvania. The grant supports a multi-year research effort to identify biomarkers and molecular targets for breast cancer prevention, with a specific focus on understanding the relationship between the gut microbiome, metabolites, and high mammographic breast density (MBD). The research aims to provide...
- This Project Grant award from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) provides $217,863 to the University of Colorado-Denver to compare natural killer (NK) cell profiles within melanoma tumors and during pregnancy. The objectives are to: 1) identify biomarkers that can predict risk of disease progression and response to immune checkpoint blockade (ICB) therapy for melanoma patients, and 2) define new therapeutic targets to limit disease progression or improve...
DETERMINING THE EFFECTS OF PREGNANCY AND AGING ON THE MAMMARY GLAND - PROJECT SUMMARY/ABSTRACT THE LONG-TERM GOAL OF THIS PROPOSAL IS TO ELUCIDATE THE MOLECULAR AND CELLULAR PROCESSES UNDERLYING BREAST CANCER RISK REDUCTION BY AN EARLY FULL-TERM PREGNANCY. SPECIFICALLY, THE OBJECTIVE OF THIS PROJECT IS TO DETERMINE THE IMPACT OF AGE AND PREGNANCY ON MAMMARY EPITHELIAL CELLS (MECS). PRELIMINARY ANALYSIS OF BULK SINGLE-CELL RNA SEQUENCING DATA FROM 18 MONTH OLD NULLIPAROUS (NO PREGNANCY) AND 18 MONTH OLD PAROUS (AT LEAST 2 PREGNANCIES) REVEALS THAT PREGNANCY INDUCES A PERSISTENT INFLAMMATORY AND DIFFERENTIATED STATE IN MECS. INTRIGUINGLY, LUMINAL MECS FROM AGED, PAROUS MICE EXHIBIT HEIGHTENED INFLAMMATORY SIGNALING BUT REDUCED PROLIFERATIVE CAPACITY WHEN CHALLENGED WITH TNFA. I HAVE ALSO IDENTIFIED A MINORITY POPULATION OF KRT6A+ HYBRID MECS THAT INCREASE WITH AGE BUT ARE LOST IN PAROUS MICE. BUILDING ON THESE EXCITING PRELIMINARY RESULTS, I HYPOTHESIZE THAT AN EARLY PREGNANCY ALTERS THE AGING TRAJECTORY OF STEM/PROGENITOR MECS TO INDUCE DIFFERENTIATION AND INFLAMMATION PROGRAMS THAT REDUCE CELLULAR PLASTICITY AND ONCOGENIC VULNERABILITY. AIM 1 WILL DETERMINE THE IMPACT OF AGING AND PREGNANCY ON TNFA-MEDIATED INFLAMMATORY RESPONSES AND ONCOGENIC VULNERABILITY IN MECS. AIM 1A WILL DETERMINE WHETHER TNFRSF11B, AN INHIBITOR OF TNFA-INDUCED APOPTOSIS THAT IS DOWNREGULATED IN AGED, PAROUS LUMINAL CELLS, IS RESPONSIBLE FOR THE RESTRICTED GROWTH OF TNFA-TREATED LUMINAL ORGANOIDS FROM AGED, PAROUS MICE. AIM 1B FURTHER EXPLORES WHETHER THE ALTERED INFLAMMATORY PROFILE IN AGED, PAROUS MECS DIMINISHES THEIR TUMOR INITIATION CAPACITY, A CRITICAL FACTOR IN UNDERSTANDING BREAST CANCER RISK DYNAMICS. AIM 2 ADDRESSES THE ROLES OF KRT6A+ HYBRID MECS IN LINEAGE PLASTICITY AND ONCOGENESIS. PRELIMINARY DATA SHOW THAT KRT6A+ HYBRID CELLS ACCUMULATE WITH AGE BUT ARE LOST BY PREGNANCY. RECENT STUDIES HIGHLIGHT THE IMPORTANCE OF LINEAGE PLASTICITY AS A PRECURSOR TO TUMOR INITIATION, PROVIDING A UNIQUE ANGLE FOR UNDERSTANDING THE DYNAMICS OF BREAST CANCER PROTECTION. AIM 2A INVESTIGATES WHETHER THE PREGNANCY-INDUCED REDUCTION OF KRT6A+ CELLS LESSENS TUMOR BURDEN BY INDUCING SPECIFIC MUTATIONS. AIM 2B EXPLORES THE ROLES OF UNIQUE KRT6A+ GENES, ALDH3A1 AND IL33, IN MAINTAINING A PLASTIC CELL STATE THROUGH OVEREXPRESSION AND KNOCK-DOWN ASSAYS. THIS APPROACH AIMS TO DEFINE THE ROLE OF KRT6A+ PROGENITORS IN PREGNANCY-INDUCED PROTECTION IN BREAST CANCER, POTENTIALLY SERVING AS A FUTURE BIOMARKER. IN SUMMARY, THIS PROJECT WILL ADDRESS THE SIGNIFICANT GAP IN UNDERSTANDING HOW AN EARLY FULL-TERM PREGNANCY ALTERS AGE- INDUCED SENESCENCE PATHWAYS IN THE MAMMARY GLAND TO ULTIMATELY REDUCE BREAST CANCER RISK. THE EXPERIMENTS WILL BE CONDUCTED UNDER THE GUIDANCE OF DR. SHAHEEN SIKANDAR AND WITH THE EXCEPTIONAL RESOURCES PROVIDED BY UC SANTA CRUZ. THIS PROPOSAL NOT ONLY HAS THE POTENTIAL TO ILLUMINATE THE DYNAMICS OF BREAST CANCER VULNERABILITY, BUT THE TRAINING OPPORTUNITY ALSO PLACES ME IN A POSITION TO DEVELOP INTO A SELF-DIRECTED AND INDEPENDENT SCIENTIST.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $42.8k | 7/14/25 | ||
| Not listed | $42.8k | 7/14/25 | ||
| Not listed | $0 | 7/14/25 |