Growth factors and sensory neuron function in pain and nerve injury.
We are studying the mechanisms that underlie sensory neuron development, differentiation and function in the adult system. One area of interest is how neurotrophic growth factors control sensory neuron survival and regulate their functional properties. Survival and differentiation factors of particular interest are proteins in the neurotrophin (NGF, NT-3, BDNF, NT-4) and glial cell line-derived growth factor families (GDNF, artemin, neurturin and persephin). In these studies transgenic mouse lines (overexpresser and knockout models) and cultured neurons are used to identify how signaling pathways activated by growth factor binding alters survival, phenotypic expression, and physiological response properties of sensory neuron populations.
Another area of interest is how growth factor-mediated changes in signaling affects expression of ion channels involved in the perception and processing of pain signaling. A goal of this research is to identify novel transcriptional pathways activated following inflammatory or neuropathic injury in peripheral structures. One transcriptional regulator we identified as important for nerve growth and survival following injury is Sox11, a member of the Sry-type high mobility group (HMG) box family of transcription factors. Sox proteins are emerging as important transcriptional regulators best known for their key role in embryonic neuron development. The increased expression of Sox11 in adult neurons following injury suggests an important role in neuron plasticity and recovery as well. We are testing this role using RNAi treated cultured neurons combined with molecular level assays (microarray and luciferase assays, ChIPs) to identify transcriptional targets. By understanding how transcriptional signaling is regulated following nerve injury, we hope to improve our understanding of injury-associated changes in order to identify new therapeutic targets and better defined points of intervention.
Dr. Albers is a member of the Pittsburgh Center for Pain Research, a multi-departmental center comprised of basic and clinical scientists whose research centers on identifying the molecular, cellular and physiologic changes that occur in neuronal pathways that underlie persistent pain states that can develop following nerve injury or disease.
Jing, X.J., Wang, T., Huang, S., Glorioso, J.C. and Albers, K.M. Sox11 stimulates peripheral nerve regeneration in part by transcriptional activation of the regeneration-associated gene Sprr1a. Exp Neurol, 2011.
Malin, S., Molliver, D., Christianson, J., Schwartz, E.S., Cornuet, P., Albers, K.M. and Davis, B. TRPV1 and TRPA1 function and modulation are target tissue-dependent. J. Neurosci. 31: 10516, 2011.
Schwartz, E.S., Christianson, J.A., Chen, X., La, J.-H., Davis, B.M., Albers, K.M. and Gebhart, G.F. Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology, 140: 1283, 2010.
Jankowski, M., McIlwrath, S., Cornuet, P.K., Salerno, K., Koerber, H.R. and Albers, K.M. The developmentally expressed transcription factor Sox11 regulates peripheral nerve regeneration in the adult. Brain Res., 1256: 43, 2008. PMID: 19133245.
Elitt, C.M., McIlwrath, S., Lawson, J., Malin, S., Molliver, D.C., Cornuet, P.K., Koerber, H.R., Davis, B.M. and Albers, K.M. Artemin overexpression in skin enhances expression of TRPV1 and TRPA1 in cutaneous sensory neurons and leads to behavioral sensitivity to heat and cold. J. Neurosci. 26: 8578-8587, 2006. PMID: 16914684.
Albers, K.M., Woodbury, C.J., Ritter, A.M., Davis, B.M. and Koerber, H.R. Glial cell line-derived growth factor expression in skin alters the mechanical sensitivity of cutaneous nociceptors. J. Neurosci. 26: 2981-2990, 2006.