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Debbie’s Dream Foundation-AACR Gastric Cancer Research Fellowships

The Debbie’s Dream Foundation-AACR Gastric Cancer Research Fellowships represent a joint effort to encourage and support mentored young investigators to conduct gastric cancer research and to establish successful career paths 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, clinical, or epidemiological in nature and must have direct applicability and relevance to gastric cancer.

2019 Grantees

Debbie’s Dream Foundation-Stupid Strong-AACR Gastric Cancer Research Fellowship, in Memory of Candice Netzer
Ankur Nagaraja, MD, PhD

Ankur Nagaraja, MD, PhD

Postdoctoral Fellow
Dana-Farber Cancer Institute
Boston, Massachusetts
Replication stress as a therapeutic vulnerability in gastric cancer

Scientific Statement of Research
Gastric and esophageal adenocarcinomas (GEAs), now classified as a single entity, are devastating diseases that account for over 750,000 deaths annually. Seventy percent of these cancers are characterized by marked chromosomal instability (CIN), which is especially prevalent in tumors emerging near the gastroesophageal junction, the precise type of cancer where incidence rates have been increasing dramatically. To build a foundation for the development of rational combination therapies in GEA, this proposal focuses on Cyclin E1 (CCNE1), one of the most frequently amplified oncogenes in GEA and a key driver of CIN in this disease. A functional genomic screen revealed a key class of CCNE1-related vulnerability – replication stress – including several readily translatable candidate targets for these cancers. The goals of this project are to validate enhancement of replication stress as a therapeutic vulnerability and to determine optimal therapeutic combinations that exploit replication stress in CCNE1-amplified GEA.

Biography
Dr. Nagaraja earned his BS in biological sciences from Stanford University and his MD and PhD from Baylor College of Medicine in the Department of Molecular and Human Genetics. He completed his residency in internal medicine at Massachusetts General Hospital and fellowship in medical oncology at Dana-Farber Cancer Institute, where he is currently an instructor of medicine in the Division of Gastrointestinal POncology. His research seeks to address two key challenges in conquering gastroesophageal cancer: i) the scarcity of models that faithfully reflect the genetics and pathogenesis of the disease, and ii) the absence of highly effective biomarker-driven therapeutic approaches.

Acknowledgment of Support
I am deeply honored and grateful to receive the 2019 Debbie’s Dream Foundation-Stupid Strong-AACR Gastric Cancer Research Fellowship, in Memory of Candice Netzer. This award enables me to protect additional time for research and provides integral support for my career development into an independent academic investigator leading a laboratory focused on translational research in gastroesophageal cancer.

Debbie’s Dream Foundation-AACR Gastric Cancer Research Fellowship, in Memory of Debbie Zelman, Esq.
Katsumi Yamaguchi, PhD

Katsumi Yamaguchi, PhD

Research Fellow
Johns Hopkins University
Baltimore, Maryland
Role of LINE-1 retrotransposition in gastric cancer

Scientific Statement of Research
Gastric cancer (GC) is multifactorial, with complex host genetic and environmental factors contributing to its development and progression. Varieties of molecular dysfunctions occur simultaneously with many genetic changes, leading to high clonal heterogeneity in GC. Somatic retrotransposon insertions in the cancer genome have recently been established as a widespread mutational phenomenon. Previously, the lab developed a technique, called L1-seq, to find L1 retrotransposons in the human genome and used it to find somatic L1 insertions in various cancers, including GC. In addition, Dr. Yamaguchi modified the L1-seq protocol, to allow identification of somatic L1 insertions in specific individual cells in frozen tissues. By studying GC, Dr. Yamaguchi will detect L1 insertions in single cell nuclei. Those insertions can be hallmarks to trace tumor patterns of evolution and development. This will help to determine the heterogeneity of novel insertions in GC and define the relationship between retrotransposon insertions and progression of GC.

Biography
Dr. Yamaguchi has been a postdoctoral fellow in Haig Kazazian’s lab at Johns Hopkins University School of Medicine since 2016. He is modifying current L1-seq protocols to better identify somatic retrotransposon insertions in individual cells. He previously worked at the Tokyo Institute of Technology, Japan where he received his PhD studying mechanisms of retrotransposon integration into the genome. He is currently working on the relationship between caner and L1 retrotransposon insertions.

Acknowledgement of Support
I am greatly honored to be a recipient of the 2019 Debbie’s Dream Foundation-AACR Gastric Cancer Research Fellowship, in Memory of Debbie Zelman, Esq. The fellowship provides funding that will allow me to continue pursuing my research in understanding the relationship between cancer and retrotransposons and enable me to contribute to the advancement of the field.

Debbie’s Dream Foundation-AACR Gastric Cancer Research Fellowship, in Memory of Petros Palandjian
Youn-Sang Jung, PhD

Youn-Sang Jung, PhD

Postdoctoral Fellow
University of Texas MD Anderson Cancer Center
Houston, Texas
CRAD, a cytoskeletal tumor suppressor, in diffuse-type gastric cancer

Scientific Statement of Research
Diffuse-type gastric cancer (DGC) displays distinct features including poor differentiation, excessive mucin deposition, signet-ring cell morphology, and cell polarity loss. However, the detailed mechanism of DGC development remains elusive. Recently, Dr. Jung and colleagues found that CRAD plays crucial roles in filamentous actin (F-actin) assembly and Cadherin-Catenin-Actin (CCA) complex maintenance through capping protein inhibition. Moreover, several studies have shown that nuclear F-actin is required for DNA damage response (DDR) and chromosomal stability. Comparable to the mutations in the CDH1 gene, CRAD gene is frequently altered in gastric cancer, which led Dr. Jung to hypothesize that CRAD inactivation impairs the CCA complex and DDR, which hyperactivates Wnt signaling and leads to genomic instability for DGC development. To test this, he will determine the role of CRAD inactivation in CCA complex destabilization using Crad genetically engineered mouse (GEM) models and will elucidate the detailed molecular mechanism of how CRAD loss results in the genomic instability in DGC.

Biography
Dr. Jung is a postdoctoral fellow in the Jae-Il Park laboratory at MD Anderson Cancer Center. He completed his BS in molecular biology and MS/PhD in cancer biology at Pusan National University (South Korea). Dr. Jung unveiled the new roles of Wnt/β-catenin signaling in cancer cell stemness and therapeutic resistance and revealed the mechanism of β-catenin paradox. Recently, he identified a new tumor suppressor gene associated with mucinous adenocarcinoma and continuously found cancer-specific regulators of Wnt/β-catenin signaling. His research goal is to determine the molecular basis and therapeutic targets of deregulated actin dynamics-induced tumorigenesis, including mucinous adenocarcinoma.

Acknowledgement of Support
I am extremely honored to be awarded the prestigious Debbie’s Dream Foundation-AACR Gastric Cancer Research Fellowship, in Memory of Petros Palandjian. This fellowship will strongly support my research into gastric cancer-associated actin deregulation and my career development to be an independent cancer researcher.