# Lipid-based Cancer Therapeutics

> **NIH NIH K00** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $85,960

## Abstract

Project Summary
Significant progress in human cancer therapy in the last decade has been driven by conceptionally new
approaches to targeting cancer, including cancer immunotherapy, cancer nanotherapy, or new types of biologics
and small molecules. Both my dissertation and postdoc research will be focused on the development of
fundamentally new approaches to targeting cancer.
My dissertation research is focused on the development of photoswitchable lipids for the optical control of lipid
metabolism and function. In addition to targeting specific receptors, ion-channels, or enzymes, light-induced
structural changes in a lipid nanoparticle (LNP) could serve as trigger for the release of encapsulated drugs.
Triggered release could markedly improve the efficacy of clinically approved LNP-based cancer therapeutics,
which include Doxil/Caelyx, DaunoXome, Myocet, Lipo-Dox, or Marqibo. I seek to design and synthesize
photoswitchable lipids for `photoactivable lipid nanoparticles', herein termed paLNPs, that allow for effective light-
triggered release of encapsulated cancer drugs. Two complementary approaches will be developed for small
molecule drugs and RNA-based therapeutics and the pharmacological properties of paLNPs will be
systematically investigated in vitro and in cell culture.
In my postdoctoral research I seek to use my acquired knowledge in chemistry, lipid-biology, and medicine to
develop lipid-drug conjugates for biological targets that function at plasma-membrane signaling hotspots. The
initial target will be the mutated oncogene KRAS G12C, which is ideally suited for this new approach. Conjugating
selective covalent modifier of this oncogene with a lipid will attach an additional lipid tail to the surface of KRAS
that could largely alter its membrane-protein interaction and in the best case completely inhibit its function. This
could markedly increase the efficacy of the covalent pharmacophores currently in clinical trials. I seek to
synthesize and systematically study these lipid-drug conjugates in vitro and in cell culture.

## Key facts

- **NIH application ID:** 10415232
- **Project number:** 5K00CA253758-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Johannes Morstein
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $85,960
- **Award type:** 5
- **Project period:** 2021-06-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415232

## Citation

> US National Institutes of Health, RePORTER application 10415232, Lipid-based Cancer Therapeutics (5K00CA253758-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10415232. Licensed CC0.

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