# Epigenetic deregulation and tumor progression due to the loss of a novel interaction between HDAC1 and BAP1 in uveal melanoma

> **NIH NIH F31** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $50,520

## Abstract

Project Summary
 Uveal melanoma (UM) is a highly aggressive eye cancer that leads to metastatic death in up to half of
patients. UM can be divided into two prognostic groups based on a clinically validated gene expression profile
(GEP), with class 1 GEP being associated with good prognosis and class 2 GEP with bad prognosis. Each
tumor class is associated with specific driver mutations, several of which were discovered in our laboratory. In
particular, the highly metastatic Class 2 tumors are associated with inactivating mutations in the tumor
suppressor BAP1. However, a major gap exists in our knowledge of how BAP1 mutations lead to metastatic
death, which has thwarted the development of targeted precision therapy. To address this deficiency, my
objective is to identify and characterize proteins that interact with BAP1. In preliminary studies, I performed a
biotin-labeling mass spectrometry technique called BioID2 and identified HDAC1 as a novel BAP1-interacting
protein. Thus, I propose to investigate the role of HDAC1 in mediating the tumor suppressor function of BAP1.
I hypothesize that BAP1 regulates the epigenetic functions of HDAC1 by maintaining it in a de-ubiquitinated
state. Accordingly, I predict that mutational inactivation of BAP1 deregulates HDAC1, leading to changes in
histone acetylation and gene expression that promote tumor progression. I will test this hypothesis with the
following Aims: (1) Determine how BAP1 interacts with HDAC1 and regulates its ubiquitination state, and (2)
Identify how BAP1 loss deregulates transcription through histone acetylation changes catalyzed by HDAC1.
My overall objective is to characterize the BAP1-HDAC1 interaction and the consequences of its disruption by
BAP1 mutations as an avenue to discovering new therapeutic strategies.

## Key facts

- **NIH application ID:** 10048639
- **Project number:** 5F31CA243426-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Daniel Alexander Rodriguez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2019-09-30 → 2023-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048639

## Citation

> US National Institutes of Health, RePORTER application 10048639, Epigenetic deregulation and tumor progression due to the loss of a novel interaction between HDAC1 and BAP1 in uveal melanoma (5F31CA243426-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10048639. Licensed CC0.

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