PhD, University of Minnesota, Minneapolis, MN, 1995
Postdoctoral, University of Würzburg, Würzburg, Germany and Max Delbrück Center for Molecular Medicine, Berlin, Germany
Chronic pain affects approximately 100 million adults in the United States, costing around $635 billion and many patients are sub-optimally treated as a result of limited understanding of the mechanistic causes of the chronic pain. The Stucky Lab has made key contributions to the pain field’s understanding of how ion channels on pain-sensing neurons contribute to pain and touch sensation. We are known for the unique “skin-nerve” recording technique whereby sensory afferent responses from rodents are measured in their native skin environment. We were the first lab to demonstrate that the Transient Receptor Potential Ankyrin 1 (TRPA1) channel is essential for detection of painful mechanical stimuli in normal, non-injured skin by using parallel genetic deletion and pharmacological inhibition of the TRPA1 channel. This work was published in the Journal of Neuroscience and Molecular Pain in 2009. Since that time, numerous publications have emerged that further build upon this work, including a widely-cited manuscript demonstrating that TRPA1 is responsible for the mechanical sensitization of pain receptors after tissue inflammation (Lennertz et al., 2012, PLoS ONE), and therefore, can serve as a target for inhibiting pain in many common inflammatory disorders.
An exciting current direction in our lab is identifying the mechanisms underlying the role of chronic pain in damaged skin, by examining the bidirectional signaling between keratinocytes and sensory neurons in normal and tissue-injured skin. While sensory neurons have long been known to mediate touch and pain transduction, epidermal keratinocytes are the initial “first responders” to tactile stimuli. We are dissecting the cellular mechanisms by which keratinocytes communicate with sensory nerve terminals, and conversely, the mechanisms by which sensory neurons communicate and sensitize keratinocytes during tissue injury. We are using multiple complementary pharmacological and cutting edge site-selective genetic approaches, such as optogenetic silencing, CRISPR/Cas9 gene editing and “cell sniffer” assays to interrogate the mechanistic direction and molecules underlying keratinocyte to sensory neuron signaling in vivo.
Another major area of focus is on translational models of chronic pain including inflammation, nerve injury and diseases associated with devastating pain, particularly in areas of unmet medical need. For example, patients with sickle cell disease have severe pain during red cell sickling crises and develop chronic underlying pain; effective treatments for this pain are lacking. We have made key discoveries in mechanisms that underlie the severe pain in sickle cell disease by performing parallel studies in mouse models of sickle cell disease and concomitantly measuring pain in patients with sickle cell disease (Hillery et al., 2011, Blood; Brandow et al., 2013, American Journal of Hematology; Zappia et al., 2014, Pain). Sickle cell disease is of particular interest because 1) it has aspects of chronic as well as acute pain, 2) the pain develops naturally as part of the underlying disease and therefore, may serve as a model for other naturally-occurring types of chronic pain in humans, and 3) parallel studies in the animal models and in patients with sickle cell disease can be conducted by the same laboratory.
Support for these projects
R01 NS40538; R01 NS070711; R21 NS095627-01; Advancing a Healthier Wisconsin
(Cowie AM, Moehring F, O'Hara C, Stucky CL.) J Neurosci. 2018 Jun 20;38(25):5807-5825.
(Moehring F, Waas M, Keppel TR, Rathore D, Cowie AM, Stucky CL, Gundry RL.) J Proteome Res. 2018 Aug 03;17(8):2635-2648.
(Sadler KE, Zappia KJ, OʼHara CL, Langer SN, Weyer AD, Hillery CA, Stucky CL.) Pain. 2018 Aug;159(8):1652-1663.
(Miller JJ, Aoki K, Moehring F, Murphy CA, O'Hara CL, Tiemeyer M, Stucky CL, Dahms NM.) JCI Insight. 2018 Mar 22;3(6).
(Moehring F, Cowie AM, Menzel AD, Weyer AD, Grzybowski M, Arzua T, Geurts AM, Palygin O, Stucky CL.) Elife. 2018 01 16;7.
(Zappia KJ, Guo Y, Retherford D, Wandersee NJ, Stucky CL, Hillery CA.) Br J Haematol. 2017 11;179(4):657-666.
(Zappia KJ, O'Hara CL, Moehring F, Kwan KY, Stucky CL.) eNeuro. 2017 Jan-Feb;4(1).
(Brandow AM, Zappia KJ, Stucky CL.) Pain. 2017 04;158 Suppl 1:S79-S84.
(Lehto SG, Weyer AD, Youngblood BD, Zhang M, Yin R, Wang W, Teffera Y, Cooke M, Stucky CL, Schenkel L, Geuns-Meyer S, Moyer BD, Wild KD, Gavva NR.) Mol Pain. 2016;12.
(Brandow AM, Wandersee NJ, Dasgupta M, Hoffmann RG, Hillery CA, Stucky CL, Panepinto JA.) Br J Haematol. 2016 Oct;175(2):237-245.
(Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, Castro J, Garcia-Caraballo S, Grundy L, Rychkov GY, Weyer AD, Dekan Z, Undheim EA, Alewood P, Stucky CL, Brierley SM, Basbaum AI, Bosmans F, King GF, Julius D.) Nature. 2016 06 23;534(7608):494-9.
(Zappia KJ, Garrison SR, Palygin O, Weyer AD, Barabas ME, Lawlor MW, Staruschenko A, Stucky CL.) PLoS One. 2016;11(3):e0151602.
Francie Moehring, Ashley Reynolds, Crystal O'Hara, Cheryl Stucky, Kate Sadler, Sarah Langer, Tony Menzel
Summer 2017 students
Melissa Stagg, Christina Mecca
Recent News in the Stucky Lab
Congrats to Kate Sadler, PhD, who has been awarded an NINDS Ruth L. Kirchstein National Research Service Award (NRSA) for Training of Postdoctoral Fellows (F32). Kate’s proposal entitled “Fibroblast-to-neuron communication in muscle pain” will explore the extent and mechanisms through which muscle support cells communicate with sensory neurons to relay both painful and non-painful signals to the central nervous system. This unique award is presented to promising, early-stage postdoctoral fellows and will fund Kate’s position until January 2020.
Congrats to Kate Sadler, PhD who has been selected to participate in the 2018 North American Pain School. The meeting will be held in Quebec from June 24-28 and will bring together basic and clinical pain trainees from the US and Canada. Read more on the North American Pain School site.
Congrats to Cheryl Stucky, PhD who has been selected to participate in the Mayday Pain & Society Fellowship program as one of 12 national experts in pain science and care.
Congratulations to Ashley Cowie, graduate student in the Stucky Lab. The National Institutes of Health (NIH) has invited Ashley Cowie to present her research at their poster session at the 13th Annual Symposium on Advances in Pain Research to be held on May 31 and June 1, 2018 at the NIH Campus in Bethesda, MD. The intent of the symposium is to present new and exciting advances in pain research, featuring work done through NIH support!
Congratulations to Francie Moehring, graduate student in the Stucky Lab. Francie recently won the best Early Career Basic Science Poster at the American Pain Society Meeting.
The following manuscript, Neuropathic pain in a new Fabry Disease rat model has been accepted for publication by JCI Insight.
Co-corresponding authors are Dr. Cheryl Stucky, Dr. Nancy Dahms & Dr. Michael Tiemeyer.
The publication demonstrates that a novel rat model of Fabry disease mimics many of the patient pathologies such as prominent mechanical hypersensitivity and extensive accumulations of lipids in tissues such as dorsal root ganglia. Sensory neurons from these animals were also sensitized to mechanical probing, and TRPA1 antagonism reversed the behavioral mechanical sensitization, pointing towards TRPA1 as a novel target to treat the pain experienced by patients with Fabry disease.
James J. Miller1§, Kazuhiro Aoki2§, Francie Moehring3§, Carly A. Murphy1, Crystal L. O’Hara3, Michael Tiemeyer2*, Cheryl L. Stucky3*, Nancy M. Dahms1*. Neuropathic pain in a new Fabry Disease rat model JCI Insight. in press.
Congratulations to Francie Moehring, graduate student in the Stucky Lab. Francie is first author on a new publication in the journal eLife entitled: Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling.
The publication reveals the signaling mechanism between skin keratinocytes and sensory neurons, which is essential for our normal sensitivity to gentle and painful touch in the skin. Francie's work has also been featured in Technology Networks entitled: Touching: Skin cell to nerve cell communication uncovered
Ashley Cowie, graduate student in the Stucky Lab, presented her work in a nanosymposium at the Society for Neuroscience meeting in Washington DC in November 2017.
Her research has been featured on the Pain Research Forum.
The Stucky Lab recently attended a team based learning activity off campus at Escape Milwaukee. They solved "Mr. K's Lethal Injection" with 9 minutes to spare! This was quite impressive to the organizer since this was the fastest they have seen any group escape!
Awards, interviews & articles
- The Quest to Ease the Pain of Sickle Cell Disease article
- Women’s History Month
- International Innovation (PDF)
- Standing Ovation Award for 2008 from MCW Medical Students for teaching Medical Neuroscience
- Bethel College Young Alumni Award for 2004
- John C. Liebeskind Early Career Scholar Award for 2002 for outstanding accomplishments in pain scholarship
Supplementary Information for published manuscripts
Garrison & Stucky 2014