# Investigating the non-cell autonomous immune effects of mutant p53 in pancreatic cancer

> **NIH NIH K08** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $225,979

## Abstract

Project Summary/Abstract
The prognosis for pancreatic cancer patients is unequivocally poor. This is due in part to the fibrotic and
immunosuppressive microenvironment of pancreatic tumors, which serves as a physical barrier to
chemotherapy and immunotherapy. Intratumoral genetic alterations can cause remodeling of the immune
environment through distinct cellular mechanisms. Oncogenic Kras gene mutations are the most frequently
occurring genetic event in pancreatic cancer, followed by transforming alterations in TP53. Using both mouse
models and human samples, we will characterize the changes in the immune cell composition of pancreatic
tumors with specific p53 mutations. My proposal will delineate the underlying cellular mechanism of p53-
dependent immune cell recruitment to the tumor microenvironment in the context of pancreatic cancer. In
addition, we will investigate the potential of mutant p53 to serve as a marker of resistance to immunotherapy.
This proposal could support changing clinical practice as integrated analysis of tumor genetic makeup and
immune profiles may be used to develop precision immunotherapy. Building on my background in molecular
genetics, I plan to study the relationship between intra-tumoral gene alterations and the immune system. I will
need training in pancreatic cancer, immunology and cell biology and have decided to study under the
mentorship of Dr. Dafna Bar-Sagi and Dr. George Miller. Dr. Bar-Sagi, an international expert in oncogenic Ras
and cell biology, has trained over 50 individuals at the graduate and post-graduate level over her 30 years in
academia and has authored over 150 peer-reviewed manuscripts. Dr. Miller, leader of NYU Perlmutter Cancer
Center’s Tumor Immunology Program, is a well published immunologist whose research has formed the
basis for four separate clinical trials in pancreatic cancer. Over the course of my training, I will develop
expertise in pancreatic cancer and immunological techniques and principles, receive mentorship in
professional development and collaborate with academic leaders. My career plan consists of laboratory
training, regular meetings with my mentor and co-mentor, active conference participation and formal didactic
coursework. My advisory committee will help me attain my goal of becoming an independent physician
scientist and leader in pancreatic cancer research. Dr. Diane Simeone, Director of the NYU Pancreatic Cancer
Center and world-renowned surgeon scientist, will provide valuable guidance on pancreatic cancer and Dr.
Paul Oberstein, chair of our Gastrointestinal Medical Oncology Group, will help place my studies in a
translational context. Dr. Kwok-Kin Wong, Director of the Division of Hematology and Oncology, is a successful
clinician scientist with a well published laboratory that studies clinical therapeutics using pre-clinical models.
NYU Langone Health has robust scientific and clinical programs dedicated to pancreatic cancer, making it a
world leader. I will b...

## Key facts

- **NIH application ID:** 9991799
- **Project number:** 5K08CA241341-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Despina Siolas
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $225,979
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991799

## Citation

> US National Institutes of Health, RePORTER application 9991799, Investigating the non-cell autonomous immune effects of mutant p53 in pancreatic cancer (5K08CA241341-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991799. Licensed CC0.

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