Lung Cancer
Posted November 1, 2022
Akhil Srivastava, Ph.D., University of Missouri School of Medicine
Ana Sofia Mendes, Ph.D., Michigan State University
Alexander Tsankov, Ph.D., Icahn School of Medicine at Mount Sinai
The Lung Cancer Research Program (LCRP) aims to encourage new investigators and attract them to the field, hoping to foster their growth and retention as well as bring their innovative ideas to the lung cancer research community. To do so, since fiscal year 2013 (FY13) the LCRP has offered the Career Development Award (CDA) to young, newly independent investigators, and for FY21, three investigators were awarded.
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Dr. Akhil Srivastava, Assistant Professor in the Department of Pathology and Anatomical Sciences at the University of Missouri School of Medicine, was awarded an FY21 LCRP CDA for his interest in developing a productive lung cancer translational research program and an enhanced combination therapeutic and diagnostic (“theranostic”) modality for the imaging and treatment of lung cancer. Specifically, Dr. Srivastava aims to focus his translational program on engineering extracellular vesicles (EV) isolated from patient-derived organoids (PDOs) and test them on patient-derived xenograft (PDX) mouse models. The intent is that the engineered EVs will display a high precision tumor-targeted therapeutic response that will reduce unintended cytotoxicity. By design, siRNA and recognized chemotherapy drugs like cisplatin will be conjugated to an EV; these loaded EVs will then locate cancer cells and deliver their therapeutic payload to them in PDX models. Alongside his mentors, Dr. Rajagopal Ramesh, Dr. Carolyn J. Anderson, and collaborator Dr. Jussuf T. Kaifi, Dr. Srivastava’s research will explore the ability of these EVs to operate as an additional diagnostic system that works with SPION nanoparticles, used for magnetic resonance imaging (MRI) to provide advanced tumor imaging. Dr. Srivastava aims to uncover a new form of therapeutic delivery that is organically produced by the body. Organically produced EVs are not anticipated to create an adverse immune response during their administration into the body; thus, they are less likely to face rejection, making them a more stable option for therapeutic delivery and an important avenue for personalized cancer therapy.
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Dr. Ana Sofia Mendes Leal, Assistant Professor in the Department of Pharmacology and Toxicology at Michigan State University, seeks to understand the interaction of cancer cells with the surrounding immune cells. Guided by her mentor, Dr. Karen Liby, Dr. Mendes Leal’s research is primarily focused on the immunosuppressive tumor microenvironment. In healthy lungs, macrophages, a type of immune cell, are heavily involved in the removal of reactive oxygen species (ROS) by way of the NRF2/HO-1 pathway. Dr. Mendes Leal has identified that KRAS-mutated lung cancer cells hijack the NRF2/HO-1 pathway activation, supporting the infiltration and activation of immune suppressive HO-1-positive/NRF2-activated macrophages. An increase in the quantity of HO-1-positive/NRF2-activated macrophages support tumor growth through removal of ROS and suppression of tumor-killing T cells. The FY21 LCRP CDA provides Dr. Mendes Leal an opportunity to explore the biological interaction between cancer cells and macrophages to better support cancer prevention and uncover new targets in cancer development and progression.
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Dr. Alexander Tsankov, Assistant Professor at Icahn School of Medicine at Mount Sinai, seeks to explore the role nuclear transcription factor p53 plays in shaping the tumor microenvironment (TME) in lung adenocarcinomas (LUADs). Transcription factor p53 assists in regulating the cell cycle, DNA repair, and programmed cell death, but its effects on the TME are not as well known, especially in human tumors. With guidance from his mentors Dr. Miriam Merad and Dr. Fred Hirsch, Dr. Tsankov aims to combine single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and advanced computational modeling to better understand the effect of p53 mutation on the TME of LUAD tumors. Single-cell resolution data across a large cohort of LUAD patients will inform on changes in cancer-intrinsic expression programs, cell-cell interactions, and putative therapeutic targets in patients with p53 mutation. Hence, the FY21 LCRP CDA will enable Dr. Tsankov to delineate important biomarkers that improve the stratification of patients in LUAD and lead to more optimal use of immunotherapy or combination-therapy techniques.
Links:
Abstract for Dr. Srivastava
Public and Technical Abstracts: Extracellular Vesicles (EVs) as Tumor-Targeting Theranostic for Lung Cancer
Abstract for Dr. Mendes
Public and Technical Abstracts: NRF2 Pathway Activation in the Lung Tumor Microenvironment Macrophages
Abstract for Dr. Tsankov
Public and Technical Abstracts: Deciphering the Cell-Cell Interactions and Therapeutic Targets in p53-Mutant Adenocarcinoma at a Single-Cell Resolution
Last updated Tuesday, November 1, 2022