Tannin A. Schmidt, PhDAssociate Professor of Biomedical Engineering
|
My basic and translational research interests in biomedical engineering lie within biomechanics (biotribology), biomaterials, biointerface science and biochemistry/biophysics, all within the context of engineering health.
The goal of my program is to understand the fundamental mechanisms and properties of proteoglycan 4 (PRG4), also known as lubricin (a critical lubricating protein found throughout the human body), at relevant biointerfaces and biomaterials, and to apply that knowledge to the development of PRG4-containing biotherapeutics and biomaterials.
I have been successful in translating basic findings as a scientific co-founder of Lubris BioPharma, a clinical stage start-up company developing recombinant human PRG4 (rhPRG4)-based treatments for osteoarthritis, dry eye, and other diseases. I contributed to the development and characterization of rhPRG4, and have significant experience with the protein. In a recently completed clinical trial, rhPRG4 was demonstrated to be safe and effective in treating dry eye disease (signs and symptoms). Based on these promising results, Novartis exercised an option to in-license rhPRG4 from Lubris, for all ophthalmic indications worldwide (outside Europe) license. Lubris continues to evaluate other applications, such as treating post-surgical adhesions and is engaged with other pharmaceutical companies for development of the osteoarthritis treatment.
The forward-looking vision of my program involves rhPRG4 as a platform technology, either alone or in combination with other molecules or biomaterials, for the treatment of OA (both surgical non-surgical approaches), dry eye, and other diseases/conditions (e.g. cancer, Sjogren’s syndrome, inflammatory arthritis, cataracts) where rhPRG4 may have clinical utility. Sophisticated basic research of PRG4 and its properties/function at relevant biointerfaces will continue, along with subsequent expansion to clinical evaluation of rhPRG4-containing biotherapeutics and/or biomaterials for the treatment of OA and dry eye and other diseases through collaboration with surgeons, clinicians and other basic scientists/engineers.
Degree | Institution | Major |
---|---|---|
BASc | University of Toronto | Engineering Science |
MS | University of California, San Diego | Bioengineering |
PhD | University of California, San Diego | Bioengineering |
Post-Graduate Training
Training | Institution | Specialty |
---|---|---|
Postdoctoral | Rush University Medical Center | Rheumatology and Biochemistry |
The priorities and direction of my biomedical engineering research program are intimately aligned with engineering solutions in health, including biotherapeutics and biomaterials, and potential translational applications in precision and regenerative medicine.
My 5 research program priorities/objectives are:
1. Elucidate the molecular basis of articular cartilage boundary lubrication through the study of PRG4 interactions with itself, with hyaluronan and other synovial fluid constituents, and the articular cartilage surface.
2. Examine the composition and interaction of PRG4+hyaluronan in osteoarthritic synovial fluid, and their effects on articular cartilage boundary lubrication.
3. Assess PRG4’s potential as a boundary lubricant of knee implant biomaterials.
4. Characterize and develop novel PRG4, +/-hyaluronan, containing contact lens biomaterials with enhanced boundary lubricating properties.
5. Examine PRG4’s potential as an anti-inflammatory therapeutic for the treatment of inflammatory arthritis, as well as preventing post-surgical pericardial adhesions and cancer metastasis.
Collectively this work could ultimately lead to the development of new cell, protein or tissue based biomaterial therapeutics that may: 1) halt or reverse the progressive loss of cartilage after an injury or with aging and arthritis; 2) prolong the lifetime and therefore performance of implant materials used for joint arthroplasty; 3) provide a therapeutically effective treatment, in the form of artificial tears and/or novel contact lens biomaterials, for those who suffer from dry eye disease; and 4) contribute to an increased understanding of PRG4’s newly discovered anti-inflammatory properties and potential therapeutic applications in preventing tissue adhesions and cancer metastasis. One specific example of this is the recently published study evaluating recombinant human PRG4 for the treatment of dry eye disease; positive results of the clinical trial demonstrated significant improvement in both signs and symptoms of dry eye disease.
Accepting Lab Rotation Students: Spring 1 and 2 Block 2025
Journal Articles
-
Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum.
Nature communications 2024 Sep;15(1):8379
-
Benefits of In Situ Foamed and Printed Porous Scaffolds in Wound Healing.
Advanced healthcare materials 2024 Sep;e2401944
-
Endothelial to mesenchymal Notch signaling regulates skeletal repair.
JCI insight 2024 May;
-
Recombinant human proteoglycan 4 lowers inflammation and atherosclerosis susceptibility in female low-density lipoprotein receptor knockout mice.
The Journal of physiology 2024 Apr;
-
Passaged Articular Chondrocytes From the Superficial Zone and Deep Zone Can Regain Zone-Specific Properties After Redifferentiation.
The American journal of sports medicine 2024 Mar;52(4):1075-1087
-
Dissolvable Immunomodulatory Microneedles for Treatment of Skin Wounds.
Advanced healthcare materials 2024 Feb;e2302836
-
Physiochemical effects of acid exposure on bone composition and function.
Journal of the mechanical behavior of biomedical materials 2024 Feb;150106304
-
The Actin Cytoskeleton as a Regulator of Proteoglycan 4.
Cartilage 2024 Jan;19476035231223455
-
Scale-Dependent Rheology of Synovial Fluid Lubricating Macromolecules.
Small (Weinheim an der Bergstrasse, Germany) 2023 Dec;e2306207
-
PRG4 deficiency in mice alters skeletal structure, mechanics, and calvarial osteoclastogenesis, and rhPRG4 inhibits in vitro osteoclastogenesis.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2023 Dec;
-
A structural and functional comparison between two recombinant human lubricin proteins: Recombinant human proteoglycan-4 (rhPRG4) vs ECF843.
Experimental eye research 2023 Oct;235109643
-
Biodegradable piezoelectric skin-wound scaffold.
Biomaterials 2023 Oct;301122270
-
Plasma proteoglycan 4: a novel biomarker for acute lung injury after pediatric cardiac surgery.
Translational pediatrics 2023 Sep;12(9):1668-1675
-
Regenerative engineering of long bones using the small molecule forskolin.
Proceedings of the National Academy of Sciences of the United States of America 2023 May;120(22):e2219756120
-
Cleanroom-Free Fabrication of Microneedles for Multimodal Drug Delivery.
Small (Weinheim an der Bergstrasse, Germany) 2023 Apr;e2207131
-
Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis.
Nature communications 2023 Apr;14(1):1910
-
Friction reducing ability of a poly-l-lysine and dopamine modified hyaluronan coating for polycaprolactone cartilage resurfacing implants.
Journal of biomedical materials research. Part B, Applied biomaterials 2023 Mar;
-
Administration of alendronate exacerbates ammonium chloride-induced acidosis in mice.
PloS one 2023 Jan;18(9):e0291649
-
Amplification of inflammation by lubricin deficiency implicated in incident, erosive gout independent of hyperuricemia.
Arthritis & rheumatology (Hoboken, N.J.) 2022 Dec;
-
Recombinant Human Proteoglycan 4 (rhPRG4) Downregulates TNFα-Stimulated NFκB Activity and FAT10 Expression in Human Corneal Epithelial Cells.
International journal of molecular sciences 2022 Oct;23(21):
-
Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration.
NPJ Regenerative medicine 2022 Jun;7(1):32
-
Proteoglycan 4 is present within the dura mater and produced by mesenchymal progenitor cells.
Cell and tissue research 2022 Jun;
-
Novel Boundary Lubrication Mechanisms from Molecular Pillows of Lubricin Brush-Coated Graphene Oxide Nanosheets.
Langmuir : the ACS journal of surfaces and colloids 2022 May;38(18):5351-5360
-
Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes.
PloS one 2022 Jan;17(12):e0267921
-
Noncovalent hyaluronan crosslinking by TSG-6: Modulation by heparin, heparan sulfate, and PRG4.
Frontiers in molecular biosciences 2022 Jan;9990861
-
Proteoglycan 4 (PRG4) expression and function in dry eye associated inflammation.
Experimental eye research 2021 Jul;208108628
-
The role of synovial fluid constituents in the lubrication of collagen-glycosaminoglycan scaffolds for cartilage repair.
Journal of the mechanical behavior of biomedical materials 2021 Jun;118104445
-
Proteoglycan 4 reduces friction more than other synovial fluid components for both cartilage-cartilage and cartilage-metal articulation.
Osteoarthritis and cartilage 2021 Feb;
-
Investigating the Synergistic Interactions of Surface Immobilized and Free Natural Ocular Lubricants for Contact Lens Applications: A Comparative Study between Hyaluronic Acid and Proteoglycan 4 (Lubricin).
Langmuir : the ACS journal of surfaces and colloids 2021 Jan;37(3):1062-1072
-
Proteomics Analysis of Tears and Saliva From Sjogren's Syndrome Patients.
Frontiers in pharmacology 2021 Jan;12787193
-
Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation of Monocytes and Reduces IL-1β Secretion by Urate Crystal Stimulated Gout PBMCs.
Frontiers in immunology 2021 Jan;12771677
-
Effects of acidosis on the structure, composition, and function of adult murine femurs.
Acta biomaterialia 2020 Nov;
-
Proteoglycan-4 is correlated with longer survival in HCC patients and enhances sorafenib and regorafenib effectiveness via CD44 in vitro.
Cell death & disease 2020 Nov;11(11):984
-
Lubricating lipids in hydrogels.
Science (New York, N.Y.) 2020 Oct;370(6514):288-289
-
Microneedle arrays for the treatment of chronic wounds.
Expert opinion on drug delivery 2020 Oct;1-14
-
Automated Indentation Demonstrates Structural Stiffness of Femoral Articular Cartilage and Temporomandibular Joint Mandibular Condylar Cartilage Is Altered in FgF2KO Mice
Cartilage 2020 Oct;1947603520962565
-
Proteoglycan 4 reduces neuroinflammation and protects the blood-brain barrier after traumatic brain injury.
Journal of neurotrauma 2020 Sep;
-
Decrease of core-2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking.
The Journal of biological chemistry 2020 Sep;
-
Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican.
Cells 2020 Jul;9(7):
-
Proteoglycan-4 regulates fibroblast to myofibroblast transition and expression of fibrotic genes in the synovium.
Arthritis research & therapy 2020 May;22(1):113
-
Proteoglycan-4 and hyaluronan composition in synovial fluid and serum from clinical equine subjects: relationship to cartilage boundary lubrication and viscosity of synovial fluid.
Connective tissue research 2020 Apr;1-12
-
Inhibitory Effects of PRG4 on Migration and Proliferation of Human Venous Cells.
The Journal of surgical research 2020 Apr;25353-62
-
Cathepsin g Degrades Both Glycosylated and Unglycosylated Regions of Lubricin, a Synovial Mucin.
Scientific reports 2020 Mar;10(1):4215
-
The Effect of Intense Exercise on Equine Serum Proteoglycan-4/Lubricin.
Frontiers in veterinary science 2020 Jan;7599287
-
Localization of full-length recombinant human proteoglycan-4 in commercial contact lenses using confocal microscopy.
Journal of biomaterials science. Polymer edition 2019 Oct;1-13
-
Interactions between Lubricin and Hyaluronic Acid Synergistically Enhance Antiadhesive Properties.
ACS applied materials & interfaces 2019 May;11(20):18090-18102
-
Investigating the effect of proteoglycan 4 on hyaluronan solution properties using confocal fluorescence recovery after photobleaching.
BMC musculoskeletal disorders 2019 Feb;20(1):93
-
Probing the Molecular Interactions and Lubrication Mechanisms of Purified Full-Length Recombinant Human Proteoglycan 4 (rhPRG4) and Hyaluronic Acid (HA).
Biomacromolecules 2019 Feb;20(2):1056-1067
-
Lubricin/proteoglycan 4 detected in vocal folds of humans and five other mammals.
The Laryngoscope 2019 Jan;
-
Recombinant human PRG4 (rhPRG4) suppresses breast cancer cell invasion by inhibiting TGFβ-Hyaluronan-CD44 signalling pathway.
PloS one 2019 Jan;14(7):e0219697
-
A Two Compartment Pharmacokinetic Model Describes the Intra-articular Delivery and Retention of rhPRG4 Following ACL Transection in the Yucatan Mini Pig.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2018 Nov;
-
Proteoglycan 4: From Mere Lubricant to Regulator of Tissue Homeostasis and Inflammation: Does proteoglycan 4 have the ability to buffer the inflammatory response?
BioEssays : news and reviews in molecular, cellular and developmental biology 2018 Nov;41e1800166
-
Human pericardial proteoglycan 4 (lubricin): Implications for postcardiotomy intrathoracic adhesion formation.
The Journal of thoracic and cardiovascular surgery 2018 Oct;156(4):1598-1608.e1
-
Recombinant human proteoglycan-4 reduces phagocytosis of urate crystals and downstream nuclear factor kappa B and inflammasome activation and production of cytokines and chemokines in human and murine macrophages.
Arthritis research & therapy 2018 Aug;20(1):192
-
Adherent agarose mold cultures: an in vitro platform for multi-factorial assessment of passaged chondrocyte redifferentiation.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2018 Mar;362392-2405
-
Preclinical Animal Studies of Intravesical Recombinant Human Proteoglycan 4 (rhPRG4) as a Novel Potential Therapy for Diseases Resulting From Increased Bladder Permeability.
Urology 2018 Mar;116230.e1-230.e7
-
Mechanical Fatigue of Bovine Cortical Bone Using Ground Reaction Force Waveforms in Running.
Journal of biomechanical engineering 2018 Mar;140(3):
-
Versican is differentially regulated in the adventitial and medial layers of human vein grafts.
PloS one 2018 Jan;13(9):e0204045
-
A Competitive AlphaScreen Assay for Detection of Hyaluronan.
Glycobiology 2017 Dec;28137-147
-
Hyaluronan incorporation into model contact lens hydrogels as a built-in lubricant: Effect of hydrogel composition and proteoglycan 4 as a lubricant in solution.
Journal of biomedical materials research. Part B, Applied biomaterials 2017 Sep;1061818-1826
-
Degradation of proteoglycan 4/lubricin by cathepsin S: Potential mechanism for diminished ocular surface lubrication in Sjögren's syndrome.
Experimental eye research 2017 Aug;1611-9
-
Proteoglycan 4 and hyaluronan as boundary lubricants for model contact lens hydrogels.
Journal of biomedical materials research. Part B, Applied biomaterials 2017 Jul;1061329-1338
-
An in vitro study of cartilage-meniscus tribology to understand the changes caused by a meniscus implant.
Colloids and surfaces. B, Biointerfaces 2017 Jul;155294-303
-
TFOS DEWS II Tear Film Report.
The ocular surface 2017 Jul;15(3):366-403
-
Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage After Destabilization of the Medial Meniscus in the Yucatan Minipig.
The American journal of sports medicine 2017 Jun;45(7):1512-1521
-
Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease.
Acta biomaterialia 2017 Jun;55163-171
-
The autocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes.
Arthritis research & therapy 2017 May;19(1):89
-
Reduction of friction by recombinant human proteoglycan 4 in IL-1α stimulated bovine cartilage explants.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2017 Mar;35(3):580-589
-
Cellular electrophysiological principles that modulate secretion from synovial fibroblasts.
The Journal of physiology 2017 Feb;595(3):635-645
-
Recombinant human lubricin for prevention of postoperative intra-abdominal adhesions in a rat model.
The Journal of surgical research 2017 Feb;20820-25
-
A Two-Week, Randomized, Double-masked Study to Evaluate Safety and Efficacy of Lubricin (150 μg/mL) Eye Drops Versus Sodium Hyaluronate (HA) 0.18% Eye Drops (Vismed®) in Patients with Moderate Dry Eye Disease.
The ocular surface 2017 Jan;15(1):77-87
-
Rheological effects of macromolecular interactions in synovial fluid.
Biorheology 2016 Jul;53(2):49-67
-
Full-Length Recombinant Human Proteoglycan 4 Interacts with Hyaluronan to Provide Cartilage Boundary Lubrication.
Annals of biomedical engineering 2016 Apr;44(4):1128-37
-
Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro.
Scientific reports 2016 Jan;618910
-
Effect of disulfide bonding and multimerization on proteoglycan 4's cartilage boundary lubricating ability and adsorption.
Connective tissue research 2016 Jan;57(2):113-23
-
Cartilage boundary lubrication synergism is mediated by hyaluronan concentration and PRG4 concentration and structure.
BMC musculoskeletal disorders 2015 Dec;16386
-
The interaction of lubricin/proteoglycan 4 (PRG4) with toll-like receptors 2 and 4: an anti-inflammatory role of PRG4 in synovial fluid.
Arthritis research & therapy 2015 Dec;17353
-
Metabolic analysis of knee synovial fluid as a potential diagnostic approach for osteoarthritis.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2015 Nov;33(11):1631-8
-
Lubricin/Proteoglycan 4 Binding to CD44 Receptor: A Mechanism of the Suppression of Proinflammatory Cytokine-Induced Synoviocyte Proliferation by Lubricin.
Arthritis & rheumatology (Hoboken, N.J.) 2015 Jun;67(6):1503-13
-
Cartilage boundary lubrication of ovine synovial fluid following anterior cruciate ligament transection: a longitudinal study.
Osteoarthritis and cartilage 2015 Apr;23(4):640-7
-
Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered Levels and Molecular Species.
PloS one 2015 Jan;10(5):e0125192
-
The impact of early intra-articular administration of interleukin-1 receptor antagonist on lubricin metabolism and cartilage degeneration in an anterior cruciate ligament transection model.
Osteoarthritis and cartilage 2015 Jan;23(1):114-21
-
Viscoelastic Properties of Hyaluronan in Physiological Conditions.
F1000Research 2015 Jan;4622
-
Both hyaluronan and collagen type II keep proteoglycan 4 (lubricin) at the cartilage surface in a condition that provides low friction during boundary lubrication.
Langmuir : the ACS journal of surfaces and colloids 2014 Dec;30(48):14566-72
-
Characterization of full-length recombinant human Proteoglycan 4 as an ocular surface boundary lubricant.
Experimental eye research 2014 Oct;12714-9
-
Biochemical analyses of human osteoarthritic and periprosthetic synovial fluid.
Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine 2014 Feb;228(2):127-39
-
Effects of concentration and structure on proteoglycan 4 rheology and interaction with hyaluronan.
Biorheology 2014 Jan;51(6):409-22
-
The TFOS International Workshop on Contact Lens Discomfort: report of the contact lens materials, design, and care subcommittee.
Investigative ophthalmology & visual science 2013 Oct;54(11):TFOS37-70
-
Characterization of proteoglycan 4 and hyaluronan composition and lubrication function of ovine synovial fluid following knee surgery.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2013 Oct;31(10):1549-54
-
Transcription, translation, and function of lubricin, a boundary lubricant, at the ocular surface.
JAMA ophthalmology 2013 Jun;131(6):766-76
-
Muscular loading of joints triggers cellular secretion of PRG4 into the joint fluid.
Journal of biomechanics 2013 Apr;46(7):1225-30
-
Molecular weight characterization of PRG4 proteins using multi-angle laser light scattering (MALLS).
Osteoarthritis and cartilage 2013 Mar;21(3):498-504
-
Cartilage boundary lubricating ability of aldehyde modified proteoglycan 4 (PRG4-CHO).
Osteoarthritis and cartilage 2013 Jan;21(1):186-9
-
Diminished cartilage-lubricating ability of human osteoarthritic synovial fluid deficient in proteoglycan 4: Restoration through proteoglycan 4 supplementation.
Arthritis and rheumatism 2012 Dec;64(12):3963-71
-
Effects of equine joint injury on boundary lubrication of articular cartilage by synovial fluid: role of hyaluronan.
Arthritis and rheumatism 2012 Sep;64(9):2917-26
-
Dose-dependent and synergistic effects of proteoglycan 4 on boundary lubrication at a human cornea-polydimethylsiloxane biointerface.
Eye & contact lens 2012 Jan;38(1):27-35
-
The effect of molecular weight on hyaluronan's cartilage boundary lubricating ability--alone and in combination with proteoglycan 4.
Osteoarthritis and cartilage 2011 Nov;19(11):1356-62
-
Disulfide-bonded multimers of proteoglycan 4 PRG4 are present in normal synovial fluids.
Biochimica et biophysica acta 2009 May;1790(5):375-84
-
Differential regulation of proteoglycan 4 metabolism in cartilage by IL-1alpha, IGF-I, and TGF-beta1.
Osteoarthritis and cartilage 2008 Jan;16(1):90-7
-
Microenvironment regulation of PRG4 phenotype of chondrocytes.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2007 May;25(5):685-95
-
A model of synovial fluid lubricant composition in normal and injured joints.
European cells & materials 2007 Mar;1326-39
-
Boundary lubrication of articular cartilage: role of synovial fluid constituents.
Arthritis and rheumatism 2007 Mar;56(3):882-91
-
Effect of synovial fluid on boundary lubrication of articular cartilage.
Osteoarthritis and cartilage 2007 Jan;15(1):35-47
-
Tracking chondrocytes and assessing their proliferation with PKH26: effects on secretion of proteoglycan 4 (PRG4).
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2006 Jul;24(7):1499-508
-
Dynamic shear stimulation of bovine cartilage biosynthesis of proteoglycan 4.
Arthritis and rheumatism 2006 Jun;54(6):1888-96
-
Tailoring secretion of proteoglycan 4 (PRG4) in tissue-engineered cartilage.
Tissue engineering 2006 Jun;12(6):1429-39
-
Proteoglycan 4 (PRG4) synthesis and immunolocalization in bovine meniscus.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2005 May;23(3):562-8
-
Synthesis of proteoglycan 4 by chondrocyte subpopulations in cartilage explants, monolayer cultures, and resurfaced cartilage cultures.
Arthritis and rheumatism 2004 Sep;50(9):2849-57
-
Tissue engineering of stratified articular cartilage from chondrocyte subpopulations.
Osteoarthritis and cartilage 2003 Aug;11(8):595-602
-
Integrin-mediated adhesion of human articular chondrocytes to cartilage.
Arthritis and rheumatism 2003 Jan;48(1):110-8
-
Static and dynamic compression regulate cartilage metabolism of PRoteoGlycan 4 (PRG4).
Biorheology 43(3,4):191-200
Erratums
-
Author Correction: Cathepsin g Degrades Both Glycosylated and Unglycosylated Regions of Lubricin, a Synovial Mucin.
Scientific reports 2021 Feb;11(1):4238
Reviews
-
Biomaterial Drug Delivery Systems for Prominent Ocular Diseases.
Pharmaceutics 2023 Jul;15(7):