Fibrocontractile disease affects nearly 80 million people worldwide annually;yet, current treatment modalities are relatively ineffective. There is an unmet need for a novel small molecule drug to prevent fibrocontractile disease but first the mechanisms of disease formation need to be verified. Fibroblast and myofibroblast contractility is putatively responsible for fibrocontractile disease progression. Non muscle myosin II is hypothesized to be the final common effector protein in fibroblasts and myofibroblasts that promotes contractility. It is hypothesized that blockade of non muscle myosin II will prevent fibrocontractile disease progression. Non muscle myosin II isoform expression will be investigated in human ibrocontractile diseased tissue, and in contracting animal wounds. The effects of non muscle myosin II inhibition on fibrocontractile disease progression in animal models will be studied. Gain of function, loss of function and return of function approaches will be used to demonstrate the functional significance of this protein in in vitro contractility assays. The candidate is a board certified general surgeon, who has completed three years of basic wound healing research, and is expected to finish three years of Plastic Surgery training at Duke University Medical Center in July, 2008. In July 2008, he will work as an Assistant Professor in Plastic Surgery at Duke University Medical Center, with an appointment in Pathology. His short-term career development goals are to establish a career as a surgeon scientist, broaden his basic science knowledge base, improve his laboratory skills and verify that non muscle myosin II is essential for fibrocontractile disease progression. The candidate's long term goals are to translate this basic science research into clinical application by developing a novel pharmaceutical to prevent fibrocontractile disease. The candidate's primary mentor is Salvatore V. Pizzo, MD, PhD, Chairman of Pathology, and previous director of the Medical Scientist Training Program at DUMC, and his two co-meritors are L. Scott Levin, MD, Chief of Plastic Surgery at DUMC, and Daniel P Kiehart, PhD, Chairman of the Department of Biology at Duke University who investigates non muscle myosin II function and wound healing in Drosophila. The candidate foresees initially working in Dr Pizzo's laboratory for 3 years, then progressing towards independence, working for 2 years in the Keenan Plastic Surgery Laboratory as a surgeon scientist, and ultimately preparing an R01 towards the end of the 5 years.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
3K08GM085562-02S1
Application #
7941488
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Ikeda, Richard A
Project Start
2009-09-30
Project End
2011-08-31
Budget Start
2009-09-30
Budget End
2011-08-31
Support Year
2
Fiscal Year
2009
Total Cost
$108,000
Indirect Cost
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Ibrahim, Mohamed; Bond, Jennifer; Medina, Manuel A et al. (2017) Characterization of the Foreign Body Response to Common Surgical Biomaterials in a Murine Model. Eur J Plast Surg 40:383-392
Ibrahim, Mohamed M; Chen, Lei; Bond, Jennifer E et al. (2015) Myofibroblasts contribute to but are not necessary for wound contraction. Lab Invest 95:1429-38
Lorden, Elizabeth R; Levinson, Howard M; Leong, Kam W (2015) Integration of drug, protein, and gene delivery systems with regenerative medicine. Drug Deliv Transl Res 5:168-86
Ehanire, Tosan; Ren, Licheng; Bond, Jennifer et al. (2015) Angiotensin II stimulates canonical TGF-? signaling pathway through angiotensin type 1 receptor to induce granulation tissue contraction. J Mol Med (Berl) 93:289-302
Ibrahim, Mohamed Magdy; Bond, Jennifer; Bergeron, Andrew et al. (2014) A novel immune competent murine hypertrophic scar contracture model: a tool to elucidate disease mechanism and develop new therapies. Wound Repair Regen 22:755-64
Hunter, Cedric; Bond, Jennifer; Kuo, Paul C et al. (2012) The role of osteopontin and osteopontin aptamer (OPN-R3) in fibroblast activity. J Surg Res 176:348-58
Bond, Jennifer E; Kokosis, George; Ren, Licheng et al. (2011) Wound contraction is attenuated by fasudil inhibition of Rho-associated kinase. Plast Reconstr Surg 128:438e-450e
Bond, Jennifer E; Ho, Trung Q; Selim, Maria Angelica et al. (2011) Temporal spatial expression and function of non-muscle myosin II isoforms IIA and IIB in scar remodeling. Lab Invest 91:499-508
Hadeed, Josef G; Bond, Jennifer E; Selim, M Angelica et al. (2011) Calcium-dependent signaling in Dupuytren's disease. Hand (N Y) 6:159-64
Fearmonti, Regina M; Bond, Jennifer E; Erdmann, Detlev et al. (2011) The modified Patient and Observer Scar Assessment Scale: a novel approach to defining pathologic and nonpathologic scarring. Plast Reconstr Surg 127:242-7

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