AACR-Bristol-Myers Squibb Fellowships
The AACR-Bristol-Myers Squibb 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.
Treatment options for patients with lung adenocarcinoma have improved in recent years, but unfortunately these advances have not benefited patients with KRAS-driven adenocarcinoma. Patients with combined mutations in KRAS and STK11/LKB1 (KL) have among the worst overall survival even when compared to other KRAS-subsets such as KRAS and TP53 (KP). LKB1 is a serine-threonine kinase with numerous targets, including the energy sensor AMPK and influences cell metabolism. To explore the consequences of LKB1-mutation on the metabolic and immune components of the tumor microenvironment, Dr. Nabel and colleagues will use mass spectrometry-based methods to quantify absolute metabolite levels in the tumor interstitial fluid of KP and KL mouse tumors to study the effects of these metabolic changes on cancer cell proliferation and immunologic activation. Using Multiplex Fluorescence Immunohistochemistry, they will further evaluate differing immune cell populations in human patient tumor samples with KP and KL mutations.
Dr. Nabel obtained his MD and PhD in cell and molecular biology at the University of Pennsylvania studying APOBEC enzymology in the laboratory of Dr. Rahul Kohli. He completed internal medicine training at Brigham and Women’s Hospital and is a medical oncology fellow at the Massachusetts General Hospital Cancer Center, where he sees patients with the Center for Thoracic Cancers. Dr. Nabel is a postdoctoral fellow in the laboratory of Dr. Matthew Vander Heiden at Massachusetts Institute of Technology’s Koch Institute for Integrative Cancer Research, where he studies the metabolic basis of lung cancer biology and cancer cell proliferation.
Acknowledgment of Support
I am greatly appreciative for the 2020 AACR-Bristol Myers Squibb Immuno-oncology Research Fellowship. As a medical oncologist-in-training, I am dedicated to a career leading an independent basic science research group that will improve treatments for cancer patients through discovery. This fellowship allows me to bridge the gap between trainee and independent investigator.
Dr. Pritykin will use innovative genomic technologies to study T cell function in cancer and infection. A systematic characterization of the requirements of immunotherapeutic rescue of dysfunctional T cells in the tumor microenvironment is critically needed to improve clinical results of existing T-cell-stimulatory therapies such as checkpoint blockade. Dr. Pritykin seeks to uncover the universal regulatory and epigenetic mechanisms driving different functional states of T cells. He will leverage the multitude of published data and generate new data using genome-wide chromatin state and gene expression assays, including at single-cell level, in mouse models of cancer and infection. He will develop and apply new algorithms for integrative analysis of these data in order compare the establishment of T cell dysfunctional state in tumors and in chronic infection and to characterize T cell subsets most responsive to immunotherapies.
Dr. Pritykin is a postdoctoral researcher in the Computational and Systems Biology Program at Memorial Sloan Kettering Cancer Center. He received his MSc and PhD in mathematics from Lomonosov Moscow State University and his PhD in computer science from Princeton University. His main interest and expertise is in using applied statistics, machine learning, and efficient computer algorithms to address fundamental biological questions by integrative analysis and interpretation of high-throughput data. His main goal is to better understand immune cell function by creating better computational methods for analysis of multi-dimensional data in immunology, especially in cancer.
Acknowledgment of Support
I am tremendously grateful to the AACR and Bristol-Myers Squibb for their support of my research program. I also greatly appreciate their recognizing that systems biology approaches based on functional genomics and computational data analysis are productive and in fact absolutely necessary for further progress in immuno-oncology.
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.
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.