Nipun S Basrur, PhD, Postdoctoral Fellow Harvard University Cancer leads to changes in the activity of the nervous system, such that symptoms like fatigue and loss of appetite are widely observed in cancer patients, regardless of cancer type. Conversely, the nervous system can directly control inflammation, which impacts cancer progression. However, we do not understand how neurons and tumors communicate. Can neurons sense tumors, and how neuronal responses to tumor-derived cues affect tumor progression and response to immunotherapy? Dr. Basrur’s project aims to identify and characterize the signaling pathways that signal the presence of tumors to the nervous system, and to define the neuronal populations that directly interact with tumors. He will take a targeted approach, focusing on sensory neurons of the vagus nerve, which he found express receptors for inflammatory cytokines and immune checkpoint ligands. He will first verify that these neuronal subtypes respond to cytokines of interest, and then will test the role of these signaling pathways in mouse models of lung cancer where the receptors of interest are selectively deleted within specific neuronal subtypes. Next, he will focus on neurons that directly infiltrate implanted lung tumors and use tracing methods to define the neuronal subpopulations. Guided by these results, he will use transgenic mouse models to activate or inhibit the neuronal subpopulations of interest and track the effect of this manipulation on lung tumor growth. These studies will allow for the design of strategies to alleviate cancer-induced physiological changes, and strategies to manipulate neuronal activity to control tumor progression and responsiveness to therapy. Projects and Grants Characterization of the molecular and cellular basis of neuron-tumor interactions in lung cancer Albert Einstein College of Medicine | All Cancers | 2022 | Stephen Liberles, Ph.D.
