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​AACR-Bristol-MyersSquibb Fellowships

The AACR-Bristol-Myers Squibb Oncology Fellowships represent a joint effort to encourage and support mentored young investigators to conduct cancer research. Eligibility is limited to postdoctoral and clinical research fellows who have completed their most recent doctoral degree within the past five years. Proposed research projects must be translational or clinical in nature.

2018 Grantees

AACR-Bristol-Myers Squibb Fellowship for Young Investigators in Translational Immuno-oncology

Burles Avner Johnson, III, MD, PhDBurles Avner Johnson, III, MD, PhD
Clinical Fellow
Johns Hopkins University-School of Medicine
Baltimore, Maryland
headshot_1 line spacerTargeting indoleamine 2,3 dioxygenase to improve anti-tumor immunity

Scientific Statement of Research
Immunotherapy has revolutionized cancer therapy by utilizing the unique ability of the immune system to survey the entire organism. Often, the immune system detects preclinical lesions and mounts a response to block tumor growth before they become clinically relevant. However, tumors can transmit immune signals to escape attack, in part by inducing immune suppression, or “tolerance.” Thus, the goal of immunotherapy is to “break tolerance.” One strategy is to target indoleamine 2,3 dioxygenase-1 (IDO1), a tryptophan-catabolizing enzyme expressed by a subset of antigen presenting cells (APCs) and some tumors. IDO1 expressing APCs induce tolerance via regulatory T cell activation and T cell suppression. Thus, IDO1 inhibitors are being tested in clinical trials. IDO1 pathway inhibitors have had promising early results in combination with checkpoint immunotherapy in melanoma patients. Our goal is to further understand how IDO1 pathway inhibitors work to better inform future combination clinical trials involving these therapies.

Biography
Dr. Johnson is a third year medical oncology fellow at Johns Hopkins Hospital in Baltimore, MD. He obtained his MD/PhD and completed a residency in internal medicine at the Medical College of Georgia in Augusta, GA. His PhD training was under Dr. Andrew Mellor, where he elucidated the developmental lineage of antigen presenting cells expressing indoleamine 2,3 dioxygenase-1 (IDO1). Currently, he works in the laboratory of Dr. Linda Resar, where he is studying the role of IDO1 in the tumor microenvironment.

Acknowledgement of Support
I am extremely thankful for AACR’s support through its 2018 AACR Immuno-oncology Research Fellowship. It will fund experiments to better understand a promising cancer therapy, and will help me pursue a career in tumor immunology, to study potential cancer immunotherapies. This is a major honor, and I am very grateful.

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AACR-Bristol-Myers Squibb Fellowship for Young Investigators in Translational Immuno-oncology

Rocio Vicario, PhDRocio Vicario, PhD
Research Fellow
Memorial Sloan Kettering Institute for Cancer Research
New York, New York
headshot_1 line spacerSignaling pathways driving histiocytic neoplasms

Scientific Statement of Research
This proposal is aimed at understanding the cellular and molecular targets of somatic mutations in macrophages driving histiocytoses. Histiocytoses are myeloid neoplasms that result in granulomatous lesions in multiple organs with severe clinical consequences such as neurodegeneration. Recent works have reported somatic mutations in the RAS-RAF-ERK in ~60% of patients and PIK3CAH1047R activating mutation in ~10%. However, the role of PI3K activation in the pathogenesis of histiocytoses remains unexplored. In this proposal, we aim to characterize the consequences of PIK3CAH1047R mutation in macrophages in mice; to identify whether common signaling effectors are being activated in macrophages with BRAFV600E or PIK3CAH1047R and test targeted therapy and immunotherapy to improve the consequences of macrophage activation in particular of neurodegeneration. Additionally, using improved protocols we will identify mutations for patients without molecular diagnosis. Altogether, our project has basic and translational relevance and will identify therapeutic strategies to control macrophage activation in histiocytoses.

Biography
Dr. Vicario obtained her bachelor’s degree in Biology from the National University of Mar del Plata in Argentina where she investigated the role of progesterone receptor in breast cancer. She pursued her PhD degree at the Vall d'Hebron Institute of Oncology in Barcelona, Spain, where she focused on understanding therapy resistance to HER2 blockade and the development of novel immunotherapies for HER2+ breast cancers. In 2017 Rocio joined Dr. Geissmann’s lab at Memorial Sloan Kettering as a postdoctoral fellow to study the role of tissue resident macrophages in human diseases and unravel the mutations that drive their dysfunction in histiocytoses.
 
Acknowledgement of Support
The AACR Immuno-oncology Research Fellowship will provide me with extraordinary support for my research training and career development.  Thanks to this award I will be able to continue my research towards better understating of the pathophysiology of histiocytoses, a rare but occasionally severe neoplasms affecting children and adults.

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2016 Grantees

AACR-Bristol-Myers Squibb Fellowship in Translational Immuno-oncology

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 Randy F. Sweis, MD
Clinical Fellow, Division of Hematology/Oncology
The University of Chicago
Chicago, Illinois
Facilitating immunotherapy responses in non-T cell-inflamed bladder cancer

Scientific Statement of Research
Urothelial bladder cancer is a lethal disease with very few novel therapies developed over the past 30 years. Recently, the anti-PD-L1 antibody, atezolizumab, was approved for metastatic bladder cancer. Despite the impressive and durable responses observed in some patients, most do not respond to immune checkpoint blockade. Mechanisms of resistance in bladder cancer remain poorly understood. Intratumoral T-cell infiltration has been associated with improved survival and response to immunotherapy. To develop strategies that can overcome primary immunotherapy resistance, this proposal will molecularly characterize non-T cell inflamed tumor microenvironment, and mechanistically elucidate whether certain oncogenic drivers are causally related to T-cell exclusion and responsible for anti-PD-1/PD-L1 resistance. To explore this hypothesis, both clinical tissue samples and preclinical laboratory modeling will be used for experimental investigation.

Biography
Dr. Sweis attended the University of Chicago for his undergraduate studies, where he obtained bachelor’s degrees in both biological chemistry and economics. He then took a position at Merck Research Laboratories as a medicinal chemist working in drug development, until he returned to the University of Chicago Pritzker School of Medicine to obtain his MD degree. His internal medicine residency training was completed at the University of Michigan. Most recently, he returned to the University of Chicago for a combined fellowship in hematology/oncology and clinical pharmacology and pharmacogenomics.

Acknowledgement of Support
Receiving the 2016 AACR-Bristol-Myers Squibb Fellowship in Translational Immuno-oncology is a tremendous honor. It will enable me to complete an important project with high potential for rapid translation into novel treatments that will allow more patients to benefit from modern immunotherapies.

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AACR-Bristol-Myers Squibb Fellowship in Translational Immuno-oncology

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Brian Christopher Miller, MD, PhD
Clinical Fellow, Division of Hematology/Oncology
Dana-Farber Cancer Institute
Boston, Massachusetts
Dissecting mechanisms of PD-1 blockade with single-cell RNA-sequencing

Scientific Statement of Research
Anti-PD-1 therapy is an important new treatment for many different malignancies, but overall response rates are less than 40 percent and the mechanisms of action are not fully known. The goal of this study is to understand the mechanisms by which anti-PD-1 therapy augments the antitumor immune response. Dr. Miller and his collaborators have developed a novel massively parallel single-cell RNA-sequencing (scRNA-seq) platform that comprehensively defines the global expression profile of all major immune lineages in the tumor microenvironment. They will create a cellular map of the tumor immune microenvironment to identify the populations required for the efficacy of anti-PD-1 therapy. Based on their preliminary findings, they will study the contribution of NKT cells to antitumor immunity by testing the hypothesis that NKT cell activity is inhibited in tumors by PD-1 signaling. This work has the potential to discover novel pathways that regulate the immune response and suggest rational combination therapies.

Biography
Dr. Miller completed his undergraduate degree at Princeton University and earned his MD and PhD degrees from Washington University in St. Louis, where he studied the functions of autophagy genes in lymphocytes and osteoclasts. Following his residency in internal medicine at Duke University Hospital, he is now an oncology fellow and postdoctoral researcher at the Dana-Farber Cancer Institute, working with Drs. Nicholas Haining and Arlene Sharpe. Dr. Miller’s long-term research objective is to understand the complex interaction of the immune system with cancer cells, with the goal of identifying novel targets for cancer immunotherapy.

Acknowledgement of Support
I am honored to be awarded the 2016 AACR-Bristol-Myers Squibb Fellowship in Translational Immuno-oncology, which will fund my research to understand the mechanisms of anti-PD-1 therapy. This award will help me to launch my career as an independent investigator in tumor immunology.

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