The Alan and Sandra Gerry Postdoctoral Research Fellowship Recipient
The Gerry fellowship is awarded to an individual who has demonstrated excellence among their peers and whose work has a focus in metastasis research. This fellowship is set up through a generous gift from the Gerry family specifically for this purpose.
GMTEC’s current Gerry fellow is Deepti Mathur.
Mentor: Joao Xavier
Cancer cells originating from the same tumor can disseminate and form metastases in different tissues, where they respond differently to treatment and express different levels of therapeutic targets. Understanding why some lineages metastasize to specific organs is therefore important for the future of targeted cancer therapy.
Tumor metabolism is increasingly considered a fulcrum of cancer initiation and progression, but the consequences of corrupted cancer metabolism on metastasis remain understudied. We hope to determine how metabolic variables in cancer cells, in the primary tumor, and in the distal tissue shape the outcome of metastatic selection and tropism. We plan to study these questions in unique models of pancreatic and breast cancers developed at MSK, using both experimental and computational biology techniques — including live-cell imaging, experimental evolution, metabolomics, and mathematical modeling with differential equations. Ultimately, we hope this project will provide knowledge towards future interventions that disrupt interactions between tumor cells and the metabolic microenvironment.
Shulamit Katzman Endowed Postdoctoral Research Fellowship Recipient
The Katzman fellowship is a highly competitive fellowship awarded through GMTEC to an international postdoctoral researcher who has demonstrated excellence among their peers and whose work has a focus in metastasis research.
GMTEC’s current Katzman fellow is Josef Leibold.
Mentor: Scott Lowe
Stomach cancer is the fourth leading cause of cancer-associated death worldwide with more than 750000 patients dying from this disease each year. Stomach cancer readily metastasizes to the liver, peritoneal cavity and lungs, which is the main cause of patient mortality. While the genomic landscape of this disease is now well described, this has not immediately translated to improved treatments. The standard-of-care remains cytotoxic chemotherapy and patients frequently suffer recurrence and/or tumor progression. A major impediment to the progress towards better therapies has been the relative lack of preclinical models that faithfully recapitulate the biology of stomach cancer, especially with respect to metastatic dissemination.
I have developed a novel and flexible non-germline genetically engineered mouse model of stomach cancer via direct organ electroporation of genetic elements into adult tissue, known as electroporation-based genetically engineered mouse model (EPO-GEMMs). Of note, these tumors metastasize to clinically relevant organs such as the liver, the peritoneal cavity and the ovaries and the histology reliably recapitulates the human disease.
By taking advantage of this model, I found that alterations in the WNT signaling pathway lead to metastatic dissemination of the disease to the liver. Moreover, I identified natural killer cells as the immune cells responsible for inhibiting metastatic spread of stomach cancer. In the future, I aim to further elucidate the role of these cell intrinsic and extrinsic mechanisms of metastasis formation and, as a long-term goal, to identify new vulnerabilities that could be exploited therapeutically.
GMTEC’s Metastasis Scholars Fellowship Recipient
Ting-Hsiang Huang 2019/2020 GMTEC Metastasis Scholar
Mentor: Richard White
Malignant melanoma is the most life-threatening skin cancer if it has spread to other parts of the body. During the progression of malignancy, melanoma cells interact with subcutaneous adipocytes in the tumor microenvironment (TME) while migrating to the dermis. The White lab recently uncovered that melanoma cells directly take up lipids from stromal adipocytes to fuel proliferation and invasion as the consequence of low survival shown in zebrafish. However, how melanoma cells utilize extracellular lipids to reshape cell fate remains unclear. Acetyl-CoA, a key metabolite during the process of fatty acid degradation has recently been shown to serve as a major carbon source for histone acetylation. In order to address whether lipids from TME play a role in rewiring chromatin state through histone acetylation and understand the functional importance of fatty acid oxidation in melanoma metastasis, I will use human tissues and a zebrafish animal model to study the interplay between lipid metabolism, epigenetic reprogramming and melanoma progression, potentially leading to improved treatment strategies for advanced melanoma.