QuadW Foundation-AACR Fellowship for Clinical/Translational Sarcoma Research
The QuadW Foundation-AACR 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. Eligibility is limited to postdoctoral and clinical research fellows within the first five years of their fellowship. The research proposed for funding may be translational or clinical in nature and must have direct applicability and relevance to sarcoma research.
Scientific Statement of Research
Cancer associated mutations in chromatin pathways affect proteins that regulate chromatin, as well as their substrates, histone proteins. Histone mutations occur in sarcomas such as giant cell tumor of bone, chondroblastoma, chondrosarcoma, undifferentiated pleomorphic sarcoma (USP), 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, the awarded research program is designed to target H3K36M-driven differentiation blockade. Based on a preliminary screen, Dr. Nacev will explore the activity of small molecules in rescuing differentiation blockade along multiple lineages and in inhibiting growth of a H3K36M-tumor model. The effects of active compounds on H3K36M-induced chromatin changes and on transcription will be explored. This work could establish a novel approach to targeting epigenetically-driven sarcomas.
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, Dr. Nacev 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 under Dr. William Tap of the sarcoma service. Dr. Nacev conducts postdoctoral research under the mentorship of Dr. C. David Allis 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.