Injury, inflammation and a number of diseases and/or drug treatments for diseases can alter the function of sensory neurons in the periphery, spinal cord, and in the brain that result in pain or altered sensation in the periphery. The long-term goal of the Fehrenbacher laboratory is to understand how diseases and drugs can modulate the function of peripheral sensory neurons to underlie clinical neuronal dysfunction. In addition, investigators in this lab are interested in how sensory neuron function can alter cancer growth and metastasis.
With an increase in survival rates for cancer patients, a growing concern exists regarding the potential of cancer treatments—including the platinum drugs, microtubule targeted agents (taxanes, vinca alkaloids, and epothilones), proteasome inhibitors and immunomodulators—to produce neurotoxicity, which can significantly impair the quality of life in survivors. Of the various side effects of these agents, chemotherapy-induced peripheral neuropathy (CIPN) is of major concern because it occurs frequently, is debilitating, and is sometimes irreversible.
No treatment options currently exist to prevent the development or reverse the symptoms of peripheral neuropathy and this is due, at least in part, to a lack of understanding regarding the molecular mechanisms by which chemotherapeutics alter neuronal function. Therefore, a broad focus of the Fehrenbacher laboratory is on discerning the mechanisms by which chemotherapeutics alter the sensitivity and morphology of sensory neurons.
Research in the Fehrenbacher lab spans a wide scope of science, from systems biology to reductionist studies. The team currently uses animal models to examine the function of sensory neurons in vivo and in vitro. In addition, thee scientists utilize state-of-the-art molecular, cellular and biochemical techniques to identify the effects of diseases and drugs on the transcriptome and proteome of individual sensory neurons and to manipulate the neurons to mitigate these effects in an attempt to validate drug targets.
“(PQ9) Mechanistic Role of APE1 and BER in chemotherapy-induced peripheral neuropathy”
NIH R01 CA205166 (MPI: Jill Fehrenbacher/Mark Kelley)
A full list of Dr. Fehrenbacher’s publication history is available on PubMed.
Fehrenbacher JC, Guo C, Kelley MR, Vasko MR. (2017) DNA damage mediates changes in neuronal sensitivity induced by the inflammatory mediators, MCP-1 and LPS, and can be reversed by enhancing the DNA repair function of APE1. Neuroscience, 366:23-35.
Darby LM, Meng H, Fehrenbacher JC (2017). Paclitaxel inhibits the activity and membrane localization of PKCα and PKCβI/II to elicit a decrease in stimulated calcitonin gene-related peptide release from cultured sensory neurons, Mol Cell Neuro, 82: 105-117.
Shah F, Logsdon D, Messman R, Fehrenbacher JC, Fishel M, Kelley M (2017). Exploiting the APE1-Ref-1 node in cancer signaling and other diseases: from bench to clinic. Nature Partner Journals Precision Oncology. DOI: 10.1038/s41698-017-0023-0.
Fehrenbacher JC and Richardson JD (2017). NSAIDs and Acetaminophen. Brody’s Human Pharmacology: Mechanism-Based Therapeutics, 6th edition, in press.
Kelley M, Fehrenbacher JC (2017). Challenges and opportunities identifying therapeutic targets for chemotherapy-induced peripheral neuropathy resulting from oxidative DNA damage. Neural Regeneration Research, 12:72.