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DTSTART;TZID=America/New_York:20250605T100000
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DTSTAMP:20260506T094051
CREATED:20250604T223853Z
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SUMMARY:ChE PhD Dissertation Defense: Victoria Duback
DESCRIPTION:Name:\nVictoria Duback \nTitle:\nPharmacokinetic and Pharmacodynamic Assessment of a T Cell-Targeted Vector for In Vivo Car-T Cell Therapy \nDate:\n06/05/2024 \nTime:\n10:00:00 AM \nCommittee Members:\nProf. Abigail Koppes (Advisor)\nProf. Ryan Koppes\nProf. Debra Auguste\nDr. Kutlu Elpek \nLocation:\nKariotis 309 \nAbstract:\nChimeric antigen receptor (CAR) T-cell therapy has demonstrated transformative efficacy in the treatment of B-cell malignancies\, particularly through autologous approaches. However\, the clinical utility of autologous CAR-T therapy is limited by complex manufacturing processes\, patient-specific variability\, and the requirement for lymphodepletion\, which can delay or prevent treatment for critically ill patients. In vivo-generated CAR-T cell therapy offers a promising alternative by enabling the direct genetic engineering of T cells within the patient\, potentially streamlining treatment and expanding access. \nThis dissertation focuses on the preclinical characterization of a CD8-targeted lentiviral fusosome designed to deliver a CD19-specific CAR transgene in vivo. The overarching objective of this work is to understand the relationship between the pharmacokinetics (PK) and pharmacodynamics (PD) of in vivo CAR-T cell generation to inform the development and clinical translation of nextgeneration gene therapy products. In vitro experiments demonstrated efficient and selective transduction of both resting and pre-activated CD8⁺ T cells\, with enhanced CAR expression and function in pre-activated populations. A humanized mouse model was optimized to evaluate vector performance in vivo\, incorporating engraftment of human PBMCs and CD19⁺ tumor cells to assess efficacy\, biodistribution\, and dose-response relationships. \nPharmacokinetic studies revealed rapid clearance of the vector in naïve mice\, while the presence of target T cells significantly prolonged vector persistence\, likely through cellular binding and internalization. Dose-dependent CAR-T cell generation and tumor suppression were observed\, with no signs of fusosome-related toxicity. Importantly\, donor-to-donor variability was noted\, emphasizing the need for robust model systems in predicting clinical outcomes. To further enhance the fusosome potency\, novel constructs incorporating CD3-mediated activation signals were engineered\, resulting in improved gene integration and functional CAR-T activity in vitro. Together\, these studies provide critical insight into the PK/PD relationship of in vivo CAR-T cell therapies and establish a strong preclinical foundation for the continued development of clinically viable\, targeted lentiviral vectors for the treatment of B cell malignancies. \n\n \nVictoria (Tori) Duback is a third-year doctoral candidate in the Chemical Engineering department at Northeastern University\, pursuing a Ph.D. in Engineering with a focus on viral vector gene delivery. She is expected to graduate in June 2025. Her research focuses on characterizing targeted gene delivery systems\, and her thesis examines the pharmacokinetics and pharmacodynamics of a T-cell-targeted vector for the treatment of B-cell malignancies. In parallel with her academic pursuits\, Tori is a seasoned industry professional\, serving as a Senior Scientist at Sana Biotechnology in the T-cell therapeutics group. Over the past several years\, she has played a pivotal role in the design and evaluation of cutting-edge immunotherapies. She leads a team of scientists dedicated to assessing the safety and efficacy of in vivo generated CAR-T cells and allogeneic CAR-T cell therapies\, conducting studies both in vivo and in vitro. Beyond the lab\, Tori is a passionate advocate for STEM education and community engagement. She has mentored high school students across the Boston Public Schools\, promoting early exposure to careers in science and engineering. Her commitment to mentoring and education reflects her belief in creating more inclusive and accessible pathways into scientific research. Looking ahead\, she aims to continue growing as a scientist in industry\, with a focus on developing safe\, effective\, and accessible therapies for patients in need. In her free time\, Tori enjoys traveling\, outdoor activities\, and spending time at the beach.
URL:https://che.northeastern.edu/event/che-phd-dissertation-defense-victoria-duback/
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DTSTART;TZID=America/New_York:20250609T140000
DTEND;TZID=America/New_York:20250609T160000
DTSTAMP:20260506T094051
CREATED:20250604T223743Z
LAST-MODIFIED:20250604T223743Z
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SUMMARY:ChE PhD Dissertation Defense: Matthew Fernez
DESCRIPTION:Name:\nMatthew Fernez \nTitle:\nDevelopment of a Hydrogen Sulfide Biosensor and Interrogation the Role of Sulfide on Mucus Barriers \nDate:\n06/05/2024 \nTime:\n10:00:00 AM \nCommittee Members:\nProf. Benjamin Woolston (Advisor)\nProf. Rebecca Carrier (Co-Advisor)\nProf. Erel Levine\nDr. Jodie Ouahed \nLocation:\nShillman 420 \nAbstract:\nInflammatory bowel disease (IBD) is a gastrointestinal condition that is estimated to afflict more than 1% of adults\, with prevalence increasing over time. Hydrogen sulfide (H2S)\, produced by the gut microbiota and partially by the host epithelium\, has long been associated with IBD through metagenomic evidence of increased populations of sulfate producing bacteria in patients. However\, the effects of sulfide are disputed and the mechanisms underlying disease pathogenesis remain unresolved. Sulfide literature suggests both a therapeutic and restorative effect at low levels yet also implies higher levels may be toxic\, resulting in disruption of mucus barriers and promotion of an inflammatory cascade. The mucus barrier is comprised of a mucin network crosslinked by disulfide bonds\, along with myriad heterogenous components\, which provides protection for the cell lining from the microbiota and toxic byproducts. We hypothesize that in excess\, sulfide reduces disulfide bonds yielding a weaker\, more permeable barrier that is susceptible to microbial penetration. However\, studying sulfide in the gut microenvironment is technically challenging due to its high volatility and reactivity\, making accurate GI measurements challenging in vivo. Here\, we seek to address measurement limitations through the development of a sulfide biosensor and evaluate the impacts of sulfide on mucus barriers. \nThis thesis has three core elements: optimization of a functional sulfide biosensor\, exploration of implementation in a mesofluidic gut-on-chip\, and direct evaluation of sulfide on mucus barrier properties. To construct a transcriptional sulfide biosensor\, a polysulfide sensitive repressor\, SqrR\, from Rhodobacter capsulatus was codon harmonized and inserted into a plasmid with a fluorescent reporter module driven by the SqrR affiliated promoter pSqr. To convert sulfide into polysufides that de-activate SqrR\, we coupled the sensing plasmid with an enzymatic plasmid bearing codon harmonized Sqr from R. capsulatus. Initial construction failed to generate a response to sulfide\, but an 18-fold dynamic range up to 750 M in aerobic conditions was produced through pSqr engineering and SqrR tagging and titration. Sqr activity and products were characterized\, but failed to generate a response under anaerobic conditions likely due to electron transport chain dependent quinone incompatibility. Given that the gut microenvironment is largely anaerobic\, sensor response under anaerobic conditions was recovered through isolation of a novel Sqr homolog from Wolinella succinogenes\, an organism that couples sulfide oxidation to reduction of fumarate\, a compound abundant in the gut. We demonstrate sensor activity under anoxic conditions using this enzyme with both fumarate and nitrate\, a marker of the inflamed gut. The group has previously developed a gut on chip PDMS device with vertical orientation for cross sectional imaging of the mucus barrier of primary intestinal epithelium under static conditions. The gas permeability of PDMS encouraged us to attempt gel wall modifications to permit consistent delivery of sulfide via flow. While modifications of the gut chip to operate under continuous flow culture were unsuccessful\, a simple demonstration of a partial response to sulfide by the biosensor on chip is presented in the absence of epithelium\, illustrating promise for implementation as a diagnostic in the future. Finally\, the impacts of sulfide on mucus were elucidated in the third part of the thesis. Using harvested porcine intestinal mucus (PIM)\, we demonstrate that diffusivity of polystyrene nanoparticles in PIM increases 1.6 fold when treated with 1 mM sulfide. Sulfide also impacted microbial velocity and motion type\, yielding a statistically significant increase of average velocity and proportion of microbes exhibiting penetration like behavior. While structural changes were not observed through lectin staining of PIM\, the thesis culminates in a simple demonstration of deleterious effects of sulfide on a living mucus barrier in our gut on chip system. Mucus thickness was reduced and resulted in an increased proportion of nanoparticles that penetrated the mucus barrier. Taken together\, this work produced a novel sulfide biosensor that functions under aerobic and anaerobic conditions and characterized the deleterious effects of sulfide on barrier permeability suspected by the underlying hypothesis of reduction of disulfide bonds in mucus structure. \n\n \nMatt Fernez is currently a sixth year PhD student in Chemical Engineering at Northeastern University. He completed a Bachelor of Science in Chemical Engineering in May\, 2019 at University of Massachusetts Amherst where he also produced an honors thesis. In June of this year\, he will defend his PhD Thesis to complete the doctoral degree. His research is co-advised and focuses on synthetic biology and tissue engineering\, with the focus of studying mucus barrier properties utilizing genetically engineered bacteria. His dissertation is titled “Development of a Hydrogen Sulfide Biosensor and Interrogation the Role of Sulfide on Mucus Barriers”. He has contributed towards authorship on 4 publications\, including one review paper and three technical papers. His first author sulfide biosensor manuscript was recently published in ACS Synthetic Biology in Spring\, 2025. His research has been presented at 4 conferences\, culminating in an oral presentation at the American Institute of Chemical Engineering international conference in October\, 2024. He has been a mentor to several undergraduate students who have produced research posters at Northeastern’s undergraduate research conference. He also assisted in building the foundation of the now well-established Woolston Lab\, being one of the first two students and serving as the Lab Safety Officer. Outside of research\, Matt has many recreational hobbies including poker\, hiking\, travelling\, and fantasy sports. He is the president and founder of a local poker club in the greater Boston area. He also enjoys spending time with family and writing poetry.
URL:https://che.northeastern.edu/event/che-phd-dissertation-defense-matthew-fernez/
LOCATION:420 Shillman Hall\, 360 Huntington Ave\, Boston\, MA\, 02115\, United States
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DTSTART;TZID=America/New_York:20250620T103000
DTEND;TZID=America/New_York:20250620T123000
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SUMMARY:ChE PhD Dissertation Defense: Yujia Wang
DESCRIPTION:Name:\nYujia Wang \nTitle:\nMachine Learning and Spatially Resolved Spectroscopy for Controlled Synthesis and Novel Phenomena Discovery in Monolayer Molybdenum Disulfide \nDate:\n06/20/2024 \nTime:\n10:30:00 AM \nCommittee Members:\nProf. Swastik Kar (Advisor)\nProf. Joshua Gallaway\nProf. Steve Lustig\nProf. Francisco Hung \nLocation:\nBurlington Campus: Building 5\, Room C \nAbstract: \nTwo-dimensional (2D) materials\, particularly transition metal dichalcogenides like molybdenum disulfide (MoS2)\, represent a promising platform for next-generation semiconductor technologies due to their atomic-thin structure\, tunable electronic properties\, and unique optical characteristics. However\, realizing their full potential is hindered by two important challenges: the time-consuming\, trial-and-error nature of chemical vapor deposition (CVD) synthesis optimization\, and the difficulty in accurately characterizing spatially inhomogeneous material properties. In this dissertation defense\, I will present detailed investigations into the development of new methods for addressing these challenges through the integration of machine learning-guided synthesis and high-resolution spatially resolved optical characterization techniques. \nFirst\, I developed an experimental “hyperspace” design system that serves as an interface that adapts synthesis parameters to machine learning frameworks. The machine learning algorithms were developed through collaborations with Prof. Xiaoning (Sarah) Jin’s group (Department of Mechanical and Industrial Engineering). The algorithms efficiently identify pathways towards synthesis optimization in complex multidimensional experimental hyperspaces\, accelerating the synthesis towards the highest sample quality. Our results showed up to 85% reduction (two months instead of 1 year) in trial-and-error efforts\, and rapid optimization of the ideal synthesis conditions. \nSecond\, I established a spatially resolved optical spectroscopy platform for characterizing the as-grown 2D materials by combining Raman and photoluminescence (PL) mapping at micrometer resolution. Going much beyond traditional mapping techniques\, this technique enables simultaneous extraction of strain\, doping\, and excitonic properties across individual flakes\, revealing growth-intrinsic mechanisms for controlled engineering of electronic and optical properties. Through systematically varied CVD conditions\, I demonstrated deterministic control over both orbital bandgaps and spin-orbit coupling\, achieving the first purely optical experimental observation of strain-tunable spin-orbit splitting in as-grown monolayer MoS2. \nFinally\, I applied this integrated platform to explore iron-doped MoS2 – to further elucidate the role of doping in 2D semiconductors. This work established valuable synthesis protocols and identified distinctive optical signatures that serve as indicators of dopant incorporation in 2D materials. \nMy research demonstrates how coupling experimental design and scanning-based characterization approaches with advanced computational methods can substantially accelerate materials discovery and establish new pathways for deterministic property engineering in 2D semiconductors\, with implications extending to quantum technologies\, optoelectronics\, and spintronic applications.
URL:https://che.northeastern.edu/event/che-phd-dissertation-defense-yujia-wang/
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