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AACR-Incyte Corporation Fellowships  

The AACR-Incyte Corporation Fellowships represent a joint effort to encourage and support a young mentored investigator to conduct 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 five years. The research proposed for funding may be basic, translational, or clinical in nature.

2017 Grantees

AACR-Incyte Corporation Leukemia Research Fellowship

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Palaniraja Thandapani, PhD
Postdoctoral Fellow
New York University School of Medicine
New York, New York
LUNAR1, mechanism of action and validation as a therapeutic target in T-ALL

Scientific Statement of Research
T-cell acute lymphoblastic leukemia is an aggressive disease with upto 25 percent of children and 40 percent adult failing frontline therapy. The role of the non-coding genome in the pathogenesis of T-ALL remained largely unexplored until recent work from Dr. Aifantis’s group identified many long non-coding RNAs to be differentially expressed in T-ALL. LUNAR1 one such differentially expressed oncogenic lncRNA was identified to be essential for T-ALL growth in vitro and in vivo. In gaining a deeper understanding on the mechanism of action and potential to therapeutically target LUNAR1, Dr. Thandapani’s proposal involves cutting edge methods including ChIRP-seq, 4C chromosome conformation capture to identify the global targets of LUNAR1 and its influence on local chromatin architecture. Additionally, in an effort to validate LUNAR1 as a therapeutic target in T-ALL, this proposal investigates the potential of targeting of LUNAR1 using antisense oligonucleotides in in vivo T-ALL xenograft models.

Biography
Dr. Palaniraja Thandapani is a postdoctoral fellow working in the lab of Professor Iannis Aifantis at New York University. He received his PhD in experimental medicine under the supervision of Professor Stephane Richard at McGill University in 2014, where he focused on studying the role of protein arginine methylation in the translational regulation of oncogenic mRNAs harboring G-quadruplex structures. Dr. Thandapani’s current research interests include understanding how certain long non-coding RNAs contribute to T-ALL pathogenesis and the therapeutic targeting of these oncogenic long non-coding RNAs in in vivo models.

Acknowledgement of Support
I greatly acknowledge the AACR-Incyte Corporation for supporting my research in acute T cell leukemia. This fellowship will give me the opportunity to explore long non-coding RNAs as novel therapeutic targets in hematological malignancies for the first time using T-ALL as a model disease.

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AACR-Incyte Corporation Fellowship in Basic Cancer Research

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Hyun Yong Jin, PhD
Postdoctoral Scholar
University of California, San Francisco
San Francisco, California
Synthetic lethal targeting of metabolic adaptation in lymphomagenesis

Scientific Statement of Research
The emergence of acquired therapeutic resistance poses a challenge in the clinic preventing the long-term treatment of cancer patients. However, the molecular mechanisms by which cells acquire the resistance remain elusive. Here, I propose to investigate a synthetic lethal approach to target therapeutic resistance in B cell lymphoma, focusing on previously underestimated roles of metabolic reprogramming in cancer cells. Interestingly, our initial unbiased analysis of metabolic landscape revealed unexpected intracellular accumulation of specific amino acids in resistant B cells. We surmise this compensatory metabolic reprogramming may play a major role in conferring the therapeutic resistance. By combining in vivo Cas9 genome editing and ribosome profiling analysis to B cell lymphoma models, I propose to identify critical metabolic nodes that impose a synthetic lethal constraint in resistant lymphoma. I further explore possibility of utilizing dietary restriction of the specific amino acid to correct deregulated metabolic pathways in resistant tumors.

Biography
Hyun Yong Jin is a postdoctoral associate at UCSF. His research has been focused on the molecular mechanisms of non-coding RNAs that control tumorigenesis processes, with a particular emphasis on how microRNA-17~92 governs B cell lymphoamgenesis. Representatively, his graduate studies from Scripps Research Institute revealed a causative role of microRNA-17~92 in B cell lymphomagenesis, demonstrated its direct regulation of PI3K and NF-kB pathways, and elucidated mechanism of action for microRNA-17~92. Each of these studies let him to publish three first-authored papers, in EMBO, Leukemia and Plos Genetics.

Acknowledgement of Support
I want to express my appreciation for AACR’s generosity in support of basic cancer research. AACR’s long-term commitment has been incredibly helpful and allowed many post-doc scholars, including myself, to facilitate research.

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