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Principal Investigator: Johannes Morstein
Organization: NEW YORK UNIVERSITY
Fiscal Year: 2020
Award: $32,407
Funding agency: National Cancer Institute
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.
Terms: <Anti-Cancer Agents><Antineoplastic Agents><Antineoplastic Drugs><Antineoplastics><Biological><Biology><C-K-RAS><Caelyx><Cancer Biology><Cancer Drug><Cancer Genes><Cancer Treatment><Cancer-Promoting Gene><Cancers><Cell Communication and Signaling><Cell Culture Techniques><Cell Signaling><Cell membrane><Chemistry><Clinical><Clinical Trials><Complement><Complement Proteins><Conceptions><Cytoplasmic Membrane><DOX SL><DOXSL><Development><Doxilen><Doxorubicin HCl Liposome><Doxorubicin Hydrochloride Liposome><Drugs><Encapsulated><Enzyme Gene><Enzymes><Evacet><Goals><Human><In Vitro><Interdisciplinary Research><Interdisciplinary Study><Intracellular Communication and Signaling><Ion Channel><Ionic Channels><K-RAS2A><K-RAS2B><K-Ras><K-Ras 2A><K-Ras-2 Oncogene><KRAS><KRAS2><KRAS2 gene><Ki-RAS><Knowledge><Light><Lipids><LipoDox><Liposomal Doxorubicin Hydrochloride><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Medication><Medicine><Membrane Channels><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Modern Man><Multidisciplinary Collaboration><Multidisciplinary Research><Mutate><Myocet><Neoplastic Disease Chemotherapeutic Agents><Non-Polyadenylated RNA><Oncogene K-Ras><Oncogenes><Optics><Pharmaceutic Preparations><Pharmaceutical Preparations><Pharmacology><Photoradiation><Plasma Membrane><Postdoc><Postdoctoral Fellow><Property><R-Series Research Projects><R01 Mechanism><R01 Program><RASK2><RNA><RNA Gene Products><Receptor Protein><Research><Research Associate><Research Grants><Research Project Grants><Research Projects><Ribonucleic Acid><Signal Transduction><Signal Transduction Systems><Signaling><Small RNA><Structure><Surface><Surface Proteins><System><Tail><Therapeutic><Transforming Genes><Tumor-Specific Treatment Agents><anti-cancer drug><anti-cancer immunotherapy><anti-cancer therapy><anticancer agent><anticancer drug><anticancer immunotherapy><anticancer therapy><base><biological signal transduction><cancer immunotherapy><cancer therapy><cell culture><clinical efficacy><design><designing><developmental><doxil><drug/agent><fat metabolism><immune-based cancer therapies><immunotherapy for cancer><immunotherapy of cancer><improved><innovate><innovation><innovative><lipid metabolism><lipid nanoparticle><malignancy><nano therapy><nanotherapy><neoplasm/cancer><new approaches><novel><novel approaches><novel strategies><novel strategy><optical><pharmacophore><plasmalemma><post-doc><post-doctoral><receptor><small molecule><therapeutic RNA><v-Ki-RAS2 Kirsten Rat Sarcoma 2 Viral Oncogene Homolog>