# Dissecting FOSL1-mediated lineage plasticity and resistance to androgen receptor signaling inhibition in prostate cancer

> **NIH NIH K99** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $173,016

## Abstract

PROJECT SUMMARY/ABSTRACT
CANDIDATE: I am a postdoctoral research associate in the laboratory of Dr. Yu Chen in the Human Oncology
and Pathogenesis Program (HOPP) at Memorial Sloan Kettering Cancer Center. My PhD training at Boston
University School of Medicine under the supervision of Dr. Sam Thiagalingam allowed me to develop cellular
and molecular biological skills to functionally characterize candidate genes involved in cancer progression and
investigate therapeutic vulnerabilities. My current research focuses on utilizing patient-derived organoid models
to define epigenetic subtypes of castration resistant prostate cancer (CRPC) and determining the dependency
on transcription factors to mediate growth and lineage identity. My proposed research and mentoring plan will
provide me with a strong foundation towards becoming an independent investigator in academia. My long-term
career goal is to advance personalized cancer medicine, with specific interests in disease modeling, functional
characterization of drivers of lineage plasticity, and evaluation of therapeutics to target oncogenic dependency.
To achieve this goal, I have developed a career plan that will ensure my success to becoming an independent
investigator by: 1) bolstering my scientific knowledge and technical expertise, 2) assembling an advisory
committee to oversee my training progress, 3) improving my communication skills, 4) expanding my
professional network, and 4) preparing me for leading and mentoring future trainees.
RESEARCH: Prostate cancer depends on androgen receptor (AR) signaling for growth and survival. The
advent of therapies targeting AR signaling has driven the disease towards AR-independence. Using a
functional genomics approach, we have identified a new epigenetic subtype of CRPC called stem cell-like
(SCL), which is driven by FOSL1 and lacks therapeutic options. Genetic perturbation of FOSL1 and its
cooperating factors YAP/TAZ leads to impaired cell growth and loss of SCL lineage, suggesting that CRPC-
SCL cells are dependent on FOSL1 for survival. Building on these discoveries, in this proposal, I aim to: 1)
Define the role of FOSL1 in mediating lineage plasticity and resistance to enzalutamide in prostate cancer and
2) Evaluate therapeutics to target the YAP/TAZ/TEAD/FOSL1 pathway in the stem cell-like subtype of prostate
cancer.
ENVIRONMENT: The Yu Chen laboratory is a part of the HOPP under the leadership of Dr. Charles Sawyers
at Memorial Sloan Kettering Cancer Center, a top-tier institute in cancer research. The primary mentor is Dr.
Yu Chen, a pioneer in developing prostate cancer organoids from patients and an expert in the study of
epigenetics and aberrantly activated transcriptional programs. Furthermore, my advisory committee and
collaborator will provide additional support for the proposed research and career development plans.

## Key facts

- **NIH application ID:** 10785484
- **Project number:** 1K99CA286721-01
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Chen Khuan Wong
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $173,016
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785484

## Citation

> US National Institutes of Health, RePORTER application 10785484, Dissecting FOSL1-mediated lineage plasticity and resistance to androgen receptor signaling inhibition in prostate cancer (1K99CA286721-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10785484. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*