Research Interests

• Intervertebral disc degeneration:  Role of apoptosis, disc cell metabolism and production of extracellular matrix collagens and proteoglycans, growth factors and disc-cell extracellular matrix interactions in the healthy and degenerating human disc.  Tissue engineering for the disc using a small animal model with spontaneous disc degeneration (the sand rat, Psammomys obesus).  Mechanisms of optimizing human disc cell gene expression of major matrix components in vitro using three-dimensional constructs.  The role of the matricellular protein SPARC in disc health and disease.  Application of laser capture microdissection and in situ hybridization in studies of human disc cell gene expression.

• Osteoblast and osteoclast function:  Role of low magnesium intake in the development of osteopenia in small rodent models.  Bone formation, mineralization and bone loss in metabolic bone disease. 

• Chondrocyte metabolism and growth plate biology:  Physeal fractures and their effect on chondrocyte gene expression, extracellular matrix production, and growth plate physiology.

Professional Experience

• Research Group Director, Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte,  2002-present

• Senior Scientist, Department of Orthopaedic Surgery, Carolinas Medical Center,  Charlotte, 1994-2002

• Research Scientist III and Director, Skeletal Dysplasia Morphology Lab, Cedars-Sinai Medical Center, and Associate Researcher II, Department of Pediatrics, University of California at Los Angeles, Los Angeles, CA, 1986-1994

• Assistant Professor of Research Medicine, University of Southern California School of Medicine, Department of Medicine, Division of Nephrology, Los Angeles, CA, 1984-1986

• Research Fellow, University of Southern California, School of Medicine, Division of Nephrology, Los Angeles, CA, 1981-1984

• Research Instructor of Medicine, University of Washington, Seattle, WA, 1978-1981.

Education

• B.S,, Pre-Med, University of Idaho, Moscow, ID, 1969

• M.S., Cell Biology and Radiation Biology, Oregon State University, Corvallis, OR, 1974

• Ph.D., Cell Biology and Radiation Biology, Oregon State Universtiy, Corvallis, OR, 1976

• NIH Postdoctoral Fellow, Radiation Biology and Cell Biology, University of Iowa, Iowa City, IA, 1976-1978

Selected Recent Publications

1.) Rude, R.K., Gruber, H.E., Norton, H.J., Wei, L.Y., Frausto, A., Mills, B.G.: Bone loss induced by dietary magnesium reduction to 10% of nutrient requirement in rats is associated with increased release of substance P and TNF-alpha. Journal of Nutrition, 134:79-85, 2004.

2.) Gruber, H.E., Ingram, J., Hanley, E.N. Jr.:  The SOX9 transcription factor in the human disc:  Decreased immunolocalization with age and disc degeneration. Spine, 30(6):625-630, 2005.

3.) Gruber, H.E., Ingram, J.A., Leslie, K., Hanley, E.N. Jr.:  Cellular, but not matrix, immunolocalization of SPARC in the human intervertebral disc:  Decreasing localization with aging and disc degeneration.  Spine,  29(20):2223-2228, 2004.

4.) Gruber, H.E., Leslie, K, Ingram, J, Hoelscher, G., Norton, HJ, Hanley, EN Jr.:  Colony formation and matrix production by anulus cells:  Modulation in three-dimensional culture.  Spine   29(13):E267-E274, 2004.

5.) Gruber, H.E., Ingram, J, Norton, H.J.,  Wei, L.Y., Frausto, A., Mills, B.G., and Rude, R.K.:  Alterations in growth plate and articular cartilage morphology are associated with reduced SOX9 localization in the magnesium-deficient rats. Biotechnic & Histochemistry, 79(1):45-52, 2004.

6.) Rude, R.K., Gruber, H.E.:  Magnesium deficiency and osteoporosis:  Animal and human observations.  The Journal of Nutritional Biochemistry, 15(12):710-716, 2004.

7.) Bosse, M.J., Gruber, H.E., Ramp, W.K.:  Internalization of bacteria by osteoblasts in a patient with recurrent, long-term osteomyelitis.  A case report. Journal of Bone and Joint Surgery, Amer., 87A:1343-1347.  June, 2005

8.) Gruber, H.E., Hoelscher, G., Leslie, K., Ingram, J., Hanley, E.N. Jr.:  Three-dimensional culture of human disc cells within agarose or a collagen sponge:  assessment of proteoglycan production.   Published online 8/11/05.  Biomaterials 27:371-376, 2006.

9.) Gruber, H.E., Norton, H.J., Ingram, J., Hanley, E.N. Jr.:  The SOX9 transcription factor in the human disc:  Decreased immunolocalization with age and disc degeneration. Spine, 30(6):625-630, 2005.

11.) Gruber, H.E., Ashraf, N., Kilburn, J.M., Williams, C., H.J. Norton, Gordon, B.E., and  Hanley, E.N. Jr.:  Vertebral end plate architecture and vascularization:  Application of micro-computerized tomography, a vascular tracer, and immunocytochemistry in analyses of disc degeneration in the aging sand rat. Spine 30(23): 2593-2600, Dec. 2005

12.) Rude, R.K., Gruber, H.E., Norton, H.J., Wei, L.Y., Frausto, A., Kilburn, J.:   Dietary Magnesium Reduction to 25% of Nutrient Requirement Disrupts Bone and Mineral Metabolism in the Rat. Bone. 37:211-219, 2005.

13.) Gruber, H.E., Ingram, J.A., Hanley, E.N. Jr.:  Immunolocalization of MMP-19 in the human intervertebral disc:  Implications for disc aging and degeneration.  Biotechnic & Histochemistry, 80(3-4):157-162, 2005.

14.) Rude, RK, Gruber, HE, Wei LY, Frausto A:  Immunolocalization of RANKL is increased and OPG decreased during dietary magnesium deficiency in the rat.  BioMed Central, Nutrition & Metabolism.  Published online 9/14/05.  http://www.nutritionandmetabolism.com/content/2/1/24.

15.) Gruber, H.E., Leslie K., Norton, H.J., Heiner, D., Patt, J., Hanley, E.N.  Demographic factors that influence human disc cell proliferation in vitro. The Spine Journal, 6:120-124, 2006.

16.) Yokoyama, Y., Wawrzyniak, A., Sarmadi, A.M., Baveja, R., Gruber, H.E., Clemens, M.G., Zhang, J.X.:  Hepatic arterial flow becomes the primary supply of sinusoids following partial portal vein ligation in rats.  Journal of Gastroenterology and Hepatology.  21:1567-1574.

17.) Rude, RK, Gruber, HE, Norton, HJ, Wei, LY, Frausto, A, Kilburn, J.: Reduction of dietary magnesium by only 50% in the rat disrupts bone and mineral metabolism. Osteoporosis International 17:1022-1032, July, 2006

18.) Knupp, C, Pinali C, Munro PM, Gruber, HE, Sherratt M, Baldock C, Squire JM. Structural correlation between collagen VI microfibrils and collagen VI banded aggregates. Journal of Structural Biology 154:312-326, 2006

19.) Gruber, H.E., Ingram, J.A., Hanley, E.N.: Immunolocalization of thrombospondin in the human and sand rat intervertebral disc. Spine 31:2556-2561. 2006

20.) Gruber, H.E., Ingram, JA, Hoelscher, G., Norton, HJ, Hanley, EN.: Senescence in cells of the aging and degenerating intervertebral disc: Immunolocalization of senescence associated-ß-galactosidase in human and sand rat discs. Spine. 32(3):321-327, 2007.

21.) Gruber, H.E., Ingram, J.A., Hanley, E.N. Jr.: Cellular immunohistochemical localization of the matricellular protein myocilin in the intervertebral disc. Biotechnic & Histochemistry, 81:119-124, 2006.

22.) Gruber, HE, Ingram J, Hoelscher G, Hanley EN: Leptin expression by annulus cells in the human intervertebral disc. The Spine Journal, 7(4):437-443, 2007

23.) Gruber, H.E., H.J. Norton, and Hanley, E.N. Jr.: Crystal deposits in the human intervertebral disc: Implications for disc degeneration. The Spine Journal, 7(4):444-450, 2007

24.) Gruber, HE, Ingram, JA, Hoelscher, G, Norton, HJ, and Hanley EN Jr: Cell Polarity in the Annulus of the Human Intervertebral Disc: Morphologic, Immunocytochemical and Molecular Evidence. Spine 32(12):1287-1294, 2007.

25.) Gruber, HE, Hanley, EN Jr.: “Do we need biomarkers for disc degeneration?” Biomarker Insights 2:131-133, 2006

26.) Singer, FR, Mills, BG, Gruber, HE, Windle, JJ, Roodman, GD. Ultrastructure of bone cells in Paget’s disease of bone. J. Bone Mineral Res. 21(Suppl. 2):P51-P54, 2006.

27.) 2007 Kurihara, N., Hiruma, Y., Zhou, H., Subler, M.A., Dempster, D.W., Singer, F.R., Reddy, S.V., Gruber, H.E., Windle, J., Roodman, G.D. Mutation of the sequestasome-1 gene (p62) increases osteoclastogenesis but does not induce Paget disease. Journal of Clinical Investigation. 117:133-142, 2007

28.) Gruber HE, Mougeot J-L, Hoelscher GL, Ingram JA, Hanley, EN Jr.: Microarray analysis of laser capture microdissected-annulus cells from the human intervertebral disc. Spine 32:1181-1187, 2007

29.) Gruber, H.E., Gordon, B., Norton, HJ, Kilburn J, Williams C., Zinchenko, N., Hanley, E.N.: Analysis of cell death and vertebral endplate bone mineral density in the annulus of the aging sand rat. The Spine Journal, in press. Available on line 2/7/07.

30.) Gruber, H.E., Hanley, E.N.: Optimization of extracellular matrix production and gene expression by human annulus cells in three-dimensional culture. European Cells and Materials. 13(Suppl. 2):49, 2007.
http://www.ecmjournal.org/journal/supplements/vol013supp02/AOBAB.htm

31.) Gruber, HE, Gordon B, Williams C, Norton HJ, Hanley EN Jr.: Vertebral endplate and disc changes in the aging sand rat lumbar spine: Cross-sectional analyses of a large male and female population. Spine. In press, May 30, 2007

32.) Gruber, H.E., Ingram, J.A., Hanley, E.N. Jr.: Morphologic complexity of the pericellular matrix in the annulus of the human intervertebral disc. Biotechnic & Histochemistry, in press.