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. Funded research projects are translational or clinical in nature.
In lung cancer, 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 are set to 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. 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 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.
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 is set to 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 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 using applied statistics, machine learning, and efficient computer algorithms to address fundamental biological questions by integrative analysis and interpretation of high-throughput data. He is currently a postdoctoral researcher in the Computational and Systems Biology Program at Memorial Sloan Kettering Cancer Center. 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.
Histiocytoses are myeloid neoplasms that result in granulomatous lesions in multiple organs with severe clinical consequences, such as neurodegeneration. Previous works have reported somatic mutations in the RAS-RAF-ERK in ~60% of patients and PIK3CAH1047R activating mutation in ~10% patients. Dr. Vicario has been characterizing the consequences of PIK3CAH1047R mutation in macrophages in mice, identifying whether common signaling effectors are being activated in macrophages with BRAFV600E or PIK3CAH1047R, and testing targeted therapy and immunotherapy to improve the consequences of macrophage activation.
Dr. Vicario obtained her PhD degree at the Vall d’Hebron Institute of Oncology in Barcelona, Spain. She is currently a postdoctoral fellow at Memorial Sloan Kettering, where she studies the role of tissue resident macrophages in human diseases and unravels 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.