Affiliation: Solomon H. Snyder Professor of Neurosurgery, Professor of Biological Chemistry, Professor of Neuroscience
Director, Department of Biological Chemistry
Director, Neurosurgery Pain Research Institute
Description of Research
The Caterina lab studies mechanisms underlying neuropathic and inflammatory pain, predominantly using mice as a model system. We employ a wide array of methods, including mouse pain behavioral assays, sensory neuroanatomy, in vitro and in vivo neuronal imaging and electrophysiology, cell culture, biochemistry, transcriptomic analysis, and CAS9/Crispr mouse mutagenesis. Through the complementary application of these approaches, and in collaboration with multiple laboratories (e.g., Meffert, Gould, Margolis), we seek to understand the cell types and molecules that contribute to the pathological sensation of pain, with the goal of guiding improvements in pain therapy.
Pain Mechanisms in Hereditary Palmoplantar Keratodermas
Hereditary Palmoplantar Keratodermas (PPK) are a heterogeneous group of rare disorders characterized by thickening of the epidermis on the palms of the hand and soles of the feet. Mutations in any of at least 25 different genes can result in PPK. In some, but not all patients with hereditary PPK, pain at the site of lesions is a prominent symptom, and is very difficult to treat. Using mouse models of human hereditary PPKs, we seek to identify specific molecular and cellular mechanisms that lead to enhanced pain sensitivity in PPK lesions. Through these efforts, we hope to identify therapeutic targets for improved treatment of pain in PPK and also to define novel mechanisms that might be relevant to other, more common pain disorders.
Cellular and Molecular Mechanisms of Neuropathic Pain
Peripheral nerve injury, whether due to traumatic, metabolic, infectious, or toxic causes, often results in abnormally enhanced pain sensitivity known as neuropathic pain. Using an array of surgical nerve injury models, we seek to understand the complex interplay between injured neurons, uninjured neurons, and nonneuronal cells (e.g. immune cells, keratinocytes, glial cells) that produce neuropathic pain and to understand how the processes of nerve regeneration and collateral sprouting, two additional consequences of nerve injury, influence and are influenced by pathological pain mechanisms.
Synthetic Biology Approaches to Treat Pathological Pain
One hallmark of many inflammatory and neuropathic pain mechanisms is an imbalance between signal transduction pathways that augment the sensitivity of nociceptive neurons and those that attenuate that sensitivity. Using a synthetic biology approach, we are seeking to develop genetically encoded “smart” systems that produce analgesia only during times of excess pro-nociceptive signaling. These systems, which are triggered by common pathological signaling processes such as receptor tyrosine kinase hyperfunction or elevated intracellular calcium, may prove beneficial not only in the setting of pathological pain but also in other disease states where such pathways are hyperactive.
Lab Members:
- Dr. Sangmin Jeon (Assistant Professor)
- Dr. Dennis Chang (Postdoctoral Fellow)
- Suyeon Kim (PhD student)
- Yijing Gong (PhD student)
- Austin Dabbs (PhD student)
- Trupti Tripathi (PhD student)
- Lanzhuo Wu (MS student)
- Stella Du (MS student)
- Jahnavi Gupta (Research Specialist)
- Matthew Russell (Research Technologist)
Recent Publications:
- Weinberg R.L.*, Kim S.*, Pang Z., Awad S., Hanback T., Pan B., Bettin L., Chang D., Polydefkis M.J., Qu L., Caterina M.J. Pain Hypersensitivity in Slurp1 and Slurp2 Knockout Models of Hereditary Palmoplatar Keratoderma. Under revision for J Neuroscience.*Denotes equal contributions
- Jeon S.M.*, Pradeep A., Chang, D., McDonough L., Chen Y., Latremoliere A., Crawford L.K., and Caterina M.J. Skin Reinnervation by Collateral Sprouting Following Spared Nerve Injury in Mice. Accepted, J. Neuroscience *Denotes communicating author. (also presented as bioRxiv. 2023 Sep 13:2023.09.12.557420. doi: 10.1101/2023.09.12.557420. Preprint.PMID: 37745384)
- Li X., Jin D.S., Eadara S., Caterina M.J., and Meffert M.K. (2023) Regulation by Noncoding RNAs of Local Translation, Injury Responses, and Pain in the Peripheral Nervous System Neurobiology of Pain, Jan 24:13:100119. doi: 10.1016/j.ynpai.2023.100119.
- Beauchene C., Zurn C.A., Eherns, D., Duff I., Duan W., Caterina M., Guan Y., Sarma S.V. (2022) Steering Towards Normative Wide-Dynamic-Range Neuron Activity in Nerve-Injured Rats with Closed-Loop Peripheral Nerve Stimulation. Neuromodulation: Technology at the Neural Interface. 2022 Nov 16:S1094-7159(22)013290. PMID: 36402658
- Liu U., Caterina M.J., and Qu, L. (2022) Sensory Neuron Expressed FcγRI Mediates Postinflammatory Arthritis Pain in Female Mice Front Immunol. 2022 Jun 27;13:889286. doi: 10.3389/fimmu.2022.889286. PMID: 35833115
- Liu Y, Liu Y, Limjunyawong N, Narang C, Jamaldeen H, Yu S, Patiram S, Nie H, Caterina MJ, Dong X, Qu L. (2022) Sensory neuron expressed TRPC3 mediates acute and chronic itch. Pain. 2022 May 4. doi: 10.1097/j.pain.0000000000002668. PMID: 35507377
- Liu Y, Jeon SM, Caterina MJ, Qu L. (2021) miR-544-3p mediates arthritis pain through regulation of FcγRI. Pain. 2021 Nov 12. doi: 10.1097/j.pain.0000000000002531. Online ahead of print.PMID: 34784311 (also presented as bioRxiv 2021.06.13.448256; doi: https://doi.org/10.1101/2021.06.13.448256)
- Xu Q., Ford N.C., He S., Huang Q., Anderson M., Chen Z., Yang F., Crawford L.K., Caterina M.J., Guan Y., and Dong X. (2021) Astrocytes contribute to pain gating in the spinal cord Sci Adv. 2021 Nov 5;7(45):eabi6287. doi: 10.1126/sciadv.abi6287. Epub 2021 Nov 3.PMID: 34730998
- Li X., Eadara S., Jeon S. Liu Y., Muwanga G., Qu L., Caterina M.J., and Meffert, M.K. (2021) Combined single-molecule fluorescence in-situ hybridization and immunohistochemistry analysis in intact dorsal root ganglia and sciatic nerve. STAR Protoc. 2021 Jun 3;2(2):100555. doi: 10.1016/j.xpro.2021.100555. eCollection 2021 Jun 18.PMID: 34142098
- Jeon, S.*, Chang, D.*, Geske, A., Ginty, D.D., and Caterina, M.J. (2021) Sex-Dependent Reduction in Mechanical Allodynia in the Sural-Sparing Nerve Injury Model in Mice Lacking Merkel Cells. J Neurosci. 2021 Jun 30;41(26):5595-5619. https://pubmed.ncbi.nlm.nih.gov/34031166/.*Denotes equal contributions
- Weinberg R.L., Polydefkis M., Coulombe P.A., and Caterina M.J. Pain mechanisms in hereditary palmoplantar keratodermas (2020) Br. J. Dermatol. 182(3):543-551. PMID:30883689 https://pubmed.ncbi.nlm.nih.gov/30883689/
- Joseph J., Qu L., Wang S., Kim M., Bennett D., Ro J., Caterina M., and Chung M.K. (2019) Phosphorylation of TRPV1 S801 contributes to modality-specific hyperalgesia in mice J. Neuroscience Dec 11;39(50):9954-9966. https://pubmed.ncbi.nlm.nih.gov/31676602/
- Ostrow, K., Donaldson K.J., Caterina M.J., Belzberg A., and Hoke A. (2019) The Secretomes of Painful Versus Nonpainful Human Schwannomatosis Tumor Cells Differentially Influence Sensory Neuron Gene Expression and Sensitivity Scientific Reports Sep 11;9(1):13098
- Wang L., Jiang X., Zheng Q., Jeon S.M., Chen T., Kulaga H., Reed R., Dong X., Caterina M.J., and Qu L. (2019) Neuronal FcgRI mediates acute and chronic joint pain through a noninflammatory mechanism J Clin Invest. Jun 18;130:3754-3769. PMID:31211699
- A more extensive list of publications can be found at https://www.ncbi.nlm.nih.gov/myncbi/1XyKtr6en1Y50/bibliography/public/