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Clinton T. Rubin

T: 631.632.8521
F: 631.632.8577
E: Clinton.Rubin@sunysb.edu

Office:
Psychology A, 3rd Floor
Stony Brook, NY
11794-2580

Clinton T. Rubin

 

Research Focus

The major research focus of my work is targeted towards understanding the cellular mechanisms responsible for the growth, healing, and homeostasis of bone. More specifically, I am interested in how biophysical stimuli (i.e., mechanical, electrical, temperature, magnetic, pressure) mediate these responses. The clinical significance of this work is applicable to the inhibition of osteopenia, the promotion of bony ingrowth into prostheses or skeletal defects, and the acceleration of fracture healing. These goals are approached via interdisciplinary studies at the biochemical, molecular, cellular, tissue, organ, computational (e.g., FEM) and clinical levels.

Dr. Rubin’s research into non-invasive, non-pharmacological intervention to control osteoporosis was referenced in National Geographic’s January 2001 article about surviving space travel. His studies show that the application of extremely low level strains to animals and humans will increase bone formation, and thus may represent the much sought after “anabolic” stimulus in bone.

Our work on mechanical biasing of stem cells away from fat and towards bone, has inspired cartoonist Nicole Hollander to capture the "translational essence" of the work. The two-panel carton strip titled "Sylvia" was published around the world, on May 5, 2008.

Cartoon Posted with permission of N. Hollander.

Education

• Res. Fellow - Biomechanics, Brigham & Women's Hosp. Boston, MA, 1984-5
• Res. Assoc. - Cell Biology, Tufts Univ., Boston, MA, 1983-4
• Ph.D. - Anatomy, Univ. of Bristol, Bristol, U.K., 1983
• B.A. - Physiology, Harvard Univ., Cambridge, MA, 1977

Academic Appointments

• 2000- Chair, Department of Biomedical Engineering
• 1997- Visiting Scientist, Brookhaven National Laboratory, Upton, NY
• 1997- Director, Center for Advanced Technology in Medical Biotechnology, New York State office of Science, Technology and Academic Research
• 1995- Director, Program in Biomedical Engineering, S.U.N.Y., Stony Brook.
• 1992- Professor of Orthopaedics, Anatomy, Molecular Biophysics & Mechanical Eng. S.U.N.Y., Stony Brook.
• 1987- Director, Musculo-Skeletal Research Laboratory, S.U.N.Y., Stony Brook.
• 1987-92 Associate Professor of Orthopaedics, Anatomy, & Mechanical Engineering, S.U.N.Y., Stony Brook.
• 1984-87 Assistant Professor of Anatomy & Cell Biol., Tufts Univ. School Med., Boston, Mass.

Honors

• 2005 Distinguished Professor; highest academic rank in SUNY system, as conferred by SUNY Trustees
• 2003 Elizabeth Winston Lanier Kappa Delta Award for Outstanding Research, Amer. Academy of Orthopaedic Surgeons
• 2002 Fellow, American Institute of Medical and Biological Engineers
• 2002 Calgary Award in Orthopaedic Biomechanics, IV World Cong. Biomechanics
• 2001 NYSTAR Distinguished Professor, New York State Office of Technology and Academic Research
• 2000 Giovanni Borelli Award, American Society of Biomechanics
• 1998- Board of Directors, New York Biotechnology Association
• 1997- The Whitaker Foundation, Fellowship Advisory Committee
• 1996 Fuller Albright Award, American Society of Bone and Mineral Research
• 1994 Founder, Exogen, Inc.
• 1993 John Charnley Award, The Hip Society, Amer. Acad. Orthop. Surgeons
• 1990 Kappa Delta Award for Outstanding Research, Bioelectric Repair and Growth Society.
• 1989-1994 Committee on Space Biology & Medicine, Space Studies Board, National Research Council
• 1987-1992 Presidential Young Investigator Award, National Science Foundation.
• 1986 European Society of Biomechanics Award for Excellence in Research.
• 1985 Kappa Delta Society Young Investigator Award, Amer. Acad. Orthop. Surgeons.

Publications

• Luu, Y.K., Ozcivici, E., Capilla, E., Adler, B., Chan, E., Shroyer, K., Judex, S., Pessin, J.E. & Rubin, C.T., (2010). Development of diet induced fatty liver disease in the aging mouse is attenuated by low magnitude mechanical signals. (2010) Int. J. Obesity (in press).
• Ozcivici, E., Luu, Y-K, Adler, B., Qin, Y-X, Rubin, J., Judex, S & Rubin, C.T. (2009) Mechanical Signals as Anabolic Agents in Bone Nature Reviews Rheumatology. 6:50-59.
• Goodship, A., Lawes, T. & Rubin, C. (2009) Low magnitude high frequency mechanical signals accelerate and augment endochondral bone repair. J. Orth. Res. 27:922-930.
• Lee, B.J., Cox, G.A., Maddatu, T.P., Judex, S. & Rubin, C.T. (2009) Devastation of bone tissue in the appendicular skeleton parallels the progression of neuromuscular disease. J. Neuromusc. Int. 9:215-24.
• Sen, B., Styner, M., Xie, Z., Case, N., Rubin, C.T. & Rubin, J. (2009) Mechanical loading regulates NFATC1 and & b-catenin signaling through a GSK3 &b- control node. J. Biol. Chem. 284:34607-17.
• Luu, Y.K., Pessin, J.E., Judex, S., Rubin, J. & Rubin, C.T. (2009) Mechanical signals as a non-invasive means to influence mesenchymal stem cell fate, promoting bone and suppressing the fat phenotype. Int. Soc. Bone & Mineral Res. Bone-Key 2009 6:132-149.
• Patel, M., Talish, R., Rubin, C. & Jo, H. (2009) Low magnitude and high frequency mechanical loading prevents decreased bone formation responses of 2T3 preosteoblasts. J. Chem. Bio. 106:306-16.
• Holguin, N., Muir, J., Rubin, C & Judex, S. (2009) Short applications of very low-magnitude vibrations attenuate expansion of the intervertebral disc during extended bed rest. Spine 9:470-477.
• Luu, Y.K., Capilla, E., Pessin, J., Rosen, C., Gilsanz, V., Judex, S. & Rubin, C. (2009) Mechanical promotion of mesenchymal stem cell proliferation and differentiation prevents dietary induced obesity while enhancing osteogenesis. J. Bone & Min. Res. 24:50-61.
• Luu, Y.K., Lublinsky, S., Ozcivici, E., Capilla, E., Pessin, J., Rubin, C & Judex, S. (2008). In vivo quantification of subcutaneous and visceral adiposity by micro computed tomography in a small animal model. J. Engineering Medical Physics. (in press).
• Sen, B., Xie, Z., Case, N., Ma, M., Rubin, C. & Rubin, J. (2008) Mechanical strain prevents adipogenesis in mesenchymal stem cells by stimulating a durable β-catenin signal. Endocrinology. (in press).
• Lublinsky, S., Luu, Y.K., Rubin, C.T., & Judex, S. (2008) Automated Separation of Visceral and Subcutaneous Adiposity in Micro Computed Tomographies of Mice. J. Digital Imaging. (in press).
• Mittra, E., Rubin, C., Gruber, B., Qin, Y. (2008) Evaluation of trabecular mechanical and microstructural propertiesin human calcaneal bone of advanced age using mechanical testing, microCT, and DXA. Journal of Biomechanics. 41: 368-375.
• Zhi, J., Xu, G., Rubin, C. & Hadjiargyrou, M. (2008) The lipogenic gene Spot 14 is activated in bone by disuse, yet remains unaffected by mechanical signals anabolic to the skeleton. Calc. Tiss. Intl. 82(2):148-54.
• Xie, L., Rubin, C. & Judex, S. (2008) Enhancement of the adolescent murine musculoskeletal system using low-level mechanical vibrations. J. Applied Phys. 104:1056-62.
• Rubin, J. & Rubin, C. (2008) Commentary: Functional Adaptation to Loading of a Single Bone Is Neuronally Regulated and Involves Multiple Bones. J. Bone & Min. Res. 23:1369-1371.
• Rubin, C., Capilla, E., Luu, Y-K, Busa, B., Rosen, C., Pessin, J. & Judex, S. (2007) Adipogenesis is Suppressed by Brief, Daily Exposure to High Frequency, Extremely Low Magnitude Mechanical Signals. Proc. Nat. Acad. Sci. 104:17879-17884
• Judex, S, Lei, X, Han, D. & Rubin, C. (2007) Low-Magnitude Mechanical Signals that Stimulate Bone Formation in the Ovariectomized Rat are Dependent on the Applied Frequency but not on the Strain Magnitude. J. Biomechanics. 40:1333-1339
• Garman, R.A., Gaudette, G., Donahue, L.R, Rubin, C.T., Judex, S. (2007) Acceleratory motions, applied in the absence of weightbearing, can be anabolic to bone. J. Orth. Research . J. Orthopaedic Research. 25:732-740
• Garman R, Rubin C & Judex S (2007) Small Oscillatory Accelerations, Independent of Matrix Deformations, Increase Osteoblast Activity and Enhance Bone Morphology. PLoS ONE 2(7): e653. doi:10.1371/journal.pone.0000653
• Mittra, E., Rubin, C., Gruber, B. & Qin, Y-X. (2007) Evaluation of trabecular mechanical and microstructural properties in human calcaneal bone of advanced age using mechanical testing, micro-CT, and DXA. J. Biomech. Epub ahead of print
• Rubin, C., Judex, S. & Qin, Y-X. (2006) Low-level mechanical signals and their potential as a non-pharmacologic intervention for osteoporosis. /Age and Ageing / 35:32-36
• Judex, S, Lei, X, Han, D. & Rubin, C. (2006) Low-Magnitude Mechanical Signals that Stimulate Bone Formation in the Ovariectomized Rat are Dependent on the Applied Frequency but not on the Strain Magnitude. J. Biomechanics. /(in press).
• Rubin, J., Rubin, C. & Jacobs, C. (2006). Molecular Pathways Mediating Mechanical Signaling in Bone. Gene. (in press, available on line).
• Mittra, E., Rubin, C. & Qin, Y-X. (2005) Interrelationship of trabecular mechanical and microstructural properties in sheep trabecular bone. J. Biomech. 38:1229-1237
• Busa B, Miller LM, Rubin CT, Qin YX, & Judex S. (2005) Rapid establishment of chemical and mechanical properties during lamellar bone formation. Calcif Tissue Int. 77:386-94.
• Murfee, W., Hammett, L., Evans, C., Xie, L., Squire, M., Rubin, C., Judex, S. & Skalak, T. (2005). High-frequency low-magnitude vibrations suppress the number of blood vessels per muscle fiber in mouse soleus muscle. J. App. Physiol. 98:2376-2380
• Judex S, Zhong N, Squire ME, Ye K, Donahue LR, & Rubin, C. (2005) Mechanical modulation of molecular signals which regulate anabolic and catabolic activity in bone tissue. J Cell Biochem. 94:982-994.
• Zhong N, Garman RA, Squire ME, Donahue LR, Rubin C & Judex, S. (2005) Gene expression patterns in bone after 4 days of hind-limb unloading in two inbred strains of mice. Aviat Space Environ Med; 76:530-535.
• Hannan, M., Cheng, D., Greeen, E., Swift, C., Rubin, C. & Kiel, D. (2004) Establishing the compliance in elderly women for use of a low level mechanical stress device in a clinical osteoporosis study. Osteoporosis International 15:918-926
• Judex, S., Garman, S., Squire, M., Bhusa, B., Donahue, L.R. & Rubin, C.T. (2004) Genetically linked site-specificity of disuse osteoporosis. J.Bone and Mineral Research. 19:607-614
• Squire, M., Donahue, L.R., Rubin, C.T., Judex, S. (2004) Genetic variations that regulate bone morphology in the male skeleton do not influence its susceptibility to mechanical unloading. Bone 35(6), 1353-1360.
• Judex, S., Garman, S., Squire, M., Donahue, L.R. & Rubin, C.T.(2004) Genetically based influences on the site-specific regulation of trabecular and cortical bone morphology. Journal of Bone and Mineral Research. 19:600-607
• Rubin, C.T., Recker, R., Raab, D., Ryaby, J., McCabe, J. & McLeod,K.J. (2004) Prevention of Post-Menopausal Bone Loss by a Low Magnitude, High Frequency Mechanical Stimuli; A Clinical Trial Assessing Compliance, Efficacy And Safety. J. Bone & Mineral Research. 19:343-351
• Ward, K., Alsop, C., Brown, S., Caulton, J., Rubin, C., Adams, J.& Mughal, M. (2004) Low magnitude, high frequency loading therapy increases volumetric tibial bone mineral density in children with disabling conditions. J. Bone & Mineral Research: 19:360-369  
• Rubin, C., Pope, M, Fritton, C., Magnusson, M., Hansson, T. & McLeod, K. (2003). Transmissibilityof 15-35 Hz vibrations to the human hip and lumbar spine: Determiningthe physiologic feasibility of delivering low-level, anabolic mechanicalstimuli to skeletal regions at greatest risk of fracture due to osteoporosis.Spine; 28:2621-2627
• Qin, Y-X., Kaplan, T., Saldana, A. and Rubin, C.T. (2003): Fluid Pressure Gradients, Arising from Oscillations in Intramedullary Pressure, is Correlated with the Formation of Bone and Inhibition of Intracortical Porosity. J Biomech, 36:1427-1437.
• Judex S, Boyd SK, Qin YX, Turner S, Ye K, Mueller R, Rubin C (2003)Adaptations of Trabecular Bone to Low Magnitude Vibrations Result in More UniformStress and Strain Under Load. Ann Biomed Eng. 31:12-20.
• Judex, S., Boyd, S., Qin, Y-X, Miller, L., Müller, R., Rubin, C. (2003) Combining High-Resolution MicroCT with Material Composition to Define the Quality of Bone Tissue. Current Osteoporosis Reports. 1:11-19
• Judex, S., Donahue, L.R., Rubin, C.T. (2002) Genotypic predisposition to osteoporosis is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. The FASEB Journa Express Article. 10.1096/fj.01-0913fje
• Hadjiargyrou M, Lombardo F, Zhao S, Ahrens W, Joo J, Ahn H, White DW, Rubin CT. Transciptional profiling of bone regeneration: Insight into the molecular complexity of wound repair. J Biol Chem 2002.
• Rubin C, Turner AS, Mallinckrodt C, Jerome C, McLeod K, Bain S. Mechanical strain, induced noninvasively in the high-frequency domain, is anabolic to cancellous bone, but not cortical bone. Bone 2002 Mar; 30(3):445-52.
• Rubin C, Turner AS, Muller R, Mittra E, McLeod K, Lin W, Qin YX. Quantity and quality of trabecular bone in the femur are enhanced by a strongly anabolic, noninvasive mechanical intervention. J Bone Miner Res 2002 Feb; 17(2):349-57.
• Rubin, C., Turner, S. Bain, S., Mallinckrodt, C. & McLeod, K. (2001) Extremely Low Level Mechanical Signals are Anabolic to Trabecular Bone. Nature 412:603-604.
• Rubin C, Xu G, Judex S. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli. FASEB J. 2001; 15(12):2225-9.
• D. W. Sommerfeldt, C. T. Rubin. (2001) Biology of bone and how it orchestrates the form and function of the skeleton. Eur Spine J, DOI 10.1007/s005860100283
• Rubin, C, Sommerfeldt, D, Judex, S & Qin, Y-X. (2001) Inhibition of Osteopenia by Low Magnitude, High Frequency Mechanical Stimuli. Drug Discovery Today 6:848-858.
• Rubin, C., Bolander, M., Ryaby, J. & Hadjiargyrou, M. (2001) The use of low intensity ultrasound to accelerate the healing of fractures. J. Bone & Jt. Surg. 83:259-70.
• Lin, W., Qin, Y.-X. & Rubin, C.T. (2001) Ultrasonic wave propagation in trabecular bone predicted by the stratified model. Annals of Biomed. Eng. 29(9):1-10.
• Rubin, C., Alikhani, M. and Rubin, J. (2001) Comparative Skeletal Structure. In: Encyclopedia Life Sciences; Nature Press.
• Sommerfeldt DW, McLeod KJ, Rubin CT, Hadjiargyrou M. Differential phosphorylation of paxillin in response to surface-bound serum proteins during early osteoblast adhesion. Biochem Biophys Res Commun. 2001 Jul 13; 285(2):355-63.
• Fritton, S.P., McLeod, K.J., Rubin, C.T. (2000) Quantifying the strain history of bone: spatial uniformity and self-similarity of low magnitude strains. J. Biomech. 33:317-326.
• Hadjiargyrou, M., Ahrens, W. & Rubin, C. (2000) Expression and function of CYR-61 in the healing fracture. J. Bone & Min. Res 15:1014-1023
• Rubin, C. and Rubin, J. (2000) Biomechanics of Bone. Primer for Metabolic Bone Diseases and Disorders of Mineral Metabolism. ed: M. Fauvus. Lippincott-Raven ch 5: p 39-42
• Vander Molen, M.A., Donahue. H.J., Rubin, C.T. & McLeod, K.J. (2000) Gap junctions alter the kinetics of electric field induced differentiation in osteoblastic cells. Bone . 27(2):227-31
• Rubin, J., Rubin, H., & Rubin, C. (1999) Constraints of experimental paradigms used to model the aging skeleton. The Aging Skeleton, eds: C.Rosen, J.Glowacki & J.Bilizekian. Acad. Press Ch.4; p27-36.
• Rubin, C., Zhi, J., Xu, G., Cute, M., McLeod, K. and Hadjiargyrou, M. (1999) Expression of novel gene products upregulated by disuse is normalized by an osteogenic mechanical stimulus: NASA Space Biology Program; Biomedical Investigators' Workshop, Jan. 11-13, League City, Texas.
• McLeod, K.J., Turner, A.S., Mallinckrodt, C.H. & Rubin, C.T. (1999) Frequency and duration optimization of dynamic loading protocols for the reversal of osteopenia. 45th Ann. Mtg. Orthop. Res. Soc.:24:571
• Qin, Y.X., McLeod, K.J., Lin, W., Gray, J., Turner, A.S. & Rubin, C.T. (1999) Trabecular strength is enhanced by low magnitude and high frequency mechanical stimuli as determined by CT number, ultrasonic velocity and force-displacement measurements. 45th Ann. Mtg. Orthop. Res. Soc. 24:568.
• Rubin, J. & Rubin, C. (1999) Genetic and Epigenetic Influences on Bone Strength. In: Osteoporosis: Genetics, Prevention and Treatment, eds: J. Adams & B. Lukert, Kluwer Publ., Newt., MA p.57-72 .
• Rubin, J., Fan, X., Biskobing, D., Taylor, W. & Rubin, C. (1999) Osteoclast formation is attenuated in a dose-dependent and site-specific manner by physiologic levels of strain. J. Orth. Res, 17:639-645.
• Huang, R., McLeod, K. & Rubin, C. (1999) Changes in the dynamics of muscle contraction as a function of age; A contributing factor to the etiology of osteoporosis? J. Gerontology 54:352-357.
• Rubin, C., Recker, R., Cullen, D., Ryaby, J. & McLeod, K. (1998) Prevention of bone loss in a post-menopausal population by low-level biomechanical intervention. Amer. Sc. Bone Min Res: 23:1106
• Rubin, C. Turner, S., Jerome, C. Strachan, M., Bain, S., & McLeod, K. (1998). Low magnitude, high frequency mechanical stimulation increases trabecular density of the proximal femur. Amer Soc.Bone Min Res: 23:1126
• Qin, Y-X., Rubin, C. & McLeod, K. (1998) Nonlinear dependence of loading intensity and cycle number in the maintenance of bone mass and morphology. J. Orth. Res. 16:482-489.
• Hadjiargyrou, M., Halsey, M., Ahrens, W., Rightmire, E., McLeod, K & Rubin, C. (1998) Cloning of a novel cDNA expressed during the early stages of fracture healing. Biochm & Biophys. Res. Com 249:879-884
• Otter, M., Rubin, C., and McLeod, K. (1998) Stochastic modulation of cell shape by low-level mechanical loading. The Amer. J. Med. Sciences 316(3):176-183.
• Demes, B., Stern, J., Larson, S. & Hausman, M, Rubin, C., (1998) Bone strain in the macaque ulna during locomotion. J. Phys. Anthrop 106:87-100
• Hadjiargyrou, M., McLeod, K., Ryaby, J. & Rubin, C.(1998) Augmentation of Fracture Healing by Low Intensity Ultrasound.. Clin. Orth. Rel. Res. 355:216-229
• Adams, D., Spirt, A., Brown, T., Fritton, S., Rubin, C. & Brand, R. (1997) Testing the "daily stress stimulus" hypothesis of bone remodeling. J. Biomech30:671-678.
• Fritton, J., Rubin, C., Qin, Y.-X. & McLeod, K. (1997) Vibration in the skeleton. Part I: Development of a resonance-based whole body vibration device. J. Biomed Eng. 25:831-839.
• Gross, T.S., Edwards, J.L., McLeod, K.J. & Rubin, C.T. (1997) Strain gradients correlate with sites of periosteal bone formation. J. Bone Min. Res. 12(6):982-988.
• Rubin, C. T. & McLeod, K. (1996) Inhibition of osteopenia by biophysical intervention. In: Osteoporosis, Eds: R. Marcus, J. Kelsey & D. Feldman. Academic Press Ch. ch. 5, pp351-371.
• Rubin, C., Sun, Y-Q, Hadjiargyrou, M. & McLeod, K. (1999) Increased expression of MMP-1 mRNA in osteocytes precedes bone resorption as stimulated by disuse: Evidence for the autoregulation of the bone's mechanical environment? J. Orth. Res.; 17: 354-361.
• Rubin, C., Gross, T., Qin, Y., Fritton, S., Guilak, F. & McLeod, K.J. (1996) Differentiation of bone-tissue remodeling response to axial and torsional loading. J. Bone Jt. Surg. 78(10):1523-1533.
• Qin, Y., McLeod, K., Guilak, F. and Rubin, C. (1996) Correlation of bony ingrowth with the distribution of stress and strain parameters surrounding a porous-coated implant. J. Orth. Res. 14:862-870.
• Rubin, J., McLeod, K., Titus, L., Nanes, M., Catherwood, B. and Rubin, C. (1996) Formation of osteoclast-like cells is suppressed by low frequency, low intensity electric fields. J. Orth. Res. 14:7-15.
• Ricos, V., Pedersen, D., Brown, T, Rubin, C., & Brand, R. (1996) Effects of anisotropy and material axis registration on computed stress and strain distributions in the turkey ulna. J. Biomec. 29:261-267.
• Sun, Y-Q., McLeod, K. & Rubin, C. (1995) Mechanically induced periosteal bone formation is paralleled by the upregulation of collagen type one mRNA in osteocytes as measured by IS-RT-PCR. Calc. Tiss. Intl. 57:456-462.
• Gross, T. and Rubin, C. (1995) Uniformity of resorptive bone loss induced by disuse. J. Orth. Res. 13(5):708-714.
• Rubin, C.T., Gross, T.S., McLeod, K.J. & Bain, S.D. (1995) Morphologic stages in lamellar bone formation stimulated by a potent mechanical stimulus. J. Bone Min. Res. 10(3):488-495.
• Rubin, C. & McLeod (1994) Promotion of bony ingrowth by frequency specific, low amplitude mechanical strains. John Charnley Award of The Hip Society. Clin. Orth. Rel. Res. 298:165-174

Patents

• Method for inducing a current and voltage in living tissue for the prevention of bone loss. Patent #4,993,413
• Mechanical loading protocol for the prevention of osteoporosis, acceleration of fracture healing, and the promotion of bony ingrowth. #5,103,808
• Method for the promotion of growth, ingrowth and healing of bone tissue and the prevention of osteopenia by mechanical loading of the bone tissue. #5,191,880
• Apparatus for the induction of high frequency strains into the axial skeleton to promote growth and repair. #5,273,028
• Non-Invasive method and means for in-vivo bone-growth stimulation. #5,376,065
• Method and system for therapeutically treating bone fractures and osteoporosis. #5,997,490
• Method and system for therapeutically treating bone fractures and osteoporosis. #6,022,349
• Chondrogenic and osteogenic genes to be used in the treatment of metabolic bone disease. Pending
• Frequency scanning ultrasound as a non-invasive means to determine the physical properties of bone. Pending
• Improvement of postural stability using low level, high frequency mechanical oscillations. Pending