# Therapeutic rescue of the transcriptional repressor Capicua to inhibit lung cancer metastasis

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $177,372

## Abstract

Project Summary Abstract
Candidate: Ross Okimoto, MD is a medical oncologist who believes that disease focused basic science research can
improve outcomes for patients with cancer. Dr. Okimoto's long-term goal is to lead an independent laboratory-based
translational research program aimed at identifying and targeting the molecular underpinnings of cancer metastasis.
With two recent first author publications in Nature Genetics and PNAS, Dr. Okimoto has demonstrated potential as a
translational cancer researcher. This K08 application will be critical for his ongoing career development, providing him
with key mentorship and training in 1) oncogene mediated transcriptional regulation of normal and malignant
progression; 2) advanced microscopy techniques; and 3) employing disease specific preclinical tools to enhance
therapeutic modeling and enable clinical translation.
Research: Metastasis accounts for >90% of cancer related death, yet the ability to inhibit the spread of cancer is
hindered by the lack of pro-metastatic targets and robust preclinical models that recapitulate human disease. Through
development of an in vivo orthotoptic lung cancer metastasis model, Dr. Okimoto recently found that the transcriptional
repressor, Capicua (CIC), suppresses lung cancer metastasis. Since the candidate found that CIC expression is
decreased upon ERK activation, he hypothesizes that ERK inhibition can restore CIC expression to block metastasis.
The following specific aims are proposed: 1) to test if CIC is a direct physical and functional substrate of ERK signaling;
2) to test if MEK-ERK inhibition restores CIC expression to inhibit metastasis in a well-defined orthotopic mouse model.
Mentorship and Training: Dr. Okimoto's training will be accomplished through formal coursework and under direct
mentorship of world leaders including Trever Bivona, MD, PhD, a thoracic oncologist with expertise in molecular
targeted therapies. Dr. Bivona has extensive research support from the NIH (3 NCI-funded R01's and the DP2 Directors
New Innovator's Award), and has mentored five fellows to independence within the past five years. Dr. Okimoto will be
co-mentored by Zena Werb, PhD, an expert in transcriptional metastatic regulation. Dr. Werb was the recipient of the
UCSF Lifetime Achievement in Mentoring Award in 2015, recognizing her devotion to mentoring young physician-
scientist to independence. In addition to his mentorship committee, Dr. Okimoto has assembled a word class team of
physician-scientist advisors including, Kevin Shannon, MD (expert in mouse models and MAPK signaling), Andrei Goga,
MD, PhD (oncogenic transcriptional control), and Neil Shah, MD, PhD (preclinical/clinical therapeutics) to provide
guidance and to ensure he succeeds in transitioning into an independent physician-scientist.
Environment: The candidate's training and research will be performed at the University of California, San Francisco, a
world-renowned center of excellence in translational med...

## Key facts

- **NIH application ID:** 10082441
- **Project number:** 5K08CA222625-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Ross Okimoto
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $177,372
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082441

## Citation

> US National Institutes of Health, RePORTER application 10082441, Therapeutic rescue of the transcriptional repressor Capicua to inhibit lung cancer metastasis (5K08CA222625-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10082441. Licensed CC0.

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