The AACR-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowship encourages and supports a postdoctoral or clinical research fellow to conduct basic cancer research and establish a successful career path in this field.

2023 Grantee

Research

Leptomeningeal metastasis (LM), or spread of cancer cells into the tissues surrounding the brain and spinal cord, is an increasingly common, fatal complication of cancer. Despite aggressive treatment, neurologic deficits accumulate rapidly, and patients generally succumb to LM within months. Under homeostatic conditions, choroid plexus (ChP), highly vascularized structures within the brain ventricles, restrict the entry of macromolecules and cells into the leptomeninges; however, select cancer cells can cross this barrier and grow within this space suggesting that interactions between cancer and ChP niche cells alter both the niche and the cancer cells, ultimately supporting LM. The use of clinically-annotated human cancer samples and mouse models of LM, and the integration of transcriptomics and proteomics can enable Dr. Nobre to identify novel therapeutic targets in both LM cells and their microenvironment prior to the accumulation of neurologic deficits, enabling both prevention and treatment of LM.

Biography

Dr. Nobre performed her PhD studies at Mount Sinai Hospital, New York, in breast cancer early dissemination and cancer dormancy. She is currently a postdoctoral fellow at Memorial Sloan Kettering, where she is integrating the use of human samples, mouse models, and cutting-edge techniques to uncover the crosstalk between the microenvironment and metastatic cancer cells in the leptomeningeal space.

Acknowledgment of Support

I am honored and grateful to have been selected to receive the AACR-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowship. This invaluable support will provide me with an opportunity to better understand and address a devastating disease, and it is a great recognition in my scientific career.

2021 Grantee

Research
SWI/SNF complexes activate transcription by regulating nucleosome positioning and providing access to transcriptional machinery. On the other hand, PRC1/2 complexes orchestrate chromatin condensation and gene repression. Recent studies suggest that an important tumor suppressive function of SWI/SNF complex is to oppose PRC2 activity on chromatin. Despite the mounting evidence that tumors containing gain- and loss-of function SWI/SNF perturbations are driven principally by a disrupted antagonism between PRC1/2 and SWI/SNF complexes, the biochemical mechanism of this antagonism remains elusive. Dr. Jain aims to 1) characterize the biochemical mechanism by which SWI/SNF evicts PRC1/2 from chromatin in an ATP-dependent manner and 2) define the molecular function of SWI/SNF- PRC1/2 opposition in tumors driven by either SWI/SNF or histone mutations.

Biography
Dr. Jain received his PhD in biomolecular chemistry at the University of Wisconsin-Madison, where he studied the biochemical mechanisms underlying the “oncohistones” found in pediatric cancers and characterized the oncoprotein, EZHIP (CXorf67). He is a postdoctoral research fellow at Dana Farber Cancer Institute, where he studies the biochemical functions of the SWI/SNF family of chromatin remodelers in normal cells and in cancers.

Acknowledgment of Support
I am honored and grateful to have received the 2021 AACR-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowship. This invaluable support provides me with an opportunity to address some outstanding questions about these aggressive pediatric sarcomas and will substantially potentiate my current scientific aims and future career trajectory.