Lori Ann Setton

Last updated
Lori Ann Setton
Born
NationalityAmerican
Alma mater Princeton University
Columbia University
Known for mechanics
mechanobiology of the intervertebral disc
articular cartilagemechanics
drug delivery
pathomechanisms of osteoarthritis
Awards AIMBE Fellow (2005)
BMES Fellow (2009)
Van C. Mow Medal(2007)
Scientific career
FieldsBiomechanical Engineer
Institutions Washington University in St. Louis, Duke University
Doctoral advisor Van C. Mow
Website engineering.wustl.edu/Profiles/Pages/Lori-Setton.aspx

Lori Ann Setton is an American biomechanical engineer noted for her research on mechanics and mechanobiology of the intervertebral disc, articular cartilage mechanics, drug delivery, and pathomechanisms of osteoarthritis. She is currently the department chair as well as the Lucy and Stanley Lopata Distinguished Professor of Biomedical Engineering at McKelvey School of Engineering at Washington University in St. Louis.

Contents

Biography

Setton was born in Queens, New York. She received a B.S.E. in Mechanical and Aerospace Engineering from Princeton University in 1984. Subsequently, she pursued graduate degrees under the tutelage of Professor Van C. Mow at Columbia University. She received an M.S. degree and Ph.D degree in Mechanical Engineering/Biomechanics in 1988 and 1993, respectively.

She joined the Department of Biomedical Engineering at Duke University as an assistant professor in 1995. Promotions to tenured associate professor in and professor followed in 2004 and 2007.

Her most noticeable work has documented the biological responses of cartilage and intervertebral disc to mechanical loading, [1] [2] [3] [4] [5] [6] understanding a role for collagen genetic mutations in onset of arthritis and intervertebral disc pathology, [7] [8] development of injectable hydrogels for articular cartilage repair, [9] [10] [11] [12] and development of injectable drug delivery vehicles for fighting inflammation in musculoskeletal disease. [13] [14] [15] [16] [17] As of June 1, 2017, her work has been cited over 17,500 times. [18] She has an h-index of 65.

Awards

Setton has several awards:

Related Research Articles

<span class="mw-page-title-main">Collagen</span> Most abundant structural protein in animals

Collagen is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole-body protein content. Collagen consists of amino acids bound together to form a triple helix of elongated fibril known as a collagen helix. It is mostly found in connective tissue such as cartilage, bones, tendons, ligaments, and skin. Vitamin C is vital for collagen synthesis, and Vitamin E improves the production of collagen.

<span class="mw-page-title-main">Cartilage</span> Resilient and smooth elastic tissue present in animals

Cartilage is a resilient and smooth type of connective tissue. It is a semi-transparent and non-porous type of tissue. It is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck and the bronchial tubes, and the intervertebral discs. In other taxa, such as chondrichthyans, but also in cyclostomes, it may constitute a much greater proportion of the skeleton. It is not as hard and rigid as bone, but it is much stiffer and much less flexible than muscle. The matrix of cartilage is made up of glycosaminoglycans, proteoglycans, collagen fibers and, sometimes, elastin. It usually grows quicker than bone.

<span class="mw-page-title-main">Joint</span> Location at which two or more bones make contact

A joint or articulation is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole. They are constructed to allow for different degrees and types of movement. Some joints, such as the knee, elbow, and shoulder, are self-lubricating, almost frictionless, and are able to withstand compression and maintain heavy loads while still executing smooth and precise movements. Other joints such as sutures between the bones of the skull permit very little movement in order to protect the brain and the sense organs. The connection between a tooth and the jawbone is also called a joint, and is described as a fibrous joint known as a gomphosis. Joints are classified both structurally and functionally.

<span class="mw-page-title-main">Intervertebral disc</span> Cartilage of spine

An intervertebral disc lies between adjacent vertebrae in the vertebral column. Each disc forms a fibrocartilaginous joint, to allow slight movement of the vertebrae, to act as a ligament to hold the vertebrae together, and to function as a shock absorber for the spine.

<span class="mw-page-title-main">Osteoarthritis</span> Form of arthritis caused by degeneration of joints

Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone. It is believed to be the fourth leading cause of disability in the world, affecting 1 in 7 adults in the United States alone. The most common symptoms are joint pain and stiffness. Usually the symptoms progress slowly over years. Other symptoms may include joint swelling, decreased range of motion, and, when the back is affected, weakness or numbness of the arms and legs. The most commonly involved joints are the two near the ends of the fingers and the joint at the base of the thumbs, the knee and hip joints, and the joints of the neck and lower back. The symptoms can interfere with work and normal daily activities. Unlike some other types of arthritis, only the joints, not internal organs, are affected.

<span class="mw-page-title-main">Synovial joint</span> Articulation which admits free motion in the joint; the most common type of articulation

A synovial joint, also known as diarthrosis, joins bones or cartilage with a fibrous joint capsule that is continuous with the periosteum of the joined bones, constitutes the outer boundary of a synovial cavity, and surrounds the bones' articulating surfaces. This joint unites long bones and permits free bone movement and greater mobility. The synovial cavity/joint is filled with synovial fluid. The joint capsule is made up of an outer layer of fibrous membrane, which keeps the bones together structurally, and an inner layer, the synovial membrane, which seals in the synovial fluid.

<span class="mw-page-title-main">Synovial fluid</span> Fluid found in the cavities of synovial joints

Synovial fluid, also called synovia,[help 1] is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement. Synovial fluid is a small component of the transcellular fluid component of extracellular fluid.

<span class="mw-page-title-main">ADAMTS5</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloproteinase with thrombospondin motifs 5 also known as ADAMTS5 is an enzyme that in humans is encoded by the ADAMTS5 gene.

<span class="mw-page-title-main">Mechanotransduction</span> Conversion of mechanical stimulus of a cell into electrochemical activity

In cellular biology, mechanotransduction is any of various mechanisms by which cells convert mechanical stimulus into electrochemical activity. This form of sensory transduction is responsible for a number of senses and physiological processes in the body, including proprioception, touch, balance, and hearing. The basic mechanism of mechanotransduction involves converting mechanical signals into electrical or chemical signals.

A meniscus transplant or meniscal transplant is a transplant of the meniscus of the knee, which separates the thigh bone (femur) from the lower leg bone (tibia). The worn or damaged meniscus is removed and is replaced with a new one from a donor. The meniscus to be transplanted is taken from a cadaver, and, as such, is known as an allograft. Meniscal transplantation is technically difficult, as it must be sized accurately for each person, positioned properly and secured to the tibial plateau. Its success also depends on donor compatibility, stability of the transplant, and long-term health of the underlying articular cartilage.

Type II collagen is the basis for hyaline cartilage, including the articular cartilages at joint surfaces. It is formed by homotrimers of collagen, type II, alpha 1 chains.

<span class="mw-page-title-main">Aggrecan</span>

Aggrecan (ACAN), also known as cartilage-specific proteoglycan core protein (CSPCP) or chondroitin sulfate proteoglycan 1, is a protein that in humans is encoded by the ACAN gene. This gene is a member of the lectican (chondroitin sulfate proteoglycan) family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage.

<span class="mw-page-title-main">Cartilage oligomeric matrix protein</span> Protein found in humans

Cartilage oligomeric matrix protein (COMP), also known as thrombospondin-5, is an extracellular matrix (ECM) protein primarily present in cartilage. In humans it is encoded by the COMP gene.

<span class="mw-page-title-main">Collagen, type IX, alpha 2</span> Protein found in humans

Collagen alpha-2(IX) chain is a protein that in humans is encoded by the COL9A2 gene.

Kyriacos A. Athanasiou is a Greek Cypriot-American bioengineer who has contributed significantly to both academic advancements as well as high-technology industries. He is currently a Distinguished Professor at the University of California, Irvine. He joined UCI from the University of California, Davis where he also served as the Chair of the Biomedical Engineering department. Before joining the University of California in 2009, he was the Karl F. Hasselmann Professor at Rice University. He has published hundreds of scientific articles detailing structure-function relationships and tissue engineering approaches for articular cartilage, the knee meniscus, and the temporomandibular joint.

Mechanobiology is an emerging field of science at the interface of biology, engineering, chemistry and physics. It focuses on how physical forces and changes in the mechanical properties of cells and tissues contribute to development, cell differentiation, physiology, and disease. Mechanical forces are experienced and may be interpreted to give biological responses in cells. The movement of joints, compressive loads on the cartilage and bone during exercise, and shear pressure on the blood vessel during blood circulation are all examples of mechanical forces in human tissues. A major challenge in the field is understanding mechanotransduction—the molecular mechanisms by which cells sense and respond to mechanical signals. While medicine has typically looked for the genetic and biochemical basis of disease, advances in mechanobiology suggest that changes in cell mechanics, extracellular matrix structure, or mechanotransduction may contribute to the development of many diseases, including atherosclerosis, fibrosis, asthma, osteoporosis, heart failure, and cancer. There is also a strong mechanical basis for many generalized medical disabilities, such as lower back pain, foot and postural injury, deformity, and irritable bowel syndrome.

Gene therapy for osteoarthritis is the application of gene therapy to treat osteoarthritis (OA). Unlike pharmacological treatments which are administered locally or systemically as a series of interventions, gene therapy aims to establish sustained therapeutic effect after a single, local injection.

Nasal chondrocytes (NC) are present in the hyaline cartilage of the nasal septum and in fact are the only cell type within the tissue. Similar to chondrocytes present in articular cartilage, NC express extracellular matrix proteins such as glycosaminoglycans and collagen.

Artificial cartilage is a synthetic material made of hydrogels or polymers that aims to mimic the functional properties of natural cartilage in the human body. Tissue engineering principles are used in order to create a non-degradable and biocompatible material that can replace cartilage. While creating a useful synthetic cartilage material, certain challenges need to be overcome. First, cartilage is an avascular structure in the body and therefore does not repair itself. This creates issues in regeneration of the tissue. Synthetic cartilage also needs to be stably attached to its underlying surface i.e. the bone. Lastly, in the case of creating synthetic cartilage to be used in joint spaces, high mechanical strength under compression needs to be an intrinsic property of the material.

Farshid Guilak is an American engineer and orthopedic researcher. He is the Mildred B. Simon Professor of Orthopaedic Surgery at Washington University in St. Louis and director of research at Shriners Hospitals for Children. He is also on the faculty of the departments of Biomedical Engineering, Mechanical Engineering & Materials Science, and Developmental Biology at Washington University.

References

  1. Setton, LA; Chen, J (2006). "Mechanobiology of the intervertebral disc and relevance to disc degeneration". J Bone Joint Surg Am. 88 (2): 52–57. doi:10.2106/JBJS.F.00001. PMID   16595444.(cited 154 times)
  2. Setton, LA; Mow, VC; Müller, FJ; Pita, JC; Howell, DS (1994). "Mechanical properties of canine articular cartilage are significantly altered following transection of the anterior cruciate ligament". Journal of Orthopaedic Research. 12 (4): 451–463. doi:10.1002/jor.1100120402. PMID   8064477. S2CID   41257875.(cited 168 times)
  3. LeRoux, MA; Arokoski, J; Vail, TP; Guilak, F; Hyttinen, MM; Kiviranta, I; Setton, LA (2000). "Simultaneous changes in the mechanical properties, quantitative collagen organization, and proteoglycan concentration of articular cartilage following canine meniscectomy". Journal of Orthopaedic Research. 18 (3): 383–392. doi:10.1002/jor.1100180309. PMID   10937624. S2CID   1697626.(cited 122 times)
  4. Leroux, MA; Cheung, HS; Bau, JL; Wang, JY; Howell, DS; Setton, LA (2001). "Altered mechanics and histomorphometry of canine tibial cartilage following joint immobilization". Osteoarthritis and Cartilage. 9 (7): 633–640. doi: 10.1053/joca.2001.0432 . PMID   11597176.(cited 62 times)
  5. Boyd, LM; Richardson, WJ; Chen, J; Kraus, VB; Tewari, A; Setton, LA (2005). "Osmolarity regulates gene expression in intervertebral disc cells determined by gene array and real-time quantitative RT-PCR". Annals of Biomedical Engineering. 33 (8): 1071–1077. CiteSeerX   10.1.1.419.5226 . doi:10.1007/s10439-005-5775-y. PMID   16133915. S2CID   18286177.(cited 35 times)
  6. Chen, J; Yan, W; Setton, LA (2004). "Static compression induces zonal-specific changes in gene expression for extracellular matrix and cytoskeletal proteins in intervertebral disc cells in vitro". Matrix Biology. 22 (7): 573–583. doi:10.1016/j.matbio.2003.11.008. PMID   14996437.(cited 74 times)
  7. Boyd, LM; Richardson, WJ; Allen, KD; Flahiff, C; Jing, L; Li, Y; Chen, J; Setton, LA (2008). "Early-onset degeneration of the intervertebral disc and vertebral end plate in mice deficient in type IX collagen". Arthritis Rheum. 58 (1): 164–171. doi: 10.1002/art.23231 . PMID   18163498.(cited 40 times)
  8. Allen, KD; Griffin, TM; Rodriguiz, RM; Wetsel, WC; Kraus, VB; Huebner, JL; Boyd LM; Setton, LA (2009). "Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen". Arthritis Rheum. 60 (9): 2684–2693. doi:10.1002/art.24783. PMC   2760314 . PMID   19714629.(cited 29 times)
  9. Nettles, DL; Chilkoti, A; Setton, LA (2010). "Applications of elastin-like polypeptides in tissue engineering". Adv Drug Deliv Rev. 62 (15): 1479–1485. doi:10.1016/j.addr.2010.04.002. PMC   2935943 . PMID   20385185.(cited 114 times)
  10. Nettles DL; Kitaoka, K; Hanson, NA; Flahiff, CM; Mata, BA; Hsu, EW; Chilkoti, A; Setton, LA (2008). "In situ crosslinking elastin-like polypeptide gels for application to articular cartilage repair in a goat osteochondral defect model". Tissue Eng Part A. 14 (7): 1133–1140. doi:10.1089/tea.2007.0245. PMC   3312393 . PMID   18433311.(cited 50times)
  11. Betre, H; Ong, SR; Guilak, F; Chilkoti, A; Fermor, B; Setton, LA (2006). "Chondrocytic differentiation of human adipose-derived adult stem cells in elastin-like polypeptide". Biomaterials. 27 (1): 91–99. doi:10.1016/j.biomaterials.2005.05.071. PMID   16023192.
  12. Nettles, DL; Vail, TP; Morgan, MT; Grinstaff, MW; Setton, LA (2004). "Photocrosslinkable hyaluronan as a scaffold for articular cartilage repair". Ann Biomed Eng. 32 (3): 391–397. doi:10.1023/b:abme.0000017552.65260.94. PMID   15095813. S2CID   1334471.
  13. Allen, KD; Adams, SB Jr; Mata, BA; Shamji, MF; Gouze, E; Jing, L; Nettles, DL; Latt, LD; Setton, LA (2010). "Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist". Journal of Orthopaedic Research. 29 (5): 694–703. doi:10.1002/jor.21309. PMC   3100769 . PMID   21437948.
  14. Shamji, MF; Chen, J; Friedman, AH; Richardson, WJ; Chilkoti, A; Setton, LA (2008). "Synthesis and characterization of a thermally-responsive tumor necrosis factor antagonist". J Control Release. 129 (3): 179–186. doi:10.1016/j.jconrel.2008.04.021. PMC   2637771 . PMID   18547669.
  15. Shamji, MF; Betre, H; Kraus, VB; Chen, J; Chilkoti, A; Pichika, R; Masuda, K; Setton LA (2007). "Development and characterization of a fusion protein between thermally responsive elastin-like polypeptide and interleukin-1 receptor antagonist: sustained release of a local antiinflammatory therapeutic". Arthritis Rheum. 56 (11): 3650–3661. doi:10.1002/art.22952. PMID   17968946. S2CID   32108692.
  16. Betre, H; Liu, W; Zalutsky, MR; Chilkoti, A; Kraus, VB; Setton, LA (2006). "A thermally responsive biopolymer for intra-articular drug delivery". J Control Release. 115 (2): 175–182. doi:10.1016/j.jconrel.2006.07.022. PMID   16959360.
  17. Allen, KD; Shamji, MF; Mata, BA; Gabr, MA; Sinclair, SM; Schmitt, DO; Richardson, WJ; Setton LA (2011). "Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism". Arthritis Research & Therapy . 13 (4): R137. doi: 10.1186/ar3451 . PMC   3239380 . PMID   21871102.
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  20. bmes.org (2009). "BMES Fellows". Biomedical Engineering Society. Retrieved 2013-05-23.
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  22. "All Fellows" (PDF). ASME. 2022.
  23. www.nsf.gov (1997-10-24). "Twenty NSF-Supported Young Scientists and Engineers Receive Presidential Award". National Science Foundation. Retrieved 2013-05-25.