@article{aw_cho_wang_cooper_doherty_rocco_huang_kubik_whitworth_armstrong_et al._2023, title={Microphysiological model of PIK3CA-driven vascular malformations reveals a role of dysregulated Rac1 and mTORC1/2 in lesion formation}, volume={9}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.ade8939}, abstractNote={
            Somatic activating mutations of
            PIK3CA
            are associated with development of vascular malformations (VMs). Here, we describe a microfluidic model of
            PIK3CA
            -driven VMs consisting of human umbilical vein endothelial cells expressing
            PIK3CA
            activating mutations embedded in three-dimensional hydrogels. We observed enlarged, irregular vessel phenotypes and the formation of cyst-like structures consistent with clinical signatures and not previously observed in cell culture models. Pathologic morphologies occurred concomitant with up-regulation of Rac1/p21-activated kinase (PAK), mitogen-activated protein kinase cascades (MEK/ERK), and mammalian target of rapamycin (mTORC1/2) signaling networks. We observed differential effects between alpelisib, a PIK3CA inhibitor, and rapamycin, an mTORC1 inhibitor, in mitigating matrix degradation and network topology. While both were effective in preventing vessel enlargement, rapamycin failed to reduce MEK/ERK and mTORC2 activity and resulted in hyperbranching, while inhibiting PAK, MEK1/2, and mTORC1/2 mitigates abnormal growth and vascular dilation. Collectively, these findings demonstrate an in vitro platform for VMs and establish a role of dysregulated Rac1/PAK and mTORC1/2 signaling in
            PIK3CA
            -driven VMs.
          }, number={7}, journal={SCIENCE ADVANCES}, author={Aw, Wen Yih and Cho, Crescentia and Wang, Hao and Cooper, Anne Hope and Doherty, Elizabeth L. and Rocco, David and Huang, Stephanie A. and Kubik, Sarah and Whitworth, Chloe P. and Armstrong, Ryan and et al.}, year={2023}, month={Feb} }
 @article{anand_kolahdouz_homeister_smith_griffith_gallippi_2022, title={Concurrent ARFI Plaque Imaging and Wall Shear Stress Measurement in Human Carotid Artery, with Validation by Fluid Structure Interaction Models}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958828}, abstractNote={The rupture potential of an atherosclerotic plaque is dependent on both the plaque's composition and the shear stresses it encounters from blood flow. Because plaques move and deform throughout the cardiac cycle, resulting in changes to plaque position and shape as well as to the encountered shear stresses, concurrent imaging of both risk factors over time is required to accurately predict plaque vulnerability. To evaluate the potential to achieve as much, multi-angle plane wave (PW) ARFI and least-squares vector Doppler data were acquired in a calibrated flow phantom with channels of 4–8 mm diameters and flow rates of 100–600 ml/min. The wall shear stress (WSS) was measured to within 15% of the ground-truth analytical solutions. The same methods were then implemented in an excised human cadaveric carotid with a x% stenotic plaque. ARFI VoA detected plaque regions of calcium and intraplaque hemorrhage that were validated by spatially-matched histology. Concurrent vector Doppler yielded a peak WSS of 5.2 Pa on the plaque shoulder, which was consistent with the 6.4 Pa WSS predicted by an immersed interface fluid-solid interation (FSI) model developed using the specific geometry of the examined cadaveric carotid. Overall our results demonstrate the feasibility of concurrent imaging of carotid plaque composition by ARFI VoA, vector flow, and WSS to better assess stroke risk.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Anand, Keerthi S. and Kolahdouz, Ebrahim M. and Homeister, Jonathon and Smith, Margaret-Anne and Griffith, Boyce E. and Gallippi, Caterina M.}, year={2022} }
 @article{smith_griffith_zaharoff_2019, title={Analyzing the effects of instillation volume on intravesical delivery using biphasic solute transport in a deformable geometry}, volume={36}, ISSN={["1477-8602"]}, DOI={10.1093/imammb/dqy004}, abstractNote={Ailments of the bladder are often treated via intravesical delivery-direct application of therapeutic into the bladder through a catheter. This technique is employed hundreds of thousands of times every year, but protocol development has largely been limited to empirical determination. Furthermore, the numerical analyses of intravesical delivery performed to date have been restricted to static geometries and have not accounted for bladder deformation. This study uses a finite element analysis approach with biphasic solute transport to investigate several parameters pertinent to intravesical delivery including solute concentration, solute transport properties and instillation volume. The volume of instillation was found to have a substantial impact on the exposure of solute to the deeper muscle layers of the bladder, which are typically more difficult to reach. Indeed, increasing the instillation volume from 50-100 ml raised the muscle solute exposure as a percentage of overall bladder exposure from 60-70% with higher levels achieved for larger instillation volumes. Similar increases were not seen for changes in solute concentration or solute transport properties. These results indicate the role that instillation volume may play in targeting particular layers of the bladder during an intravesical delivery.}, number={2}, journal={MATHEMATICAL MEDICINE AND BIOLOGY-A JOURNAL OF THE IMA}, author={Smith, Sean G. and Griffith, Boyce E. and Zaharoff, David A.}, year={2019}, month={Jun}, pages={139–156} }