# Contributions of SETD2 mutations in clear cell renal cell carcinoma (ccRCC)

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $37,261

## Abstract

Project Summary
 Cancer epigenetics has driven a surge of research in recent years as several chromatin-
associated factors have been identified in the process of tumorigenesis. A critical chromatin-
modifying protein involved in active transcription, SETD2, has been found to be mutated in
approximately 15% of clear cell renal cell carcinomas (ccRCCs). ccRCC patients have shown
resistance to both chemotherapy and conventional radiation therapies, and although major
therapeutic advances have been made, only a fraction of patients shows durable clinical
responses and long-term remission; thus, there is an urgent need for novel therapies in the field.
 Typically, SETD2 mutations are grouped as functionally identical; however, they can be
grouped according to their structural or enzymatic characteristics. This project seeks to answer
the question of how the loss of SETD2 protein is molecularly distinct from loss of its enzymatic
activities. The first aim will use ChIP-seq and biochemical studies to determine the relationship
between SETD2 mutation and differential chromatin dysregulation and to elucidate the particular
mechanism in which another protein or peptide fragment acts aberrantly in the absence of SETD2.
The second aim will use ChIP-seq and cellular studies to determine how distinct molecular
mechanisms of SETD2 mutations in the context of ccRCC results in differential ccRCC
development and progression.
 The multi-disciplinary environment in the Banaszynski laboratory fosters collaboration
amongst diverse scientists and trainees benefit from the guidance of Dr. Banaszynski and
established scientists in the Green Center for Reproductive Biology. By the end of this training
fellowship period, I will accomplish four goals, I will : 1) become a disciplined experimentalist, 2)
gain ownership of my data, 3) grasp a thorough understanding of the foundational and current
literature that shapes the field of cancer biology, and 4) be an effective scientific communicator
and leader.

## Key facts

- **NIH application ID:** 10395442
- **Project number:** 5F31CA261155-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Shilpa Dhar
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $37,261
- **Award type:** 5
- **Project period:** 2021-04-16 → 2025-04-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395442

## Citation

> US National Institutes of Health, RePORTER application 10395442, Contributions of SETD2 mutations in clear cell renal cell carcinoma (ccRCC) (5F31CA261155-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10395442. Licensed CC0.

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