AACR-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowship

The AACR-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowship represents a joint effort to encourage and support mentored young investigators to conduct basic cancer research and to establish a successful career path in this field.

2021 Grantee

Siddhant U. Jain, PhD

Siddhant U. Jain, PhD

Research Fellow 
Dana-Farber Cancer Institute 
Boston, Massachusetts 
Probing the dysregulation of SWI/SNF and PRC1/2 interplay in tumorigenesis

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.

2019 Grantee

Paola Kuri, PhD

Paola Kuri, PhD

Postdoctoral Fellow
University of Pennsylvania
Philadelphia, Pennsylvania
In vivo imaging of mutant cell growth dynamics in adult skin carcinogenesis

Research
Exposure to UV irradiation causes spontaneous mutations that may disrupt a stem cell’s homeostatic program and lead to skin cancer. Dr. Kuri has been investigating how mutations that are linked to skin carcinogenesis, but are also paradoxically highly prevalent in normal skin, alter the activity of stem cells and increase disease susceptibility. Non-invasive monitoring and visualization of cell activity in the intact skin after acquisition of tumor-driver mutations is performed using long-term live imaging of both genetic and humanized mouse models. In these systems, single differentially labeled cells are genetically manipulated to recapitulate the appearance of spontaneous mutations. The fate of these individual cells is followed over time using live imaging to determine the conditions that favor or limit cellular expansion in vivo, ultimately revealing critical information for disease prognosis.

Biography
Dr. Kuri obtained her PhD at EMBL in Heidelberg. There, she visualized and characterized inflammasome-dependent pyroptosis in keratinocytes by in vivo imaging of zebrafish skin. She is currently a postdoctoral fellow at the University of Pennsylvania, where she uses intravital imaging of mammalian skin to study how oncogenic mutations disrupt tissue homeostasis and promote carcinogenesis at the single-cell level.

Acknowledgement of Support
I am honored to have been selected as a recipient of the AACR-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowship. This invaluable support and recognition will significantly contribute to the development of my research project and will certainly always be a highlight of my scientific career.