Areas of Expertise (3)
Duke University: BS, Biomedical & Electrical Engineering 2008
Duke University: MS, Biomedical Engineering 2012
Duke University: PhD, Biomedical Engineering 2015
Media Appearances (1)
Walk to remember and inspire: Making Strides Against Breast Cancer
Fox2 News tv
The number of deaths related to breast cancer is in decline. The upcoming Making Strides Against Breast Cancer Walk is a major boost in the effort to find a cure. The American Cancer Society funds $6 million in research grants right here in St. Louis. One of those grants helped develop tumor-on-a-chip. Priscilla Hwang, Ph.D., is a trained biomedical engineer and a postdoctoral research fellow at Washington University. Her combined interests offer life-saving hope for breast cancer patients. “We’re looking at how we can investigate ways to prevent cancer metastasis,” said Dr. Hwang.
EGRB303 (Biotransport Processes)
Course involves the study of fundamental principles of fluid mechanics and mass transport as well as application of these principles to physiological systems. Fluid mechanics principles covered will include conservation of mass and momentum, laminar and turbulent flow, Navier-Stokes equations, dimensional analysis, Bernoulli’s equation, and boundary layer theory. Mass transport principles will include diffusion, convection, transport in porous media, and transmembrane transport. Concepts will be applied to studying diffusion in biological tissues, electrolyte transport, vascular transport, blood flow mechanics, and cardiovascular flow. The course will also cover organ-specific transport processes, including oxygen transport in the lungs and blood, and mass transport in the kidney.
Selected Articles (3)
Bayer SV, Grither WR, Brenot A, Hwang PY, Barcus CE, Ernst M, Pence P, Walter C, Pathak A, Longmore GD.
Biomechanical changes in the tumor microenvironment influence tumor progression and metastases. Collagen content and fiber organization within the tumor stroma are major contributors to biomechanical changes (e., tumor stiffness) and correlated with tumor aggressiveness and outcome. What signals and in what cells control collagen organization within the tumors, and how, is not fully understood. We show in mouse breast tumors that the action of the collagen receptor DDR2 in CAFs controls tumor stiffness by reorganizing collagen fibers specifically at the tumor-stromal boundary. These changes were associated with lung metastases. The action of DDR2 in mouse and human CAFs, and tumors in vivo, was found to influence mechanotransduction by controlling full collagen-binding integrin activation via Rap1-mediated Talin1 and Kindlin2 recruitment. The action of DDR2 in tumor CAFs is thus critical for remodeling collagen fibers at the tumor-stromal boundary to generate a physically permissive tumor microenvironment for tumor cell invasion and metastases.
Hwang PY, Brenot A, King AC, Longmore GD, George SC.
Collective cell migration is an adaptive, coordinated interactive process involving cell-cell and cell-extracellular matrix (ECM) microenvironmental interactions. A critical aspect of collective migration is the sensing and establishment of directional movement. It has been proposed that a subgroup of cells known as leader cells localize at the front edge of a collectively migrating cluster and are responsible for directing migration. However, it is unknown how and when leader cells arrive at the front edge and what environmental cues dictate leader cell development and behavior. Here, we addressed these questions by combining a microfluidic device design that mimics multiple tumor microenvironmental cues concurrently with biologically relevant primary, heterogeneous tumor cell organoids. Prior to migration, breast tumor leader cells (K14+) were present throughout a tumor organoid and migrated (polarized) to the leading edge in response to biochemical and biomechanical cues. Impairment of either CXCR4 (biochemical responsive) or the collagen receptor DDR2 (biomechanical responsive) abrogated polarization of leader cells and directed collective migration. This work demonstrates that K14+ leader cells utilize both chemical and mechanical cues from the microenvironment to polarize to the leading edge of collectively migrating tumors. SIGNIFICANCE: These findings demonstrate that pre-existing, randomly distributed leader cells within primary tumor organoids use CXCR4 and DDR2 to polarize to the leading edge and direct migration.
Hwang PY, Jing L, Chen J, Lim FL, Tang R, Choi H, Cheung KM, Risbud MV, Gersbach CA, Guilak F, Leung VY, Setton LA.
Nucleus pulposus (NP) cells of the intervertebral disc are essential for synthesizing extracellular matrix that contributes to disc health and mechanical function. NP cells have a unique morphology and molecular expression pattern derived from their notochordal origin, and reside in N-cadherin (CDH2) positive cell clusters in vivo. With disc degeneration, NP cells undergo morphologic and phenotypic changes including loss of CDH2 expression and ability to form cell clusters. Here, we investigate the role of CDH2 positive cell clusters in preserving healthy, biosynthetically active NP cells. Using a laminin-functionalized hydrogel system designed to mimic features of the native NP microenvironment, we demonstrate NP cell phenotype and morphology is preserved only when NP cells form CDH2 positive cell clusters. Knockdown (CRISPRi) or blocking CDH2 expression in vitro and in vivo results in loss of a healthy NP cell. Findings also reveal that degenerate human NP cells that are CDH2 negative can be promoted to re-express CDH2 and healthy, juvenile NP matrix synthesis patterns by promoting cell clustering for controlled microenvironment conditions. This work also identifies CDH2 interactions with β-catenin-regulated signaling as one mechanism by which CDH2-mediated cell interactions can control NP cell phenotype and biosynthesis towards maintenance of healthy intervertebral disc tissues.