I am an engineer with training and interests in biology and solid mechanics. My research addresses problems in both basic science and translational medicine. At the core of my work is the desire to understand the dynamic interactions between cells, the extracellular matrix and mechanical stimuli and how these interactions change with aging, disease and injury. Examples of my past and ongoing projects include:
My first introduction to research was in the cornea tissue engineering lab at Harvey Mudd where I designed and tested a bioreactor system for culturing corneal fibroblasts under mechanical stretch. As part of my thesis, I tested this system and found that mechanical stretch reduced the levels of alpha-smooth muscle actin expressed by corneal fibroblasts, indicating a less myofibroblastic phenotype. As part of my postdoc, I have been collaborating with Dr. James Funderburgh at the University of Pittsburgh to study how mechanical stretch and cell culture surface topology influence the differentiation of corneal stromal stem cells into keratocytes and the deposition of extracellular matrix by these cells. My preliminary data suggests that both mechanical stretch and the curvature of the cell culture surface enhance collagen deposition and organization.
Glaucomatous vision loss is due to the loss of retinal ganglion cells responsible for transmitting visual stimuli from the retina to the brain. It is widely hypothesized that these cells are lost due to excessive mechanical deformation and damage within the lamina cribrosa, a meshwork of connective tissue that supports the retinal ganglion cell axons as they exit the eye. My work has focused on the creation of multiscale finite element models that allow us to understand how the neural tissues within the lamina cribrosa deform when pressure in the eye is increased. These models are the first specimen-specific models to distinguish between the fragile neural tissues and the stiff collagenous beams of the lamina cribrosa. My work suggests that the organization of the collagen of the lamina cribrosa creates large localized strains within the neural tissues, which can be similar in magnitude to the level of deformation seen in traumatic brain injury. These models have also identified structural characteristics of the lamina cribrosa that may make an eye more susceptible to tissue damage.
My doctoral research was performed in collaboration with the San Antonio Cardiovascular Proteomics Center. The focus of my work was on determining how the organization and mechanical properties of myocardial scar tissue determine the function of the left ventricle and the risk for cardiac rupture. Further, my work examined how the properties of the scar tissue were effected by matrix metalloproteinases and aging. One of the key findings of my research was that the knockout of matrix metalloproteinase-9 limited the dilation of the left ventricle following myocardial infarction by reducing the degradation of fibronectin and promoting the activation of the cross-linking enzyme lysyl oxidase. This increased cross-linking activity led to the more rapid creation of a stiffer myocardial scar despite having less collagen content.
1) The role of mechanical signaling in the development and aging of soft tissues.
2) The mechanobiology of the innate immune system and its contributions to chronic inflammatory diseases and wound healing.
3) The development of therapeutic strategies to reduce adverse tissue remodeling and promote functional tissue restoration.
Department: Biomedical Engineering
Mentor: Hai-Chao Han
Institution: University of Texas at San Antonio and University of Texas Health Science Center San Antonio
Department: Mechanical Engineering
Mentor: Ronald Bagley and Harry Millwater
Institution: University of Texas at San Antonio
Mentor: Elizabeth Orwin
Institution: Harvey Mudd College
AP Voorhees, N-J Jan, ME Austin, JG Flanagan, JM Sivak, RA Bilonick and IA Sigal, “Lamina Cribrosa Pore Shape and Size as Predictors of Neural Tissue Mechanical Insult.” Investigative Ophthalmology and Visual Science, Vol. 58, pp. 5336-5346, 2017.
H Tran, N-J Jan, D Hu, AP Voorhees, JS Schuman, MA Smith, G Wollstein and IA Sigal, “Formalin Fixation and Cryosectioning Cause Only Minimal Changes in Shape or Size of Ocular Tissues.” Scientific Reports, Vol. 7, No. 12065, 2017.
AP Voorhees, N-J Jan, and IA Sigal, “Effects of Collagen Microstructure on the Deformation of the Neural Tissues of the Lamina Cribrosa.” Acta Biomaterialia, Vol. 58, pp. 278-290, 2017.
AP Voorhees, LC Ho, N-J Jan, H Tran, Y van der Merwe, K Chan and IA Sigal “Whole-Globe Biomechanics using High-Field MRI.” Experimental Eye Research, Vol. 160, pp. 85-95, 2017.
N-J Jan, C Gomez, S Moed, AP Voorhees, JS Schuman, RA Bilonick, and IA Sigal, “Microstructural Crimp of the Lamina Cribrosa and Peripapillary Sclera Collagen Fibers” Investigative Ophthalmology and Visual Science, Vol. 58, pp. 3378-3388, 2017.
AP Voorhees, JL Grimm, RA Bilonick, L Kagemann, G Wollstein, H Ishikawa, JS Schuman, and IA Sigal. “What is a Typical Optic Nerve Head?” Experimental Eye Research, Vol 149., pp. 40-47, 2016.
A Yabluchanskiy, Y Ma, KY DeLeon-Pennell, GV Halade, AP Voorhees, NT Nguyen, Y-J Jin, MD Winniford, ME Hall, H-C Han, and ML Lindsey. “Myocardial Infarction Superimposed on Aging: MMP-9 Deletion Promotes M2 Macrophage Polarization.” Journal of Gerontology: Biological Science, Vol. 71, No. 4, pp. 475-83, 2016.
AP Voorhees and H-C Han. “Biomechanics of Cardiac Function.” (Review) Comprehensive Physiology, Vol. 5. No. 4, pp. 1623-44, 2015.
AP Voorhees, KY Deleon-Pennell, Y. Ma, GV Halade, A Yabluchanskiy, RP Iyer, E Flynn, CA Cates, ML Lindsey, and H-C Han. “Building a Better Infarct: Modulation of Collagen Cross-Linking to Increase Infarct Stiffness and Reduce Left Ventricular Dilation post-Myocardial Infarction.” Journal of Molecular and Cellular Cardiology, Vol. 85, pp. 229-39, 2015.
G-L Wang, Y Xiao, AP Voorhees, Y-X Qi, Z-L Jiang, and H-C. Han. “Artery Remodeling under Axial Twist in Three Days Organ Culture.” Annals of Biomedical Engineering. Vol. 43. No. 8. pp. 1738-47 2015.
A Yabluchanskiy, Y Ma, YA Chiao, EF Lopez, AP Voorhees, H Toba, ME Hall, H-C Han, ML Lindsey, and Y-F Jin. “Cardiac Aging is Initiated by Matrix Metalloproteinase-9 Mediated Endothelial Dysfunction.” AJP-Heart and Circulatory Physiology. Vol. 306, No. 10, H1398-H1407, 2014.
AP Voorhees, H-C Han, “A Model to Determine the Effect of Collagen Fiber Alignment on Heart Function Post Myocardial Infarction.” Theoretical Biology and Medical Modeling. Vol. 11, No. 6, 2014.
K Grimes, AP Voorhees, Y Chiao, H-C Han, ML Lindsey, R Buffenstein, “Cardiac Function of the Naked Mole-Rat: Ecophysiological Responses to Working Underground.” AJP-Heart and Circulatory Physiology. Vol. 306, No. H730-H737, 2014.
Y Ma, GV Halade, J Zhang, TA Ramirez, D Levin, AP Voorhees, Y Jin, H-C Han, AM Manicone, ML Lindsey, “Matrix Metalloproteinase-28 Deletion Exacerbates Cardiac Dysfunction and Rupture Following Myocardial Infarction in Mice by Inhibiting M2 Macrophage Activation.” Circulation Research. Vol. 112, pp. 675-88, 2013.
T Yang, Y Chiao, Y Wang, AP Voorhees, H-C Han, ML Lindsey, Y-F Jin, “Mathematical Modeling of Left Ventricular Geometry Changes in Aging Mice.” BMC Systems Biology. 6(Suppl 3): S10, 2012.
AP Voorhees, H Millwater, R Bagley, P Golden, “Fatigue Sensitivity Analysis Using Complex Variable Methods.” International Journal of Fatigue. Vol. 40, pp. 61-73, 2012.
AP Voorhees, H Millwater, R Bagley, “Complex Variable Methods for Shape Sensitivity of Finite Element Models.” Finite Elements in Analysis and Design. Vol. 47, No. 10, 1146-1156, 2011.
EJ Orwin, A Shah, AP Voorhees, V Ravi, “Bioreactor Design for Cornea Tissue Engineering: Material-Cell Interactions.” Acta Biomaterialia. Vol. 3, No. 6, pp. 1041-1049, 2007.