Christopher S. Adams, PhD

Education:

Professional Experience:


Research Projects

The overarching goal of Dr. Adam's research is an understanding of the physiology of skeletal tissues, with a focus on issues related to skeletal diseases and repair. These research activities have two areas of primary concentration. The first is the regulation of chondrocyte and osteoblast apoptosis. The second is the modification of orthopaedic implants for the stimulation of osseointegration and the prevention of peri-prosthetic infection.

Regulation of Chondrocyte and Osteoblast Apoptosis

Dr. Adams has had a long-standing interest in articular cartilage apoptosis, dating back to his work at the National Institute on Aging with Dr. Walter Horton. At that time, Dr. Adams demonstrated that cellular apoptotic rates increased with age in rats and mice. He continued to study apoptosis in growth plate chondrocytes, as well as in the resident cells of bone. They developed the hypothesis that in bone, where most apoptotic cells are found at locations of active remodeling, specific molecules released by cells that resorb bone (osteoclasts) induce apoptosis of vicinal osteoblasts. In cartilage, where apoptotic cells are found at the bottom of the growth plate, they developed a similar hypothesis, where cartilage resorbing cells release factors from the extracellular matrix that induce chondrocyte apoptosis. Included in these factors are calcium and phosphate ions and RGD-containing peptides. They demonstrated that calcium and phosphate-mediated apoptosis is mediated through the mitochondria. They also demonstrated that short peptides containing the sequence RGDS induce caspase-dependent apoptosis. They have also explored the possibility that manipulation of survival pathways can regulate apoptosis externally in these cells. They published evidence that survival pathways can be upregulated in osteoblasts in two ways. The first way is through the modification of the surface upon which the cells sit, second by application of mechanical strain. By grafting RGD containing peptides to the stratum upon which osteoblasts are placed, they have demonstrated that apoptosis can be completely abrogated. Furthermore, they have demonstrated activation of these survival pathways by mechanical strain. While it is clear that one of the primary regulatory environmental factors in bones is the mechanical environment, the method by which mechanical strain modulates bone tissue function remains a mystery. Dr. Adams continues to test the hypothesis that factors present in the environment of skeletal cells modulate the sensitivity of those cells to programmed cell death.

Modification of Orthopaedic Implants for Enhancement of Osseointegration and Prevention of Peri-Prosthetic Infection

The primary focus of their work in this area concerns the major causes of orthopaedic implant failure - peri-prosthetic infection and the subsequent failure to osseointegrate. In recent years, a broad collaboration consisting of scientists here at the Philadelphia College of Osteopathic Medicine, Thomas Jefferson University, the University of Pennsylvania and University College London have worked to advance technology that allows us to tether antibiotics and other molecules of interest to a number of implant surfaces, including titanium, plastics, and bone itself. The chimeric surface has proved to effectively prevent bacterial colonization in both in vitro and in vivo examinations. Such surfaces are of enormous clinical importance and their use should extend far beyond the field of orthopaedics. Currently funded projects include work to create prosthetic anchors that remain infection-free and work creating bone allograft that also resists bacterial colonization. The future of limb prosthetics is thought to be focused on the creation of osseointegrated prosthesis anchors, orthopaedic devices anchored in bone that traverse the skin to attach to a prosthetic limb. The critical weakness in this design is the extremely high rate of infection in transcutaneous implants. We have proposed to alleviate this problem by linking these anchors with antibiotics, preventing bacterial biofilms from traveling the length of the implant. This work has been proposed in concert with the ground-breaking work on osseointegrated prosthesis anchors performed by Dr. Gordon Blunn and Catherine Pendergrass at University College, London. In addition, allograft bone is frequently used clinically to repair large scale defects in bone caused by traumatic loss. Allograft bone is usually decellularized and, as such, can serve as a site for bacterial colonization, potentially creating an even greater clinical problem. Their work has focused on linking antibiotics to these materials, preventing contamination by bacteria while the material is replaced by healthy replacement bone.


Selected Publications

Adams, C.S., and Horton, W.E.: Chondrocyte apoptosis increases with age in the articular cartilage of adult animals. Anatomical Record. 250(4): 418-425, 1998.

Horton, W.E., Feng, L., and Adams, C.S.: Chondrocyte apoptosis in development, aging and disease. Matrix Biology 17(2): 107-115, 1998.

Meleti, Z., Shapiro, I.M., Adams, C.S.: Inorganic phosphate induces apoptosis of osteoblast-like cells in culture. Bone, 27(3): 359-366, 2000.

Mansfield, K.M., Teixeira, C.C., Adams, C.S., and Shapiro, I.M.: Phosphate Ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism. Bone, 28 (1):1-8, 2001.

Adams, C.S., Korytko, A., and Blank, J.: A non-humoral pathway for body weight regulation. Journal of Experimental Biology, 204: 1729-1734, 2001.

Adams, C.S., Mansfield, K.D., Perlot, R.L., Shapiro, I.M.: Matrix Regulation of Skeletal cell apoptosis: Role of Calcium and Phosphate Ions. Journal of Biological Chemistry, 276 (23): 20316-20322. 2001.

Perlot, R.L., Shapiro, I.M., Mansfield, K. and Adams, C.S.: Matrix Regulation of Skeletal cell apoptosis II: Role of RGD-containing peptides. Journal of Bone and Mineral Research, 17(1): 66-76, 2002.

Billings, P.C., Whitlock, C., Lear, J.D., Adams, C.S., Engelsberg, B.N., Rosenbloom, J.: The TGF-ß-inducible matrix protein, ßig-H3 interacts with fibronectin. Journal of Biological Chemistry, 277(31): 28003-28009, 2002.

Adams, C.S, Mansfield, K.D., Rajpurohit, R., Tachibana, H., Teixeira, C.M., Shapiro, I.M.: Components of Extracellular Matrix Regulate Chondrocyte Apoptosis. In: Growth Plate 2001: Proceedings of the First International Conference on the Growth Plate (Shapiro, I.M., Boyan, B.D., Anderson, H.C., eds.): 63-76, Amsterdam: IOS Press, 2002.

Cavalcanti-Adam, E.A., Shapiro, I.M., Composto, R.J., Macarak, E.J., Adams, C.S.: RGD Peptides Immobilized on a mechanically deformable surface promotes osteoblast differentiation.. Journal of Bone and Mineral Research, 17(12): 2130-2140, 2002.

Adams, C.S., and Shapiro, I.M.: The fate of the terminally differentiated chondrocyte: Evidence for microenvironmental regulation of chondrocyte apoptosis. Critical Reviews in Oral Biology and Medicine 13(6): 465-473, 2002.

Adams, C.S., and Shapiro, I.M.: Mechanism By Which Extracellular Matrix Components Induce Osteoblast Apoptosis. Connective Tissue Research, 44: 230-239 Suppl. 1 2003.

Mansfield, K., Pucci, B., Adams, C.S. and Shapiro, I.M.: Induction of apoptosis in skeletal tissues: phosphate mediated chick chondrocyte is calcium dependent. Calcified Tissue International, 73 (2): 161-172, 2003.

Szymczyk, K.H., Shapiro, I.M., and Adams, C.S.: Ionizing radiation sensitizes bone cells to pro-apoptotic agents. Bone, 34:148-156, 2004.

El-Ghanam, A., Ducheyne, P., Adams, C.S., Composto, R., and Shapiro, I.M.: Model surfaces engineered with nanoscale roughness and RGD tripeptides promote osteoblast adhesion. Journal of Biomedical Materials Research, 68A (4):615-627, 2004.

Bucaro, M., Fertala, J., Adams, C.S., Steinbeck, M., Ayyaswamy, P., Mukundakrishnan, Shapiro, I.M., and Risbud, M.V.: Bone cell survival in microgravity: Evidence that modeled microgravity increases osteoblast sensitivity to apoptogens. Annals of the New York Academy of Sciences, 1027:1-10, 2004.

Toworfe, G.K., Composto, R.J., Adams, C.S., Shapiro, I.M., Ducheyne, P.: Fibronectin adsorption on surface-activated poly(dimethylsiloxane) and its effect on cellular function. Journal of Biomedical Materials Research, 71A (3): 449-461, 2004.

Parvizi, J., Wickstrom, E., Adams, C.S., Purtill, J.J., Sharkey, P.F., Hozack, W.J., Shapiro, I.M., Rothman, R.H., and Hickok, N.J.: Titanium Surface with Biologic Activity Against Infection. Clinical Orthopaedics and Related Research, 429:33-38, 2004.

Grigoriou, V., Shapiro, I.M., Cavalcanti-Adam, E.A., Composto, R.J., Ducheyne, P., Adams, C.S.: Osteoblast apoptosis and survival is regulated by integrin-mediated surface attachment. Journal of Biological Chemistry, 280 (3):1733-1739, 2005.

Han, F, Adams, C.S., Tao, Z., Williams, C.J., Zaka, R., Tuan, R.S., Norton, P.A., Hickok, N.J.: Transforming Growth Factor-(1 (TGF-(1) Regulates ATDC5 Chondrogenic Differentiation, and Fibronectin Isoform Expression, Journal of Cellular Biochemistry, 95(4): 750-762, 2005.

Toworfe, GK, Composto, RJ, Adams, CS, Shapiro, IM, and Ducheyne, P: Initial attachment of osteoblast-like cells on functionalized surfaces coated with calcium phosphate. Bioceramics 18, Pts 1 and 2 Key Engineering Materials, 309-311: 275-278, Part 1-2 2006.

Szymczyk, KH, Kerr, BAE, Freeman, TA, Adams, CS, and Steinbeck, MJ: Involvement of hydrogen peroxide in the differentiation and apoptosis of preosteoclastic cells exposed to arsenite. Biochemical Pharmacology, 72(6):761-769 2006.

Szymczyk, KH, Freeman, TA, Adams, CS, Srinivas, V, and Steinbeck, MJ: Active Caspase-3 is required for osteoclast differentiation. Journal of Cellular Physiology, 209(3):836-44, 2006.

Pucci, B, Adams, CS, Fertala, J, Snyder, BC, Mansfield, KD, Tafani, M, Freeman, T, and Shapiro, IM: Development of the Terminally Differentiated State Sensitizes Epiphyseal Chondrocytes to Apoptosis. Journal of Cellular Physiology, 210(3): 609-615, 2007.

Saunders, RK, Szymczyk, KH, Shapiro, IM, Adams, CS: Matrix Regulation of Skeletal Cell apoptosis III: Mechanism of Ca and Pi induced apoptosis. Journal of Cellular Biochemistry, 100(3): 703-715, 2007.

Lee, DC, Adams, CS, Albert, TJ, Shapiro, IM, Evans, SM, and Koch, CJ: Determination of the intracellular oxygen tension in the rat intervertebral disc. Journal of Anatomy, 210:294-303, 2007.

Lee, MH, Adams, CS, Boettinger, D, DeGrado, WF, Shapiro, IM, Composto, RJ, Ducheyne, P: Adhesion of MC3T3-E1 cells to RGD peptides of different flanking residues: Detachment strength and correlation with long-term cellular function, Journal of Biomedical Materials Research 81A:150-160, 2007.

Bohensky, J., Shapiro, I.M., Leshinsky, S., Terkhorn, S., Adams, C.S., Srinivas, V.: Hif-1 regulation of chondrocyte apoptosis: Induction of the autophagic pathway. Autophagy, 3 (3):207-214, 2007.

Edupuganti, OP, Antoci, V Jr, King, SB, Jose, B, Adams, CS, Parvizi, J, Shapiro, IM, Zeiger, AR, Hickok, NJ, Wickstrom, E: Vancomycin covalently bound to Ti6Al4V alloy pins prevents biofilm formation by Staphylococcus aureus. Bioorganic and Medicinal Chemistry Letters 17:2692-2696, 2007.

Han, F, Gilbert, JR, Harrison, G, Adams, CS, Freeman, T, Tao, Z, Zaka, R, Liang, H, Williams, C, Tuan, RS, Norton, P, and Hickok, NJ: Transforming growth factor 1 regulates fibronectin isoform expression and splicing factor SRp40 expression during ATDC5 chondrogenic maturation. Experimental Cell Research, 313(8): 1518-1532, 2007.

Antoci, V, King, SB, Jose, B, Parvizi, J, Zeiger, AR, Wickstrom, E, Freeman, TA, Composto, RJ, Ducheyne, P, Shapiro, IM, Hickok, NH, and Adams, CS: Vancomycin covalently bonded to Titanium alloy prevents bacterial colonization. Journal of Orthopaedic Research. 25:858-866, 2007.

Antoci, V Jr., Adams, CS, Parvizi, J, Ducheyne, P, Shapiro, IM, Hickok, NJ: Covalently Attached Vancomycin Provides a Nanoscale Antibacterial Surface, Clinical Orthopaedics and Related Research, 461:81-87, 2007.

Antoci, V Jr., Adams, CS, Hickok, NJ, Shapiro, IM, Parvizi, J: Vancomycin Bound to Ti Rods Reduces Periprosthetic Infection: A Preliminary Study. Clinical Orthopaedics and Related Research, 461:88-95, 2007.

Antoci, V Jr., Adams, CS, Hickok, NJ, Shapiro, IM, Parvizi, J: Antibiotics for Local Delivery Systems Cause Skeletal Cell Toxicity In Vitro, Clinical Orthopaedics and Related Research, 462:200-206, 2007.

Bucaro, MA, Zahm, AM, Risbud, MV, Ayyaswamy, PS, Mukundakrishnan, K, Steinbeck, MJ, Shapiro, IM, and Adams, CS: Vector-averaged gravity does not induce cell death in osteoblast-like cells in a rotating wall vessel using novel alginate carriers. Journal of Cellular Biochemistry, 102(2):483-495, 2007.

Secchi, A, Grigoriou, V, Cavalcanti-Adam, EA, Composto, RJ, Shapiro, IM, and Adams, CS: RGDS Peptides Immobilized On Titanium stimulate bone cell attachment, differentiation and resistance to apoptosis. Journal of Biomedical Materials Research, 83A:577-584, 2007.

Radin, SA, Antoci, V, Hickok, N, Adams, CS, Parvizi, J, Shapiro, IM, Ducheyne P: In vitro and in vivo bactericidal effect of sol-gel/antibiotic thin films on fixation devices. Key Engineering Materials 330/332: 1323-1326, 2007.

Shapiro, IM, Adams, CS, Srinivas, V, and Freeman, TA.: Chondrocyte Hypertrophy and Apoptosis at the Cartilage-Bone Interface. In: Bone and Osteoarthritis (Topics in Bone Biology Vol 4)(F. Bronner and M.C. Farach-Carson, eds.) Springer-Verlag: London pp. 109-129, 2007.

Zahm, A., Shapiro, I.M., Srinivas, V., and Adams, C.S.: Oxygen tension regulates osteoblasts maturation and mineralization. Bone, 43(1):25-31, 2008.

Antoci, V, Adams, CS, Parvizi, J, Davidson, HM, Composto, RJ, Freeman, TA, Wickstrom, E, Zeiger, AR, Ducheyne, P, Jungkind, D, Shapiro, IM, Hickok, NJ: Vancomycin-modified Ti alloy inhibits S. epidermidis biofilm formation: Implications for treatment of periprosthetic infection. Biomaterials, 29:4684-4690, 2008.

Bohensky, J, Terkhorn, SP, Freeman, T, Adams, CS, Garcia, J, Shapiro, IM, Srinivas, V: Regulation of Autophagy in Cartilage: HIF-2 Suppresses Chondrocyte Autophagy. Arthritis and Rheumatism, 60(5):1406-1415, 2009.

Toworfe, GK, Bhattacharyya, S, Composto, RJ, Adams, CS, Shapiro, IM, Ducheyne, P.: Effect of functional end groups of silane self assembled monolayer surfaces on apatite formation, fibronectin adsorption and osteoblast cell function. Journal of Tissue Engineering and Regenerative Medicine, 3:26-36, 2009.

Ketonis, C., Parvizi, J., Adams, C.S., Shapiro, I.M., Hickok, N.J.: Modification of Ti alloy surfaces: Retention of topography with attachment of antibiotics. Current Orthopaedics and Related Research. (467):1678-1687, 2009.

Adams, CS, Antoci, V Jr, Harrison, G, Patal, P, Freeman, TA, Shapiro, IM, Parvizi, J, Hickock, NJ, Radin, S, Ducheyne, P: Controlled Release of Vancomycin from Thin Sol-Gel Films on Implant Surfaces Successfully Inhibits Osteomyelitis. Journal of Orthopaedic Research, 27:701-709, 2009.

Gilbert, JR, Adams, CS, Shapiro, IM, Hickok, NJ: A Novel Short Hairpin RNA (shRNA) Expression System Promotes SOX9-Dependent Gene Silencing. Plasmid. 62:50-55, 2009.

Ketonis, C, Aiyer, A, Adams, CS, Shapiro, IM, Hickok, NJ, Parvizi, J.: Bacterial Colonization of Bone Allografts: Establishment and Effects of Antibiotics Current Orthopaedics and Related Research, in press, 2010.

Ketonis, C, Aiyer, A, Adams, CS, Barr, S, Shapiro, IM, Parvizi, J, Hickok, NJ: Antibiotic modification of native grafts: Improving upon Nature's scaffolds. Tissue Engineering, In press, 2010.

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