Research Description
My general research interests lie in developing computational models that couple biochemical signaling and mechanics in biological cells. I am currently working on understanding the physics of excitation-contraction coupling in skeletal muscle in the Rangmani Lab at UCSD. My previous work in UC Davis in the Heinrich Lab examined the role of calcium bursts in human neutrophil chemotaxis (chasing after pathogens) and phagocytosis (consuming pathogens). Read below for more information, and see my publications page for a full list of papers.
Postdoctoral Research: Computational models of excitation-contraction coupling in skeletal muscle
UC San Diego, Rangamani Lab
In August 2022, I joined Dr. Padmini Rangamani’s group at UC San Diego as a postdoctoral scholar. My primary project focuses on modeling excitation-contraction coupling in skeletal muscle. I am starting by developing a spatiotemporal model of calcium signaling in skeletal muscle fibers. This work builds on the vast work done over the past century to characterize calcium signaling pathways in skeletal muscle, recapitulating this knowledge as a system of nonlinear partial differential equations describing the reaction-diffusion of calcium within muscle fibers. I will then construct a mechanical model of a single muscle fiber, relying on the well-known relationships between fiber stretching and active and passive forces. Finally, I plan to couple signaling and mechanics in a single model of excitation-contraction coupling. These models will be built using the finite element method, implemented using the FEniCS package. We will use these models to address concrete, quantitative questions about the roles of calcium in force development within muscle fibers. For instance, how does the spatial organization of calcium stores (primarily the sarcoplasmic reticulum) within muscle fibers impact the efficiency of global calcium elevations and fiber contractility? How might calcium and force be altered when the cell is in an energy deficit during intense exercise?
Check out all the videos below and more at the Heinrich Lab YouTube page!
PhD Dissertation: Calcium bursts and mechanics in human neutrophil chemotaxis and phagocytosis
UC Davis, Heinrich Lab
A stunning video of a calcium burst (calcium in green!) in a human neutrophil during phagocytosis.
In my dissertation research, I first examined the mechanical underpinnings of human neutrophil phagocytosis, the process by which immune cells consume pathogens such as bacteria or fungi. I specifically examined the process of cell spreading during frustrated phagocytosis, a case in which the target is too large for the cell to completely consume. In collaboration with talented undergraduate researchers in our lab, Hugh Xiao and Lay Heng Teng, I experimentally probed the effects of ligand density on phagocytic spreading. We coated glass surfaces with different densities of antibodies (molecules from the bloodstream that label pathogens as “the enemy”) and showed that the speed of spreading is similar across many different densities of IgG antibody. I developed a computational model of immune cell spreading, which revealed that this spreading process must be driven by active forces within the cell.
The second portion of my dissertation focused on the role of calcium bursts in neutrophil chemotaxis and phagocytosis.
Undergraduate Research: Studying adhesion-free neutrophil chemotaxis
UC Davis, Heinrich Lab
No calcium bursts occur during chemotaxis!
Chemotaxis is traditionally studied in conjunction with cell adhesion to surfaces. While this is obviously physiologically relevant, the cell is receiving multiple inputs in parallel: adhesive cues from the surface, as well as stimulus from the chemoattractant(s) being considered. In our dual micropipette manipulation system, we hold the cell off a surface to observe “pure” chemotaxis in which the chemoattractants should provide the only relevant stimulus. This proved invaluable in two separate research endeavors.
Neutrophil chemotaxis neither causes nor requires calcium bursts (first video on the right). I gave a presentation on this topic in 2016 at my first Biophysical Society Annual Meeting (I’ve been every year since as well!) We then published this work in 2018 in Science Signaling!
Pure chemotaxis experiments allow us to measure the relationship between particle size and maximum distance at which a neutrophil responds (lower video on the right). We published a letter in Biophysical Journal in which we presented the experimental side of this, supported by a theoretical paper in Frontiers of Immunology.
Other projects
UC Davis, Heinrich Lab
In the Heinrich Lab, I have also assisted and led out in multiple other projects, working together with several talented undergraduate researchers.
Measuring the relationship between phagocytic efficiency and IgG surface concentration on microparticles using flow cytometry.
In collaboration with the Roijjakkers Lab at the University of Utrecht, undergraduate researcher Jonathan Brand (now a PhD student at UCLA) and myself have worked to explore the mechanics of C3b-mediated phagocytosis. Materials from the Roijjakkers Lab allowed us to coat particles and surfaces with the human complement component C3b in a controlled manner. Jonathan conducted a series of phagocytosis experiments with our dual micropipette setup to observe phagocytosis of beads coated in C3b, and I have recently explored the dynamics of frustrated phagocytic spreading on C3b surfaces. Look out for a paper soon!
Eosinophil phagocytosis: We are very interested in how the neutrophil’s “cousin” behaves during phagocytosis. Our previous experiments have revealed key differences between neutrophil phagocytosis and eosinophil phagocytosis; I’ve worked with Julie Zimmer, Yiting Chen, and currently Sahand Salari-Namin to systematically characterize eosinophil phagocytosis, manuscript in the works.