By conducting hands-on experiments, students learn about cutting-edge engineering and technologies relevant to medical problems and the development of medical devices. They are exposed to multidisciplinary research, how it is structured and implemented, and how to work and communicate within a team with very diverse backgrounds. Students also learn to think about problems creatively and actively pursue their research objectives by seeking input from experts, trying out new approaches, and developing skills to delve deeper into their problems. Students will document their efforts, writing up the outcomes for conference abstracts and papers, among others. 

The REU thematic elements of this program are inclusion, innovation, and medical devices. The research project offerings go beyond medical devices because it is important to understand physiological environments to innovate solutions, and the solutions should not be constrained by the method. In line with our four intellectual foci — learning, innovating, exploring, and applying — we offer various research projects that the students can choose from.

Project 1. Computational Strategies for Characterizing Sensory Neuron Phenotypes Based on Extracellular Electrophysiology

Faculty Mentor: Prof. Bryan Black
Students working on this project will help develop or validate computational tools for analyzing multi-parametric phenotypic data sets collected from hiPSC models of acute and inflammatory nociception. The overarching goal of this funded research is to develop and characterize a novel phenotypic model of acute and chronic nociception based on hiPSC sensory neurons cultured and differentiated on microelectrode arrays (MEAs). However, the currently proposed methods of analysis may not capture the complexity of the MEA data or how it relates to biomolecular data sets. Therefore, there is a need in our lab and in the field of pain science and neuroscience research to develop or validate novel statistical approaches to extracellular electrophysiology data analysis (e.g., hierarchical clustering analysis) and correspond these outcomes with biomolecular assays. This project will provide students the opportunity to learn extracellular electrophysiology data collection, signal processing and filtering, Matlab coding, and statistical tools for multi-parametric analysis. 

Project 2. Behavioral, Biomolecular, and Immunoarchitectural Characterization of Amputation Neuroma

Faculty Mentor: Prof. Bryan Black
In collaboration with clinicians at Brigham and Women’s Hospital in Boston, MA, students will help collect and analyze behavioral, secretomic, and immunoarchitectural data from animal models of traumatic injury/amputation pain. The overarching goal of this funded research is to better understand the histological and architectural features of traumatic/amputation neuroma – a benign peripheral nerve tumor that serves as a focal point for pain in many patients. To do so, we employ an established rodent model of amputation pain to develop and characterize symptomatic neuromas. Additionally, students will have the opportunity to interact with clinicians and perform preliminary histochemical analyses from human neuroma samples. During this project, the students will learn clinical outcomes related to traumatic peripheral nerve injury and amputation, clinical strategies for intervention and/or pain management, as well as technical skills related to antibody staining and subsequent image analysis/quantification. The data processed in this project will inform preclinical and, subsequently, clinical/commercial strategies for traumatic neuroma intervention.

Project 3. Developing Functional Biomaterials that Mimic Natural Tissues and Facilitate the Repair and Regeneration of Damaged Tissues

Faculty Mentor: Prof. Gulden Camci-Unal
The goal of this research project is to control and modulate cellular behavior for directing the repair and regeneration of tissues. Students will learn about using diverse tools from chemistry, cell biology, materials science, microfabrication, and engineering. Students will contribute to the development of multicellular and compartmentalized tissue mimetics for clinical applications, such as endothelialization of cardiovascular tissues, regeneration of bone, and invasion of tumors.

Project 4. Developing Point-of-Care Diagnostic Platforms for the Rapid Detection of Pathogenic Diseases, Health Conditions and Environmental Reagents

Faculty Mentor: Prof. Gulden Camci-Unal
This project aims to develop in vitro disease models for personalized medicine and low-cost point-of-care diagnostics to solve problems in global health. An exemplary project is the development of rapid and simple tests for the detection of the COVID-19 virus from bodily fluids in only 5 minutes, contributing to improving global health outcomes. Students will learn about applying diverse tools from chemistry, cell biology, materials science, microfabrication, and engineering to develop devices and methods for personalized medicine and low-cost point-of-care diagnostics to solve problems in global health.

Project 5. Development of Tissue Micro-Sampling Devices for Assembling Skin Constructs for Regenerating Skin

Faculty Mentor: Prof. Walfre Franco
More than half of all hospital deaths are caused by sepsis, and patients who die of sepsis succumb to the ensuing multiorgan failure. As oxygen utilization in a cell becomes deficient, changes in mitochondrial redox state precede cellular, tissue, and organ function changes. Mitochondrial damage occurs during sepsis, such as the impairment of oxygen extraction and utilization, and the severity of mitochondrial dysfunction has been shown to correlate with increased patient mortality. Therefore, a major need exists for methods to continuously evaluate mitochondrial utilization of oxygen. This project focuses on developing optical, acoustic, and machine-learning systems and methods for continuous noninvasive monitoring and real-time analysis of cellular oxygen utilization. Students will help develop computer algorithms and photoacoustic methods for quantifying and analyzing variations in the optical environment of tissues. Students will learn about computational modeling, machine learning, and how light is used to measure tissue oxygenation and could be used to measure oxygen consumption. 

Project 6. Characterization of the Flow-Induced Mechanical Forces that Modulate Ovarian Cancer

Faculty Mentor: Prof. Walfre Franco
Within the ovarian tumor microenvironment, flow-induced mechanical stimuli are a poorly understood factor that plays a crucial role in facilitating dismay clinical outcomes. This project aims to study the hydrodynamic forces that modulate ovarian cancer biology in a chip perfusion model for 3D tumor microenvironment growth. Students' activities include building microfluidic chips, imaging particle tracers, and inputting experimental measurements to existing computational models to characterize forces around tumor nodules. Students will learn about microfluidic chip fabrication, particle image velocimetry, computer fluid dynamics, and mechanotransduction.

Project 7. Development of Gingival Tissue Models

Faculty Mentor: Prof. Chiara Ghezzi
A major paradigm shift in medicine underscores the central role of the microbiome, communities of commensal organisms, in human healthy and diseased states.  Complex interactions between members of the oral microbiota were demonstrated by direct visualization within the supragingival plaque, implying that potential interactions between different organisms are determined by proximity and function.  Plaque topography suggests that gradients of nutrients, wetness, and oxygen promote the formation of these microenvironments in which oral commensals actively maintain healthy homeostasis. In order to understand these systems, in vitro reconstructions of plaque are key tools for mechanistic studies with great translational impact.  Our hypothesis is that an anatomical 3D gingival tissue model with the capacity to replicate native physical and structural conditions in combination with commensal oral bacteria will provide a more authentic metabolic environment with which to study pathogen organization and to investigate in vitro tissue responses to physical changes and exposure to therapeutics. We developed an in vitro 3D gingival tissue model based on a silk and collagen biopolymer scaffold populated with human primary gingival epithelial and stromal cells. In addition, our system allows the replication of low oxygen conditions in a physiologically relevant gingival pocket to support the maintenance and organization of inoculated human plaque.  A relevant level of microbial diversity and visualization of microbial aggregates were successfully maintained in the model.  Sustainability of these cultures over longer periods of time will provide a system for long-term studies of oral pathogenic colonization and infection and calibration of biomarkers from clinical exudates in the cases of periodontal health and dental-plaque induced gingivitis. The REU students will work closely with the PI (Ghezzi) and the lab graduate students to support the research activities in this thrust. The student will be responsible for routine activities such as protein and construct preparation, histology, immunohistochemistry, and microfluidic system setup and validation.

Project 8. Cortical Tissue Model to Study the Effect of Ionizing Radiation

Faculty Mentor: Prof. Chiara Ghezzi
After the 9/11 attacks, research efforts have been established to ensure medical readiness to address civilian casualties in the wake of a radiation public health emergency. Ionizing radiation, such as gamma rays, x-rays, or protons, is also associated with radiation-induced cognitive decline, likely due to a disruption of ‘healthy’ neuronal network function. We aim to develop a novel 3D, human cell-based cortical tissue model exposed to ionizing radiation that enables high-content assessment of neuronal network function. We will use commercially available and well-characterized iPSC glutamatergic/GABAergic neurons, astrocytes, oligodendrocytes, and microglia. Leveraging our UMass Lowell Radiation Laboratory facilities, we will expose our CTM to radiation mimicking external exposure in a nuclear fallout situation and subsequently quantify cell viability, DNA damage, cell morphology, reactive oxygen species abundance, and changes in neuronal network activity using a multi-well microelectrode array system. The REU students will work closely with the PIs (Ghezzi and Black) and the lab graduate students to support the research activities in this thrust. The student will be responsible for routine activities such as protein and construct preparation, experimental setup preparation, and functional assessment readouts.

Project 9. Developing Microfluidic Diagnostic Devices for Crime Labs

Faculty Mentor: Prof. Yanfen Li
According to RAINN statistics, out of every 1000 sexual assaults, 995 perpetrators will walk free. Hundreds of rape kits in the state of Massachusetts remain untested, the oldest dating back to the 1970s. Many factors could contribute to this statistic, including poor tracking of the kits, inefficiencies in the testing process, or insufficient funding. The aim of this project is to use an enzyme-linked immunosorbent assay (ELISA) based technology to develop a more efficient and affordable rape test testing kit for use by crime labs. Students in this project will learn about paper microfluidic devices, ELISA, and 3-D printing. Students will aid in developing the test strip by experimenting with different concentrations of antibodies to maximize efficacy. 

Project 10. Plant-Based Scaffolds for Tissue Engineering Applications

Faculty Mentor: Prof. Yanfen Li
In tissue engineering applications, scaffolds are necessary to provide structure and rigidity to the new tissue and guide cells toward desirable functions. Instead of artificially replicating the complexity of scaffolds in nature, it is possible to repurpose existing plant matter by removing the native cells (decellularization), leaving behind a natural scaffold for new cells to inhabit. This project aims to analyze the mechanical properties of several plant-based scaffolds to optimize the matching of scaffolds to future intended tissues. In this project, students will learn how to decellularize plants, how to perform cell culture, and how to conduct a variety of mechanical testing. Students will also learn how to translate their learning to develop an at-home learning kit that teaches high school and undergraduate students about tissue decellularization.

Project 11. Developing an Optical Imaging Approach for Characterizing the Tumor Aggression

Faculty Mentor: Prof. Zeinab Hajjarian
Breast carcinoma remains the second leading cause of cancer-related death among women. Tumor grade is an independent prognostic and predictive criterion for identifying candidates for neoadjuvant and targeted therapies. Together with other prognostic criteria, it also informs the disease stage. In the current clinical practice, grading malignant tumor cells is largely based on eyeballing the size distribution of cells and their nuclei in the stained slides of tissue through a semi-numeric scoring method by assessing tubule formation (scored 1 to 3), nuclear pleomorphism (i.e., having enlarged nuclei with wide size distribution scored 1-3), and presence of mitotic figures (scored 1-3). The primary objective of this project is to pioneer an optical imaging approach capable of quantitatively assessing tumor grade in freshly excised tissue in its native state. This innovative approach will address the urgent need for a new, more objective metric for tumor grade assessment. Moreover, it will significantly enhance our understanding of tumor aggressiveness and open new avenues for developing novel therapeutic strategies. Through this project, students will actively contribute to advancing optical instrumentation and delve into signal and image processing to quantify and precisely characterize the scattering size distribution in phantoms and biological tissues. They will also learn about tissue optics, ray tracing models, and machine learning and will be exposed to the histopathological analysis and clinical management of breast cancer. 

Project 12: Laser SpeckLe fIeld Microscopy (SLIM) for 3-dimensional Micro-mechanical Imaging of the Extra-Cellular Matrix (ECM)

Faculty Mentor: Prof. Zeinab Hajjarian
Excessive and irregular micro-mechanical remodeling of the ECM is implicated in a broad spectrum of pathologies, including cardiovascular disease, fibrotic disorders, and cancer, which together account for over 50% of deaths worldwide. Nevertheless, our understanding of the underlying mechanisms is severely limited as no imaging tools are currently available for micromechanical mapping of the ECM at length scales pertinent to cells. This project aims to develop and validate a laser SpeckLe fIeld Microrheology (SLIM) technology for micromechanical tissue mapping with high spatial resolution and long depth range. The proposed technology is based on measuring the time-varying speckle intensity fluctuations. A speckle is a grainy intensity pattern formed when a coherent laser beam is backscattered from tissue. Brownian displacements of scattering particles within the ECM dynamically modulate the speckle fluctuations. These fluctuations are intimately related to the viscoelastic properties of imaged tissue. In compliant regions, unrestricted Brownian displacements provoke rapidly fluctuating speckle spots, whereas, in rigid areas, restrained motions elicit limited intensity variations of speckle grains. The capability of SLIM for 3-dimensional, high-resolution, micromechanical imaging of the ECM will provide new insight and scientific knowledge regarding the micro-mechanical basis of pathogenesis at the onset of disease. It will also allow the testing of multiple hypotheses of high clinical impact about therapeutic targeting of the ECM and the downstream mechanical-transduction signaling pathways, which could likely prevent the pathogenesis at its source. During this project, students will be deeply engaged in the setup of the optical instrumentation and creating image reconstruction algorithms. Additionally, they will be involved in validating and benchmarking the performance parameters of the SLIM modality. This will be accomplished by characterizing hydrogel phantoms and biological tissues using the SLIM technique and well-established mechanical testing methods.

How to Apply

Apply by Feb. 16, 2024. And be sure to fulfill all application requirements.