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Investigating The Escape Mechanism Of Sre Bearing Mrna Transcripts During Viral Host Shutoff, Daniel Macveigh-Fierro Mar 2024

Investigating The Escape Mechanism Of Sre Bearing Mrna Transcripts During Viral Host Shutoff, Daniel Macveigh-Fierro

Doctoral Dissertations

During viral infection, the virus and host clash for control over gene expression in an evolutionarily arms race that has raged for thousands of years. During lytic replication, Kaposi’s sarcoma associated herpesvirus (KSHV) triggers a massive RNA decay event known as host shut off. This causes over 70% of all RNA to be degraded suppressing the host antiviral response while freeing resources for viral replication. Our lab focuses on a subset of transcripts that escape from this viral degradation event using a cis acting 3’ UTR element known as a “SOX resistant element” or SRE. Although we have identified a …


Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff Nov 2023

Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff

Doctoral Dissertations

The endoplasmic reticulum (ER) is a large, multifunctional organelle that acts as the entrance into the secretory pathway, which accounts for the folding and maturation of approximately one third of the human proteome. It is the largest organelle in most cell types and is comprised of a single lumen and a contiguous membrane. The ER is responsible for a multitude of roles including protein translocation, folding, maturation, quality control, and glycosylation to name a few. These processes are buoyed by a large collection of chaperones and cochaperones, the largest subfamily of which is characterized by the presence of tetratricopeptide repeat …


Caulobacter Clpxp Adaptor Popa’S Domain Interactions In The Adaptor Hierarchy Of Ctra Degradation, Thomas P. Scudder Nov 2023

Caulobacter Clpxp Adaptor Popa’S Domain Interactions In The Adaptor Hierarchy Of Ctra Degradation, Thomas P. Scudder

Masters Theses

The degradation and recycling of protein is a process essential for the maintenance and regulation of cellular function. More specifically, in Caulobacter crescentus, the ClpXP protease is responsible for driving progression through the cell cycle and protein quality control. This protease utilizes three known adaptors to selectively degrade proteins that initiate different stages of development. This thesis will elaborate on the specific binding interface on one of these adaptors, PopA, with another, RcdA, and focus in on specific residues on PopA and investigate their roles in adaptor binding and delivery of CtrA, the master regulator of Caulobacter. Finally, I …


Surface Engineering And Microfabrication Of Pdms-Based Devices For Women’S Health Applications, Jamar Hawkins Apr 2023

Surface Engineering And Microfabrication Of Pdms-Based Devices For Women’S Health Applications, Jamar Hawkins

Doctoral Dissertations

Poly(dimethylsiloxane) (PDMS) is a widely used polymer in biomedical and microfluidics research due to its optical transparency, castability, gas permeability, and relative biocompatibility. However, while the favorable intrinsic properties of the polymer are typically suitable for preventing experimental artifacts, the true advantage of these devices often comes from their customized patterning and design, which can be tailored to specific applications. Critical parameters in biomedical applications such as chemical concentration profiles, fluid streamlines, substrate topography, and mechanical stiffness can all be fine-tuned simply by selecting the appropriate dimensions and arrangement of PDMS microstructures. To address challenges in expanding the application of …


Human Milk: From Covid-19 Immunity To Breast Cancer Risk Assessment, Vignesh Narayanaswamy Feb 2023

Human Milk: From Covid-19 Immunity To Breast Cancer Risk Assessment, Vignesh Narayanaswamy

Doctoral Dissertations

Breastmilk is a complex biological fluid containing macromolecules including lipids, oligosaccharides, proteins as well as several types of cells. Several studies have reported in detail of these components. My focus is studying the protein component of breastmilk, specifically antibodies, cytokines, and other secreted factors in the setting of different pathogenicity in women. Studies have demonstrated that the levels of numerous cytokines as well as the levels of pathogen-specific antibodies are altered in milk upon either maternal or infant infections. Additionally, there are reports that the levels of certain inflammatory markers are altered in milk among women with breast cancer or …


Exposure To Endocrine Disrupting Chemicals And The Effects On Inflammation And Mammary Tumor Progression, Stephanie Morin Oct 2022

Exposure To Endocrine Disrupting Chemicals And The Effects On Inflammation And Mammary Tumor Progression, Stephanie Morin

Doctoral Dissertations

The vast majority of breast cancers, ~70%, are not directly related to an inherited genetic mutation. Environmental factors play a dominant role in the etiology of most breast cancers. There is a subset of chemicals that are able to affect the homeostasis of hormones called endocrine disrupting chemicals (EDCs). Many of these chemicals are pervasive and persistent making the chances for lifetime exposure more prevalent. While many of these chemicals have been deemed safe, a subset of them have come under review to reassess their safety. As estrogen is critical for breast development and can act as a mitogen in …


Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario Oct 2022

Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario

Doctoral Dissertations

Macrophages are white blood cells of the innate immune system that have the ability to change phenotypically depending on the stimuli present in their surroundings through a process commonly referred to as polarization. Macrophage phenotypes broadly range from pro-inflammatory, anti-tumor (M1) to immune-suppressing (M2). Of particular interest to this work, breast cancer progression and metastasis rely on the presence of M2-like tumor-associated macrophages (TAMs). While many studies have shown the involvement of macrophages in tumor progression and metastasis, there remains a need to further explore these interactions and the polarization process, including tracking of macrophage subtypes. Toward this end, I …


Principles Of Aaa+ Proteases, Samar Mahmoud Oct 2022

Principles Of Aaa+ Proteases, Samar Mahmoud

Doctoral Dissertations

ATPases associated with diverse cellular activities (AAA+) proteases in bacteria help maintain protein homeostasis by degrading misfolded and regulatory proteins. While a handful of protein targets for these proteases have been identified in Caulobacter crescentus and other organisms, more research is needed to elucidate mechanisms that govern substrate specificity. In the second chapter of this thesis, I will elaborate on how AAA+ substrate specificity is less rigid than previous work has suggested and how limiting ATP or mutations can alter substrate preferences of the ClpXP protease. In the third chapter, I will highlight our efforts to use a quantitative proteomics …


Characterizing The Multifaceted Roles Of The Proteasomal Deubiquitinase Uch37 In Proteostasis, Heather A. Bisbee Oct 2022

Characterizing The Multifaceted Roles Of The Proteasomal Deubiquitinase Uch37 In Proteostasis, Heather A. Bisbee

Doctoral Dissertations

Cellular protein pools are maintained through the biological processes of synthesis, degradation and quality control. As the dysregulation of these processes has been implicated in diseases such as neurodegeneration and cancer, understanding their functions is critical for drug development. Modification of proteins with ubiquitin may direct them to the proteasome, a large cellular protease complex, for degradation. Yet, the proteasome contains three deubiquitinating enzymes (DUBs) which remove ubiquitin from proteins, potentially altering their fate. As each DUB recognizes specific ubiquitin linkages and architectures, their activity may regulate how the proteasome handles substrates in dynamic cellular contexts. In this work, we …


Developmental Exposures To Pfas Mixtures Impair Elongation Of The Exocrine Pancreas In Zebrafish (Danio Rerio), Emily M. Formato Sep 2022

Developmental Exposures To Pfas Mixtures Impair Elongation Of The Exocrine Pancreas In Zebrafish (Danio Rerio), Emily M. Formato

Masters Theses

Poly- and perfluoroalkyl substances (PFAS) are a class of bioaccumulative toxicants used in numerous industrial and commercial products. Perfluorooctanesulfonic acid (PFOS) alters pancreatic organogenesis during development, and perfluorohexanesulfonic acid (PFHxS) has been suggested as a replacement for PFOS due to its shorter carbon chain, but they are often found together in surfactants, such as legacy aqueous film-forming foam. This study investigates how developmental exposures to a PFAS mixture (PFHxS + PFOS) impact the developing exocrine pancreas. Zebrafish embryos (Tg(ptf1a:GFP)) were exposed to 0.01% DMSO, or 8, 16, 32 μM PFHxS alone, 16 μM PFOS alone, and 8, 16, and 32 …


Extracellular Matrix Stiffness As A Cue To Shape Phenotypic Evolution Of Triple Negative Breast Cancer, Ning-Hsuan Tseng Jun 2022

Extracellular Matrix Stiffness As A Cue To Shape Phenotypic Evolution Of Triple Negative Breast Cancer, Ning-Hsuan Tseng

Doctoral Dissertations

Accumulation of epigenetic and genetic changes results in oncogenic transformation of epithelial cells. During breast cancer metastasis, while the extracellular matrix (ECM) becomes stiffer, breast cancer cells transmit mechanical forces into intracellular tension and activate signaling pathways influencing growth, migration, and metastasis. Once cancer cells detach from the primary tumor, they intravasate into the vasculature, survive in the circulation, extravasate and adapt to a new microenvironment of a secondary site. Throughout the process, only a very small population of cancer cells survive, and they are likely to reside at the metastatic sites for several years. The most frequent metastatic sites …


Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don Jun 2022

Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don

Doctoral Dissertations

Circadian rhythms are 24–hour activity cycles that exist for all organisms, from yeast and bacteria to mammals. Epidemiological data has shown that disruptions to circadian rhythms are associated with various diseases, including cancers. Circadian rhythms are regulated at the cellular level by a "molecular clock,” whose oscillations in protein transcription and translation control a range of downstream pathways. However, the connections between altered rhythms and diseases at the molecular level is unclear. Therefore, in this project, I tracked circadian rhythms in a high-resolution manner and thoroughly analyzed them to more completely reflect circadian behaviors and clock functioning at the molecular …


Utilizing Fluorescence Microscopy To Characterize The Subcellular Distribution Of The Novel Protein Acheron, Varun Sheel Oct 2021

Utilizing Fluorescence Microscopy To Characterize The Subcellular Distribution Of The Novel Protein Acheron, Varun Sheel

Masters Theses

All cells carry the genetic machinery required to commit cell suicide; a process known as programmed cell death (PCD). While the ability to initiate PCD serves a number of useful purposes during development and homeostasis, misregulation of PCD is the underlying basis of most human diseases, including cancer, autoimmunity disorders and neurodegeneration. Using the tobacco hawkmoth Manduca sexta as a model organism, the Schwartz lab at UMass has demonstrated that PCD requires de novo gene expression and has cloned many death-associated genes. One of these genes encodes a novel protein that was named Acheron after one of the rivers of …


Activation Of Nrf2 At Critical Windows Of Development Alters Protein S-Glutathionylation In The Zebrafish Embryo (Danio Rerio), Emily G. Severance Oct 2021

Activation Of Nrf2 At Critical Windows Of Development Alters Protein S-Glutathionylation In The Zebrafish Embryo (Danio Rerio), Emily G. Severance

Masters Theses

Perturbation of cellular redox homeostasis to a more oxidized state has been linked to adverse human health effects such as diabetes and cancer. However, the impact of altering the regulation of redox homeostasis during development is not fully understood. Specifically, this project investigates the role of the Nrf2 antioxidant response pathway and its effect on glutathione (GSH; cellular redox buffer) at critical windows of development. To explore this, we used zebrafish embryos (Danio rerio) as a model due to the function of GSH and the Nrf2 being conserved among vertebrates. We exposed zebrafish embryos to three Nrf2 activators: two antioxidant …


Investigating The Developmental Impacts Of 3,3’-Dichlorobiphenyl (Pcb-11) In Zebrafish (Danio Rerio), Monika A. Roy Oct 2021

Investigating The Developmental Impacts Of 3,3’-Dichlorobiphenyl (Pcb-11) In Zebrafish (Danio Rerio), Monika A. Roy

Doctoral Dissertations

The environmental pollutant 3,3’-dichlorobiphenyl (PCB-11) is a lower-chlorinated polychlorinated biphenyl (PCB) congener present in air and water samples. Both PCB-11 and its metabolite, 4-PCB-11-Sulfate, are detected in humans, including in pregnant women. The work conducted for this dissertation takes a developmental toxicology approach and uses zebrafish (Danio rerio) to investigate PCB-11’s potential impacts to the liver and pancreas. Chapter 1 introduces PCBs and the current knowledge gaps. Chapter 2 investigates PCB-11 interactions in short-term 4-day exposures with the Aryl hydrocarbon receptor (Ahr) pathway in both 0-20 mM individual and mixture exposures with other Ahr agonists. In Chapter 3, …


Defining The Role Of Rbbp4 In Oocyte Maturation And Preimplantation Development Using Trim-Away, Holly L. Barletta Jul 2021

Defining The Role Of Rbbp4 In Oocyte Maturation And Preimplantation Development Using Trim-Away, Holly L. Barletta

Masters Theses

Retinoblastoma-binding protein 4 (RBBP4) is a subunit of chromatin remodeling factor 1 (CAF-1) and is essential for mammalian oocyte maturation, embryo survival, and embryo implantation. RBBP4 also localizes to the chromatin and is a ubiquitously expressed nuclear protein. Previous methods used to study this protein include short interfacing RNAs (siRNAs) and CRISPR/Cas9. These techniques have limitations such as determining an indirect depletion of proteins, may trigger compensatory mechanisms, and may not be useful in non-dividing primary cells. A new, acute, and rapid endogenous protein depletion technique called Trim-Away, can overcome these limitations. Trim-Away is also widely applicable since it can …


Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng Jun 2021

Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng

Doctoral Dissertations

Cell surface harbors rich information regarding the status of cell health. Being able to monitor and detect its changes in response to stimuli will provide crucial information in drug discovery, disease diagnosis, and human health. Despite the efforts and breakthroughs made possible through the specific sensing approach, there are significant challenges in extracting the information on the cell surface in a quantitative and reliable way. To address this challenge, I took the approach of array-based, hypothesis-free sensing in which the engineered sensors selectively interact with target analytes, producing a distinct pattern of response that enables analyte identification. This signature-based pattern …


Investigative Mechanisms To Exploit Caspase-Induced Apoptosis Using Polymeric Nanogels, Francesca Edith Anson May 2021

Investigative Mechanisms To Exploit Caspase-Induced Apoptosis Using Polymeric Nanogels, Francesca Edith Anson

Doctoral Dissertations

Cysteine aspartate proteases (caspases) act as the molecular scissors of cell death, disintegrating diverse cellular components necessary for survival and growth via proteolysis. Caspases are tightly regulated through a myriad of mechanisms including proteolytic processing, structural changes, post-translational modifications and metal binding. Correspondingly, cancers have evolved numerous resistance and desensitization mechanisms upstream or within the caspase pathway to avoid death signals. These mechanisms are extremely diverse and are not fully understood however, the field overwhelming suggests caspase activity and caspase inhibition antagonism to be critical for efficacious cancer therapies. Accordingly, exploiting the role of caspases in apoptosis has become an …


Substrate Selection In Endoplasmic Reticulum Protein Quality Control, Ben Adams Apr 2021

Substrate Selection In Endoplasmic Reticulum Protein Quality Control, Ben Adams

Doctoral Dissertations

Protein folding and maturation is a complex and error-prone process. Errors in this process may lead to deleterious effects ranging from non-functional single proteins to large-scale protein aggregation leading to cell death. It is essential for cellular function that protein misfolding does not occur unchecked, and therefore numerous chaperone systems exist within the cell. For the thousands of proteins which traffic through the secretory pathway, the primary site of folding and maturation is the endoplasmic reticulum (ER). Multiple chaperone pathways within the ER, generally termed ER protein quality control, must support the proper maturation process of these thousands of substrates. …


Investigating Optimal Chemotherapy Options For Osteosarcoma Patients Through A Mathematical Model, Trang M. Le, Sumeyye Su, Leili Shahriyari Jan 2021

Investigating Optimal Chemotherapy Options For Osteosarcoma Patients Through A Mathematical Model, Trang M. Le, Sumeyye Su, Leili Shahriyari

Mathematics and Statistics Department Faculty Publication Series

Since all tumors are unique, they may respond differently to the same treatments. Therefore, it is necessary to study their characteristics individually to find their best treatment options. We built a mathematical model for the interactions between the most common chemotherapy drugs and the osteosarcoma microenvironments of three clusters of tumors with unique immune profiles. We then investigated the effects of chemotherapy with different treatment regimens and various treatment start times on the behaviors of immune and cancer cells in each cluster. Saliently, we suggest the optimal drug dosages for the tumors in each cluster. The results show that abundances …


Exploration Of The Association Between Muscle Volume And Bone Geometry Reveals Surprising Relationship At The Genetic Level, Prakrit Subba Dec 2020

Exploration Of The Association Between Muscle Volume And Bone Geometry Reveals Surprising Relationship At The Genetic Level, Prakrit Subba

Masters Theses

The evolution of jaws in cichlid fishes of the East African Great Lakes is a textbook example of adaptive radiation in vertebrates. Karl Liem postulated that this adaptive radiation has been possible due to the functional decoupling of two cichlid functional units – the pharyngeal jaw (PJ) and the oral jaw (OJ). This functional decoupling of the jaws has enabled the OJ to be relieved of its dual role of prey capturing and processing and has allowed the PJ to take on the role of prey processing. As a result, African cichlids have adapted the morphology of their functional units …


Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta Dec 2020

Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta

Doctoral Dissertations

Biologic drugs have gained enormous research attention in recent years as reflected by the development of multiple candidates to the clinical pipelines and an increased percentage of FDA approval. This is reasoned by the fact that biologics have been proven to deliver more predictive and promising benefits for many hard-to-cure diseases by ‘drugging the undruggable’ targets. However, the challenges associated with biologic drug development are multi-fold, viz, poor encapsulation efficacy, systemic instability, low cellular internalization and endosomal escape capability. Thus, it is essential to develop new molecular strategies that can not only address the associated drug delivery challenges, but also …


Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma Dec 2020

Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma

Doctoral Dissertations

The mucosal barrier in the intestine is vital to maintain selective absorption of nutrients while protecting internal tissues and maintaining symbiotic relationship with luminal microbiota. This bio-barrier consists of a cellular epithelial barrier and an acellular mucus barrier. Secreted mucus regulates barrier function via in situ biochemical and biophysical interaction with luminal content that continually evolves during digestion and absorption. Increasing evidence suggests that a mucus barrier is indispensable to maintain homeostasis in the gastrointestinal tract. However, the importance of mucus barrier is largely underrated for in vitro mucosal tissue modeling. The major gap is the lack of experimental material …


Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois Dec 2020

Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois

Doctoral Dissertations

Cancer is a significant global health concern; and traditional therapies, including chemotherapeutics, are often simultaneously toxic yet ineffective. There is a critical need to develop targeted cancer therapeutics which specifically inhibit molecules or molecular pathways essential for tumor growth and maintenance. Furthermore, a targeted therapy is only effective when a patient's tumor expresses the molecular target; therefore, companion diagnostics, including molecular imaging agents, are a necessary counterpart of targeted therapies. Mesothelin (MSLN) is a cell surface protein overexpressed in numerous cancers, including triple-negative breast, pancreatic, ovarian, liver, and lung, with limited expression in normal tissues. Aberrant MSLN expression promotes tumor …


Hedgehog Signaling (Hh/Gli) Regulates Neurogenesis In The Zebrafish Hypothalamus, Ira Male Jul 2020

Hedgehog Signaling (Hh/Gli) Regulates Neurogenesis In The Zebrafish Hypothalamus, Ira Male

Doctoral Dissertations

The hypothalamus is the central regulator of a diverse homeostatic processes that are essential for the survival of the animal. Recently, the hypothalamus has been shown to be a neurogenic zone in many animal species including mice, zebrafish, sheep and potentially even humans with hypothalamic neurogenesis implicated in energy metabolism, stress, anxiety and reproduction. However, the identification of the cellular components and the signaling mechanisms regulating hypothalamic neurogenesis are only beginning to be elucidated. My dissertation research elucidates the role of Hh signaling in regulating hypothalamic neurogenesis throughout life. The first chapter of the dissertation offers a survey into the …


Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter Jul 2020

Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter

Doctoral Dissertations

Metastasis is the leading cause of cancer related deaths, yet it remains the most poorly understood aspect of tumor biology. This can be attributed to the lack of relevant experimental models that can recapitulate the complex and lengthy progression of metastatic relapse observed in patients. Mouse models have been widely used to study cancer, however they are critically limited to study metastasis. Most models generate aggressive metastases in the lung without the use of unique cell lines or specialized injection techniques. This limits the ability to study disseminated tumor cells (DTCs) in other relevant metastasis prone tissues. Prolonged observation of …


Redox Signaling In The Zebrafish Embryo And Implications For Endocrine Pancreas Morphogenesis, Archit Rastogi Jul 2020

Redox Signaling In The Zebrafish Embryo And Implications For Endocrine Pancreas Morphogenesis, Archit Rastogi

Doctoral Dissertations

The glutathione (GSH) system evolved to combat oxygen toxicity in nearly all living organisms, and serves as the predominant cellular redox buffer in vertebrates. This dissertation explores the roles of GSH during embryogenesis using the zebrafish (Danio rerio). The first agnostic in vivo characterization of GSH utilization in the embryo revealed strict spatiotemporal GSH profiles in developing organ systems. Interruption of these GSH profiles by exogenous xenobiotics led to organ specific adverse developmental outcomes; pancreatic β-cells were found to be especially susceptible and developed atypical morphologies following redox active xenobiotic exposures. Pancreatic β-cells lacked expression of Nrf2a (Nuclear …


Involvement Of Calcium-Dependent Protein Kinases And Phosphatases In Sperm Capacitation-Associated Events, Bidur Paudel Jul 2020

Involvement Of Calcium-Dependent Protein Kinases And Phosphatases In Sperm Capacitation-Associated Events, Bidur Paudel

Doctoral Dissertations

ABSTRACT To acquire fertilizing ability, mammalian sperm undergo a series of biochemical and physiological changes collectively known as capacitation1,2. At the molecular level, capacitation is associated with a fast bicarbonate (HCO3-)-dependent activation of a unique type of soluble adenyl cyclase (sAC) and a consequent increase in cyclic AMP (cAMP) levels and PKA activation3. Activation of a cAMP/PKA pathway results in the phosphorylation of PKA substrates, which in turn initiates activation of several signaling cascades ultimately leading to an increase in phosphorylation on tyrosine residues (P-Tyr) of sperm axonemal proteins4,5. Increase in …


Cation Channels, Ca2+ Homeostasis, And Fertility In The Mouse, Goli Ardestani May 2020

Cation Channels, Ca2+ Homeostasis, And Fertility In The Mouse, Goli Ardestani

Doctoral Dissertations

In mammals, fully grown immature oocytes, also known as germinal vesicle (GV), are arrested at prophase of meiosis I. Upon increase of the luteinizing hormone (LH), GV oocytes resume meiosis and reach the metaphase II (MII) stage of the second meiosis, a process known as oocyte maturation. These mature oocytes, henceforth referred to as eggs, are ovulated arrested at the MII stage, from which they are released at the time of fertilization. As in many other cells, Ca2+ homeostasis plays a pivotal role in oocytes during maturation and following fertilization, and it is therefore carefully regulated in these cells. …


Inter-Individual Variation In Response To Estrogen And Implications For Breast Cancer Risk, Amye L. Black May 2020

Inter-Individual Variation In Response To Estrogen And Implications For Breast Cancer Risk, Amye L. Black

Doctoral Dissertations

Breast cancer is the second leading cause of cancer related death among women and the most prevalent cancer type in women worldwide. Many risk factors for breast cancer are related to estrogen exposure and all involve prolonged or high levels of estrogen exposure. However, estrogen exposure during early pregnancy reduces breast cancer risk by up to 50%. Estrogen’s paradoxical role in both contributing to and reducing breast cancer risk is still not understood. We hypothesized that a subset of women may be more sensitive to estrogen exposure, and the following experiments were designed to test this hypothesis and determine if …