AACR-QuadW Foundation Fellowship for Clinical/Translational Sarcoma Research
The AACR-QuadW Foundation Fellowship for Clinical/Translational Sarcoma Research represents a joint effort to encourage and support a postdoctoral or clinical research fellow to work on mentored sarcoma research and to establish a successful career path in this field. Funded research may be translational or clinical in nature.
Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive soft tissue sarcoma, most commonly seen in adolescent and young adult males. DSRCT is defined by a single recurrent mutation, EWS-WT1, a dysregulated transcription factor, that alters the expression of more than 1500 genes. Dr. Gedminas’ previous work defined DSRCT cells as absolutely dependent on EWS-WT1 for survival. Dr. Gedminas’ current work will exploit this dependency as a therapeutic vulnerability using the small molecule lurbinectedin which she has shown to inhibit the expression of EWS-WT1. The goal of this study is to elucidate the mechanism of EWS-WT1 suppression by lurbinectedin to guide the administration of this compound and identify novel combination therapies.
Dr. Gedminas received her MD from the Chicago Medical School at Rosalind Franklin University of Medicine and Science, followed by residency training in pediatrics at Advocate Children’s Hospital. Following completion of her fellowship in pediatric hematology and oncology at Helen DeVos Children’s Hospital/Michigan State University, Dr. Gedminas received additional training as a pediatric solid tumor fellow at the Children’s Hospital of Philadelphia, where she now continues as an instructor and conducts sarcoma research.
Acknowledgement of Support
The AACR-QuadW Foundation Fellowship for Clinical/Translational Sarcoma Research provides me with essential support to continue my work developing novel therapeutic approaches for desmoplastic small round cell tumor while I continue the path toward becoming an independent investigator in the field of pediatric sarcoma.
Histone mutations occur in sarcomas such as giant cell tumor of bone, chondroblastoma, chondrosarcoma, undifferentiated pleomorphic sarcoma (UPS), and osteosarcoma. A sarcoma-associated mutation in histone H3 at lysine 36 (H3K36M) is sufficient to induce a UPS-like tumor in a murine model and blocks differentiation of mesenchymal progenitor cells. Given the role of chromatin in controlling cell fate, a process which is often dysregulated in cancer, Dr. Nacev aims to target H3K36M-driven differentiation blockade.
Dr. Nacev earned his MD and PhD degrees from the Johns Hopkins University School of Medicine, where his work focused on the mechanisms of small molecule inhibitors of angiogenesis. Following his doctoral training, he completed internal medicine residency in the Osler Medical Training Program at the Johns Hopkins Hospital before being recruited to the Memorial Sloan Kettering Cancer Center, where he is currently a medical oncology fellow in the sarcoma service. He also conducts postdoctoral research at the Rockefeller University.
Acknowledgement of Support
The QuadW Foundation-AACR Fellowship for Clinical/Translational Sarcoma Research provides essential support during the critical final stage of my training as I prepare to embark on an independent career as a sarcoma medical oncologist and scientist studying novel therapies for epigenetically-driven sarcomas.