Prostate cancer has a significant heritable component. It is estimated that 10-15% of patients with advanced prostate cancer carry an inherited predisposing genetic mutation, and these patients generally present with a younger age of onset and a strong family history of cancer. The standard in the field of oncology is to conduct short-read DNA sequencing on such patients to find predisposing mutations. While short-read sequencing does well to identify simple mutations that cause disease in many families, our lab concluded that short-read sequencing misses critical mutations in many prostate cancer susceptibility genes. We hypothesized that prostate cancer in many families is due to complex inherited mutations such as genomic deletions, inversions, and mobile element insertions that are not detectable by conventional genomic technologies such as short-read sequencing. To test this hypothesis, our lab specifically recruited prostate cancer patients who, despite having family histories of cancer, did not have any mutations detected via conventional genetic sequencing methods. This project utilizes Nanopore long-read DNA sequencing, which reads DNA in longer fragments and can reliably detect complex mutations. My role is to conduct long-read sequencing on DNA samples from these patients, then analyze the DNA sequence for mutations. I have sequenced 32 patients so far and identified 4 complex mutations through long-read sequencing which were missed by other approaches. These complex mutations include insertions of repeat sequences and duplications which disrupt gene function in BRCA1 and BRCA2. This suggests that, consistent with our hypothesis, some patients who do not have mutations found via conventional sequencing methods do indeed carry causative mutations in well-established prostate cancer risk genes. By finding these mutations, patients can receive more targeted and effective cancer treatment, and undiagnosed family members stand a better chance of catching cancers at earlier stages.

Extreme operating temperatures in rocket engines severely degrades their lifespan, function and reusability. One mitigating approach to help cool rocket engines and extend their lifespans is called Regenerative Cooling, which has been a method actively used in liquid rocket engines (LREs) since 1923. The cooling system utilizes many narrow coolant channels to draw heat away from the liquid propellant near the rocket nozzle. However, experimental research on these channels is rarely done as they are very small and a single channel is difficult to manufacture for basic research testing thereby causing many researchers to look to non-experimentally tested CFD (Computational Fluid Dynamics) simulations to perform their studies. Our experiment aims to fill the gap between simulation and practical testing by testing scaled up models with V-shaped ribs based on a study done by Zhang et al. These scaled up models would allow for more easily obtainable thermal distribution, stress, and pressure data while also being simpler and cheaper to manufacture. We believe our data could offer an alternative to non-tested CFD simulation data and, as access to experimental data increases, result in the expansion of this area of research.

Electromagnetic launchers currently use a combination of magnetic forces and complex electronic timing to propel objects. One example is the US Navy EMALS system, which uses a linear electromagnetic launcher to launch aircrafts from aircraft carriers. However, using complex electronic timing introduces more failure points within the system, increasing its complexity, making such systems susceptible to being disabled by external electromagnetic interference. Inspired by the design of Tom Stanton, this project explores a new approach that removes the digital-based electronic timing and replaces it with a mechanical timing system that can be used to propel drones or other payloads into the air quickly and efficiently. The goal of reducing the design’s complexity is to create a launcher that is a reliable method for drone and payload deployment. By removing electronic switching and using a mechanically driven circuit closure, this project develops a durable, efficient launch system. The prototype is built using 3D-printed components, powerful magnets, and a coil on a sled with contact arms that touch the conductive rail to complete the circuit. Rather than lining the rail with multiple coils, stationary magnets replace the coils with alternating currents to provide the acceleration when the coil becomes powered. The results allow us to have a competitive design that provides a practical alternative to the typical electromagnetic launchers. Expected results include improved durability, reliable performance due to the simplification of electronics, and reduced energy losses. Our research provides a new way to launch drones or other payloads to be integrated into systems where they would be less susceptible to external electromagnetic interference and jamming.

Robots must be able to pick objects from densely packed shelves in order to automate industrial warehouses. Dense packing gives rise to challenges in grabbing targeted objects efficiently as the shelves can be clustered, objects can be stacked, and the target object can be obstructed from direct reach. The goal of this research project is to create a new gripper combined with reinforcement learning to manipulate objects within a shelf without multiple attempts or repositioning of the robot arm. The new gripper design includes four fingers that are linear actuators with vacuum units and suction cups attached to the ends of each finger. Additionally, each finger contains a time-of-flight sensor at the tips which provide spatial information for different objects within the shelf. I integrated time-of-flight sensors into the multi-fingered gripper and filtering algorithms for the sensor’s data. I modified the previous vacuum ejector unit which only provided support for one unit to four vacuum ejector units. I also conducted a series of experiments that provided cases where the new gripper design proved to be better than the previous design. We also collected suction cup vacuum data and trained a neural network to predict the success rate of suction cup attachment. The results of this project will inspire new designs for increasing the success rate of robotic grasps within densely packed environments.

Fuel sloshing in aircraft fuel tanks plays a crucial role in affecting stability and control. This study examines the dynamics of sloshing in wing tanks, integrating theoretical models and practical calculations. The displacement of the fluid’s free surface is analyzed over time, and the resulting shift in the center of gravity (CG) is determined based on liquid distribution. Experimental data were obtained by recording video footage of turbulence simulations and measuring wave heights from the video frames. The measurements were analyzed using manual calculations and Google Spreadsheet functions. Additionally, Computational Fluid Dynamics (CFD) software, LiquiGen, was employed to compare the experimental results. For tanks with baffles, the total liquid mass and CG shift were computed in sections, summing the contributions from all sections to determine the overall shift. The experiments showed notable differences: the total CG shift for a tank without baffles was measured at 1.1 m over 5 seconds, compared to 0.08 m for a baffled tank under identical conditions. Similarly, for CFD simulations, the CG shift was 1.2 m for the tank without baffles and 0.07 m for the baffled tank during the same period. Statistical analysis, including the Shapiro-Wilk test for normality, showed no significant departure from normality for both CFD (p = 0.617) and experimental data (p = 0.116). However, a two-tailed t-test revealed a highly statistically significant difference between the two datasets (p < 0.0001), suggesting that LiquiGen does not accurately replicate experimental results. These results clearly demonstrate the effectiveness of baffles in reducing CG shifts and stabilizing liquid motion. Moreover, they underscore that LiquiGen is unreliable for precise fuel sloshing simulations, which are critical for aircraft stability assessments.

DNA concentration sensing is important for accurate reagent input measurement and output data collection for various molecular biology applications, such as genomics, biotechnology, and clinical diagnostics. Common use cases for DNA concentration sensing include polymerase chain reaction (PCR), gel electrophoresis, and enzymatic assays. Off-the-shelf spectrophotometry systems, used today to measure DNA concentration, require an aliquot of DNA to be pipetted onto a sensor. The sample is then discarded to avoid contamination. Our goal is to develop a novel, cost-effective, and contactless method of containing and directly measuring DNA concentration in individual microliter droplets in real-time. Advantages of contactless containment are: (1) no sample is lost to adhesion to the container, (2) no spectral signature from the container material is added to the sample’s spectrum, and (3) samples can be weighed without contact for closed loop control of sample mass. To contain the droplets of DNA without contact, we use an acoustic levitation system. This system emits focused ultrasonic sound to lift, move and contain liquid droplets in air without making direct contact. Since DNA absorbs ultraviolet (UV) light at a wavelength of 260 nm, we use a low-cost, off-the-shelf spectroscopy sensor to build a portable DNA concentration measurement system within the levitation system to measure the amount of 260 nm UV light absorbed by the DNA. Preliminary results show that the device can distinguish samples containing different concentrations of DNA. Further research will focus on enhancing the device’s sensitivity and expanding its application to other fields related to biology.

The kidney plays an important role in blood filtration, regulation of blood pressure, acid/base homeostasis, and electrolyte balance. Studying the different kidney compartments provides critical insights into the metabolic mechanisms underlying these essential functions. Ziyu Guo, my research mentor has recently developed a highly multiplexed fluorescence microscopy using semiconducting polymer dots (Pdots) that allows one round of immunostaining and imaging of up to 21 targets. However, this technique is restricted to thin samples (50-100 µm), which may oversimplify biological systems by lacking depth and structural integrity. To overcome this limitation, my research integrates multiplexed fluorescence imaging with ELAST, a technology to transform thick tissues into elastic hydrogels, reinforcing the tissue's structure while allowing for better antibody penetration. This approach allows for simultaneously labeling multiple targets in the thick tissue while preserving tissue architecture. Overall, my project seeks to improve our understanding of kidney architecture in their natural spatial 3D context and further provide insights into disease mechanisms and potential therapeutic targets.

Western media has perpetuated society’s perspective of the nursing role through a sexual lens rather than a professional. Nurses face high levels of sexual harassment and violence, with some studies showing up to 80% of nurses experiencing some form of sexual harassment in the workplace at some point in their career. The relationship between the media’s sexualization of nurses has led to an increase in harassment and violence in the profession, as well as proliferating the stereotype of ‘sexy nurses.’ In this literature review, I examine both the media and cultural perception of the nurse and the data surrounding sexual harassment and violence of nurses in the workplace. We know that workplace harassment can lead to increased rates of burnout and staff turnover, if the image of nursing is changed then we can create a healthier work environment with higher levels of job satisfaction and safety.

Robotic movement between waypoints—specific points a robot must travel to—is often perceived as stiff and choppy. This is primarily because paths between these points are typically treated as straight lines. A more effective solution for smoother robotic motion involves forming polynomial curves composed of points–or re-discretizing points–rather than linear segments. The process begins by calculating the diameter of the robot’s orbit, which is determined by computing the maximum distance between any two points. With the orbit dimensions defined, a polynomial trajectory can be fitted to the points and constrained within the robotic arm’s circumference, resulting in a smoother and more fluid movement pattern. The use of this approach of spline trajectories as compared to straight line segments will be demonstrated for a robotic application being used to emulate spacecraft motion for relative proximity operation.

Multidrug resistant Gram-negative bacteria are an emerging threat to public health, continuously evolving to survive under an increasing number of antibiotics and evade the immune system. A major feature of these bacteria is a polysaccharide capsule, which prevents their immune detection. Thus, there is a need to therapeutically restore an effective immune response against them. The Woodward Lab verified that bacteriophage tail spike proteins (TSPs) act as opsonins, which coat and increase phagocytosis of bacteria by macrophages as part of a novel phagocytic pathway. To expand on these data, I am assessing how the adaptive immune system is influenced by the TSP opsonization pathway, analyzing markers of T cell activation and macrophage polarization as starting points. I hypothesize that this pathway has distinct effects on antigen presentation, costimulation, and cytokine expression, compared to better known opsonization pathways like complement and immunoglobulins, and that some of these effects are conserved across bacterial species. To first assess this, I infected macrophages in tissue culture with bacteria, with or without TSP, and measured MHC-II and costimulatory marker expression, an increase which would be associated with enhanced ability to induce T cell responses. I did not observe any differences when TSP was added to the infection. To characterize macrophage cytokine expression, I am treating cultured macrophages with TSP and bacteria-specific antibodies, with the latter serving as a point of comparison between the TSP and antibody opsonization pathways, and quantifying proinflammatory and anti-inflammatory cytokines resulting from this treatment. These studies will reveal whether the TSP opsonization pathway promotes or inhibits adaptive immune responses, which would implicate their utility as a therapeutic and contribute to our understanding of the interaction between bacteriophages, bacteria, and the immune system.

Correct segregation of chromosomes in cell division relies on kinetochores forming end-on, bioriented attachments to microtubule plus ends. In vivo, kinetochores are known to first bind to the lattice of the microtubule and then transit to the plus end either by tip disassembly or the action of plus end directed motor proteins. Force spectroscopy has recently revealed that kinetochores grip the microtubule lattice asymmetrically. Only ‘on-path’ kinetochores that are pulled toward the microtubule plus end form strong, load-bearing attachments, while minus end directed kinetochores weakly grip the lattice. The weak grip of minus end directed kinetochores limits tension across sister kinetochores and makes them susceptible to detachment by error correction machinery. We seek to investigate the molecular mechanism underlying the asymmetric grip of the kinetochore. We purified recombinant kinetochore subcomplexes and tested them individually for asymmetry. We show that the Ndc80 complex exhibits a similar asymmetry as the kinetochore, albeit weaker, while the Dam1 complex is ambivalent to microtubule polarity. Single molecule fluorescence microscopy shows that kinetochores pulled toward the minus end of microtubules are deformed relative to plus end directed kinetochores. We propose that the asymmetric grip strength of kinetochores arises from a network of interactions between polar-sensitive and polar-insensitive subcomplexes that is disrupted when the kinetochore is pulled toward the minus end of a microtubule. A better understanding of the specific mechanisms of kinetochore-microtubule binding is valuable for understanding control of mitotic progression and could potentially inform more targeted anti-cancer therapies that focus specifically on dividing cells without impacting regular cell function.

In our biochemistry teaching labs, students conduct 10-week projects using recombinant protein expression and purification protocols, adapted from Fred Hutch, distributed and tracked via GENI-ACT.org, to identify immunoproteins of research or biomedical interest. We hypothesize they can produce antigen fragments for antibody studies and siderocalin proteins, which bind bacterial siderophores, yielding different amounts and results. In Winter 2023, students modeled antibody fragments with I-TASSER, expressed top constructs with His-tags, and purified them using Ni-NTA resin. In Winter and Fall 2024, siderocalins were expressed as GST-tagged constructs in BL21 and DH5alpha cells using longer expression. The human siderocalin in DH5alpha formed an orange solution, consistent with known siderocalin-enterobactin-Fe complexes. Unexpectedly, other species’ siderocalins appeared yellow, pink, or blue, suggesting functional diversity. Students produced enough immunoproteins for viability tests and are now expressing homologs of the blue siderocalin. They participated in all stages, developing spectroscopy and protein crystallization skills for research careers.

Regenerative braking is a well-tested and ubiquitous technology currently used in electric and hybrid vehicles. It recovers electrical energy while stopping or slowing a vehicle rather than simply wasting the energy as heat losses. However, another much-less studied source of untapped energy also exists in vehicle suspension systems, where shock absorbers also dissipate kinetic energy as heat. This study investigates the practicality of regenerative shock absorbers for transforming oscillatory motion (vehicle bouncing) into recoverable electrical energy. In our study, a motor-driven oscillation system simulates vehicle-like suspension movements in controlled experiments. We have created an experimental regenerative electric shock design that uses oscillatory linear actuation of a series of magnets passing through a series of coils to convert mechanical energy into recoverable electrical energy. We have examined the electrical current, voltage and power characteristics and are able to quantify energy-recapture efficiency over broad operating conditions ranging from single-frequency vibrational modes to more complicated and realistic pulse (sudden impact) conditions. Our findings advance knowledge of the feasibility of using regenerative suspension systems to charge auxiliary electronics or augment vehicle power and identify an alternate method of energy recapture for the automobile industry that maximizes vehicle efficiency without sacrificing ride enjoyment.

The global pandemic of obesity has increased the prevalence and burden of metabolic diseases, including type 2 diabetes and cardiovascular disease. Obesity and its comorbidities are frequently associated with hypogonadism (low levels of testosterone (T) in men), and both preclinical and clinical evidence support a causative role of hypogonadism in predisposing individuals to metabolic diseases. However, the mechanisms remain unknown. One potential mechanism arises from our recent discovery that in mice, surgical castration (reducing T levels) amplifies the pro-inflammatory response to consumption of a high-fat diet, specifically leading to activation of astrocytes within the hypothalamus, a brain region critical for regulating whole-body metabolism. Concomitantly, there is a striking reduction of the anti-inflammatory neuropeptide neurokinin B (NKB; encoded by the Tac2 gene) in the same brain region. Therefore, we hypothesized that T limits astrocyte inflammation via enhanced NKB-neurokinin-3 receptor (NK3R) signaling. Using primary astrocytes harvested from newborn mice, we found that T and dihydrotestosterone (DHT; a non-aromatizable androgen) increase the expression of tachykinin genes like Tac2. Further, androgen treatment blunted the proinflammatory response of primary astrocytes to lipopolysaccharide (LPS), a sepsis-inducing bacterial cell wall component. To assess the anti-inflammatory capacity of NK3R signaling, we co-incubated astrocytes with the NK3R agonist Senktide and LPS, finding a significant attenuation of proinflammatory cytokine expression. Together, these data suggested that androgen receptor signaling might constrain astrocyte inflammation through induction of NKB-NK3R. However, the ability of DHT to reduce cytokine expression in response to LPS was preserved in the presence of Osanetant, an NK3R antagonist, indicating that the anti-inflammatory actions of androgens are independent of NK3R signaling. These findings form the foundation for future pharmacologic and genetic interventions in obese mouse models to further clarify the role of astrocyte T and NK3R signaling in hypogonadism-associated metabolic diseases.

Understanding complex disease processes requires visualizing both nanoscale details and their impact on larger structures. The Vaughan group has developed a method that achieves this using conventional optical microscopes by physically expanding tissue via hydrogel chemistry, enabling sub-diffraction-limit resolution. This approach preserves physiological context through fluorescent labeling of macromolecules (DNA, proteins, carbohydrates). Using mouse renal glomeruli—spherical kidney filtration units (~70-100 µm in diameter)—as a model, I demonstrate the method’s ability to capture nanoscale features, specifically global variations in basement membrane thickness (100-2000nm), with validation that the expansion process does not introduce significant distortion.

Radio Detection and Ranging (RADAR) uses radio waves for object detection in applications such as air traffic control, radio astronomy, and defense systems. This project explores the feasibility of performing RADAR using Modulated Johnson Noise (MJN), which leverages the thermal noise inherent in electrical conductors to transmit information without the use of a conventional radio frequency (RF) carrier. Unlike traditional RADAR, MJN enables stealthier, low-interference operation and ability to function in areas with no ambient radio frequency. In this project we test the hypothesis that RADAR can be performed with MJN by transmitting a square wave signal made with two different noise levels and timing its reflection. To establish a proof of concept, the project follows a multi-phase approach. First, prior MJN research is reproduced by implementing a noise-modulated transmitting system using a Raspberry Pi, an RF switch board, and a Software Defined Radio (SDR) in an anechoic chamber. Next, signal control (transmit) and processing (receive) are integrated into a single microcontroller unit for synchronized operation. The electrical components for the receiving system are validated for amplification and filtering of the reflected signal. The antennas for transmitting and receiving the signal are selected based on their radiation pattern and optimal placement for the RADAR application. Once the transmit and receive systems are finalized, a microcontroller (ie. STM32 Nucleo board)  is used to synchronously transmit and receive reflected signals. Then, indirect time of flight methods are used for distance measurement by analyzing the phase shift between the transmitted and the received signal. The findings will contribute to the development of a RADAR system suitable for resource-constrained environments such as remote locations on Earth or in space and is beneficial for stealth operations where the object emitting the signal must be unidentifiable.