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​AACR-AstraZeneca Cancer Research Fellowships   

The AACR-AstraZeneca Cancer Research Fellowships represent a joint effort to encourage and support mentored young investigators to conduct cancer research and to establish a successful career path in this field. The research proposed for funding must have direct applicability to lung cancer, immuno-oncology research, or DNA damage repair pathways in ovarian cancer and may be basic, translational, clinical, or epidemiological in nature.

2017 Grantees

AACR-AstraZeneca Fellowship in Immuno-oncology Research

Peran_90x110.jpgIvana Peran, PhD
Postdoctoral Fellow
Georgetown University
Washington, D.C.
The role of cadherin-11 in immunomodulation of pancreatic adenocarcinoma

Scientific Statement of Research
Pancreatic ductal adenocarcinoma (PDAC) is a desmoplastic disease with abundant fibrotic stroma containing activated pancreatic stellate cells (PSCs). As existing  therapies that target the epithelial component of PDAC do not improve overall survival, targeting tumor-stroma crosstalk and interaction with the immune system is gaining attention as a therapeutic strategy. Inflammatory cells can modulate cancer microenvironment through PSCs by both immunosuppressive and immunostimulatory activities. Depleting the PSCs affects both activities and is just as likely to promote PDAC as inhibit it. Therefore, Dr. Peran proposes to attenuate PDAC progression in immunocompetent transgenic mouse model by targeting an important molecular component of activated PSCs, without depleting the stromal compartment, and shift the PSC/immune system toward an immunostimulatory response against cancer. Upon the treatment, identified immunomodulatory components are going to be used as targets to potentiate chemo- and immunotherapy.

Biography
Ivana Peran is a postdoctoral fellow at the Lombardi Comprehensive Cancer Center. Ivana graduated from the University of Zagreb with an engineering degree in molecular biology in 2008. As a Fulbright Science and Technology Scholar, Ivana pursued her doctoral degree in tumor biology by working on treatment response markers and new therapies in pancreatic cancer. She received her PhD degree from Georgetown University in 2014. Currently, her project is focused on the role of activated stellate cells in immunomodulation of pancreatic ductal adenocarcinoma and identifying new combination therapy strategies based on immune-related components.

Acknowledgement of Support
The 2017 AACR-AstraZeneca Fellowship in Immuno-oncology Research is of extraordinary importance to understand the involvement of immunomodulatory components in pancreatic cancer progression. Once translated into the clinic, this research will lead to better treatment options for cancer patients. I am truly honored for this opportunity to make advancements in the immuno-oncology field.

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AACR-AstraZeneca Fellowship in Immuno-oncology Research

Song_90x110.jpgMingyang Song, MBBS, ScD
Instructor
Massachusetts General Hospital
Boston, Massachusetts
Marine omega-3 fatty acids for the immunotherapy of colorectal cancer

Scientific Statement of Research
Drugs interrupting immune checkpoints have shown great promise in treating a range of late-stage malignancies. However, their clinical efficacy in colorectal cancer remains very limited. One reason for the poor response may be related to additional mechanisms of intratumoral T-cell suppression that are not sufficiently overcome by the treatment. Therefore, identifying effective combinatorial agents represents the next critical step to optimize the clinical benefit for immunotherapy.

Marine omega-3 fatty acid possesses potent immunomodulatory and potential anticancer effects. Recent data show that the anticancer effect of omega-3 may be mediated by suppression of regulatory T cells in the tumor microenvironment. Based on these findings, this proposal aims to investigate the hypothesis that omega-3 improves colorectal cancer prognosis and sensitizes tumors to checkpoint blockade therapy by inhibiting Treg-mediated immunosuppression and unleashing anti-tumor immunity. The clinical utility of this diet-based strategy is particularly appealing due to its cost and safety advantages.

Biography
Dr. Song is an instructor in medicine in the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital and Harvard Medical School. After receiving his medical training from Shandong University in China (2003-2008), Dr. Song studied cancer epidemiology at Peking University (2008-2011), and obtained his doctoral degree in nutritional epidemiology from Harvard University (2011-2015). His research focuses on the role of inflammation-related diet and lifestyle factors in the development and progression of colorectal neoplasia. In particular, he is interested in identifying nutritional factors that can be used to perturb this process for the purpose of cancer prevention and treatment.

Acknowledgement of Support
The proposed research in the AACR-AstraZeneca Fellowship will not only provide translational insights into novel dietary strategies for cancer immunotherapy, but also facilitate my transition into an independent investigator with interdisciplinary expertise in the diet–immune research  for cancer prevention and treatment.

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AACR-AstraZeneca Fellowship in Lung Cancer Research

Dardaei_90x110.jpgLeila Dardaei, PhD
Postdoctoral Research Fellow
Massachusetts General Hospital
Boston, Massachusetts
Overcoming acquired drug resistance in ALK fusion-positive lung cancers

Scientific Statement of Research
The vast majority of ALK-rearranged NSCLCs initially respond to small molecule ALK inhibitors but resistance invariably develops and limits the efficacy of these inhibitors in the clinic. The major classes of resistance are on-target genetic alterations and activation of bypass signaling pathways. The highly potent and selective third generation ALK inhibitor lorlatinib is active against all known secondary ALK kinase domain mutations that confer resistance to first and second generation ALK inhibitor therapies. However, lorlatinib fails to suppress growth of resistant cells with activated bypass signaling pathways which are detected in ~50 percent of cancers. Thus, there is an urgent need to develop new treatments for this subset of patients who develop ALK-independent resistance mechanisms and are resistant to all known ALK inhibitors. In this project, Dr. Dardaei will utilize a unique panel of patient-derived cell lines and patient-derived xenograft mouse models developed from MGH patients who developed resistance to ALK inhibitors. She will perform complementary synthetic lethal pooled shRNA screens and high-throughput combination drug screens to elucidate ALK-independent resistant mechanisms and identify effective ALK inhibitor combination therapies to overcome them.

Biography
Dr. Dardaei received her BSc degree in microbiology from Alzahra University, Iran in 2005. She obtained her MSc degree in molecular genetics from Tarbiat Modares University, Iran in 2008. She then completed her PhD in molecular medicine with a focus on molecular oncology and human genetics at the University of Milan, Italy in 2013. As a PhD student in Professor Francesco Blasi’s laboratory at IFOM in Milan, she developed a project centered on the concept of competition between oncogenes and tumor suppressors in solid and hematological malignancies. In 2014, she joined the laboratory of Dr. Engelman and recently Dr. Hata at the MGH Cancer Center as a postdoctoral research fellow, where she is currently studying targeted therapy and drug resistance in lung cancer and pursuing clinically relevant questions in the field.

Acknowledgement of Support
The 2017 AACR-AstraZeneca Fellowship in Lung Cancer Research will provide critical funding to support my research training and career development, and enable me to compete for additional funding from foundation and government funding sources. The knowledge, skills, research experience and scientific insight gained from this project will facilitate my career development towards becoming an independent investigator and help move the field of molecular targeted cancer therapy forward by studying basis of acquired resistance to targeted therapies and develop novel therapeutic strategies for cancer.

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 AACR-AstraZeneca Ovarian Cancer Research Fellowship

He_90x110.jpgYizhou J. He, PhD
Postdoctoral Fellow
Dana-Farber Cancer Institute
Boston, Massachusetts
Investigation of PARP inhibitor resistance in BRCA1-mutant ovarian tumors

Scientific Statement of Research
Ovarian cancer is the fifth leading cause of mortality in women and the most lethal of all gynecologic tumors. PARP inhibitors (PARPi) have emerged as potent antitumor agents against BRCA1/2 mutated ovarian tumors and were very recently FDA approved. However, a number of resistance mechanisms are emerging in patients being treated with PARPi. Dr. He has undertaken a systematic genome-wide investigation of the underlying cause of PARPi resistance using novel gene-editing (CRISPR) technology, and has identified genes and pathways whose loss make patients resistant to PARPi. Dr. He proposes a multi-pronged approach of investigating the molecular mechanism of resistance in cell–based assays and close examination of these genes/pathways in tumors from ovarian cancer patients that are resistant to PARPi. The goal is to define genetic alterations that drive resistance to PARP inhibitors and that will serve as the basis for rational approach to novel drug development.

Biography
Dr. He received his bachelor’s degree at Nanchang University (China) studying bio-engineering and computer science. In 2001, he came to the United States to work as a computational biology research assistant in Dr. Yue Xiong’s laboratory at UNC-Chapel Hill. In 2006, He joined graduate school at UNC-Chapel Hill mentored by Dr. Yanping Zhang studying the mechanism of genomic instability caused by altered p53 function. In 2014, he joined Dr. Dipanjan Chowdhury’s lab in the radiation oncology department at the Dana-Farber Cancer Institute. His current work focuses on exploring resistance mechanisms to chemotherapy in BRCA-mutant ovarian cancer using genome-wide CRISPR screen.

Acknowledgement of Support
I am honored to be selected for the AACR-AstraZeneca fellowship this year. This is an excellent opportunity to advance our understanding into the multifactorial chemotherapeutic response in BCRA mutated ovarian cancer, towards ultimately adapting therapeutic approaches personalized to each patient’s genome.

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