# Project 1: Elucidating the role of AAA ATPase TRIP13 in prostate cancer

> **NIH NIH U54** · MOREHOUSE SCHOOL OF MEDICINE · 2023 · $222,656

## Abstract

PROJECT SUMMARY: PROJECT-1 (This Project is identical for all three Partnering Institutions)
Despite recent advancements in diagnosing and treating prostate cancer (PCa), it remains the most common
epithelial malignancy and is the 2nd most common cause of cancer death in men in the U.S. High throughput
technologies have enabled identifying several driving molecular aberrations in prostate cancer. Research
suggests diverse genetic, epigenetic and environmental factors influence prostate cancer initiation and growth
eventually leading to incurable metastatic disease. To understand the different forms of PCa, classify indolent
from aggressive conditions, and develop effective therapeutic strategies, it is essential to investigate the
underlying complex molecular events. Using an integrative approach and multiple high throughput data sets, we
nominated AAA ATPase TRIP13 as a potential oncogene in prostate cancer growth and progression. Preliminary
data revealed an amplification and overexpression of TRIP13 in prostate cancer samples and suggested a role
for TRIP13 in PCa cell proliferation and tumor growth. Thus, our central hypothesis is that amplification and
overexpression of TRIP13 contribute to PCa aggressiveness and progression. The specific aims of this project
will validate the role of TRIP13 in prostate cancer progression and determine its value as a therapeutic target.
As TRIP13 harbors enzymatic activity, it may be amenable to inhibition by small molecules. The aims of this
proposal are as follows: Aim 1. Characterize TRIP13 expression and regulation during PCa progression. This
aim will evaluate the expression pattern of TRIP13 during prostate cancer progression, evaluate if TRIP13
expression can predict disease progression, and investigate the mechanism of dysregulation of TRIP13 in
prostate cancer. These investigations are critical to target TRIP13 effectively. Aim 2. Determine the mechanism
of action of TRIP13 in PCas. This aim will provide insight into the role of TRIP13 and downstream molecular
pathways in prostate cancer cell proliferation, invasion, and epithelial-mesenchymal transition, thus validating it
as a useful therapeutic target. Aim 3. Determine the therapeutic efficacy of TRIP13 using its inhibitor in
combination with docetaxel loaded-planetary ball milled (PBM) nanoparticles specific to PCa. In this aim, we will
optimize the PBM nanoparticle formulation and the process condition for TRIP13 specific small-molecule inhibitor
(DCZ0415) delivery in vivo along with docetaxel or Erlotinib. This proposal has a significant translational impact
for managing a subset of prostate cancer patients as TRIP13 can be directly targeted by developing novel
compounds or via downstream effectors and pathways such as EGFR using currently available therapies.

## Key facts

- **NIH application ID:** 10693351
- **Project number:** 5U54CA118638-18
- **Recipient organization:** MOREHOUSE SCHOOL OF MEDICINE
- **Principal Investigator:** Rajesh Singh
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $222,656
- **Award type:** 5
- **Project period:** 2005-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693351

## Citation

> US National Institutes of Health, RePORTER application 10693351, Project 1: Elucidating the role of AAA ATPase TRIP13 in prostate cancer (5U54CA118638-18). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10693351. Licensed CC0.

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