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Biomedical Sciences
Cornelia E. Farnum, D.V.M., Ph.D.
James Law Professor of Anatomy

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Phone: 607 253 3543
E-mail: cef2@cornell.edu
RESEARCH INTERESTS

My long term research objective is to understand fundamental control mechanisms at different levels of skeletal integration-from the molecular to the cellular to that of the whole animal-that are responsible for co-ordinated long bone growth. This objective includes the understanding of perturbations of normal growth, with the intent of understanding the possibilities and limitations of intervention procedures for the correction of abnormalities of long bone growth. I divide this research into three major themes:

- analysis of chondrocytic control of differential bone growth in the postnatal animal;

- analysis of altered growth plate activity during naturally occurring and experimentally induced perturbations of growth, including spontaneous disease;

- analysis of routes of vascular access to the postnatal growth plate; and

Particularly important in my most recent research is the analysis of a variety of transgenic and knockout mutants that have specific perturbations leading to abnormal growth plate activity.

Current collaborations include:

Multiphoton imaging of vascular access routes to the growth plate: This project is in collaboration with Dr. Rebecca Williams in the Department of Applied and Engineering Physics at Cornell. Collaborators on the project include Dr. Warren Zipfel from Cornell and Dr. Jill Urban from the Department of Physiology at Oxford University. Dr. William Horton, Research Director of the Shriner's Hospital in Portland, Oregon, also is a collaborator and he has given us Col II-GFP mice to use in the project. In addition, we will be analyzing VEGF-GFP mice kindly donated to us by Dr. Rakesh Jain of Harvard University. Dr. Chris Schaffer from the Department of Biomedical Engineering at Cornell also is collaborating with us on this project.

Analysis of the incidence and orientation of primary cilia in connective tissues: This is an experimental project to develop a rapid method using pre-embedment immunocytochemistry and imaging with multiphoton microscopy to analyze the presence, incidence and three-dimensional orientation of primary cilia on cells of multiple kinds of connective tissues. We are doing these studies in growth plate cartilage, articular cartilage, meniscus, intervertebral disc, tendon and ligament. Methodology for the three-dimensional analysis is being done with Dr. Maria-Grazia Ascenzi at UCLA. Other collaborators on this project include Dr. Kadler of Manchester University, Dr. Jill Urban of Oxford University, and Dr. Maurizio Pacifici of the University of Pennsylvania.

Analysis of catch-up growth using two models of restricted alimentation during periods of rapid bone elongation in rats: Cilia GroupThe purpose of this project is to use stereological approaches together with OTC labeling as a measure of bone elongation rate and BrdU labeling as a measure of mitotic index to analyze growth plate kinetic responses to a) reduced but balanced nutrition achieved by raising pups in small and large litters; and b) fasting young rapidly growing rats for a three day period. This work has been done in collaboration with Dr. Norman Wilsman at the University of Wisconsin-Madison.

 

 

Analysis of radiation-induced damage to rat growth plates: The aim of this study is to analyze radiation effects and possible treatments for growth plate damage following irradiation of limbs in children for the treatment of bone tumors. I am a collaborator on this grant, with Drs. Tim Damron and Joseph Spadaro at Syracuse University.

Analysis of the growth plate differentiation cascade and its conversion to longitudinal growth in non-mammals and mammals that push the limits: To date this interest is being pursued through the comparative analysis of bone elongation in the bat carpus compared to the bat tarsus, with Dr. John Hermanson in my department. I also have collaborated with Dr. Thom Sanger of Harvard University in his study of growth plates in lizards.

EDUCATION

 

B. A., 1964

Stanford University, Stanford, California
       Major: Biology, Minor: Italian
 

 

Teaching Certificate, 1966

University of Wisconsin, Madison, Wisconsin
       Secondary Education
 

 

D.V.M., 1980

University of Minnesota, St. Paul, Minnesota
 

 

Ph.D., 1985

Department of Anatomy
     School of Medicine
         University of Wisconsin, Madison, Wisconsin

SELECT PUBLICATIONS

  1. Serrat, M.A., Williams, R.M., Farnum, C.E. 2009. Temperature alters solute transport in growth plate cartilage measured by in vivo multiphoton microscopy. Journal of Applied Physiology 107: e-pub.
  2. Wilsman, N.J., Bernardini, E.S., Leiferman, E., Noonan, K., Farnum, C.E. 2008 Age and pattern of the onset of differential growth amoung growth plates in rats. Journal of Orthopaedic Research, 26:1457-1465.
  3. Donnelly, E., Williams, R., Farnum, C.E. 2008. The primary cilium of connective tissue cells: Imaging by multiphoton microscopy. Anatomical Record, in press
  4. Farnum, C.E., Tinsley, M., Hermanson, J.W. 2008. Forelimb versus Hindlimb Skeletal Development in the Big Brown bat, Eptesicus fuscus: Functional Divergence is Reflected in Chondrocytic Performance in Autopodial Growth Plates. Cells, Tissues, Organs 187:35-47.
  5. Farnum, C.E., Tinsley, M., Hermanson, J.W. 2008. Postnatal Bone Elongation of the Manus versus the pes: Analysis of the Chondrocytic Differentiation Cascade in Mus musculus and Eptesicus fuscus. Cells, Tissues, Organs 187:48-58.
  6. Farnum, Cornelia E. 2007 Postnatal growth of limbs and fins through endochondral ossification. In: Fins into Limbs Ed: Brian Hall. University of Chicago Press, Chicago, pp. 118-151.
  7. Williams, R.M., Zipfel, W.R., Tinsley, M., Farnum, C.E. 2007. Solute transport in growth plate cartilage: in vitro and in vivo. Biophysical Journal 93:1039-1050.
  8. Stokes, I.A.F., Clark, K.C., Farnum, C.E., Aronsson, D.D. 2007. Alterations in the growth plate associated with growth modulation by sustained compression or distraction. Bone 41:197-205.
  9. Wang, Y., Zhang, M., Middleton, F.A., Horton, J.A., Pritchard, M., Spadaro, J.A., Farnum, C.E., Damron, T.A. 2007. Connective tissue growth factor and insulin-like growth factor 2 show upregulation in early growth plate radiorecovery response following irradiation. Cells Tissues Organs 186:192-203.
  10. Zhang, M., Wang, Y., Middleton, F.A., Horton, J.A., Farnum, C.E., Damron, T.A. 2007. Growth plate zonal array analysis shows upregulation of extracellular matrix genes and downregulation of metalloproteinases and cathepsins following irradiation. Calcified Tissue International 81:26-38.
  11. Ascenzi, M-G., Tinsley, M., Farnum, C.E. 2007 Analysis of the orientation of primary cilia in growth plate cartilage: a mathematical method based on multiphoton microscopical images. Journal of Structural Biology, 293-306.
  12. Farnum, C.E., Lenox. M., Zipfel, W., Horton, W., Williams, R. 2006 In vivo delivery of fluoresceinated dextrans to the murine growth plate: imaging of three vascular routes by multiphoton microscopy. The Anatomical Record Part A:288A:91-103.
  13. Horton, J.A., Marguiles, B.S., Strauss, J.A., Bariteau, J.Y., Damron, T.A., Spadaro, J.A., Farnum, C.E. 2006 Restoration of growth plate function following radiotherapy is driven by increased proliferative and synthetic activity of expansion of chondrocytic clones. Journal of Orthopaedic Research 24:1945-1956.
  14. Damron, T.A., Horton, J.A., Naqvi, A., Loomis, R.L., Margulies, B.S., Strauss, J.A., Farnum, C.E., Spadaro, J.A. 2006 Combination radioprotectors maintain proliferation better than single agents by decreasing early parathyroid hormone related protein changes after growth plate irradiation. Radiation Research,165:350-358.
  15. Damron, T.A., Spadaro, J.A., Horton, J.A., Marguiles, B.S., Strauss, J.A., Farnum, C.E. 2005 Radioprotectant combinations spare radiation-induced damage to the physis more than fractionation alone. International Journal of Radiation Biology 81:759-765.
  16. Stokes, I.A., Gwadera, J., Dimock, A., Farnum, C.E. 2005 Modulation of vertebral and tibial growth by compression loading: diurnal versus full-time loading. Journal of Orthopaedic Research 23:188-195.
  17. Wang, Y., Middleton, F., Horton, J., Reichel, L., Farnum, C.E., Damron, T.A. 2005. Microarray analysis of proliferative and hypertrophic growth plate zones identifies differentiation markers and signal pathways. Bone 35:1273-1293.
  18. Noonan, K.J., Farnum, C.E., Leiferman, E.M., Lampl, M., Markel, M.D., Wilsman, N.J. 2004. Growing pains: are they due to increased growth during recumbency as documented in a lamb model? Journal of Pediatric Orthopaedics 24:726-731.
  19. Damron, T.A., Spadaro, J.A., Horton, J.A., Marguiles, B.S., Strauss, J.A., Farnum, C.E. 2004. Novel radioprotectant drugs for sparing radiation-induced damage to the physis. International Journal of Radiation Biology 80 (3):217-222.
  20. Damron, T.A., Horton, JA., Naqvi, A., Marguiles, B., Strauss, J.A., Grant, W., Farnum, C.E., Spadaro, J.A. 2004. Decreased proliferation precedes growth factor changes after physeal irradiation. Clinical Orthopaedics 1(422):233-242.
  21. Damron, T.A., Spadaro, J.A., Horton, J.A., Marguiles, B.S., Strauss, J.A., Farnum, C.E. 2004. Combinations of radioprotectants spare radiation-induced damage to the physis. Clinical Orthopaedic and Related Research 426:110-116.
  22. Damron, T.A., Mathur, S., Horton, J.A., Strauss, J., Margulies, B., Grant, W., Farnum, C.E., Spadaro, J.A. 2004. Temporal changes in PTHrP, Bcl-2, Bax, Caspase, TGF-B, and FGF-2 expression following growth plate irradiation with or without radioprotectant. Journal of Histochemistry and Cytochemistry 52:157-167.
  23. Damron, T.A., Marguiles, B.S., Strauss, J.A., O'Hara, K., Spadaro, J.A., Farnum, C.E. 2003. Sequential histomorphometric analysis of the growth plate following irradiation with and without radioprotection. Journal of Bone and Joint Surgery 85-A:1302-131.
  24. Farnum, C.E., Lee, A.O., O'Hara, K., and Wilsman, N.J. 2003. Effect of short-term fasting on bone elongation rates: an analysis of catch-up growth in young male rats. Pediatric Research 53(1):33-41.
  25. Stokes, I.A., Mente, P.L., Iatridis, J.C., Farnum, C.E., and Aronsson, D.D. 2002. Enlargement of growth plate chondrocytes modulated by sustained mechanical loading. Journal of Bone and Joint Surgery 84-A:1842-1848.
  26. Farnum, C.E. and Wilsman, N.J. Chondrocyte Kinetics in the Growth Plate. In: The Growth Plate. Ed. I.M. Shapiro, B. Boyan, H.C. Anderson, IOS press, Washington, pp. 245-257, 2002.
  27. Farnum, C.E., Lee, R., O'Hara, K. and Urban, J.P.G. 2002. Volume increase in growth plate chondrocytes during hypertrophy: the contribution of organic osmolytes. Bone 30:574-581.
  28. Farnum, C.E. and Wilsman, N.J. 2001. Converting a differentiation cascade into longitudinal growth: stereology and analysis of transgenic animals as tools for understanding growth plate function. Current Opinion in Orthopaedics, 12:428-433.
  29. Farnum, C.E., Nixon, A., Lee, A.O., Kwan, D.T., Belanger, L. Wilsman, N.J. 2000. Quantitative three-dimensional analysis of chondrocytic kinetic responses to short-term stapling of the rat proximal tibial growth plate. Cells, Tissues and Organs, 167:247-258.
  30. Bailón-Plaza, A., Lee, A.O., Veson, E., Farnum, C.E., and van der Meulen M.C.H. 1999. BMP-5 deficiency alters chondrocytic activity in the mouse proximal tibial growth plate. Bone, 24:211-216.
  31. Wilsman, N.J., Farnum, C.E., Leiferman, E.M., and Lampl, M. 1999. Consideration of growth plate biology in the context of growth by saltations and stasis. In: Saltations, Stasis, and Human Growth. ed. M. Lampl, Smith Gordon, London, pp. 71-87.
  32. Farnum C. E. and Wilsman, N. J. 1998. Growth plate cellular function, in Skeletal Morphogenesis and Growth. J.A. Buckwalter, et al., eds. American Academy of Orthopaedic Surgeons, Rosemont, IL. pp.203-224.
  33. Farnum C. E. and Wilsman, N. J. 1998. Effects of distraction and compression on growth plate function, in Skeletal Morphogenesis and Growth. J.A. Buckwalter, et al., eds. American Academy of Orthopaedic Surgeons, Rosemont, IL. 517-532.
  34. Stewart, M. C., Farnum, C. E., and MacLeod, J. N. 1997. Expression of p21CIP1/WAF1 in chondrocytes. Calcified Tissue International, 61:199-204.
  35. Wilsman, N. J., Farnum, C. E., Leiferman, E., Fry, M. and Barreto, C. 1996. Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics. Journal of Orthopaedic Research, 14:927-935.
  36. Wilsman, N. J., Farnum, C. E., Green, E. M., Clayton, M. K., and Leiferman, E. 1996. Cell cycle analysis of proliferative zone chondrocytes in growth plates elongating at different rates. Journal of Orthopaedic Research, 14:562-572.
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