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

The AACR-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowships represent 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. Eligibility is limited to postdoctoral and clinical research fellows who will 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.

2018 Grantee

Sicong Zhang, PhDSicong Zhang, PhD
Postdoctoral Associate
The Rockefeller University
New York, New York
headshot_1 line spacerMolecular Basis of Transcriptional Dysregulation in Breast Cancer

Scientific Statement of Research
Estrogen receptor (ER)-mediated transcription requires several classes of coactivators that include the Mediator complex. Strong Mediator interactions with nuclear receptors are mediated through MED1 subunit. Upregulation of MED1 expression and phosphorylation is correlated with higher tumor grade or tamoxifen recurrence of breast cancer. Notably, both knockdown of MED1 and mutations in MED1 phosphorylation sites restore tamoxifen sensitivity, but the mechanisms underlying the causal role of MED1 in conferring the resistant state remain unclear. I aim to elucidate mechanisms by which ER interactions with the Mediator, through MED1, effect the development of breast cancer and the agonist versus antagonist tamoxifen activity in transcription of ER target genes. This project will provide detailed insights into the transcription regulatory processes in breast cancer and advance our understanding of the clinical failure of tamoxifen by deciphering the transcriptional mechanism from test tube to preclinical model, with an ultimate goal to cure breast cancer patients.

Biography
Dr. Zhang received his BS degree in biological sciences from Fudan University and PhD in cancer biology from MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences. He identified an oncogenic role of m6A demethylase in solid tumor by using epitranscriptomic study, molecular analyses and PDX models during his PhD in Dr. Suyun Huang’s lab. With a research interest of regulation of gene expression, Dr. Zhang joined Dr. Robert Roeder’s lab as a postdoctoral associate to study the molecular mechanisms for dysregulated gene transcription in breast cancer at The Rockefeller University in 2017.

Acknowledgement of Support
It’s my great honor to receive the 2018 AACR Basic Cancer Research Fellowship. This award is of critical importance to successful completion of my project. I deeply thank AACR for its continuous and generous support during my career toward an independent researcher in cancer biology.

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2017 Grantee

Gao_90x110.jpgRuli Gao, PhD
Postdoctoral Fellow
University of Texas MD Anderson Cancer Center
Houston, Texas
Tracking stromal interactions in TNBC chemoresistance by single cell RNAseq

Scientific Statement of Research
Due to lack of hormonal receptors, triple-negative breast cancer (TNBC) patients are usually treated with neoadjuvant chemotherapy followed by surgery/radiation therapy. However the majority of patients evolved resistance, often leaving no further treatment options. To date, the genetic and molecular mechanisms of chemo-resistance in TNBC patients are still poorly understood.

Dr. Gao hypothesized that chemo-resistant subclones are pre-existing in primary tumors with mesenchymal phenotypes and are maintained through stromal interactions. She will investigate tumor cell plasticity, tumor-stroma interactions, and their roles in TNBC chemo-resistance evolution by unbiased profiling thousands of single cell transcriptomes. Dr. Gao’s studies will reveal the transcriptional basis of chemo-resistance in TNBC patients, and will identify stromal cell types that play important roles in this process. Her research is expected to identify therapeutic targets in both the tumor and stromal cells that can be exploited to overcome chemo-resistance, and will, therefore, greatly benefit resistant TNBC patients.

Biography
Dr. Gao received her bachelor's degree in biotechnology and a master's degree in biochemistry and molecular biology from Yangzhou University in China. She then came to United States, and received a second master's degree in statistics and a doctoral degree in genetics and genomics with Dr. Frederic Kaye from University of Florida in 2014. To further pursue trainings in single cell genomic researches, she moved the UT MD Anderson Cancer Center to work with Dr. Nicholas Navin, where she studied the punctuated copy number evolution in triple-negative breast cancer using single cell DNA sequencing methods. Her current researches are migrating to tracing chemo-resistance in triple negative breast cancer by delineating single cell transcriptomes. To perform these studies, she and colleagues have developed a high throughput nanogrid single nuclei RNAseq method to profile thousands of single cells at low costs (~$1 per cell). Her long-term goal is to become a statistical geneticist to understand how genomic and phenotypic diversity play roles in tumor evolution and therapy resistance in cancer patients.

Acknowledgement of Support
I sincerely thank the generous funding support from the AACR Basic Cancer Research Fellowship program. This prestigious fellowship will greatly help my researches and promote my career success by expanding my knowledge and expertise in cancer genomic researches, and allowing me to become an active member of AACR research community.

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