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AACR Basic Cancer Research Fellowships

The AACR Basic Cancer Research Fellowships are intended to encourage and support mentored young investigators to conduct basic cancer research and to establish a successful career path in this field. Eligibility is limited to postdoctoral and clinical research fellows who have completed their most recent doctoral degree within the past three years. The research proposed for funding may be in any area of basic cancer research.

2017 Grantees

Mao_90x110.jpgPingping Mao, PhD
Postdoctoral Research Fellow
Dana-Farber Cancer Institute
Boston, Massachusetts
Characterization of endocrine resistance mechanisms in ER+ breast cancer

Scientific Statement of Research
Selective estrogen receptor degraders (SERDs) such as fulvestrant have become important therapeutic option for patients with advanced estrogen receptor-positive (ER+) breast cancer. The goal of this study is to systematically study resistance mechanisms for fulvestrant and GDC-0810 (a new oral SERD) through integration of large-scale functional screening and genomic analysis of resistant tumor samples. 

A gain-of-function lentiviral open reading frame (ORF) screen (with 17255 ORFs in the library) showed that the top resistance genes for fulvestrant and GDC-0810 in ER+ T47D cells are enriched in PI3K/Akt, ERbB/HER and FGF/FGFR pathways. In addition, several genes in Wnt pathway conferred SERD resistance. Dr. Mao hypothesizes that activation of Wnt pathway is sufficient to cause SERD resistance and inhibition of Wnt pathway can restore sensitivity to SERDs. She will conduct in vitro studies to test this hypothesis and further interrogate the clinical significance of Wnt pathway in over 200 SERD-resistant tumor samples. 

Dr. Mao aims to identify additional resistance genes for SERDs through a secondary screen and functional validation studies. These results will be cross-referenced with genomic and transcriptomic analysis of resistant tumors to identify clinically significant resistant mechanisms. Completion of this study will enable us to discover novel therapeutic target and rationally design combination therapies to overcome or prevent resistance to a single SERD agent.

Biography
Dr. Mao received a BS in biological science and biotechnology in 2009 from Tsinghua University in China. She received her PhD in experimental and molecular medicine in 2014 from Geisel Medical School at Dartmouth College, after completing her thesis under the mentorship of Dr. Michael Spinella. Dr. Mao presented her work at the 2012 and 2014 AACR Annual Meeting and has published her findings in the Journal of Biological Chemistry and PLOS One. In 2015, she joined the Wagle laboratory at Dana-Farber Cancer Institute as a postdoctoral fellow to work on understanding and overcoming mechanisms of resistance in advanced breast cancer.

Acknowledgement of Support
I gratefully thank the grant review committee for selecting me as a recipient for this fellowship. The fellowship will provide funding for laboratory equipment and supplies required for my proposed research project, financially support my effort in pursuing drug resistance mechanisms in breast cancer and allow me to attend AACR conferences to broaden my knowledge in cancer research.

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Huang_90x110.jpg

Chun-Hao Huang, PhD
Postdoctoral Scholar
University of California, Berkeley
Berkeley, California
Understanding cellular response to viral translation during tumorigenesis

Scientific Statement of Research
The central dogma of molecular biology describes the flow of the genetic code from DNA through RNA to proteins. Beyond its role for protein production, how RNA can facilitate translational control is incompletely understood. Hepatitis C virus, which infects 170 million people globally, employs an unusual strategy to hijack the host translation machinery to synthesize viral proteins using an internal ribosome entry site (IRES) RNA. Although this mechanism is known to play an important role, a detailed understanding of the interplay between host immunity and virus infection is essential. Therefore, this proposal applies genomic, biochemical, and animal modeling approaches to: 1) determine IRES RNA-mediated mechanisms for controlling HCV translation, and 2) study the cellular immune response to HCV translation. Successful completion of the proposed work will provide a deep understanding of translational interactions between virus and host during tumorigenesis, and could lead to development of effective cancer prevention and immunotherapy.

Biography
Dr. Huang is a postdoctoral scholar in the laboratory of Prof. Jennifer Doudna at UC Berkeley. Dr. Huang received his BS from National Taiwan University and PhD from Weill Cornell Medicine/Memorial Sloan Kettering Cancer Center under the mentorship of Dr. Scott Lowe and Dr. Charles Sherr. During his PhD, he studied transcriptional drivers and dependencies in liver cancer by integrating functional genomics, pharmacological approaches and transgenic mouse models. Dr. Huang received several awards, including AACR Scholar-in-Training Award, Robert Bosch Stiftung Fellow of the 64th Lindau Nobel Laureate Meeting, and Google Scholarship to attend Singularity University at NASA Ames Research Center.

Acknowledgement of Support
I deeply thank AACR for its continuous support during my journey in cancer research. The 2014 AACR Scholar-in-Training Award granted me the opportunity to present my graduate work at Annual Meeting. The 2017 AACR Basic Cancer Research Fellowship will support me in pursuing my project and a successful career.

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