# Tumor-associated macrophage reprogramming through PARP14 inhibition in muscle-invasive bladder cancer

> **NIH NIH P30** · DANA-FARBER CANCER INST · 2024 · $147,902

## Abstract

Project summary
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as
NOT-CA-21-100.
 This NCI Early-stage Surgeon Scientist Program proposal for Dr. Filipe de Carvalho describes a
research plan and career development program leading up to an academic career as an independent Urologic
Oncologist surgeon-scientist investigator. Dr. De Carvalho is a urologist at Brigham and Women’s Hospital
committed to an independent research career focused on accelerating the development of therapeutic
strategies to target the immune-suppressive tumor microenvironment in bladder cancer. This Early-stage
Surgeon Scientist Program will allow Dr. De Carvalho to become proficient in tumor-associated macrophage
biology in bladder cancer with the ultimate goal of developing novel macrophage-directed therapeutic
strategies for bladder cancer patients. Dr. De Carvalho will be mentored by Dr. Eliezer Van Allen and co-
mentors Drs. Kent Mouw and Elizabeth Mittendorf, leaders in bladder cancer genomics and cancer
immunology. Dr. Van Allen is Chief of Division of Population Sciences, Dana-Farber Cancer Institute, and has
mentored over a dozen of young investigators that moved to successful independent academic positions. Dr.
De Carvalho also gathered an outstanding scientific advisory committee and collaborators that excel in mouse
models, statistics and cancer genomics to guide career development and scientific progress.
 The research proposal focuses on tumor-associated macrophages, which are immune cells with a
critical role in tumor growth and immune evasion. Recent evidence revealed a therapy-induced conversion of
normally anti-tumor TAMs to a tumor-permissive phenotype. The central hypothesis is that cisplatin
induces chronic immunosuppressive IFN signaling in cancer cells leading to a TAM-infiltrated phenotype and
immune evasion in treatment-resistant tumors. The central hypothesis will be tested by pursuing two specific
aims: 1) Determine the mechanism and effectiveness of targeting TAMs to improve sensitivity of bladder
cancer to combined cisplatin and immune checkpoint inhibition. 2) Dissect the tumor-TAM crosstalk that
mediates cisplatin resistance. These studies are expected to dissect how TAMs inhibit cytotoxic T-cells in
cisplatin-resistant bladder cancer in territories of immune evasion across bladder tumors as well as position
Dr. De Carvalho to submit a competitive R01 near the completion of this Program.

## Key facts

- **NIH application ID:** 10996834
- **Project number:** 3P30CA006516-59S2
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** LAURIE Hollis GLIMCHER
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $147,902
- **Award type:** 3
- **Project period:** 2024-03-01 → 2024-09-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996834

## Citation

> US National Institutes of Health, RePORTER application 10996834, Tumor-associated macrophage reprogramming through PARP14 inhibition in muscle-invasive bladder cancer (3P30CA006516-59S2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10996834. Licensed CC0.

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