Ameliorating Alzheimer's Disease Effects via Novel Light Stimulation

Synchronous gamma wave brain oscillations, which oscillate at a frequency of 40 Hz, underlie healthy cognitive functioning and are disrupted in Alzheimer’s Disease, leading researchers to explore sensory stimuli delivered at 40 Hz as a potential therapy to resynchronize neuronal firing and thus slow cognitive decline. However, the stroboscopic nature of 40 Hz lighting makes it an unlikely treatment for humans. This project hopes to overcome the challenges posed by stroboscopic 40 Hz white-light by testing the efficacy of a novel invisible spectral flicker (ISF) light system, which masks the visible flicker of 40 Hz light by fusing two light waves together in antiphase. By examining the effects of ISF on cognition and microglia clearance of Aβ plaques, I hypothesize that ISF treatment will lead to synchrony of gamma oscillations in the brain, increased microglia activation, and a resulting decrease in Aβ concentration in our rodent models. Results from this […]

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Probing the CP Properties of the Top-Higgs Interaction

What is the universe made of? This fundamental question haunting us for thousands of years has been answered by the Standard Model (SM), which gives us the results with unprecedented accuracy. The SM provides a set of rules that governs elementary particle interactions, but there must be something missing. A big hint here is that SM doesnt explain the asymmetry between matter and antimatter, the nature of dark matter, and the quantum behavior of gravity. Physics beyond the Standard Model (BSM) must exist. The ATLAS experiment at the Large Hadron Collider (LHC) investigates a wide range of BSM physics. Measuring the properties of the Higgs boson is a powerful path. This project will focus on searching for single top Higgs production. Specifically, I will design analysis to measure the event rate of the tH process in which the Higgs boson has a high transverse momentum and decays to a pair […]

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Investigating the Synergistic Anti-tumor Effect of Akkermansia and ICI

The gut microbiota plays a salient role in mediating host physiology and immunity. Several studies link immune checkpoint inhibitor (ICI) efficacy in extraintestinal cancers to gut microbiota composition, with commensals, such as Akkermansia muciniphila (A. muciniphila). Recently, studies found that A. muciniphila treatment during anti-PD1 immunotherapy showed potential clinical relevance; however, the differential effects on antitumor responses by the different strains of A. muciniphila are not yet elucidated. Becken et al. (2021) genotyped 71 strains of A. muciniphila, together representing the Am (A. muciniphila) I, AmII, and AmIV clades, and identified clade-specific characteristics that may influence interactions with the host immune system in vivo. Using the collection of A. muciniphila strains from the Valdivia Lab, I will test the hypothesis that A. muciniphila clade-specific traits can lead to varied effects on systemic anti-tumor responses. I will first examine whether gnotobiotic mice colonized with representative A. muciniphila strains from each of […]

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Understanding Mechanisms Behind Memory Cells in PTSD Susceptibility

Memories in the brain are encoded in specialized neurons called “engram cells,” which are active during an initial event and the recall of that event. Little is known about how these cells form, but exposure to traumatic stress has previously been linked to an increase in the number of engram cells. The goal of my research is to examine the formation of engram cells in multiple areas of the brain after exposure to stress and determine if the increased presence of these cells results in PTSD-like behavior in mice. Understanding the beginning of engram formation will allow for a better understanding of how individuals respond to stress and the neural mechanism that results in maladaptive methods of handling stress. Over the summer, I will subject mice to stress by exposing them to a chronic social defeat stress paradigm, performing a series of behavior tests, and comparing the molecular markers for […]

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Modeling Diagenetic Effects on Marine Carbonate Clumped Isotope Values

The stable isotopic composition of marine carbonates is an exemplary standard for reconstructing past Cenozoic climate. But, a fundamental question is whether these carbonates faithfully record their original isotopic composition, and to what extent have they been modified during burial. The relative abundance of isotopologues of carbonate with two rare isotopes (clumped isotopes) is a function of formation temperature and is leveraged to understand how carbonate samples were formed and modified through time. Recent work to reconstruct paleotemperatures from carbonate clumped isotopes found that samples from below 1,000 meters below the sea floor appear to record either a warmer past or a more significant role of diagenetic alteration. My study will focus on measuring carbonate clumped isotopes in an ocean core from the Rio Grande Rise in the Atlantic Ocean. Alongside the measurements, I will also work on a model that characterizes how diagenetic alteration affects the isotopic composition of […]

...Read More about Forrest McCann

Developing Molecular Glue Degraders for Target Protein Degradation

Since the mid-20th century, the field of drug discovery for disease regulation has focused on the concept of occupancy-driven pharmacology. However, more than 90 percent of the proteome is currently deemed undruggable due to a lack of surface-lying ligandable hotspots. Many of these undruggable proteins, such as transcription factors and protein complexes, are implicated in disease but cannot be targeted through active site directed inhibitors, creating a need for new therapeutic modalities that can control protein function. One method for targeting undruggable proteins is through the use of molecular glue degraders, small molecules that chemically elicit target protein degradation. My project seeks to determine the essential chemical elements that define molecular glue degraders and use these findings to create guidelines for the creation of effective molecular glues. My project will make it easier to target disease-related proteins currently deemed undruggable by current pharmaceutical techniques.

...Read More about Kaila Nishikawa

Applying Proximity-Assisted Photoactivation to Study PTEF-b Regulation

  In humans, Positive Transcription Elongation Factor b (P-TEFb) is an RNA Polymerase II regulator crucial for proper gene expression. To execute its regulatory function, P-TEFb itself is precisely regulated via reversible interactions with an snRNP complex. Using biochemical techniques, past studies have confirmed LARP7, HEXIM1, and BRD4 to be protein partners of P-TEFb. My project aims to study the dynamic regulatory role of known protein partners LARP7, HEXIM1, and BRD4 in P-TEFb regulation. I will apply a new technique called proximity-assisted photoactivation (PAPA) to single particle tracking (SPT) and live cell imaging in order to examine protein-protein interactions between P-TEFb and each protein partner in human osteosarcoma cells. PAPA involves a sender fluorophore reactivating a receiver fluorophore when the two are in proximity. By tagging P-TEFb and each partner with these fluorophores, PAPA can be used to detect their interaction corresponding to the sub-population of protein complexes showing sender […]

...Read More about Britney Weng