# Defining the Essential Determinants of Prostate Cancer Differentiation States

> **NIH NIH R00** · DUKE UNIVERSITY · 2021 · $248,999

## Abstract

Project Summary/Abstract
 My long-term career objective is to be an independent scientist in an academic laboratory. I would like
to improve our molecular understanding of cancer initiation and progression and translate these findings to
new therapeutic approaches for cancer patients. The K99/R00 Pathway to Independence Award and the
proposed research in this application will be instrumental in my professional career development as a scientist
as I transition to a faculty position.
 MENTORING TEAM: During the mentored K99 phase of the award, I will perform the proposed
research under the direct guidance of Dr. Owen Witte at the University of California at Los Angeles (UCLA). Dr.
Witte is a world-renowned leader in the field of cancer research. His laboratory has developed a unique set of
research approaches with human materials to address scientific questions and hypotheses in prostate cancer
pathogenesis and cancer immunology. I have assembled an advisory board with a co-mentor and two
consultants including Dr. Siavash Kurdistani, Professor in the Department of Biological Chemistry at UCLA and
an expert in functional genomics; Dr. Thomas Graeber, Professor in the Department of Molecular & Medical
Pharmacology at UCLA and an expert in systems biology; and Dr. Jiaoti Huang, Chairman and Professor in the
Department of Pathology at Duke University who is a world expert in genitourinary pathology. I will obtain
knowledge and new skills in the areas of functional genomics, computational biology, and translation of basic
scientific findings therapeutic strategies for cancer patients. This training will allow me to reach my career goal
as a scientist who can significantly contribute to the field of cancer biology and the many men and women who
are affected by cancer.
 RESEARCH: We hypothesize that, under the pressure of current therapies, prostate adenocarcinoma
(PrAd) undergoes cellular reprogramming and trans-differentiation to a lethal variant, neuroendocrine prostate
cancer (NEPC), and this process is driven by dysregulated transcriptional networks. The goal of this proposal
is to define the critical genetic elements required for the progression from PrAd to NEPC. The lack of human
prostate cancer models has hampered functional studies investigating the molecular mechanisms by which
advanced prostate cancer evolves. To address the hypothesis, we will conduct these aims: Aim 1. I will
establish a diverse panel of advanced prostate cancer cell lines derived from the transformation of basal and
luminal epithelial cells of origin by defined oncogenic drivers. Aim 2. I will perform integrative next-generation
sequencing to define transcription factor networks in cancer differentiation states of advanced prostate cancer.
Aim 3. I will functionally define a minimal essential set of transcription factors required to reprogram PrAd to
NEPC. In future studies, we will build on the insight gained from these studies to pursue therapeutic
approaches to prevent t...

## Key facts

- **NIH application ID:** 10232122
- **Project number:** 5R00CA218731-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jung Wook Park
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $248,999
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232122

## Citation

> US National Institutes of Health, RePORTER application 10232122, Defining the Essential Determinants of Prostate Cancer Differentiation States (5R00CA218731-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10232122. Licensed CC0.

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