Biomechanics
Pedro Cabrales, PhD
Engineering a Mechanically Durable Whole Blood Analog
Hemorrhage accounts for ~90% of potentially survivable battlefield deaths, and if in-field transfusion were available, 1,000+ (24%) combat fatalities in the last decade could have been survivable. A mechanically durable, field-deployable whole blood analogue (WBA), treating both shock and coagulopathy, would enable on-scene treatment. The participant will help establish a program to develop, evaluate the mechanical and chemical properties of, and rapidly translate a first-in-class preparation of a WBA within the constraints of the intended operational environment. Participants will work directly with Dr. Cabrales and graduate student mentors and will learn tools for the study, engineering, development, and evaluation of WBA.
Adam J. Engler, PhD
Understanding Mechanical Memories in Cancer
All metastatic cells must detach from their stiff tumor and migrate through soft, adjacent tissue to reach a blood vessel. Cells within the tumor transform from epithelial into mesenchymal cells in part due to the stiffness of that environment20, but once outside the tumor, why does the soft niche not cause the cells to become epithelial again? The participant will use biomaterials with dynamic properties to mimic tumor mechanics, assess cell responses, and determine the epigenetic changes that occur in the nucleus to create “mechanical memory.”
Lingyan Shi, PhD
Using stimulated Raman scattering to Understand Cell Mechanics
The Shi lab is developing novel multimodal optical imaging platforms integrating stimulated Raman scattering (SRS), multiphoton fluorescence (MPF), and second harmonic generation (SHG) for visualizing metabolic dynamics in cells and tissues and their impact on tissue mechanics. The participant will learn how to use these cutting-edge state-of-the-art high resolution imaging technologies and code custom designed algorithms for imaging analysis. These methods will be applied to heart tissues undergoing stretch, which will provide training in the use of powerful tools for disease detection, diagnosis, and prognosis.
Daniela Valdez-Jasso, PhD
Mechanics of Pulmonary Arterial Hypertension (PAH)
PAH is a rapid, progressive vascular disease that commonly results in intractable right-heart failure and premature death. To better understand the remodeling process undergone by the pulmonary arteries, the participant will characterize the time course of the pulmonary vascular changes that occur in pulmonary vessels and the relation of these changes to cardiac mechanics. To this end, the participant will mechanically stimulate cells derived from pulmonary arteries and right ventricles from control animals to mimic in vivo conditions and compare them to cell phenotypes from hypertensive animals.
Biosystems
Francisco Contijoch, PhD
Systems Analyses of Disease Imaging
Translational imaging methods are becoming an increasingly common but complex way to evaluate patients for cardiopulmonary disease. Participant projects will focus on congenital heart disease and pulmonary hypertension where the participant will use systems level analytical tools to extract new measurements of cardiopulmonary dysfunction from medical images. These tools examine function across length scales to quickly determine Pressure-Volume loops and Frank-Starling relations.
Jeff Hasty, PhD
Systems Analyses of Microbial Communities
Natural selection dictates that cells respond optimally to environmental changes. The nature of such an optimal response is likely to depend on the specifics of the dynamically changing environment. The participant will work with an inducible quorum sensing system (iQS)21 engineered into E. Coli to examine response dynamics to environmental changes and assess whether responses rates are beneficial, e.g., at a rate to effectively filter undesirable environmental fluctuations, or not. The participant will learn control system fabrication, microbial culture, and assess cell behavior as a system. Our current understanding of most cellular regulation relies on static or semi-static environments, hence the participant’s focus on dynamic microbial community signaling will impact lab projects.
Benjamin Smarr, PhD
Analyzing Large Scale Biometric Data Systems
Wearable devices and online records are becoming ubiquitous, and our group maintains several large databases that continuously track the health of approximately 85,000 individuals. The participant will be involved in projects mining these databases for "natural experiments" to discover novel patterns, develop quantitative assessment methods, and/or improve efforts at de-biasing algorithmic performance. Examples include assessing physiological responses to wildfires, assessing sex differences in sleep quality, or quantifying ethnicity and age differences in COVID-19 infection.
Biotechnology
Karen L. Christman, PhD
Nano-aggregation strategies for the Heart
Nanoparticle delivery strategies are particularly attractive since they can be delivered via leaky vasculature created by a heart attack. We have developed nanoparticles that aggregate after matrix metalloproteinase cleavage of a protective layer 23. Aggregates remain at the infarction site, so we hypothesize that nanoparticle aggregates significantly improve yield and release to minimize remodeling. Participants will learn the polymer synthesis, nanoparticle fabrication, and drug loading and release assessment. Participants will also alter how drug loading (surface erosion vs. diffusion).
Stephanie I. Fraley, PhD
Collagen Biomaterials as Tools for Tissue Engineering
A challenge to using fibrillar collagen as a scaffold is the limited reproducibility of gelation, which impacts cellular functions. Gelation temperature and pH impact porosity, fiber diameter and alignment, and mechanical properties22 impact gel structure and subsequent cell responses. The participant will work with a Research Mentor on experimental design and then study how this material environment affects the complex interactions between highly metastatic cancer cells and cells found adjacent to tumors. The participant will learn confocal, two-photon, and electron microscopy.
Kevin R. King, MD, PhD
Spatial Single-Nuclei Transcriptomics in Heart Disease
Acute ischemia (i.e., lack of blood flow) causes a heart attack, leading to cell death and heart failure. Surrounding the infarct area is the borderzone, a vulnerable cell population subject to scarring where current therapies have been ineffective at regeneration. The participant will test the hypothesis that during ischemic injury, functional heterogeneity among endothelial cells enables a sub-population to form new vessels and partially mitigate remodeling. Using single-cell transcriptomics, the participant will profile ECs and identify subsets that show transcriptional signatures of adaptive angiogenesis.
Ester Kwon, PhD
Nanoscale delivery for traumatic brain injury
Drug delivery to the brain remains a challenge. Design of nanoscale materials may offer a strategy to improve access of therapeutics to injured brain tissue. This project focuses on engineering a nanomaterial that can interact with injured brain tissue and deliver therapeutics. The participant will synthesize nanomaterials, characterize nanomaterials, and evaluate interaction of nanomaterials with living cells. The participant will work directly with Dr. Kwon and a mentor to develop an individual training plan, learn experimental techniques, and communicate research findings.
Prashant Mali, PhD
Systematic study and engineering of pancreatic organogenesis
Stem cell-derived organoids are a valuable tool for modeling human development but are limited in size and maturity. Stem cell teratomas offer a promising alternative due to their ability to differentiate into all three germ layers and form 3D vascularized structures. MicroRNA’s (miRNA), which aid in post-transcriptional gene silencing, have been used to indicate the direction of cell differentiation in teratomas. In this project, participants will build a suicide circuit (HSV-tk-GFP) and screen microRNAs to determine essential genes for pancreatic beta cell maturation.