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FINDING CURES TOGETHER<sup>SM</sup>

​AACR-Bayer Fellowships 

The AACR-Bayer Fellowships represent a joint effort to promote hepatocellular or prostate cancer research. These grants encourage and support mentored young investigators to conduct cancer research and to establish successful career paths in the 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.

2018 Grantees

AACR-Bayer Stimulating Therapeutic Advances through Research Training (START) Grant

Labrecque_MarkMark P. Labrecque, PhD
Senior Fellow
University of Washington
Seattle, Washington
spacer_1lineFGF and AR pathway inhibition in AR-expressing CRPC

Scientific Statement of Research
Prostate cancer cell survival and proliferation are driven by androgen receptor (AR) function. Despite the implementation of potent AR pathway inhibitors, the majority of tumors recur as metastatic castration-resistant prostate cancer (mCRPC). The proposed research is guided by the hypothesis that AR-expressing mCRPC bypass AR pathway blockade through activation of the fibroblast growth factor (FGF) pathway. Thus, combined FGF and AR pathway inhibition will be more effective at preventing tumor cell proliferation and survival than AR inhibitor monotherapy. Dr. Labrecque will investigate the efficacy of FGF and AR pathway inhibitors alone or in combination in AR-expressing CRPC cell lines, organoids and preclinical patient-derived xenograft (PDX) models. Additionally, the mechanisms driving combination therapy response and resistance will be determined through deep molecular profiling of treatment-resistant cell lines and PDX tumors. The overarching goal of the research is to support a combination therapy clinical trial in men with AR-expressing mCRPC.

Biography
Dr. Labrecque received his BSc in Cell Biology and Genetics from the University of British Columbia and his PhD in Health Sciences from Simon Fraser University. His doctoral research was supported through a Prostate Cancer Canada fellowship and focused on transcription factor crosstalk and the role of the retinoblastoma protein in hypoxic tumor microenvironments. In 2017, he joined the Department of Urology at the University of Washington as an Institute for Prostate Cancer Research postdoctoral fellow. Currently, he uses metastatic biospecimens, patient-derived xenograft models and in vitro approaches to understand and target the molecular underpinnings driving treatment-resistance in advanced prostate cancer.

Acknowledgement of Support
I am profoundly thankful and honored to be awarded an AACR-Bayer START Grant. This generous support and the opportunity to train with an industry leader like Bayer will be instrumental for my career development and will hopefully lead to better therapies for men with advanced prostate cancer.

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AACR-Bayer Stimulating Therapeutic Advances through Research Training (START) Grant

Subramanyam_ShyamalShyamal Subramanyam, PhD
Research Fellow
Memorial Sloan Kettering Cancer Center
New York, New York
spacer_1lineTargeting CHK2 regulation of BRCA1 in DNA end resection for novel therapies

Scientific Statement of Research
A large percentage of cancers have mutated genes involved in DNA repair and homologous recombination. The cellular capacity to repair DNA damage via homologous recombination depends on a process called DNA end resection, defects in which cause severe genomic instability often leading to cancer. Utilizing genome editing tools to precisely calculate the extent of DNA resection, Dr. Subramanyam aims to determine how DNA end resection is regulated. These studies complement his second aim, where through live cell super-resolution microscopy he plans to characterize the spatio-temporal dynamics of proteins involved in DNA end resection. These studies allow real time visualization of DNA end resection in response to induced DNA damage. Precise understanding of this process will aid in development and validation of the mechanisms of inhibitors targeting end resection. These inhibitors can be utilized toward combination therapy with existing drugs, exploiting synergistic lethality in cancers that are resistant to standard treatment.

Biography
Growing up in India, Dr. Subramanyam was introduced to the world of experimental biology at a very young age. This led him to pursue an undergraduate program in biotechnology at Visvesvaraya Technological University. While working at the Biocon Bristol-Myers Research Center in India, Dr. Subramanyam contributed to several early drug discovery programs and discovered a keen interest in cancer biology. He later moved to the United States (University of Illinois at Urbana-Champaign) to pursue his graduate studies where, in Dr. Maria Spies’s lab, he focused on understanding molecular mechanisms in DNA repair at a single molecule level in vitro. Dr. Subramanyam’s postdoctoral research focuses on building on his experiences from graduate school to visualize molecular mechanisms of DNA repair within living cells. In his spare time, he likes to explore wildernesses around the world and to experience new cultures. At home, he is trying to teach himself how to play the guitar and learn two languages. 

Acknowledgement of Support
I thank the committee for appreciating and generously supporting my proposed work for the 2018 AACR-Bayer Stimulating Therapeutic Advances through Research Training Grant. In addition to facilitating my development as an independent scientist, I hope we can make significant inroads into further understanding the fundamental mechanisms that regulate DNA repair.

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2017 Grantees

AACR-Bayer Hepatocellular Carcinoma Research Fellowship

Bhan_90x110.jpgIrun Bhan, MD
Clinical and Research Fellow, Gastroenterology
Massachusetts General Hospital
Boston, Massachusetts
Transcriptomics of hepatocellular carcinoma in diagnosis and immunotherapy

Scientific Statement of Research
Hepatocellular carcinoma (HCC), which arises in the setting of chronic liver disease, is the second most common cause of cancer-related death worldwide. As HCC occurs in an at-risk population and early-stage disease can be cured, surveillance can reduce mortality through early detection. For late-stage disease, immunotherapy holds great promise for an as-yet undefined subgroup of patients. For both early detection and immunotherapy response prediction, novel biomarkers are urgently needed. Promising biomarkers include those derived from circulating tumor cells and cancer exosomes, both of which are shed by tumors into the vasculature where they can be detected by “liquid biopsy.” This work will develop novel RNA-based biomarkers from primary HCC tissue and liquid biopsies that will enable early detection, monitoring, risk stratification, and treatment selection for patients with HCC.

Biography
Dr. Irun Bhan is a clinical and research fellow in gastroenterology/hepatology at Massachusetts General Hospital. He graduated from Johns Hopkins University where he studied biophysics. He earned his MD degree from the Harvard-MIT Health Sciences and Technology program at Harvard Medical School, graduating magna cum laude and serving as a Howard Hughes Medical Institute fellow. He subsequently completed internal medicine residency and chief residency at Columbia University.  Working in the laboratories of Dr. Daniel Haber and Dr. David Ting, Dr. Bhan’s current research interests include the early detection and treatment of hepatocellular carcinoma in chronic liver disease patients.

Acknowledgement of Support
I am immensely thankful for the 2017 AACR Gertrude B. Elion Cancer Research Award which will allow me to pursue a career in innovative cancer research. My hope is that the funded project will have a major impact for patients suffering from chronic liver disease and hepatocellular carcinoma.

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AACR-Bayer Prostate Cancer Research Fellowship

Conn_90x110.jpgCrystal S. Conn, PhD
Postdoctoral Fellow
University of California, San Francisco
San Francisco, California
                     Deciphering and targeting translational adaptations in prostate cancer

Scientific Statement of Research
Recent insights into the genetic landscape of cancer have depicted an explosion of diagnostic and clinical biomarkers using gene expression profiling. However, not all changes at the transcription level translate into proteomic expression; limiting the predictive power of mRNA based prognostic biomarkers. Genetic alterations creating oncogenic lesions also remain difficult to target pharmacologically. Despite these limitations, there arise phenotypic ‘crutches’ that cancer cells rely on for their unlimited growth and adaptation for survival. Dr. Conn’s research, proposes to uncover and mechanistically determine adaptive signaling advantages that are translationally activated to rewire the proteome in cancer cells. Her results in the Ruggero Lab at UCSF will be vital in delineating the role of adaptive responses during cancer progression, identifying relevant biomarkers, and offering an innovative line of therapies targeting select vulnerabilities for advanced prostate cancer associated with decreased patient survival.

Biography
Dr. Conn received her bachelor's degree in biochemical molecular biology from Penn State University and completed her doctorate in molecular biology and genetics in 2013 from Cornell University. She joined Dr. Davide Ruggero's lab at UCSF in Fall 2013 to pursue the study of mRNA translational regulation, and the molecular mechanisms behind the oncogenic stress response in cancer. As a postdoctoral fellow, she is currently testing the therapeutic implications of targeting translation initiation in combination with oncogenic stress response pathways using novel genetic mouse models and pharmacological agents.

Acknowledgement of Support
I am extremely humbled and thankful for the generous support provided by the AACR-Bayer Prostate Cancer Research Fellowship, not only for the development in my own research progress within the Ruggero Lab at UCSF, but also at such a pivotal moment for science funding. My sincerest gratitude.

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