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Shane Lloyd

Class Year: G3

Department/Institute/Center(s):

M.D./Ph.D. Program

Biographical Information:

Hometown: Vancouver, British Columbia, Canada

Education:

Undergraduate Education: BS/07 Pharmacology/University of British Columbia, Canada

Research Interests:

Research Interest:

Understanding the role of direct cell-to-cell communication via gap junctions in mediating the bone loss associated with mechanical unloading; The effect of clinical and spaceflight relevant types and doses of radiation on bone and the development of therapeutic countermeasures to prevent radiation-induced bone loss.

Advisor: Henry Donahue, PhD
Graduate Program: Cell & Molecular Biology

Thesis: "The Role of Connexin 43-mediated Gap Junctional Intercellular Communication in the Skeletal Response to Mechanical Unloading:

Description: Communication between bone cells via gap junctionsx is integral to their ability to adapt the skeletal system in response to mechanical forces. I have undertaken a study of hbone cell communication via Connexin 43, the predominant gap junction protein in bone, and its role in the skeletal response to mechanical unloading. I bred Cx43 conditional knockout mice and have subjected them to a ground-based model of unloading. I have determined that Cx43 deficiency attenuates unloading-induced bone loss, particularly in the trabecular bone compartment. Quantitative histomorphometry data also suggests that Cx43 deficiency prevents the characteristic suppression of bone formation associated with unloading. The next phase of my research will be to determine what mechanisms are underlying this response. I will examine the effect of Cx43 deficiency during unloading on critical hbone signaling pathways, including the Wnt/ß-catenin pathway and RANK/RANKL/OPG axis. These studies will be conducted both in vivo and in vitro. I hope to be able to identify Cx43 as a potential target for the prevention of unloading-induced bone loss.

Meeting Presentations

2005
UBC Multidisciplinary Undergrad Res. Conference, Vancouver, BC
Cleveland Clinic Symposium on Bone Loss in Space, Cleveland, OH
Am. Soc, for Gravitational & Space Biology Annual Mtg., Reno, NV
2007
Am. Soc. for Gravitational & Space Biology Annual Mtg., San Francisco, CA
NASA Human Res. Program Investigators Conference, League City, TX
2010
38th Scientific Assembly of the Committee on Space Research, Bremen, Germany (oral)
Annual Meeting of the American Society for bone and Mineral Research, Toronto, Canada
2011
Annual Meeting of the American Society for bone and Mineral Research, San Diego, CA (oral)
Annual Meeting of the Orthopaedic Research Society, San Francisco, CA
2012
Penn State College of Medicine Graduate Student Research Forum, Hershey, PA (oral)

Publications:

Leander BS, Lloyd SAJ, Marshall W, Landers SC (2006) Phylogeny of marine gregarines (Apicomplexa)-Pterospora, Lithocystis and Lankesteria-and the origin(s) of coelomic parasitism Protist 157(1):45-60 PMID: 16352468

Bateman TA, Bandstra ER, Willey JS, Yuan YY, Lloyd SAJ, Bourne J (2007) How Animal Models Inform the Debate in Bone Loss During Spaceflight edited by PR Cavanaugh 1-20 Cleveland Clinic Press 189-199 ISBN:978-1-59624-093-3

Lloyd SA, Travis ND, Lu T, Bateman TA (2007) Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse J of Applied Physio 104(3):729-38 PMID: 18174391

Lloyd SA, Yuan YY, Kostenuik PJ, Ominsky MS, Lau AG, Morony S, Stolina M, Asuncion FJ, Bateman TA (2008) Soluble RANKL Induces High Bone Turnover and Decreases Bone Volume, Density and Strength in Mice Calcif Tissue Int 82(5):361-72 PMID: 18465074

Lloyd SAJ, Banstra ER, Travis ND, Nelson G, Bourland JD, Pecaut MJ, Gridley DS, Willey JS, Bateman TA (2008) Spaceflight-Relevant Types of Ionizing Radiation and Cortical Bone: Potential LET Effect? Adv in Space Res 42(12):1889-97 PMID: 19122806

Willey JS, Lloyd SA, Robbins ME, Bourland JD, Smith-Sielicki H, Bowman LC, Norridin RW, Bateman TA (2008) Early Increase in Osteoclast Number in Mice after Whole-Body Irradiation with 2 Gy X Rays Radiat Res 170(3):388-92 PMID: 18763868

Lloyd SA, Yuan YY, Simske SJ, Riffle SE, Ferguson VL, Bateman TA (2009) Administration of High-Dose Macrophage Colony-Stimulating Factor Increases Bone Turnover and Trabecular Volume Fraction J Bone Miner Met 27(5): 546-54 PMID: 19326045

Lloyd SA, Donahue HJ (2010) Gap Junctions and Biophysical Regulation of Bone Cells Clin Rev in Bone and Miner Metab 8(4):189-200

Lloyd SA, Simske SJ, Bogren LK, Olesiak SE, Bateman TA, Ferguson VF (2011) Effects of Combined Insulin-Like Growth Factor 1 and Macrophage Colony-Stimulating Factor on the Skeletal Properties of Mice In Vivo 25(3):297-305 PMID: 21576402

Willey JS, Lloyd SA, Nelson GA, Bateman TA (2011) Ionizing Radiation and Bone Loss: Space Exploration and Clinical Therapy Applications Clin Rev in Bone and Miner Metab 9(1):54-62

Willey JS, Lloyd SA, Nelson GA, Bateman TA (2011) Space Radiation and Bone Loss Gravit Space Biol 25(1):14-21

Willey JS, Lloyd SA, Bateman TA (2012) Radiation Therapy-Induced Osteoporosis in Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 98th Edition edited by Justin Jeffryews. John Wiley & Sons (accepted)

Lloyd SA, Lewis GS, Zhang Y, Paul EM,, Donahue HJ (2012) Connexin 43 deficiency attenuates loss of trabecular bone and prevents suppression of cortical bone formation during unloading Bone Miner Res 27(11):2359-72