Vocal fold injury engenders a complex inflammation and wound healing response in laryngeal mucosal tissue, which commonly leads to scarring. Because individual variability in the formation and treatment for vocal fold scarring is considerable, the clinical decision making process for medical management is daunting. The work proposed in this R03 application exploits a systems biology approach that combines experimental and computational techniques to develop a computational model to assist in understanding the inflammatory and healing process associated with vocal fold scarring. Such models have provided valuable insights into the pathophysiology at the individual level and suggested pathways for inflammation treatment and healing optimization that are patient-specific. The overarching goal is to generate a clinical tool that will ultimately aid clinicians i prescribing personalized treatment for patients with vocal fold injury. The development of such a clinical tool requires the collection of tissue-specific biological data. We will extend our preliminary computational model's infrastructure, based on the new vocal fold data, to enhance its biological representation.
The specific aims of this application are: (1) to count immune and repair cells including neutrophils, macrophages, endothelial cells and fibroblasts in surgically injured rat vocal folds using flow cytometry, up to 4 weeks post injury;(2) to identify the cell source of a damage-associated molecular pattern molecule (DAMP) and measure the levels of the DAMP and cytokines in vocal fold tissue and blood serum from rats following vocal fold surgery using immunohistochemistry and enzyme-linked immunosorbent assay respectively, up to 4 weeks post injury;(3) to implement our existing computational model on a high performance computing platform with an expanded infrastructure through the addition of biological data.

Public Health Relevance

This project seeks to advance the science of personalized medicine in voice care. We propose to develop a computer-based model to characterize the biological processes of wound healing in injured vocal folds. We will also upgrade the computer model to run at faster speeds. The findings obtained from this work will help us develop an effective computer-testing program for researchers and clinicians to comprehend the complex biological processes in vocal fold inflammation and healing, and eventually to tailor-make therapies for patients with vocal fold injury.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
5R03DC012112-03
Application #
8723149
Study Section
Special Emphasis Panel (ZDC1)
Program Officer
Shekim, Lana O
Project Start
2012-09-15
Project End
2015-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Maryland College Park
Department
Other Health Professions
Type
Schools of Arts and Sciences
DUNS #
City
College Park
State
MD
Country
United States
Zip Code
20742
Seekhao, Nuttiiya; Shung, Caroline; JaJa, Joseph et al. (2018) High-Performance Agent-Based Modeling Applied to Vocal Fold Inflammation and Repair. Front Physiol 9:304
Li-Jessen, Nicole Y K; Powell, Michael; Choi, Ae-Jin et al. (2017) Cellular source and proinflammatory roles of high-mobility group box 1 in surgically injured rat vocal folds. Laryngoscope 127:E193-E200
Seekhao, Nuttiiya; JaJa, Joseph; Mongeau, Luc et al. (2017) In Situ Visualization for 3D Agent-Based Vocal Fold Inflammation and Repair Simulation. Supercomput Front Innov 4:68-79
Latifi, Neda; Heris, Hossein K; Thomson, Scott L et al. (2016) A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications. Tissue Eng Part C Methods 22:823-38
Seekhao, Nuttiiya; Shung, Caroline; JaJa, Joseph et al. (2016) Real-Time Agent-Based Modeling Simulation with in-situ Visualization of Complex Biological Systems: A Case Study on Vocal Fold Inflammation and Healing. IEEE Int Symp Parallel Distrib Process Workshops Phd Forum 2016:463-472
Heris, Hossein K; Miri, Amir K; Ghattamaneni, Nageswara R et al. (2015) Microstructural and mechanical characterization of scarred vocal folds. J Biomech 48:708-11
Li, Nicole Y K; Heris, Hossein K; Mongeau, Luc (2013) Current Understanding and Future Directions for Vocal Fold Mechanobiology. J Cytol Mol Biol 1:001