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Innovative Approaches To Combat Triple-Negative Breast Cancer: Integrating Metabolic Modulation, Advanced Therapies, And Lifestyle Interventions, Ngozi Damilola Chidumebi Akingbesote

Yale Graduate School of Arts and Sciences Dissertations

Triple-negative breast cancer (TNBC), an aggressive and often lethal subtype of breast cancer, continues to challenge researchers and clinicians due to its poor prognosis and limited therapeutic options. This thesis explores novel therapeutic strategies that integrate metabolic modulation, advanced radionuclide therapies, and lifestyle interventions to combat TNBC effectively. The first component investigates metabolic scaling and its implications for cancer metabolism. Gene and protein expression analyses across species reveal that metabolic processes, including oxidative metabolism and detoxification, scale inversely with body mass. This foundational insight underscores the importance of systemic metabolic regulation in understanding cancer progression. In the realm of cancer …

Applicability Of Multilateral Environmental Agreements During International Armed Conflicts, Beatrice L. Hamilton

Loyola University Chicago Law Journal

Armed conflicts increasingly contribute to environmental damage and climate change, yet, as proven by recent and ongoing conflicts, the legal framework for the protection of the environment under the law of armed conflict (LOAC) fails to effectively mitigate these damages. With rising temperatures, already diminishing resources, the counter-acting of mitigation and adaptation efforts due to warfare and geo-political tensions on the rise, there is a strong case for considering the potential for enhancing the protection of the environment during armed conflicts.

This Article examines the terms of applicability of multilateral environmental agreements (MEAs) during international armed conflicts. The article draws …

Mental Representations Of Computational Processes, Marlene Berke

Yale Graduate School of Arts and Sciences Dissertations

Human intelligence is uniquely powerful and flexible - operating in an enormous range ofsituations, from those as everyday as driving in traffic while carrying on a conversation, to those as extraordinary as cooperating to shift a culture. Work in cognitive science over the past decades has argued that two foundational types of representations form the building blocks of human intelligence: representations of the physical world in terms of objects, forces, spaces, substances, and so on (Carey, 2009), and representations of the social world in terms of agents and their mental states, like goals, beliefs, and knowledge (Gopnik, Meltzoff, & Bryant, …

Improving Thermal Comfort Of Firefighter Personal Protective Equipment With A Focus On Enhancing Insulation And Moisture Management Abilities: A Meta-Analysis, Hallie Ivory

Major Papers by TMD Master of Science Students

Firefighters wear personal protective equipment (PPE) composed of multiple layers, each designed to serve a specific function in ensuring safety and comfort in high heat environments. The thermal liner is the innermost layer and plays a crucial role in thermal comfort by providing insulation and moisture management. Insulation provides protection from external hazards while moisture management keeps the wearer cool and dry.

Heat stress is a significant safety concern for firefighters, as prolonged exposure to high temperatures and insufficient evaporative cooling can lead to discomfort, injuries and or fatalities for them while on duty. Effective moisture management is critical in …

Investigating Non-Canonical Roles Of Atr And Chk1 Throughout The Cell Cycle, Yoon Ki Joo

Yale Graduate School of Arts and Sciences Dissertations

Chromosome Instability (CIN), which results from DNA damage in interphase and chromosome missegregation in mitosis, is considered to be a potent driver of cancer. To prevent CIN, cells harbor the DNA Damage Response (DDR) pathway, which is responsible for detecting and repairing damaged DNA. Because of their importance in preventing CIN, the core members of the DDR pathway such as Ataxia Telangiectasia and Rad3-related (ATR) and Checkpoint kinase 1 (CHK1) have been studied as promising targets in cancer therapy. However, clinical trials show that ATR and CHK1 inhibitors elicit adverse side effects with unknown reasons. Recent research suggests that one …

Investigating The Structure And Assembly Of The Hiv-2 Capsid Protein: How Does It Compare To Its More Infamous Cousin?, Matthew David Cook

Yale Graduate School of Arts and Sciences Dissertations

Several million people live with infection by human immunodeficiency virus type 2 (HIV-2). Like its pandemic-causing relative, HIV-1, infection with HIV-2 can progress to AIDS, is largely incurable, and is similarly mutation-prone, presenting a challenge for treatment. Despite this, detailed study of HIV-2 is widely lacking while most of the understanding of the virus and its proteins is borne out of comparison with HIV-1. The two are sufficiently similar that this is generally effective, but differences in infection outcomes of the two viruses must be explicable by molecular determinants. One domain of viral biology particularly worth attention in this regard …

Computational Approaches To Understanding The Proton-Coupled Electron Transfer Reactions In Ribonucleotide Reductase, Jiayun Zhong

Yale Graduate School of Arts and Sciences Dissertations

Proton-coupled electron transfer (PCET) is a fundamental chemical process where both an electron and a proton are transferred simultaneously or sequentially, playing a key role in various biological and chemical systems, including enzymatic reactions and energy conversion. This thesis investigates the PCET reactions in ribonucleotide reductase (RNR), a critical enzyme responsible for DNA synthesis and repair in all living organisms. While significant progress has been made in understanding RNR's PCET pathway, several gaps remain, particularly regarding the specific mechanisms and energetics of individual PCET steps, the role of conformational dynamics, and the influence of water molecules. Through quantum mechanical/molecular mechanical …

Resolving The Three-Dimensional Interactome Of Human Accelerated Regions During Human And Chimpanzee Neurodevelopment, Atreyo Pal

Yale Graduate School of Arts and Sciences Dissertations

Human Accelerated Regions (HARs) are regulatory elements highly conserved across species but exhibit a significant excess of human-specific sequence changes. They include transcriptional enhancers with human-specific activity and have been implicated in the evolution of the human brain. However, our understanding of how HARs contributed to uniquely human features of the brain is hindered by a lack of insight into the genes and pathways that HARs regulate. It is unclear whether HARs acted by altering the expression of gene targets conserved between HARs and their chimpanzee orthologs or by gaining new gene targets in human, a mechanism termed enhancer hijacking. …

Continization And Language Representation Of Chemical Information, Haote Li

Yale Graduate School of Arts and Sciences Dissertations

Throughout human history, our ancestors have continuously expanded the frontiers of their interests in nature. Chemistry is one of the essences of such explorations. Yet, despite countless discoveries and experiments, we are still on a journey to examine the possibilities within our finite time. With an ever-growing amount of information and open access to public resources, we are experiencing an inflection point. This moment redefines how efficiently we can solve problems, and the key lies in integrating increasing insights from the entire history of knowledge. Algorithms, in contrast to human efforts, are scalable with the amount of available hardware. In …

Mechanics And Energetics Of Cytoskeletal Assembly, Gao Sun

Yale Graduate School of Arts and Sciences Dissertations

Active matter is a subfield of soft condensed matter physics that focuses on the emergence ofcollective phenomena, as components of the system consume energy, driving them out of thermodynamic equilibrium. Living matter, a specific subfield of active matter, lies between physics and biology. In this case, the components are biomolecules, whose interactions are not only constrained by the laws of physics but may exhibit purpose and intentionality. Biophysicists, who study living matter use reductionist approaches and focus on how different components of the system can collectively give rise to novel biological phenomena through continuous consumption of energy. An example of …

Mechanisms Of Heart And Major Vessel Development: Nup107 And Cacna1g As Novel Regulators, Valentyna Kostiuk

Yale Graduate School of Arts and Sciences Dissertations

Congenital Heart Disease (CHD) is the most common congenital malformation and a leading cause of infant mortality. While advances in genomic sequencing technology have enabled a fast and inexpensive candidate gene identification, the molecular mechanisms of CHD remain mostly unknown. Both nup107 and cacna1g are novel CHD genes identified in CHD patients with no plausible mechanisms explaining their roles in cardiac development. Here, we show that nup107 plays a key role in early embryonic patterning and subsequent organ development. The loss of Nup107 has a direct impact on germ layer specification, Left-Right patterning and downstream cardiac looping. Specifically, Nup107 depletion …

Visual Circuits For Distance Estimation In Walking Drosophila, Joseph Shomar

Yale Graduate School of Arts and Sciences Dissertations

Animals must infer the three-dimensional structure of their environment from twodimensional retinal images. They use visual cues like motion parallax and binocular disparity to judge distances to objects, and studies across several animal models have foundand characterized neural signals that correlate with visual distance. However, the causal role of these neurons in distance estimation and the range of their possible neural properties remain poorly understood. Here we show that both directional and non-directional feature-selective neurons in the Drosophila visual system are involved in distance estimation during free locomotion. We used a high-throughput behavioral assay to perform a targeted silencing screen …

Bioinformatic, Genetic, And Biochemical Investigations Of The Bacterial Ole Ribonucleoprotein Complex, Chrishan Malinda Fernando

Yale Graduate School of Arts and Sciences Dissertations

Bacteria are under significant evolutionary pressures to maintain compact genomes.Therefore, they typically have high coding density compared to eukaryotes. As a result, large and highly structured noncoding RNAs (ncRNAs) are extremely rare in bacteria. However, the few classes of known large ncRNAs have unique and fundamental biological roles and are often catalytic. Furthermore, these ncRNAs reveal what may have been possible under a hypothetical ancient RNA world in which all major biological functions in existing organisms were performed by RNA, rather than DNA and protein. Further study of large ncRNAs is likely to reveal new insights into RNA catalysis and …

Analysis Of The Papillomavirus L2 Capsid Protein Structure And Protrusion, Patrick Michael Buckley

Yale Graduate School of Arts and Sciences Dissertations

Approximately 5% of human cancer worldwide is caused by Human Papillomavirus (HPV). Although there are highly effective prophylactic vaccines, HPV remains a serious public health challenge due to low vaccine uptake and the inability of the vaccine to treat anyone already infected. Understanding how HPV enters and infects cells is important, as this work may lead to the development of new antivirals or therapeutics and may also reveal new aspects of cell and protein biology. HPVs are non-enveloped viruses, containing an ~8000 base pair double-stranded DNA genome encapsidated by 360 copies of L1 major capsid protein and up to 72 …

Asymmetric Synthesis Of Bioactive Scaffolds Via Organocatalysis, Melody Guo

Yale Graduate School of Arts and Sciences Dissertations

Chiral catalysts allow chemists to access enantioenriched materials without the use of proportionate amounts of chiral reagents, while lowering the energy barrier of the original reaction. One way to form bioactive, heteroatom-containing scaffolds asymmetrically is through the use of chiral organocatalysts. This dissertation covers the development of stereoselective reaction methodology to access bioactive scaffolds and mechanistic investigations into intriguing features therein. Chapter 1 describes the development of the asymmetric synthesis of axially chiral quinazolinones. In this project, complementary applications for two different scaffold classes of chiral phosphoric acid (CPA) catalysts are found. We observe that while a C2-symmetric CPA catalyst …

The Role Of Local Factors In Shaping Microbial Communities And Biogeochemical Functions Across Scales, Alexander Polussa

Yale Graduate School of Arts and Sciences Dissertations

Microorganisms play a vital role in carbon cycling, driving the decomposition and transformation of organic matter (OM) in soils. This dissertation examines how both broad climatic and local factors shape microbial communities and influence organic matter decomposition. Through a combination of microcosm and field experiments, I demonstrate that local conditions like soil moisture, depth and plant identity impact microbial function, although these effects can be masked by broader climatic influences. I also investigate how the ericoid shrub, Kalmia latifolia, differentially affects fungal communities under arbuscular and ectomycorrhizal trees. Finally, integrating results from multiple forest sites in the eastern US, I …

Understanding The Mechanisms Regulating Neuronal Metabolic States In Vivo, Milind Singh

Yale Graduate School of Arts and Sciences Dissertations

Glycolysis, a glucose-consuming pathway required for cellular energy production, iswell conserved across species and has been extensively characterized biochemically. Less is understood regarding how it is subcellularly organized, or coordinated across tissues in vivo. Previous work from our lab found that during transient hypoxia or neuronal stimulation, the rate-limiting glycolytic enzyme phosphofructokinase-1 (PFK-1.1) dynamically re-localizes from the cytoplasm to condensates near synapses in C. elegans neurons. My research examined mechanisms by which PFK-1.1 localization is regulated in neurons, and resulted in two main findings: 1) PFK-1.1 condensate formation in neurons is regulated by a non-cell-autonomous signal derived from hypodermal (epidermal) …

The Linc Complex Component Kms1 And Cenp-B Protein Cbp1 Cooperate To Enforce Faithful Homology-Directed Dna Repair At The Nuclear Periphery, Alyssa Laffitte

Yale Graduate School of Arts and Sciences Dissertations

DNA double-stranded breaks (DSBs) represent a danger to genome stability. Cells repair DSBs mainly through one of two pathways: canonical non-homologous end-joining (cNHEJ), which requires the direct ligation of the two DSB ends, or homologous recombination (HR), which involves the use of a homologous template to create a faithful repair product. While HR is often considered to be an error-free mechanism, the ultimate fidelity of this pathway depends on the ability of the cell to identify and engage with the correct homologous template. This is particularly challenging during repair of repetitive regions of the genome for which non-allelic sequences can …

Computational Study Of Redox-Active Protein Residues And Biological Proton-Coupled Electron Transfer, Qiwen Zhu

Yale Graduate School of Arts and Sciences Dissertations

Proton-coupled electron transfer (PCET) reactions are essential processes in biological systems, fundamental to various enzymatic functions and redox biology. Key to these reactions are redox-active residues, such as tyrosine and tryptophan, which enhance the efficiency and specificity of electron transfer events. This thesis investigates the thermodynamics, kinetics, and conformational influences of PCET in proteins involving these residues through three projects, each offering significant insights into the mechanisms and broader implications for biological function. The studies have focused on two protein systems: a simple de novo protein system, α3X, and ribonucleotide reductase, an enzyme critical to DNA synthesis. Combining a wide …

A Bioluminescent Approach To Coxiella Burnetii Pathogenesis: Development And Utilization Of An In Vivo Imaging Model, Jenna Myr Andrews

Yale Graduate School of Arts and Sciences Dissertations

Coxiella burnetii is a Gram-negative, obligate intracellular bacterium that infects livestock and causes Q fever in humans, which can range from acute flu-like symptoms to severe, persistent infections. C. burnetii relies on a Dot/Icm type IVB secretion system to translocate effector proteins, manipulating host cell processes to support intracellular replication. While axenic media have facilitated in vitro pathogenesis research, in vivo studies remain limited due to the classification of the virulent Nine Mile phase I strain as a category B select agent. Although the avirulent phase II strain RSA493 is exempt from this classification, it is rapidly cleared in immunocompetent …

Dysregulation Of Transcription And Mrna Processing In Splicing Factor Mutant States: Mechanistic Insights And Implications, Prajwal Chaitanya Boddu

Yale Graduate School of Arts and Sciences Dissertations

Recurrent mutations in RNA splicing factor (SF) genes, such as SF3B1, U2AF1, SRSF2, and ZRSR2, are key drivers of oncogenesis in various cancers, particularly clonal myeloid disorders like Myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML). Over the past decade, significant insights have been gained into their molecular mechanisms and effects on RNA splicing. These mutations are typically heterozygous and non-synonymous (except ZRSR2, which involves single-allele loss-of-function mutations) and are largely mutually exclusive, suggesting shared downstream mechanisms that prevent co-occurrence. Given their pre-eminent roles in splicing, most studies to date have primarily focused on the effects of SF mutations on …

Spatial Control Of Nonlinear Interactions In Multimode Fibers, Kabish Wisal

Yale Graduate School of Arts and Sciences Dissertations

In recent years, there has been significant advancement in controlling optical scattering by structuring the wavefront of the incident light, or `wavefront shaping'. Most applications of wavefront shaping have focused on linear scattering, but there is a growing interest in tailoring nonlinear scattering. In this thesis, we explore a new approach based on wavefront shaping for suppressing certain instabilities induced by nonlinear scattering in passive and active multimode fibers (MMFs). Specifically, we focus on suppressing stimulated Brillouin scattering (SBS) and transverse mode instability (TMI). A key motivation for our work is power scaling in high power fiber lasers and amplifiers, …

Elucidating Cell Intrinsic Regulators Of Cd8 T Cell Differentiation: Klf2 Maintains Effector Cd8 Lineage Fidelity, Eric Quinn Fagerberg

Yale Graduate School of Arts and Sciences Dissertations

CD8 T cells are an integral part of the immune system, principally responsible for the cytolytic clearance of virally infected and cancerous cells. They adapt to the nature of the immune response they are partaking in by adopting distinct cell fates through a process of highly coordinated differentiation. These fates are characterized by the activation and suppression of functional programs under the control of transcription factors and epigenetic machinery, which integrate cell extrinsic signals to drive differentiation. Here we elucidate the function of a group of transcription factors in dictating CD8 T cell differentiation in infection. We go on to …

Spink1-Col18a1 Crosstalk Shapes Epigenome And Drives Cancer Stemness In Pancreatic Ductal Adenocarcinoma, Haoyu Tang

Yale Graduate School of Arts and Sciences Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with an increasing incidence and extremely dismal prognosis, due to early metastasis and the limited understanding of the mechanisms driving its progression. In this dissertation, by analyzing bulk transcriptomic profiles from PDAC patients with substantial differences in survival and deconvoluting the results using a single-cell transcriptome dataset of human PDAC, we identified serine protease inhibitor Kazal type 1 (SPINK1) as a crucial modulator of PDAC progression and patient survival. At the patient level, higher SPINK1 expression is correlated with shorter survival, and at the single cell level, SPINK1 expression showed dynamical changes …

Undergraduate Bulletin 2025-2026, Cuny John Jay College

College Bulletins

Covers academic year 2025-2026

Oltjona Muca Honors Portfolio, Oltjona Muca

Honors Capstone Portfolios

Oltjona Muca's honors portfolio captured in May 2025.

13. Mentorship Matters: Documenting The Unseen Impact Of Instructor-Student Relationships, Jeff Spears, Amanda Deliman, Hannah Mae Lewis, Jim Lamuth, Kim Hales

Documenting Teaching Excellence

This chapter explores the critical yet often unrecognized role of documenting instructor mentorship as a core component of teaching excellence in higher education. Mentorship encompasses a range of instructor-to-student interactions, including academic guidance, psychosocial support, research support (graduate and undergraduate), and career exploration for students (DeAngelo, Mason, & Winters, 2016; Thiry & Laursen, 2011). Despite its importance, mentorship is rarely documented comprehensively in teaching documentation portfolios (Ocobock et al., 2022). By systematically capturing the multifaceted impacts of mentorship, instructors enhance their teaching portfolio and contribute to the broader discourse on teaching excellence. This chapter aims to empower instructors to demonstrate …

Targeted Deletion Of Cxcl1 In Mscs Regulates Osteogenesis And Suppresses Bone-Metastatic Prostate Cancer, Catherine S. Johnson, Diane L. Costanzo-Garvey, Julio C. Valencia, Sanjana Rajgopal, Theodore Reed, Emma R. Brannon, Jeremy S. Frieling, Deanna Mosley, Todd A. Wyatt, Elijah F. Edmondson, Kabhilan Mohan, Grinu Mathew, Leah M. Cook

Journal Articles: Environmental, Agricultural & Occupational Health

Bone metastasis continues to be the greatest challenge in treating patients with prostate cancer despite ongoing research. In bone, prostate cancer tumors hijack normal bone remodeling processes to drive cancer progression. However, it is unclear how these interactions drive bone-metastatic prostate cancer growth in the bone environment. To understand the mechanisms associated with bone-metastatic prostate cancer regulation of mesenchymal stem cells (MSC), we previously identified that bone-metastatic prostate cancer induces MSC expression of the pro-inflammatory chemokine CXCL8 and its mouse functional homologue Cxcl1. To date, there has been little to no information about the role of CXCL1/8 in MSC biology …

Research News, Publications, 2025, Volume 2, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period of April 1 - June 30, 2025.

Pediatric Acute Necrotizing Encephalopathy: A Case-Based Review Of Diagnosis And Outcomes, Chance Swanson Bs, Josh Jimenez Bs, Manav Patel Bs, Phillip Alexeev Bs, Kevin Hiatt Md

SPARK Symposium Presentations

Pediatric acute necrotizing encephalopathy (ANEC) is a rare condition characterized by precipitation of a viral illness, bilateral thalamic lesions on CT and MRI, and normal cell counts with increased protein in cerebrospinal fluid [1]. ANEC typically presents with a 6-18 month child that experiences fever, seizures, rapid alteration in level of consciousness, in addition to specific findings in brain imaging such as bilateral thalamic lesions with supra and infra-tentorial lesions of variable dimensions [2]. Although the pathogenesis is not fully understood, the absence of inflammatory cells on post-mortem analysis and the lack of consistent viral detection in CSF suggest that …