INTEGRATIVE ANALYSIS OF THE AGING PERITONEUM IN METASTATIC RECEPTIVITY - THE OVERALL GOAL OF THIS PROPOSAL…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_K00AG068527_075
- FAIN
- K00AG068527
- Recipient
- THE JOHNS HOPKINS UNIVERSITY
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $223,457
- Period
- Sep 1, 2020 – Dec 31, 2026
- Fiscal year
- 2023
- Place of performance state
- MD
- Source file
- FY2023_All_Assistance_Full_20261006.zip
Description
INTEGRATIVE ANALYSIS OF THE AGING PERITONEUM IN METASTATIC RECEPTIVITY - THE OVERALL GOAL OF THIS PROPOSAL IS TO PROVIDE A COMPREHENSIVE PLAN OF RESEARCH TRAINING AND CAREER DEVELOPMENT TO ENABLE THE PRINCIPAL INVESTIGATOR TO SUCCESSFULLY COMPLETE HER PHD AND ACQUIRE A COMPETITIVE POSTDOCTORAL POSITION PERFORMING TRANSLATIONAL RESEARCH IN THE FIELDS OF AGING AND CANCER. PHASE I FOCUSES ON COMPLETION OF ONGOING PHD TRAINING INVESTIGATING THE ROLE OF THE AGING MICROENVIRONMENT IN OVARIAN CANCER (OVCA) METASTASIS. OVCA IS THE MOST FATAL GYNECOLOGIC MALIGNANCY AND THE 5TH LEADING CAUSE OF OVERALL CANCER DEATH AMONG AMERICAN WOMEN WITH A LOW 5-YEAR SURVIVAL RATE, AS 75% OF WOMEN ARE DIAGNOSED WITH DISSEMINATED INTRA-PERITONEAL (IP) METASTASIS. OVCA METASTASIS DIFFERS FROM MOST OTHER CANCERS IN THAT CELLS DETACH FROM THE PRIMARY TUMOR, SHED INTO THE PERITONEAL CAVITY, ADHERE TO THE PERITONEAL MESOTHELIAL CELL (MC) MONOLAYER, INTERCALATE WITHIN THIS LAYER, AND INVADE INTO THE SUBMESOTHELIAL MATRIX, WHERE THEY PROLIFERATE AND FORM SECONDARY LESIONS. AGING IS THE BIGGEST RISK FACTOR FOR THE DEVELOPMENT OF OVCA. HALF OF OVCA DIAGNOSES ARE IN WOMEN OVER THE AGE OF 63, AND OLDER OVCA PATIENTS HAVE A HIGHER RISK OF MORTALITY. DESPITE THIS, AGE IS UNDERSTUDIED IN THE OVCA FIELD. EVEN THOUGH THE PERITONEUM HAS NEAR THE SAME SURFACE AREA AS THE SKIN, THE EFFECT OF AGE ON THE PERITONEUM HAS NOT BEEN SYSTEMATICALLY EVALUATED. USING THREE DISTINCT MURINE PRE-CLINICAL MODELS OF AGING AND OVCA METASTASIS, OUR LAB PREVIOUSLY DEMONSTRATED ENHANCED METASTATIC SEEDING OF PERITONEAL STRUCTURES IN AGED MICE ACCOMPANIED BY ALTERED IMMUNE CELL INFILTRATION. CURRENT PRELIMINARY DATA IN THIS APPLICATION SHOW THAT THERE ARE DISTINCT DIFFERENCES OBSERVED WHEN COMPARING PERITONEAL COLLAGEN ULTRASTRUCTURE IN YOUNG AND AGED ANIMALS AT MAJOR METASTATIC SITES. MOREOVER, USING PURIFIED COLLAGEN FROM YOUNG VERSUS AGED MICE IN A PANEL OF IN VITRO ASSAYS, WE SHOWED INCREASED INVASION OF OVCA CELLS THROUGH A