Mateusz S Wietecha
University Of Illinois At Chicago
Project start date: 2010-08-01
Project end date: 2014-07-31
Sponsored Links Excellgen http://Excellgen.com
Mateusz S Wietecha
University Of Illinois At Chicago
Project start date: 2010-08-01
Project end date: 2014-07-31
Grants awarded to Mateusz S Wietecha
NIDCR INDIVIDUAL PREDOCTORAL DENTAL SCIENTIST FELLOWSHIP
Mateusz S Wietecha, Phd/dds Candidate
University Of Illinois At Chicago, 310 Aob, M/c 672, Chicago, Il 60612
Grant 1F30DE020991-01 from National Institute Of Dental & Craniofacial Research
Abstract: A vigorous angiogenic response is a prominent component of normal wound repair. Within healing wounds, angiogenesis proceeds until vessel density more than doubles compared to uninjured tissue; most of these new vessels subsequently undergo apoptosis and are removed. While the mechanisms that guide the pro- angiogenic phase of healing are well-understood, the factors that regulate vascular regression in wounds are not yet clear. This project proposes to examine the mechanisms of vascular regression in the wound using well-established in vivo models. The overarching goal of this research is to evaluate the important molecular and spatio-temporal factors that cause blood vessel pruning and blood flow stabilization, and thereby contribute to successful wound resolution. The central hypothesis is that specific endogenous anti-angiogenic factors, including pigment epithelium-derived factor (PEDF) and vasostatin-I, drive vascular regression, allowing the resolving wound to come to vascular homeostasis. The primary aim of the current project is to discover the role of PEDF and vasostatin-I in the context of wound healing. The project will explore the mRNA and protein expression patterns of PEDF and vasostatin-I throughout the time course of healing in a well- characterized murine model of full-thickness dermal wounds. These proteins will be localized in the wound to evaluate the local cellular and structural environment with which they associate and interact. Comprehensive proof-of-function in vivo experiments will be performed to assess the role of endogenous PEDF and vasostatin- I in the resolving wound. These experiments will include the addition of supra-physiological levels of exogenous anti-angiogenic recombinant proteins to healing wounds. Also, interference with function of endogenous mediators will be performed via a novel method of delivery of small interfering RNA (si-RNA) nanoparticles and/or antibodies, followed by an assessment of their effect on wound vascularity using non- invasive laser Doppler imagining. The long term goal of this project is to develop a comprehensive understanding of the complex mechanisms that regulate wound angiogenesis. This knowledge will assist in the development of novel therapeutics to modify dysfunctional neovascularization and/or vascular regression in many human pathological conditions like cancer and arthritis, and will be especially applicable to the treatment of poorly healing wounds. Dysfunctional blood vessel growth or regression is a hallmark of many human pathological conditions including cancer, arthritis, and diabetes-induced delayed wound healing. This study aims to evaluate the potential role of two mediators of blood vessel regression, PEDF and vasostatin-I, to further our understanding of the important regulatory mechanisms that contribute to successful wound resolution. This understanding will bring us closer to the development of more effective treatment methods for patients suffering from these diseases
Keywords: Angiogenic Factor; Antibodies; Apoptosis; Apoptosis Pathway; Arthritis; Autoregulation; Biosynthetic Proteins; Blood Vessels; Blood flow; Body Tissues; Cancers; Cell Death, Programmed; Complex; Dental; Dermal; Development; Diabetes Mellitus; Disease; Disorder; EPC-1 protein; Electromagnetic, Laser; Environment; Factor, Angiogenesis; Fellowship; Generalized Growth; Goals; Growth; Healed; Healing abnormal; Healing delayed; Homeostasis; Human; Human, General; Impaired healing; Impaired tissue repair; Impaired wound healing; Individual; Knowledge; Lasers; Malignant Neoplasms; Malignant Tumor; Mammals, Mice; Man (Taxonomy); Man, Modern; Mediator; Mediator of Activation; Mediator of activation protein; Messenger RNA; Methods; Mice; Modeling; Molecular; Murine; Mus; NIDR; National Institute of Dental Research; National Institute of Dental and Craniofacial Research; PEDF; Patients; Pattern; Phase; Physiologic; Physiological; Physiological Homeostasis; Proteins; RNA, Messenger; RNA, Small Interfering; Radiation, Laser; Recombinant Proteins; Research; Resolution; Role; Scientist; Small Interfering RNA; Thick; Thickness; Time; Tissue Growth; Tissues; Wound Healing; Wound Repair; abnormal tissue repair; angiogenesis; arthritic; delayed wound healing; density; diabetes; disease/disorder; early PDL protein; early population doubling level cDNA-1 protein; early population doubling level protein; effective therapy; experiment; experimental research; experimental study; gene product; healing; in vivo; in vivo Model; mRNA; malignancy; nano particle; nanoparticle; neoplasm/cancer; neovascularization; new therapeutics; next generation therapeutics; novel; novel therapeutics; ontogeny; pigment epithelium-derived factor; pre-doc; pre-doctoral; predoc; predoctoral; protein expression; public health relevance; research study; response; siRNA; social role; tissue repair; vascular; vasostatin; vessel regression; wound
Relevance: Narrative: Dysfunctional blood vessel growth or regression is a hallmark of many human pathological conditions including cancer, arthritis, and diabetes-induced delayed wound healing. This study aims to evaluate the potential role of two mediators of blood vessel regression, PEDF and vasostatin-I, to further our understanding of the important regulatory mechanisms that contribute to successful wound resolution. This understanding will bring us closer to the development of more effective treatment methods for patients suffering from these diseases
Project start date: 2010-08-01
Project end date: 2015-07-31
Budget start date: 1-AUG-2010
Budget end date: 31-JUL-2011
PFA/PA: PA-09-207
1F30DE020991-01 (2010): $47180