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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 cancer research and to establish successful career paths in this field. 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.

2019 Grantees

AACR-Takeda Oncology Lung Cancer Research Fellowship
Yun Pyo Kang, PhD

Yun Pyo Kang, PhD

Postdoctoral Fellow
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida
Metabolic consequences of cysteine depletion in non-small cell lung cancer

Scientific Statement of Research
Metabolic reprogramming occurs during tumorigenesis; however, metabolic therapies to treat cancer are generally lacking. Cysteine has a crucial role in cancer proliferation and survival through the generation of multiple functional biomolecules to promote translation, redox homeostasis, bioenergetic processes, TCA cycle metabolism, and electron transport. Promisingly, Dr. Kang has found that NSCLC cells are highly dependent on cystine (oxidized cysteine), suggesting they may be vulnerable to an engineered and pharmacologically optimized enzyme to deplete systemic cyst(e)ine that was recently developed. However, the mechanism by which cysteine depletion impairs NSCLC viability is not well understood. Surprisingly, preliminary results indicate that cysteine limitation antagonizes serine metabolism and may induce serine dependency. Therefore, Dr. Kang proposes that cysteine starvation and the resulting reliance on serine metabolism in NSCLC leads to lethal consequences and that synergistic therapy targeting serine metabolism may increase anti-cysteine therapeutic efficacy.

Biography
Dr. Kang is currently a postdoctoral fellow in Dr. Gina DeNicola’s laboratory at Moffitt Cancer Center. He received his BS and PhD degrees from Seoul National University, College of Pharmacy. During his PhD studies, he received training in GC-MS and LC-MS based metabolomics and lipidomics technologies under the guidance of Dr. Sung Won Kwon. Now, applying these high-throughput techniques, he is exploring the role of metabolism during lung cancer progression mentored by Dr. DeNicola. Dr. Kang’s ultimate research goal is development of efficacious cancer therapy targeting cancer metabolism.

Acknowledgment of Support
I am greatly honored to receive the AACR-Takeda Oncology Lung Cancer Research Fellowship. This opportunity will greatly support me on my path to become an independent scientist, aiming towards the development of efficacious cancer therapy.

AACR-Takeda Oncology Myeloma Research Fellowship
Amin Sobh, PhD

Amin Sobh, PhD

Postdoctoral Fellow
University of Florida
Gainesville, Florida
Consequences and vulnerabilities of NSD2 overexpression in multiple myeloma

Scientific Statement of Research
The histone methyltransferase NSD2 is overexpressed in 15-20 percent of multiple myeloma (MM) patients due to the t(4:14) chromosomal translocation. NSD2 overexpression in MM cells drives an oncogenic epigenetic and transcriptional program. Dr. Sobh will test the hypothesis that different genetic lesions commonly detected in MM differentially impact histone methylation and transcriptional profiles driven by NSD2 overexpression. He will generate and characterize several genetically-distinct t(4:14) MM cell lines where degradation of the rearranged NSD2 allele product can be selectively induced. RNAseq and H3K36/H3K27 methylation ChIPseq in the different NSD2-high and NSD2-low isogenic pairs will define key genes deregulated by NSD2 overexpression in the context of mutations recurrently found in MM. He will further perform genome-wide CRISPR-based loss-of-function screens to identify genetic liabilities and synthetic-lethal drug-gene interactions associated with NSD2 overexpression in MM cells. This work will provide better understanding of how NSD2 contributes to MM pathogenesis and reveal insight into novel molecular-based treatment options for t(4;14) MM.

Biography
Dr. Sobh is a postdoctoral researcher in the laboratory of Dr. Jonathan Licht at the University of Florida. He received a BSc in biochemistry from the Lebanese University, a MSc in biotechnology from the American University of Science and Technology, and a PhD in comparative biochemistry from the University of California, Berkeley. His research in graduate school focused on implementing functional genomics tools to study various cellular processes, including nutrient homeostasis as well as susceptibility to chemical carcinogens and chemotherapeutic agents. As a postdoctoral researcher, Dr. Sobh is studying the molecular consequences and vulnerabilities associated with NSD2 overexpression in multiple myeloma.

Acknowledgement of Support
Receiving the 2019 AACR-Takeda Oncology Myeloma Research Fellowship is a key milestone in establishing a career in cancer research. I am pleased and grateful to be a recipient of this fellowship that will provide support for my professional development to become an independent researcher in the field of hematologic malignancies.

2018 Grantees

AACR-Takeda Oncology Lymphoma Research Fellowship
Ming Sun, PhD

Ming Sun, PhD

Postdoctoral Scholar
University of California, San Francisco
San Francisco, California
The 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.

AACR-Takeda Oncology Myeloma Research Fellowship
Priscillia Lhoumaud, PhD

Priscillia Lhoumaud, PhD

Postdoctoral Fellow
New York University
New York, New York
Impact 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 Professor 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.