Mia M. Thi, Ph.D.

The primary focus of our laboratory is to understand the molecular and cellular mechanisms by which cells sense, transduce, and communicate mechanical signals and how these signals coordinate cellular responses across skeletal and other mechanosensitive tissues. Our research examines the roles of cytoskeletal networks, junctional proteins, focal adhesion complexes, mechanosensitive channels, and receptor-mediated signaling in the propagation of mechanically induced signals under both physiological and pathological conditions.

A major emphasis of our work is skeletal mechanobiology and the mechanisms that regulate bone adaptation to mechanical loading and exercise. We investigate signaling pathways involving pannexin 1 (Panx1) channels, P2X7 purinergic receptors, αVβ3 integrins, calcium signaling, and extracellular signaling molecules such as ATP, PGE₂, and VEGF. Our studies extend across bone, endothelium, and urothelium and examine how systemic and disease-related conditions, including diabetes, osteoarthritis, and aging, influence cellular mechanosensing, intercellular communication, and tissue physiology.

Building on these studies, we are also interested in the contribution of neural-bone communication to skeletal adaptation, including how dorsal root ganglia neurons and associated glial cells may integrate mechanical, bone-derived, and systemic signals. This work complements our broader efforts to understand how cellular communication across tissues contributes to responses to mechanical loading, exercise, and changes in the systemic environment.

Our overarching goal is to identify cellular and molecular mechanisms that contribute to tissue adaptation, health, and repair and that may ultimately provide opportunities for translational intervention. Training opportunities are available for students and research and clinical fellows across these interdisciplinary areas.

1. Seref-Ferlengez Z, Urban-Maldonado M, Uyer A, Thent ZC, Tun A, Schaffler MB, Suadicani SO, Thi MM. Panx1 and P2X7R are associated with impaired skeletal health and delayed bone development in early onset of Type 1 Diabetes. Front Endocrinol (Lausanne). 2026; May 8;17:1829463. doi: 10.3389/fendo.2026.1829463. PMID: 42181174.https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1829463/full
2. Lewis KJ, Boorman-Padgett JF, Castaneda M, Spray DC, Thi MM, Schaffler MB. A Fluorescent Intravital Imaging Approach to Study Load-Induced Calcium Signaling Dynamics in Mouse Osteocytes. J Vis Exp. 2023 Feb 24;(192). PMID: 36912542. https://www.jove.com/t/64366/a-fluorescent-intravital-imaging-approach-to-study-load-induced
3. Lewis KJ, Cabahug-Zuckerman P, Louie J, Stephen S, Spray DC, Thi MM, Seref-Ferlengez Z, Boorman-Padgett JF, Majeska RJ, Weinbaum S, Schaffler MB. Estrogen depletion on In vivo osteocyte calcium signaling responses to mechanical loading. Bone. 2021 Nov;152:116072. PMID: 34171514, PMCID: PMC8316427. https://www.sciencedirect.com/science/article/pii/S8756328221002349?via%3Dihub
4. Cibelli A, Lopez-Quintero SV, McCutcheon S, Scemes E, Spray DC, Stout Jr RF, Suadicani SO, Thi MM, Urban-Maldonado M. Generation and Characterization of Immortalized Mouse Cortical Astrocytes From Wildtype and Connexin43 Knockout Mice. Front Cell Neurosci. 2021;15(60). doi: 10.3389/fncel.2021.647109. PMID: 33790744, PMCID: PMC8005635.https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2021.647109/full
5. Harroche J, Urban-Maldonado M, Thi MM, Suadicani SO. Mechanosensitive Vaginal Epithelial ATP Release and Pannexin 1 channels in Healthy, in Type 1 Diabetic and in Surgically Castrated Female Mice.   J Sex Med, May;17(5):870-880, 2020. PMID: 32241676, PMCID: PMC7188554.https://academic.oup.com/jsm/article/17/5/870/6973737?login=true
6. Seref-Ferlengez Z, Urban-Maldonado M, Sun HB, Schaffler MB, Suadicani SO, Thi MM. Role of pannexin 1 channels in load-induced skeletal response. Ann N Y Acad Sci, 1442(1): 79-90, 2019. PMID: 29952014, PMCID: PMC6310681.https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/nyas.13914
7. Cabahug-Zukerman P, Stout R, Majeska RJ, Thi MM, Spray DC, Weinbaum S, Schaffler MB. Potential role for a specialized β3 integrin-based structure on osteocyte processes in bone mechanosensation. J Orthop Res. 36(2):642-652, 2018. PMID: 29087614, PMCID: PMC5839970. https://onlinelibrary.wiley.com/doi/10.1002/jor.23792
8. Lewis KL, Frikha-Benayed D, Louie J, Stephen S, Spray DC, Thi MM, Seref-Ferlengez Z, Majeska RJ, Weinbaum S, Schaffler MB. Osteocyte calcium signals encode strain magnitude and loading frequency  in vivo. Proc Natl Acad Sci USA. 114(44):11775-11780, 2017. PMID: 29078317, PMCID: PMC5676898. https://www.pnas.org/doi/10.1073/pnas.1707863114?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
9. Seref-Ferlengez Z, Suadicani SO, Thi MM. A New Perspective on Mechanisms Governing Skeletal Complications in Type 1 Diabetes. Ann N Y Acad Sci, 1383(1): 67-79, 2016. PMID: 27571221, PMCID: PMC5118151. https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/nyas.13202
10. Seref-Ferlengez Z, Maung S, Schaffler MB, Spray DC, Suadicani SO, Thi MM. P2X7R-Panx1 Complex Impairs Bone Mechanosignaling Under High Glucose Levels Associated with Type-1 Diabetes. PLOS ONE. 11(5):e0155107. eCollection 2016. PMID: 27159053, PMCID: PMC4861344. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0155107
11. Cheung WY, Morgan S, Seref-Ferlengez Z, Basta-Pljakic J, Thi MM, Suadicani SO, Spray DC, Majeska RJ, Fritton JC and Schaffler MB. Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes. 31: 890-899, 2016. PMID: 26553756, PMCID: PMC4915221.https://academic.oup.com/jbmr/article/31/4/890/7605171?login=true
12. Schneider JL, Villarroya J, Diaz-Carretero A, Patel B, Urbanska AM, Thi MM, Villarroya F, Santambrogio L, Cuervo AM. Loss of hepatic chaperone-mediated autophagy accelerates proteostasis failure in aging. Aging Cell. 14:249-264, 2015. PMID: 25620427, PMCID: PMC4364837. https://onlinelibrary.wiley.com/doi/10.1111/acel.12310
13. Negoro H, Urban-Maldonado M, Liou LS, Spray DC, Thi MM, Suadicani SO. Pannexin 1 channels play essential roles in urothelial mechanotransduction and intercellular signaling. PLOS ONE. 9(8):e106269. eCollection 2014. PMID: 25170954, PMCID: PCM4149561. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106269
14. Burke S, Fnu N, Thi MM, Hanani M, Scherer PE, Tanowitz HB, Spray DC. Adipocytes in both brown and white adipose tissue of adult mice are functionally connected via gap junctions: implications for Chagas disease. Microbes Infect, 16:893-901, 2014. PMID: 25150689, PMCID: PMC4353925. https://www.sciencedirect.com/science/article/pii/S1286457914001117?via%3Dihub
15. Thi MM, Suadicani SO, Schaffler MB, Weinbaum S, Spray DC. Mechanosensory responses of osteocytes to physiological forces occur along processes and not cell body and require αVβ3 Integrin. Proc Natl Acad Sci USA, 110:21012-21017, 2013. PMID: 24324138, PMCID: PMC3876252. https://www.pnas.org/doi/10.1073/pnas.1321210110?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
16. Scharf B, Clement CC, Yodmuang S, Urbanska A, Suadicani SO, Aphkhazava D, Thi MM, Perino G, Hardin J, Cobelli N, Vunjak-Novakovic G, Santambrogio L. Age-related carbonylation of fibro-cartilage structural proteins drives tissue degenerative modification. Chem Biol. 20:922-934, 2013. PMID: 23890010, PMCID: PMC3758909. https://www.sciencedirect.com/science/article/pii/S1074552113002391?via%3Dihub
17. Spray DC, Hanstein R, Stout R, Suadicani SO, Thi MM. Gap junctions and Bystander effects: Good Samaritans and executioners. WIREs Membr Transp Signal, 2:1-15, 2013. PMID: 23565352, PMCID: PMC3614363. https://pmc.ncbi.nlm.nih.gov/articles/PMC3614363/
18. Thi MM, Islam S, Suadicani SO, Spray DC. Connexin43 and Pannexin 1 in Osteoblasts: Who is the “hemichannel”? J Membr Biol, 245:401-409, 2012. PMID: 22797941, PMCID: PMC3427001. https://link.springer.com/article/10.1007/s00232-012-9462-2
19. Weinbaum S, Duan Y, Thi MM, You L. An integrative review of mechanotransduction in endothelial, epithelial (renal) and dendritic cells (osteocytes). Cell Mol Bioeng, 4:510-537, 2011. PMID: 23976901, PMCID: PMC3748935. https://link.springer.com/article/10.1007/s12195-011-0179-6
20. Thi MM, Urban-Maldonado M, Spray DC, Suadicani SO. Characterization of hTERT-immortalized osteoblast cell lines generated from wildtype and connexin43-null mouse calvaria. Am J Physiol Cell Physiol, 299:C994-C1006, 2010. PMID: 20686067, PMCID: PMC2980299.  https://journals.physiology.org/doi/full/10.1152/ajpcell.00544.2009?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
21. Thi MM, Weinbaum S, Tarbell JM, Spray DC. The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A ‘bumper-car’ model. Proc Natl Acad Sci USA, 101:16483-16488, 2004. PMID: 15545600, PMCID: PMC534550. https://www.pnas.org/doi/10.1073/pnas.0407474101?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed