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​AACR NextGen Grants for Transformative Cancer Research


The AACR NextGen Grants for Transformative Cancer Research represent the AACR’s flagship funding initiative to stimulate highly innovative research from young investigators. This grant mechanism is intended to promote and support creative, paradigm-shifting cancer research that may not be funded through conventional channels. It is expected that these grants will catalyze significant scientific discoveries and help talented young investigators gain scientific independence. Eligibility is limited to junior faculty who have held a tenure-eligible appointment at the rank of assistant professor for no more than three years. The proposed research must represent a highly innovative approach to a major contemporary challenge in cancer research. The research can be in any area of basic, translational, or clinical science.    

2017 Grantees

Breast Cancer Research Foundation-AACR NextGen Grant for Transformative Cancer Research, in honor of Nancy E. Davidson, MD

Birsoy_90x110.jpgKivanç Birsoy, PhD
Assistant Professor
The Rockefeller University
New York, New York
Dissecting the role of aspartate biosynthesis in hypoxic tumor growth

Scientific Statement of Research
The impact of low oxygen on cellular metabolism extends beyond central carbon metabolism as there are at least 150 biosynthetic reactions that require molecular oxygen. We recently discovered that the critical function of oxidative metabolism to support proliferation is surprisingly not energy production but rather aspartate synthesis. Upon inhibition of the electron transport chain, the cellular aspartate concentration drops to levels that cause growth arrest, and supplementation of this single amino acid is sufficient to enable cells with defective electron transport chain activity to proliferate. As many cancer cells are frequently starved for oxygen in tumors, this result raises the possibility that aspartate levels may be limiting for tumor growth in vivo and that suppression of aspartate levels in cancer cells is a promising approach to target cancer cells. Here, we aim delineate the role of aspartate metabolism in tumors cells in vivo and its upstream regulators.

Biography
Kivanc Birsoy received his undergraduate degree in molecular genetics from Bilkent University in 2004 and his PhD from Rockefeller University in 2009, where he studied molecular genetics of obesity in the laboratory of Jeffrey Friedman. In 2010, he joined the laboratory of David Sabatini at the Whitehead Institute. There, he combined forward genetics and metabolomics approaches to understand how different cancer types rewire their metabolism to adapt nutrient deprived environments. In 2016, he joined the Rockefeller faculty as Chapman-Perelman assistant professor and head of laboratory of Metabolic Regulation and Genetics.

Acknowledgement of Support
With the generous support from AACR, we aim to gain a better understanding of cancer metabolic adaptations and reveal previously unidentified metabolic liabilities of hard-to-treat tumors.

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AACR NextGen Grant for Transformative Cancer Research

Lyssiotis_90x110.jpgCostas Andreas Lyssiotis, PhD
Assistant Professor
University of Michigan
Ann Arbor, Michigan
Intratumoral metabolic crosstalk supports pancreatic tumor growth

Scientific Statement of Research
Pancreatic tumors are characterized by a heterogeneous cellular microenvironment, a prominent stromal reaction and deregulated metabolism. The intense stromal reaction impacts the vasculature, leading to a hypoxic and nutrient poor environment. As such, these tumors must adapt how nutrients are captured and utilized to support their metabolic needs. Recently, the Lyssiotis laboratory discovered that non-tumorigenic pancreatic stromal fibroblasts provide metabolic support for the nutrient limited cancer cells through the secretion of amino acids. The goals of this proposal are to determine the mechanisms by which metabolic crosstalk exists and then to disrupt this pathway using ex vivo co-culture systems. In addition to elucidating a novel pathway of intratumoral metabolic crosstalk and uncovering an unknown role for the stroma in PDAC, these studies may also reveal new therapeutic targets.

Biography
Costas Lyssiotis obtained his bachelor’s degree in chemistry and biochemistry from the University of Michigan in 2004 and his PhD in chemical biology from The Scripps Research Institute in 2010. Costas joined the laboratory of Lewis Cantley at Harvard Medical School to pursue postdoctoral studies where his work focused on understanding oncogene driven metabolic alterations in cancer. Dr. Lyssiotis is currently an assistant professor at the University of Michigan with appointments in the Departments of Physiology and Medicine. His lab studies the biochemical pathways and metabolic requirements that enable tumor survival and growth and how this information can be used to design targeted therapies.

Acknowledgement of Support
I am honored and extremely grateful to be the recipient of this prestigious NextGen award from the AACR. This support will provide the protected time and funds to pursue our promising research investigating the therapeutic utility of targeting pancreatic cancer metabolism.

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AACR NextGen Grants for Transformative Cancer Research

Chen_90x110.jpgSidi Chen , PhD
Assistant Professor
Yale University
New Haven, Connecticut
Versatile tools for autochthonous screening in liver cancer

Scientific Statement of Research
Genetically engineered mouse models provide a powerful way to study genetic mutations in tumor progression. However, recent large-scale cancer genomic studies revealed thousands of aberrations in the tumors of patients across multiple cancer types. This project’s goal is to develop a versatile platform for autochthonous modeling and high-throughput genetic screening. The initial development will focus on liver cancer, a highly lethal disease with many different mutations. This project will establish in vivo HCC induction platform using somatic gene editing to enable rapid, efficient and pathology-relevant generation of autochthounous HCC models in mice, and will demonstrate its ability for high-throughput in vivo genetic screens to identify key genes governing HCC progression and drug responses in autochthonous animal models. It is anticipated that such platform can be broadly applied to virtually all cancer types, with potentials for transforming cancer modeling, genetic screening of key factors, and pre-clinical testing of therapeutic agents.

Biography
Sidi Chen earned his PhD from The University of Chicago, and received postdoctoral trainings at MIT and the Broad Institute. He is current an assistant professor of genetics in Systems Biology Institute at Yale University. His group’s research centers on cancer systems biology, leveraging in vivo genome engineering approaches such as CRISPR-mediated cancer modeling and genetic screening to identify key regulators in cancer progression, tumor immunity, and therapeutic responses.

Acknowledgement of Support
The emerging complexity of cancer genome outpaced the ability of traditional genetic methods. My project’s goal is to develop a versatile platform to enable efficient and precise cancer modeling and high-throughput screening, which might transform our ability to identify key genes governing cancer progression and drug responses, thus accelerate therapeutic discovery. The AACR NextGen Grant support is a key to success of this project.

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AACR-Takeda Oncology NextGen Grant for Transformative Cancer Research

Goodarzi_90x110.jpg

Hani Goodarzi, PhD
Assistant Professor
University of California, San Francisco
San Francisco, California
The RNA structural code that drives colon cancer progression and metastasis

Scientific Statement of Research
RNA molecules carry functional information in their secondary structure. These structural elements play a crucial role in post-transcriptional regulation of gene expression. Deciphering the structural information encoded in the cancer transcriptome represents a major challenge in cancer biology. To overcome this challenge, we recently introduced TEISER, a computational platform for discovering regulatory structural elements. Using this framework, we have identified a number of structural elements that are putative targets of aberrant regulatory programs in cancer. This proposal focuses on the discovery of one such pathway, mediated through a previously uncharacterized structural element, involved in colon cancer metastasis. To functionally dissect this structural element (named CASE) and to understand its role in colon cancer progression, we propose the following aims: (1) characterize CASE and its role in gene expression regulation; (2) identify the factor(s) that mediates RNA stability by binding CASE; (3) assess the clinical relevance of the CASE-mediated regulatory pathway.

Biography
Dr. Goodarzi is an assistant professor in the Departments of Biochemistry and Biophysics and Urology, and a member of the Helen Diller Family Comprehensive Cancer Center. Dr. Goodarzi was previously an Anderson Cancer Center postdoctoral fellow in the laboratory of Dr. Sohail Tavazoie at the Rockefeller University. He received his PhD in molecular biology from Princeton University in 2010. Currently, he develops systems-level experimental and computational methods to study post-transcriptional regulatory phenomena that govern cancer progression. Dr. Goodarzi has won a number of honors and awards, including the 2015 Tri-Institutional Breakout Prize and the 2015 Regional Blavatnik Award.

Acknowledgement of Support
The AACR NextGen Grant for Transformative Cancer Research provides research support at a critical juncture in my scientific career. Through this support, my lab can focus on areas of cancer research that remain largely understudied. Moreover, this recognition provides a platform for fostering collaborations with other AACR members.

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