Collaborative Research Initiative announces inaugural award winners
Four interdisciplinary teams of physicians and scientists from Weill Cornell Medicine have been announced as recipients of the Sandra and Edward Meyer Cancer Center's inaugural Collaborative Research Initiative pilot project grants.
The awards were made in support of inter- and intra-programatic collaborations within and across the cancer center's research programs, with the objective of generating sufficient preliminary data to transition to cancer-focused R01-type grant applications.
Each team will receive $100,000.
The selected projects:
Nutrition-Based Immune Reprogramming to Enhance Cancer Immunotherapy
Juan Cubillos-Ruiz, Ph.D.
Andrew Dannenberg, M.D.
Obesity is a major cancer risk factor, and it promotes malignant progression by inducing overt inflammation while disabling the anti-tumor function of immune cells. Nonetheless, the molecular mechanisms by which high-fat diet and obesity blunt cancer immunosurveillance remain poorly defined. This proposal will characterize new obesity-driven mechanisms that provoke global immune cell dysfunction. In addition, the team will test the translational hypothesis that modulating the fatty acid composition of diet can be used to alleviate immunosuppression in cancer and improve the effectiveness of emerging immunotherapies. The collaborative project will therefore uncover new diet-driven immunomodulatory mechanisms, and provide the scientific underpinnings to propose relevant lifestyle interventions that may enhance the effects of cancer immunotherapy in the clinic.
Overcoming Gastric Cancer Treatment Resistance by Targeting CLIP-170S: a Molecular, Computational, and Translational Program
Evi Giannakakou, Ph.D
Olivier Elemento, Ph.D.
Manish Shah, M.D.
Taxanes like docetaxel have proven to be incredibly effective in most cancers, including gastric cancer. But for those with a diffuse histological subtype, docetaxel chemotherapy may be less effective due to the presence of acquired or intrinsic drug resistance. Using a combination of molecular analysis and novel computational approaches, the team has elucidated some of the mechanisms of taxane resistance in gastric cancer and have identified drugs that might be able to counter this resistance. In this project, the team hopes to collect additional data, expand the translational arm of their studies, and develop a strong predictive tool to assign drugs to patients based on their tumor’s molecular profile.
Mechanisms of Telomere Maintenance in Acute Myeloid Leukemia and Therapeutic Potential
Neal Lue, M.D., Ph.D.
Monica Guzman, Ph.D.
Acute myeloid leukemia (AML) is a disease with high incidence of relapse and this may be attributed to leukemic stem cells (LSCs). Cancer cells are often characterized by short telomeres, elevated telomerase activity, and karyotype instability. A recent report suggests that telomerase inhibition effectively targets LSCs in AML and delays relapse following chemotherapy, providing strong support for developing telomere-directed therapies for this cancer. This project will further dissect the mechanisms and functional significance of telomere maintenance protein complexes in leukemia and LSCs, determine their potential as therapeutic targets, and assess the relationship between treatment response/resistance and telomere status in leukemia and LSCs.
Functional Characterization of DNA Regulatory Regions Recurrently Deleted in Human Cancer
Yariv Houvras, M.D., Ph.D.
Lukas Dow, Ph.D.
Human cancers are characterized by recurrent alterations in genome structure including amplifications and deletions that lead to changes in gene expression. The functional consequence of a majority of alterations in the noncoding cancer genome remains unclear. We propose an integrated approach to uncover evolutionary conserved elements that are recurrently altered across human cancers. We will examine regulatory elements that are recurrently mutated, conserved across vertebrate evolution, and predicted to lead to disruption in chromatin structure. Using genetic approaches in zebrafish and mouse we will examine candidate regions using CRISPR/Cas9 genome engineering. An iterative cross species approach to functionally annotate non-coding elements that regulate gene expression and chromatin structure has potential to identify elements in non-coding DNA that play a critical role in cancer initiation and progression.