The Campbell lab

The problem

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 side effects. 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 liked to chronic pain – require de novo protein synthesis. Multiple groups have shown that inhibition of translation diminishes pain associated behaviors in relevant pre-clinical models.

Our overaching goal is to understand how mRNAs are controlled in nociceptors. To achieve this, we probe fundamental molecular mechanisms that govern pain-associated plasticity in pre-clinical rodent and human iPSC models. This work has already resulted in the identification of new targets. Several lines of investigation we are pursuing are described below.

Translation

We are interested in understanding how translation is controlled in sensory neurons. Relevant publications:

1. Smith PR, Garcia G, Meyer AR, Ryazanov AG, Ma T, Loerch S, Campbell ZT. eEF2K regulates pain through translational control of BDNF. Molecular Cell. 2024. In press. PMID: 39694034

2. de la Peña JB, Kunder N, Lou TZ, Chase R, Stanowick S, Barragan-Iglesias P, Pancrazio JJ, Campbell ZT. A role for translational regulation by S6 kinase and a downstream target in inflammatory pain. British Journal of Pharmacology. 2021 Dec;178(23):4675-4690. PMC9169231

3. Smith PR, Loerch S, Kunder N, Stanowick AD, Lou TF, Campbell ZT. Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance. Nature Communications. 2021. 12(1):1-16. PMC8611098

For an detailed explaination of translational control in pain, please click here

Functional genomics

We leverage a range of sequencing approaches to understand gene control in the sensory neurons. Relevant publications:

1. Chase R, de la Peña JB, Smith PR, Lawson J, Lou TF, Stanowick AD, Black BJ, Campbell ZT.Global analyses of mRNA expression in human sensory neurons reveal eIF5A as a conserved target for inflammatory pain. FASEB J. 2022 Jul;36(7):e22422. PMID: 35747924

2. de la Peña JB, Barragan-Iglesias P, Lou TF, 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. 15;41(37):7712-7726. PMID: 34326146

3. Barragan-Iglesias P, Kunder N, Wanghzou A, Black B, Ray PR, Lou TF, de la Peña JB, Atmaramani R, Shukla T, Pancrazio JJ, Price TJ, Campbell ZT. A peptide encoded within a 5' untranslated region promotes pain sensitization in mice. Pain. 2021. 162(6):1864-1875. PMC8119312

mRNA stability

We are interested in probing how mRNA stability, storage, and localization contribute to pain signaling. Relevant publications:

1. 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. PMC5750225

2. June Bryan de la Peña, Rebecca Chase, Nikesh Kunder, Patrick R Smith, Tzu-Fang Lou, Alexander Stanowick, Prarthana Suresh, Tarjani Shukla, Samuel E Butcher, Theodore Price, Zachary T Campbell. Inhibition of nonsense-mediated decay induces nociceptive sensitization through activation of the integrated stress response. J Neuroscience. 2022. PMID: 36894318

3. Kunder N, de la Peña JB, Lou TF, Chase R, Suresh P, Lawson J, Shukla T, Black BJ, Campbell ZT. The RNA-binding protein HuR is integral to the function of nociceptors in mice and humans. J Neuroscience. 2022. 42(49):9129-9141. PMID36270801

RNA-protein interactions

Recognition of RNA by proteins is the prerequisite for all subsequent regulation and is critical to decipher. Relevant publications:

1. Campbell ZT, Valley CT, Wickens M. A protein-RNA specificity code enables targeted activation of an endogenous human transcript. Nature Struct Mol Biol. 2014. (21): 732-738. PMC4125476

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

3. Bhat VD, McCann KL, Wang Y, Fonseca DR, Shukla T, Alexander J, Qiu C, Wickens M, Lo TW, Hall TT, Campbell ZT. Engineering a conserved RNA regulatory protein repurposes its biological function in vivo. eLife. 2019. 8 e43788. PMC6351103

An up to date list of published work can be found here

Papers

The most up to date list of our papers can be found on Pubmed or on our Google scholar page

Selected references:

1. Smith PR, Garcia G, Meyer AR, Ryazanov AG, Ma T, Loerch S, Campbell ZT. eEF2K regulates pain through translational control of BDNF. Molecular Cell. 2024. In press. PMID: 39694034

2. Smith PR, Loerch S, Kunder N, Stanowick AD, Lou TF, Campbell ZT. Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance. Nature Communications. 2021. 12(1): 1-16. PMC8611098

3. 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. PMC5750225

4. Kunder N, de la Peña JB, Lou TF, Chase R, Suresh P, Lawson J, Shukla T, Black BJ, Campbell ZT. The RNA-binding protein HuR is integral to the function of nociceptors in mice and humans. J Neuroscience. 2022. In press. PMID36270801

Open positions

We are currently recruiting postdocs and graduate students from multiple programs including: MCP, NTP, iPIB, and CMB. To apply, please email the PI a copy of your CV.

Current lab members

Zachary Campbell, Bamforth Distinguished Chair in Anesthesiology, Vice Chair for Research, and Associate Professor Department of Anesthesiology University of Wisconsin School of Medicine and Public Health, Lab head

Guadalupe Garcia Perez, PhD CINVESTAV-IPN, Postdoctoral fellow

Alex Mikesell, PhD Medical College of Wisconsin, Postdoctoral fellow

Angela Meyer, BS Purdue, iPIB graduate student

Jake Shapiro, BS Colorado College, iPIB graduate student

Sydney O'Flanagan, Genetics undergraduate student, research intern

Aleena Varghese, Molecular and Cellular Biology undergraduate student, research intern

Alumni

*This information reflects known positions after training and may not be current

Former postdocs

Prof. June Bryan De La Pena - Assistant Professor UNM, Department of Anesthesiology

Prof. Bryan Black (co-mentored with Dr. Joseph Pancrazio) - Assistant Professor UMass-Lowell, Department of Biomedical Engeneering

Prof. Paulino Barregan Iglesias (co-mentored with Dr. Price) - Assistant Professor Universidad Autónoma de Aguascalientes

Dr. Chi Zhang - Assistant Instructor, UT-Southwestern

Former doctoral students

Dr. Pat Smith (PhD 2024) - Postdoc Dr. Amy Lee, Harvard

Dr. Rebecca Chase (PhD 2023) - Postdoc Dr. Joe Dougherty, WashU

Dr. Nikesh Kunder (PhD 2022)- Postdoc Dr. Jason M. Schenkel, MD Anderson

Dr. Vandita Bhat (PhD 2020) - Postdoc Dr. Guang Hu, NIEHS Stem Cell Biology Group

Former masters students

Prathana Sursh (MS 2022) - PhD student, UT-Dallas

Sanjana Rajeev (MS 2018) - PhD student, USC

Alexa Lasley (MS 2018) - scientist at nanostring

Former staff scientists

Tzu-Fang Lou - Core facility director, UT-Dallas

Jane Song - PhD student, CU-Boulder

Eric Wistrom - PhD student, teaching abroad in Provence

Sam Rovetto - Scientist at Labcorp

Former undergraduates

Lexi Sharkus - RUSCH research intern, summer 2023, applying for graduate programs

Varun Kotipalli - undergraduate student at UT-Dallas

Amber Ho - Pharmacovigilance Specialist

Alex Stanowick - graduate student at UT-Dallas

David Kim - Applying to graduate programs

Krishnateja Kommera - medical student

Siddhardha Maligireddy - postbac NIH intramural researcher NCI

Miloni Joshi - Medical scribe

Emma Henderson - Biomedical engineer at ICA

Ali Abbas - bussiness analyst

Anaid Cándido - Medical Education Quality Officer at National health service UK

Cori Weaver - Operations Manager at Metis Genetics

Dallas Fonseca - Graduate student student University of Minnesota

Sulaiman Syed - Medical Student at University of the Incarnate Word School of Osteopathic Medicine

Abril Ruiz - Clinical Research Associate at Icon

Andrea Kibel - Graduate student University of Notre Dame

Prerana Ramadurgum - DO student UNT Health Science Center

Sanjana Rao - Senior Associate Software Engineer

Neil Mascarenhas - Student at Texas A&M College of Dentistry

Tejesh Guddanti - Medical Student at University of Oklahoma

Contact

You can reach the lab head at this email address: zcampbell /at/ wisc /dot/ edu

Elements

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