Sarafan ChEM-H awards four $25K seed grants to fund collaborations with the new chemoproteomics group at the Nucleus
The Nucleus at Sarafan ChEM-H is a set of labs that leverage scientific experts and advanced instrumentation to facilitate discoveries at the interface of chemistry and biology for the benefit of human health. The scientific directors who run research groups at the Nucleus come from backgrounds in academia and industry, together bringing over a century of expertise in techniques and approaches ranging from crystallography to medicinal chemistry to metabolomics.
Recently, the Nucleus welcomed Dr. Dina Schuster, Assistant Director of Chemoproteomics. Her group will focus on a wide range of mass spectrometry-based techniques to study proteins and their molecular interactions. This includes global protein abundance quantification, activity-based protein profiling, identification of protein-protein and protein-small molecule interactions, analysis of post-translational modifications, and more. As with all Nucleus groups, Schuster will offer support to researchers from start to finish of a project, including project design consultation, technical optimization, and data analysis—a model designed to keep young research trainees learning and closely involved in the process through regular collaboration with a Nucleus expert.
To coincide with the launch of the Chemoproteomics group at the Nucleus, Sarafan ChEM-H invited the submission of seed grant proposals that will provide up to $25,000 in in-kind support for collaborations with Dr. Schuster. The chosen projects were selected with the goal of using the proteomics capabilities at the Nucleus to advance new therapeutic approaches in cancer, with a focus on lung cancer driven by mutations in a gene that codes for a protein called epidermal growth factor receptor, or EGFR. These cancers are adept at developing resistance to drugs, making them difficult to treat. As part of the seed grant award, a trainee will work directly with Dr. Schuster over the course of one year to gain experience and knowledge in chemoproteomic techniques alongside an expert.
This year’s seed grant recipients are listed below.
Mechanically induced NETosis in ILD neutrophils as a driver of EGFR-mutant lung cancer progression
Grant Recipient: Hawa Racine Thiam, Assistant Professor of Bioengineering and of Microbiology and Immunology
Trainee: Allen Yesin, graduate student
Interstitial lung disease (ILD) causes lung scarring and inflammation, making it difficult to breathe. ILD patients are at high risk of developing lung cancer, however, the drugs used to treat EGFR-mutant lung cancer often worsen ILD and have severe side effects. To understand why this happens and help develop better treatments, the Thiam lab will leverage the proteomics expertise at the Nucleus to characterize how the rigid lung tissue in ILD may activate a specialized immune response, known as NETosis, that can damage tissue and support tumor growth.
Identifying molecular targets of fluoxetine in Glioblastoma (GBM) EGFR-driven cancers
Grant Recipient: Paul Mischel, Fortinet Founders Professor and Professor, by courtesy, of Neurosurgery
Trainee: Vishnu Shankar, graduate student
Recent studies have suggested that a commonly used antidepressant called fluoxetine--often sold under the brand name Prozac--may have surprising therapeutic benefits for treating deadly glioblastoma brain tumors, particularly those driven by EGFR. To help accelerate clinical use of fluoxetine for glioblastoma treatment, the Mischel lab will utilize the chemoproteomics expertise at the Nucleus to uncover the protein interactome of fluoxetine and how it works in conjunction with EGFR and other pathways to produce its effects.
Repurposing clinical drugs for EGFR-mutant lung cancer via chemoproteomics
Grant Recipient: Haopeng Xiao, Assistant Professor of Biochemistry
Trainee: Julius Jan, Life Science Research Professional
A current problem with many EGFR-targeting chemotherapy drugs for lung cancer is that the drugs stop working over time as the cancer develops drug resistance. To find new drugs that are not subject to the same resistance mechanisms, the Xiao lab will work with the Chemoproteomics group at the Nucleus and the Corsello lab to perform a high-throughput proteomics screen, analyzing how over 8,000 drugs change the protein landscape in cancer cells. Many drugs in this library are approved for use in humans by the FDA, thus accelerating the path to new cancer therapeutics by repurposing compounds that have previously been tested for safety.
In situ chemoproteomic profiling of molecular bident drugs targeting mutant EGFR in NSCLC
Grant Recipient: Nathanael Gray, Krishnan-Shah Family Professor of Chemical and Systems Biology
Trainee: Brendan Dwyer, postdoctoral scholar
The Gray lab has recently pioneered a new therapeutic strategy for treating EGFR-mutant non-small cell lung cancers that have become resistant to drugs like Osimertinib, prolonging life and providing hope of a new treatment option for patients who have relapsed. The drug works by targeting not one, but two distinct sites on the EGFR protein, making it less likely that the cancer cells will be able to evolve and mutate to avoid death. To accelerate drug development and mitigate any potential problems or side effects resulting from the drug binding to the wrong protein, the Gray lab will work with the Chemoproteomics group at the Nucleus to optimize a proteomic strategy for evaluating drugs that bind to a special class of proteins called kinases, including EGFR.
