Nam Viet Vo, PhD
Dr. Vo is a member of the Cellular and Molecular Pathology Graduate Training Program.
E1641 Biomedical Science Tower
University of Pittsburgh
200 Lothrop St.
Pittsburgh, PA 15261
Office Telephone: 412-648-1092
Lab Telephone: 412-648-1093
- BS - 1992 Cal St. Fullerton, California
- PhD - 1998 UC Berkeley, California
RESEARCH INTERESTThe overall goal of Dr. Vo's research is to understand the mechanisms of degeneration of matrix in the intervertebral discs and explore therapeutic strategies to minimize disc matrix loss. Loss of disc matrix is a universal hallmark of intervertebral disc (IDD), which results in many debilitating spine disorders such disabling chronic back pain. IDD is strongly correlated with age and tobacco smoking. Our laboratory is focused on investigating at the molecular and cellular levels how aging and tobacco smoking contribute to the loss of disc matrix. Project 1: Age-related intervertebral disc degeneration. Disc matrix proteoglycan (PG), a class of glycosylated proteins that impart turgidity essential for load-bearing, is invariably and progressively depleted as people age. Disc PG loss is primarily a cell-driven process due reduced PG synthesis, enhanced PG proteolytic breakdown, or a combination of both. Work in Dr. Vo's laboratory indicates that senescent intervertebral disc cells exhibit severely perturbed matrix homeostasis. Senescent disc cells show decreased capacity for new PG synthesis and enhanced secretion of catabolic factors, including key inflammatory cytokines and matrix metalloproteinases. We are now focused on determining the role of DNA damage as a driver of disc cellular senescence during aging and dissecting the NF- B signaling pathway as a mediator of perturbation of PG homeostasis in these cells. To achieve these goals, we employ disc cell and organotypic culture systems as well as the novel progeroid mouse model (Ercc1-/? mice) which age rapidly due to a defect in repair of DNA damage. We also use a variety of molecular, cellular, and immunohistological assays and techniques to carry out this research. Identifying the causes of disc cellular senescence and how PG homeostasis becomes altered in them will offer novel opportunities for targeted therapy to prevent or treat IDD.
Project 2: Tobacco smoking-related intervertebral disc degeneration. Tobacco smoking is also a major risk factor of IDD, but the mechanisms by which smoking affects intervertebral discs are largely unknown. Recently studies in our laboratory have shed new insights into the molecular basis underlying loss of disc matrix PG in smoke-related IDD. We discovered, using the mouse model, that chronic tobacco smoke exposure resulted in dramatic loss of PG and increased proteolysis of aggrecan, a key disc matrix PG, that is mediated by both matrix metalloproteinase (MMP) and aggrecanase (ADAMTS) enzymes. Using MMP genetic knockout mice, including the MMP12-/- and ADAMTS5-/- mice, our laboratory is currently working on identifying the specific proteolytic enzymes responsible for smoking-induced disc aggrecan destruction. In addition, we are investigating the role of NF- B in mediating these proteolytic events in disc tissue of smokers. These experiments are essential to elucidate the molecular mechanisms by which tobacco smoking causes IDD and reveal novel enzyme targets for inhibitors aimed at delaying the onset or ameliorating the severity of IDD in chronic smokers.
- Lee H *, Sowa G, Vo N, Vadala G, O'Connell S, Studer R, Kang J. Effect of bupivacaine on intervertebral disc cell viability. Spine J. 2010 Feb;10(2):159-66. Epub 2009 Oct 1.
- Vo, NV #; Seo, H *; Robinson, A; Sowa, G; Bentley, D; Taylor, L; Studer, R; ; Usas, A; Huard, J; Alber, S; Watkins, S; Lee, J; Coehlo, P; Wang, D; Loppini, M; Robbins, P; Niedernhofer L; Kang, J. Accelerated aging of intervertebral discs in a mouse model of progeria. J Orthop Res. 2010 Dec; 28(12):1600-7.
- Vo, NV #; Sowa, G; Seidel, C; Kang, J. Studer, R. P PGE2 and PGF2a differentially modulate matrix metabolism of human nucleus pulposus cells. J Orthop Res. 2010 Oct;28(10):1259-66.
- Sowa G, Westrick E *, Pacek C, Coelho P, Patel D, Vadala G, Georgescu H, Vo N, Studer R, Kang J. In vitro and in vivo testing of a novel regulatory system for gene therapy for intervertebral disc degeneration. Spine. 2011 May 1;36(10):E623-8.
- Vo, NV #, Wang D *, Sowa G, Hartman R, Ngo K, Choe S, Witt W, Dong Q, Lee, J, Niedernhofer L, Kang J. Bupivacaine Decreases Cell Viability and Matrix Protein Synthesis in an Intervertebral Disc Organ Model System. The Spine Journal. 2011 Feb;11(2):139-46.
- Vo, NV #, Wang D *, Sowa G,Witt W, Ngo K *, Coelho P, Bedison R, Byer B, Studer R, Lee, J, Di P, Kang J. Differential Effects of Nicotine and Tobacco Smoke Condensate on Human Annulus Fibrosus Cell Metabolism. J Orthop. Res. 2011 Feb;11(2):139-46.
- Sowa GA, Coelho JP, Vo NV, Bedison R *, Chiao A, Davies C, Studer RK, Kang JD. Determination of Annulus Fibrosus Cell Response to Tensile Strain as a Function of Duration, Magnitude and Frequency. J Orthop. Res. 2011 Aug;29(8):1275-83.
- Sowa G, Coelho JP, Bell KM, Zorn AS, Vo NV, Smolinski P, Niyonkuru C, Hartman R, Studer RK, Kang JD. Alterations in gene expression in response to compression of nucleus pulposus cells. Spine J. 2011 Jan;11(1):36-43.
- Studer RK, Vo N, Sowa G, Ondeck C, Kang J. Human Nucleus Pulposus Cells React to IL-6: Independent Actions and Amplification of Response to IL-1 and TNF-?. Spine. 2011 Apr 15;36(8):593-9.
- Steven Leckie *, Bernard Bechara, Robert Hartman, Gwendolyn Sowa, Barrett Woods *, Paulo Coelho, William Witt, Qing Dong, Brent Bowman, Kevin Bell, Nam Vo, James Kang. Injection of AAV2-BMP2 and AAV2-TIMP1 into the Nucleus Pulposus Alters the Course of Intervertebral Disc Degeneration by MRI, Histological, Serum Biochemical, and Biomechanical Criteria. The Spine Journal. 2011. Spine Journal. 2012 Jan;12(1):7-20.
- Nasto L *, Seo, H-Y *, Robinson, AR, Tilstra, JS, Clauson, CL, Sowa, GA, Ngo, K, Dong, Q, Pola, E, Lee, JY, Niedernhofer, LJ, Kang, JD, Robbins, PD, Vo, NV #. Inhibition of NFKB Activity Ameliorates Age-Associated Disc Degeneration In A Mouse Model Of Accelerated Aging. Spine 2012 Oct 1;37(21):1819-1825.
- Dong Wang *, Luigi A Nasto *, Peter Roughley, Adriana S. Leme, McGarry Houghton, Arvydas Usas, Gwendolyn Sowa, Joon Lee, Laura Niedernhofer, Steven Shapiro, James Kang, Nam Vo #. Spine degeneration in a murine model of chronic human tobacco smokers. Osteoarthritis and Cartilage. 2012 Aug;20(8):896-905.
- Chan Hong Moon, Jung-Hwan Kim, Lloydine Jacobs *, Tiejun Zhao, Gwendolyn Sowa, Nam Vo, James Kang, and Kyongtae Ty Bae. Part 1: Dual-tuned proton/sodium magnetic resonance imaging of the lumbar spine in a rabbit model. Spine 2012. 15;37(18):E1106-12.
- Chan Hong Moon, Jung-Hwan Kim, Lloydine Jacobs *, Tiejun Zhao, Gwendolyn Sowa, Nam Vo, James Kang, and Kyongtae Ty Bae. Part 2: Quantitative proton T2 and sodium MR imaging to assess intervertebral disc degeneration in a rabbit model. Spine 2012. 37(18):E1113-9
- Jeremy S. Tilstra, Andria R. Robinson, Siobhan Gregg, Daniel P. Reay, Luigi A. Nasto *, Arvydas Usas, Nam Vo, Johnny Huard, Paula R. Clemens, Donna B. Stolz, Dennis C. Guttridge, Simon C. Watkins, George A. Garinis, Laura J. Niedernhofer and Paul D. Robbins. NF-?B inhibition delays DNA damage-induced senescence and aging in mice. Journal of Clinical Investigation 2012. Jul 2;122(7):2601-12.
- Christian Isaac, Adam Wright, Hongshuai Li, Arvydas Usas, Xiadong Mu, Qing Dong, Nam Vo, Ying Tang, James Kang, Bing Wang, and Johnny Huard. Dystrophin and Utrophin ''Double Knockout'' Dystrophic Mice Exhibit a Spectrum of Degenerative Musculoskeletal Abnormalities. J Orthop. Res. 2013 Mar;31(3):343-9
- Nasto LA *, Wang D, Robinson AR, Clauson CL, Ngo K, Dong Q, Roughley P, Epperly M, Huq SM, Pola E, Sowa G, Robbins PD, Kang J, Niedernhofer LJ, Vo NV#. Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs. Mech Ageing Dev. 2013 Jan;134(1-2):35-42.
- Jacobs L*, Vo N, Coehlo JP, Dong Q, Bechara B, Woods B, Hempen E, Hartman R, Preuss H, Balk J, Kang J, Sowa G. Glucosamine Supplementation Demonstrates a Negative Effect On Intervertebral Disc Matrix in an Animal Model of Disc Degeneration. Spine. 2013 Jan 15. [Epub ahead of print]
- Sowa GA, Coelho JP, Vo NV, Pacek C, Westrick E, Kang JD. Cells from degenerative intervertebral discs demonstrate unfavorable responses to mechanical and inflammatory stimuli: a pilot study. Am J Phys Med Rehabil. 2012 Oct;91(10):846-55.
- Nasto, Luigi*; Robison, Andria; Ngo, Kevin; Dong, Qing; Croix, Claudette; Sowa, Gwendolyn; Pola, Enrico; Robbins, Paul; Kang, James; Niedernhofer, Laura; Wipf, Peter; Vo, Nam# . Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration. J Orthop. Res. 2013. Accepted.