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TFFI: Vision and Approach

Scientific Themes

Our strategy is to tackle CIPN from basic mechanisms to clinical care. We believe that new avenues for treatment and management of CIPN will stem from fundamental insights into three scientific areas.
 
  • Genes & Genomics: Our goal is to identify genetic factors that confer CIPN susceptibility.  Some patients are more susceptible to CIPN than others. The risk of CIPN can be related to the dosage of a chemotherapeutic agent, the treatment schedule, and any co-administration of other chemotherapeutic agents.  However, recent evidence suggests that common variations in genes may be associated with the occurrence or severity of CIPN. Thus, genetic screening holds promise for designing personalized treatment regimens that target malignancies while avoiding CIPN and other disabling outcomes.
     
  • Cellular Physiology: We aim to identify cellular and molecular mechanisms of peripheral neural damage and repair.  CIPN affects peripheral sensory neurons that initiate bodily sensations, including pain, warmth, cold, itch, and touch. CIPN causes dying back of peripheral axons, which can lead to permanent neuronal damage. A major impediment to the development of new prevention strategies is our poor understanding of the cellular and molecular mechanisms that govern neuronal damage in CIPN. Modern neuroscience research holds the promise of unraveling this complexity using high-throughput approaches, preclinical in vitro models, and the use of model organisms.
     
  • Systems Neuroscience: We seek to identify the nature of the neural circuits that underpin sensory dysfunction in CIPN.  Neuronal circuits in the CNS process signals from sensory neurons to produce specific sensations, such as pain or touch. CIPN ultimately reflects dysfunctions in these neuronal circuits. Using cutting edge tools such as optogenetics, genetic circuit tracing, and live-cell imaging, members of this program will map the functional organization of neural circuitry in both normal and pathological states.