REU Site: UCSD Biomaterials Research to Increase Diversity and Graduate Enrollment (UCSD-BRIDGE)
Brian Aguado, Ph.D.
Engineering biomaterials to study sex differences in heart disease
Cardiovascular disease is the leading cause of death, yet our mechanistic knowledge of the sex-specific molecular mechanisms that guide disease progression, particularly in women, remain poorly characterized. Studies evaluating mechanisms rarely state the sex of cells used or are performed primarily in male animal models, causing a knowledge gap. Student participants will test the hypothesis that X and/or Y sex chromosome dosage contributes to sex differences in cellular responses to engineered microenvironments. Participants will work with Dr. Aguado and graduate student mentors and learn hydrogel fabrication, valve cell culture, in vitro assays, and high-content imaging/analysis to investigate biological mechanisms driving sex-specific valve disease.
Pedro Cabrales, Ph.D.
Engineering a battlefield deployable whole-blood analog
Hemorrhage is the leading cause of nearly 90% of potentially survivable battlefield fatalities. While whole blood is regarded as the optimal resuscitation fluid, it presents inherent limitations, including limited viability, the requirement for cold storage, and logistical challenges on the battlefield, rendering it often inaccessible when needed most. Our current undertaking involves a program dedicated to creating a field-deployable, shelf-stable whole blood analog (WBA), which can serve as a viable alternative for resuscitating trauma patients in scenarios where conventional donated blood products are unavailable. Participants will play a pivotal role in establishing a comprehensive program centered on the development and assessment of the mechanical and chemical properties of this WBA. The participant will test the hypothesis that the WBA can effectively rescue trauma victims without demonstrating inferiority compared to stored whole blood. Participants can collaborate closely with Dr. Cabrales and experienced graduate student mentors. This experience will equip participants with valuable tools and insights for studying, engineering, developing, and evaluating this innovative whole-blood analog.
Shaochen Chen, Ph.D.
3D printing and biomaterials for regenerative medicine
Our research focuses on 3D bioprinting and biomaterials for tissue engineering and regenerative medicine applications. We explore new knowledge of cell-material interactions in the full range of physical dimensions, time span, and biological dimensions. Our group not only investigates the fundamental scientific issues, such as cell interactions with micro and nano-environments, biomaterials science, and biomechanics, but also solves the technological and translational issues associated with tissue/organ repair and regeneration. Student participants in this REU program will test the hypothesis that the biomaterials will support cell growth and the bioprinted tissues have proper functions.
Karen L. Christman, Ph.D.
Nano-material strategies for the heart
Nanomaterial delivery strategies are particularly attractive since they can be delivered via leaky vasculature created by a heart attack. We previously developed nanoparticles that aggregate after matrix metalloproteinase cleavage of a protective layer, but this still led to off target accumulation in the liver and spleen like all nanoparticles. We are now developing protein-like polymers that have improved circulation times and reduce off-target accumulation. Participants will test the hypothesis that nanomaterial targeting modifications can improve retention in the heart. Participants will learn nanomaterial characterization, and peptide therapeutic assessment in vitro and in vivo.
Adam J. Engler, Ph.D.
Understanding mechanical memory in cancer
Cells within tumors transform from epithelial into mesenchymal cells in part due to tissue stiffness, but once outside the tumor, why does the soft niche not cause the cells to become epithelial again? The participant will hypothesize that in a stiff environment, cells undergo epigenetic changes that enable them to become mesenchymal, and that they use these changes to "recall" the gene expression profiles once the dynamic hydrogel is softened. The participant will learn biomaterial characterization of dynamic hydrogels and tissues as well as learn to assess cell responses and determine the epigenetic changes that occur in the nucleus to create “mechanical memory.”
Stephanie I. Fraley, Ph.D.
Engineering a 2.5D culture format for Drug Discovery
High-throughput screening of small molecule compounds to discover novel biological activities relies heavily on planar imaging of cells to monitor changes in response to treatments. However, cells cultured on planar substrates do not retain their physiological cell state, giving rise to false positive/negative results. In this project, the participant will develop a 2.5D culture format that retains necessary 3D biomaterial cues while enabling compatibility with high-throughput imaging. The participant will hypothesize that these cell states can be recapitulated on a planar surface amenable to high-throughput screening for drug discovery by controlling cell shape using 2D patterning of collagen on glass or polyacrylamide followed by coating with high density collagen. The participant will learn microcontact printing, photolithography, collagen gelation, polyacrylamide substrate engineering, biomaterial molding, and various microscopy techniques.
Reem Khoja, Ph.D.
Assistant Teaching Professor
Machine learning for biomaterial applications
Students will explore machine learning tools for studying three-dimensional tissue cultures with a focus on biomaterial applications on organoid culture. In Dr. Khoja’s fully-equipped cell and tissue culture lab, the participant will test the hypothesis that light stimulation influences the temporal development and neural electrophysiology of cortical organoids by modulating key biological pathways, including neurogenesis, synaptic plasticity, and calcium signaling. Long-term real time imaging via biocloud platform is an essential component for testing the hypothesis by analyzing growth patterns using machine learning tools. Graduate students of Dr. Khoja’s will be available to support student researchers throughout their journey fostering a collaborative interdisciplinary bioengineering research experience.
Kevin King, MD, Ph.D.
Cardiac Injury and Repair
Cardiac injury leads to death, inflammation, fibrosis, and dysfunction in the heart, making it the most common cause of death in the US and the world. Student participants will test the overall hypothesis that mechanical forces cause and result from cardiomyocyte injury. The participant will use quantitative image analysis of tissue sections, single cell multiomics, and spatial transcriptomics to link structure and function after cardiac injury and after cardioprotective therapy to infer the causes and consequences of pathologic forces in the heart.
Vira Kravets, Ph.D.
Beta cells and diabetes pathogenesis
The participant will study whether some insulin-producing pancreatic b-cell subpopulations are more vulnerable to glucolipotoxic conditions via bioengineering approaches such as applying multiscale confocal imaging of Ca 2+ dynamics of the cellular network, paired with phasor-FLIM to measure in-vivo metabolic activity and machine learning analysis to study islets in the live pancreatic tissue slices from human and mice. The participant will test the hypothesis that responder beta cells are disproportionately affected by high glucose and fatty acid application, and lose their role in triggering insulin secretion, leading to type-2-diabetes like pattern of response.
Ester Kwon, Ph.D.
Nanomaterials for traumatic brain injury
Drug delivery to the brain remains a challenge. The participant will engage in research to test the hypothesis that the organization of biological molecules at the nanometer length scale can create nanomaterials to lead to new types of interaction with brain tissue. The participant will gain experience on how to synthesize and characterize these nanomaterials and evaluate nanomaterial interaction with constituents of the brain. 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 Mail, Ph.D.
Aberrant cell transformation processes
The major research thrusts in the Mali laboratory are two-fold: one, development of molecular toolsets for genome, transcriptome, and proteome engineering and their application to systematic genome interpretation and gene therapy applications; and two, study and engineering of cell fate specification during development utilizing human pluripotent stem cells as the core model system. Given the parallels in phenotypes (such as self-renewal and tumor forming ability) between pluripotent stem cells and cancer cells, a key research thrust is also in dissecting aberrant cellular transformation processes such as during tumorigenesis. The student participant will test the hypothesis that misregulation of developmental genes in adulthood has the potential to drive tumorigenesis.
Nicole Steinmetz, Ph.D.
Biology-inspired nanotechnologies targeting human health applications
Research in the Steinmetz lab focuses on the engineering and repurposing of plant viruses as nanotechnology for applications in human health and agriculture. Summer projects include plant virus engineering through chemistry and genetics, all the way to testing novel formulations in preclinical animal models or in plants. Student participants will test the hypothesis that the adjuvant properties of plant viruses enhance anti-tumor immunity.