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FINDING CURES TOGETHER<sup>SM</sup>


AACR-Takeda Oncology Fellowships  

The AACR-Takeda Oncology (formerly Millennium Pharmaceuticals) Fellowships represent a joint effort to promote and support mentored young investigators to conduct lymphoma and multiple myeloma research and to establish successful career paths in these fields. Eligibility is limited to postdoctoral and clinical research fellows who will have completed their most recent doctoral degree within the past five years. The research proposed for funding may be basic, translational, clinical, or epidemiological in nature. 

2018 Grantees

AACR-Takeda Oncology Myeloma Research Fellowship

Priscillia Lhoumaud, PhDPriscillia Lhoumaud, PhD
Postdoctoral Fellow
New York University
New York, New York
headshot_1 line spacerImpact of NSD2 overexpression on gene regulation in multiple myeloma

Scientific Statement of Research
In multiple myeloma (MM), the t(4;14) chromosome rearrangement detected in 15 percent of patients is associated with poor prognosis. This translocation leads to overexpression of the histone methyltransferase, NSD2. Upregulation of NSD2 globally increases H3K36me2 while reducing the level of H3K27me3, altering gene expression programs in a manner that is poorly understood. Dr. Lhoumaud has determined that an expansion of H3K36me2 and a reduction of H3K27me3 domains are linked to changes in enhancer activity and binding of the chromatin architectural protein, CTCF. She will test the hypothesis that alterations in chromatin modifications can activate oncogenic transcriptional programs through changes in chromosome organization. One important goal of this work is to investigate whether changes in gene regulation that occur downstream of NSD2 overexpression can be reversed. The findings concerning the plasticity of NSD2-mediated changes will be important for determining whether drugs that target histone modifications are a viable option for patient treatment.

Biography
Dr. Lhoumaud received her PhD in molecular biology in 2014 from the University of Toulouse in France under the mentorship of Dr. Olivier Cuvier. She studied the role of the methyltransferase dMes-4 (the Drosophila orthologue of NSD2) in transcriptional and post-transcriptional regulation and published her findings in EMBO Journal. Since 2015, Dr. Lhoumaud has been a postdoctoral scholar in the laboratory of Prof. Jane Skok at NYU Langone Health. She studies the impact of NSD2 overexpression in gene regulation in Multiple Myeloma.

Acknowledgement of Support
I am extremely grateful to the grant review committee for selecting me as a recipient of the Myeloma Research Fellowship. This award will provide financial support for me to accomplish my research goals and allow me to attend the AACR annual meeting to learn more about cancer biology and therapeutics.

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AACR-Takeda Oncology Lymphoma Research Fellowship

Ming Sun, PhDMing Sun, PhD
Postdoctoral Scholar
University of California, San Francisco
San Francisco, California
headshot_1 line spacerThe structural mechanisms governing K-RAS and PI3Kinase signaling

Scientific Statement of Research
KRAS is the most frequently mutated oncogene in human cancer. It activates a wide range of signaling pathways, including type I phosphatidylinositol 3-kinase (PI3K) as the principal downstream effector. Moreover, PI3K is also a predominant oncogene in lymphoma and other human cancers. Together, the RAS-PI3K signaling axis has received enormous attention as targets for cancer therapy. However, investigating the allosteric interplay between RAS, PI3K and their membrane-binding dynamics has continued to be challenging. To explore these questions, this project will use the advanced single particle cryo-electron microscopy approach, combined with biochemical assays, to structurally characterize full-length PI3K in different physiological settings: in solution, membrane-bound and KRAS bound. These results will provide fundamental insights into the allosteric mechanisms that regulate KRAS-PI3K signaling and pave the way for structure-based inhibitor design to restrict RAS-PI3K mutant activities in human cancers.

Biography
Dr. Sun obtained her BS degree at Tsinghua University in 2011 and PhD at Columbia University in 2016. During her graduate studies, she worked with Dr. Joachim Frank, investigating dynamical features of RNA-protein complexes using single particle cryo-electron microscopy. Her thesis work explored the parasitic translation regulation mechanisms and developed a tool to study reaction at a sub-second time scale. In 2017, she joined University of California, San Francisco, as a postdoctoral scholar working with Dr. Adam Frost and Dr. Kevan Shokat to study molecular mechanism governing RAS-PI3K signaling pathway, using a combination of structural and biochemical tools.

Acknowledgement of Support
I am absolutely honored to receive the 2018 AACR Lymphoma Research Fellowship for my research on KRAS and PI3Kinase signaling. It will provide me a valuable opportunity to bring my expertise in biophysics to the field of cancer research and prepare me to become an independent research scientist at the frontier of biomedical research.

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