Zachary T. Campbell

Credentials: Associate Professor, Departments of Biomolecular Chemistry and Anesthesiology

Address:
8451 Wisconsin Institutes for Medical Research (WIMR)
1111 Highland Avenue, Madison, WI 53705

Education: B.S., University of Arizona; Ph.D., University of Arizona; Postdoctoral, University of Wisconsin-Madison
Areas of Expertise: Cell Structure & Signaling; Gene Expression & RNA Biology

RNA control in pain sensing neurons

Pain is pervasive and devastating. Poorly treated chronic pain is the largest source of disability in America with an estimated economic cost of more than 500 billion dollars per year. Moreover, existing strategies to disrupt pain (e.g. opiates) have well known and highly undesirable effects on reward circuits in the CNS. Better strategies for preventing chronic pain are desperately needed. In the vast majority of cases, pain originates in the periphery in a specialized type of sensory neuron called a nociceptor. Long-lived changes in their excitability – which are intimately linked to chronic pain – require de novo protein synthesis. Multiple groups have shown that peripheral inhibition of translation diminishes pain associated behaviors in pre-clinical rodent models. This suggests that translation, likely in nerve fibers, is critical for nociceptive plasticity. But what are the mRNAs that need to be locally translated and what governs the specificity of protein synthesis in nociceptors? To address these key questions, we make use of biochemistry, functional genomics, pharmacology, physiology, and genetic approaches.

The Dorsal Root Ganglion image with various pathways — Left: The Dorsal Root Ganglion (DRG) contains the cell bodies for a broad array of sensory neurons – including nociceptors – that innervate the body. Right Top – Anatomy of a eukaryotic transcript. Center – key mechanisms that have been demonstrated as analgesic in rodents. Below – a key pathway known as the integrated stress response that plays a key role in diabetic neuropathies.

Publication Highlights
Smith PR, Loerch S, Kunder N, Stanowish AD, Lou TZ, Campbell ZT. Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance in sensory neurons. Nature Communications. 2021. 12 (1): 1-16. PMCID: PMC8611098

de la Peña JB, Barragan-Iglesias P, Lou TC, Loerch S, Kunder N, Shukla T, Song J, Megat S, Moy JK, Wanghzou A, Ray PR, Hoyt K, Steward O, Price TJ, Shepherd J, Campbell ZT. Intercellular Arc signaling regulates vasodilation. J Neuroscience. 2021. 37: 7712-7726. PMCID: PMC8445061

Barragán-Iglesias P, Lou TF, Bhat V, Megat S, Burton M, Price T, Campbell ZT. Inhibition of Poly(A)-Binding Protein with an RNA mimic reduces pain sensitization in mice. Nature Communications 2018. 9(1):10. PMCID: PMC5750225

Zhou Q, Kunder N, De la Paz JA, Lasley AE, Morcos F, Campbell ZT. Global pairwise RNA interaction landscapes reveal core features of protein recognition. Nature Communications 2018. 9(1):2511. PMCID: PMC6023938