# Dissecting clonal diversity in melanoma to overcome therapy resistance andmetastasis

> **NIH NIH K01** · JOHNS HOPKINS UNIVERSITY · 2020 · $119,031

## Abstract

Project Summary/Abstract
Metastatic melanoma is challenging to clinically address. Although standard of care combination BRAF and MEK
inhibitor (BRAFi/MEKi) therapy has high response rates in patients with BRAF-mutant melanoma, therapy
relapse occurs in most cases. Work from our laboratory and others in the field has identified subpopulations of
intrinsically BRAFi/MEKi-resistant melanoma cells that are highly metastatic and drivers of therapy relapse.
These “persistent” melanoma cells display molecular and biologic properties akin to neural crest stem cells
(NCSC), including high invasiveness, plasticity and self-renewal capacity. Our long-term goal is to elucidate the
dominant molecular mechanisms that mediate the plasticity and aggressiveness of NCSC-like melanoma cells.
Our preliminary studies identify a developmental LPAR1-YAP1 axis as critical for melanoma aggressiveness.
One of the main objectives of this project will assess whether LPAR1-YAP1 activity represents an actionable
vulnerability to ablate the metastatic potential and intrinsic resistance of NCSC-like cells. The proposed aims will
leverage a multidisciplinary systems-biology approach spanning inducible genetic-editing techniques, lineage
analysis of NCSC-like melanoma cells through time, metastatic patient-derived xenograft (Met-PDX) melanoma
models, scRNAseq, RNA FISH and advanced bioinformatics, with the goal of translating the gained knowledge
into novel therapeutic strategies for patients with advanced cancer.
Another main goal is to establish an independent research program conducting multidisciplinary and
collaborative research. To ensure the completion of the proposed work, my committee and I have identified four
core competencies I will strengthen with continuous training, as well as didactic courses on single cell analysis
and bioinformatic approaches. I will also participate in career training through workshops covering grant writing,
manuscript preparation and presentation, responsible conduct of research, conflicts of interest, lab/budget
management and guidance from my mentors. With the protected time and stability provided by the K01 award,
as well as the comprehensive training I will receive, I am confident that I will be able to establish an independent
research program and successfully acquire R01 funding.
My short-term career goals are to:
1. Secure an independent faculty position and expand my scientific network of colleagues.
2. Define clonal diversity and molecular vulnerabilities of NCSC-like melanoma cells.
3. Continue to develop my scientific capabilities through my mentor/advisory committee and attain R01 funding.
My long-term career goals are to:
1. Develop ongoing projects, expand into new directions and preclinical studies based on new results obtained.
2. Successfully renew R01 funding and attain alternate sources of funding, continue career development.
3. Translate discoveries clinically, train future mentees, and maintain a productive research pro...

## Key facts

- **NIH application ID:** 10238486
- **Project number:** 7K01CA245124-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Vito William Rebecca
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $119,031
- **Award type:** 7
- **Project period:** 2020-04-06 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238486

## Citation

> US National Institutes of Health, RePORTER application 10238486, Dissecting clonal diversity in melanoma to overcome therapy resistance andmetastasis (7K01CA245124-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10238486. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*