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Articles 1 - 30 of 1011
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
The Neuroprotective Effect Of Cdc42 Inhibition In The G93a Mutant Hsod1 Mouse Model Of Als, Andrea Koly
The Neuroprotective Effect Of Cdc42 Inhibition In The G93a Mutant Hsod1 Mouse Model Of Als, Andrea Koly
Undergraduate Theses, Capstones, and Recitals
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by the selective loss of upper and lower motor neurons, leading to muscle weakness, neuromuscular junction (NMJ) degeneration, paralysis, and eventual death due to respiratory failure. Despite extensive research, effective disease-modifying therapies remain limited, underscoring the need to identify novel molecular targets involved in ALS pathogenesis. Dysregulation of Rho family GTPases has been implicated in neurodegeneration, with Rac and Rho exerting opposing effects on neuronal survival; however, the role of the closely related GTPase Cdc42 remains poorly understood in ALS. In this study, the therapeutic potential of inhibiting …
Computational Insights Into Nucleosome Dynamics In Epigenetics Using Molecular Dynamics Simulations, Rutika Patel
Computational Insights Into Nucleosome Dynamics In Epigenetics Using Molecular Dynamics Simulations, Rutika Patel
Dissertations, Theses, and Capstone Projects
Nucleosome core particles (NCP) are the building blocks that form a highly organized and compact chromatin structure. Nucleosomes package DNA in the nucleus of eukaryotic cells. The NCP consists of about 147 base pairs of DNA wrapped around the histone octamer, with 1.65 superhelical turns in a left-handed manner. The histone octamer is composed of two copies of H3, H4, H2A, and H2B. Together with histone H1 and linker DNA, they further assemble into a higher-order chromatin structure. The nucleosome complex is stabilized by electrostatic interactions between positively charged histone residues and the negatively charged DNA backbone. To effectively access …
Developing Antibodies Against Galectin-3 And Galectin-9 To Target Endometriosis, Ashleigh Burger, Noah Farnsworth, Jared J. Reisnouer, Cheyenne Vue
Developing Antibodies Against Galectin-3 And Galectin-9 To Target Endometriosis, Ashleigh Burger, Noah Farnsworth, Jared J. Reisnouer, Cheyenne Vue
2026 Symposium
Endometriosis is a disease characterized by pelvic pain and the formation of endometrial-like tissue on the outside of the uterine lining. This condition affects nearly 10% of women across the globe and confirming whether someone has endometriosis requires visualization in surgery. While the specific causes of this disease remain unclear, the over-expression of the Galectins 3 and 9 in ectopic endometrial tissues suggests a role in the development and maintenance of the condition. Monoclonal antibodies (mAbs) are highly specific proteins with potential as diagnostic or treatment tools. The goal of this study is to generate antibodies against Gal3 and Gal9. …
Novel Biomarker Discovery In Multiple Sclerosis, Manisha Gangasani
Novel Biomarker Discovery In Multiple Sclerosis, Manisha Gangasani
Honors Theses
Multiple Sclerosis (MS) is a chronic neuroinflammatory disorder affecting the brain, spinal cord, and optic nerve. Patients experience cognitive, motor, autonomic, and emotional symptoms that often overlap with other neurological conditions, making early diagnosis challenging. Current diagnostic criteria require evidence of lesions with dissemination in time and space. Racial disparities in MS outcomes are well documented, with Black individuals often exhibiting greater disease severity, higher relapse rates, and increased disability compared to White individuals. These differences likely reflect a combination of genetic, biological, environmental, and healthcare access factors, underscoring the need to improve early diagnosis and reduce inequities in care. …
Developing A Protocol For Non-Cellular Transplantation Of Donor Mitochondria Into Recipient Cells, Andrew Parton
Developing A Protocol For Non-Cellular Transplantation Of Donor Mitochondria Into Recipient Cells, Andrew Parton
Honors Theses
Tumor innervation has emerged as a critical feature of cancer progression, with increased nerve density correlating with enhanced aggressiveness, metastatic dissemination, and poor clinical outcome. However, the functional contribution of neurons to tumor biology remains incompletely defined. We recently identified the intercellular transfer of mitochondria from neurons to cancer cells as a mechanism that promotes tumor progression. We therefore hypothesized that disruption of this transfer could attenuate tumor aggressivity. To directly investigate this process, we developed an approach to isolate mitochondria from donor cells and transplant them into recipient cancer cells independently of canonical cell-cell interactions. Transferred mitochondria were tracked …
Evaluating The Effects Of Akt Knockdown And Everolimus Treatment On Ewing Sarcoma, Arisha Arif, Alfie Barcenez, Nicole Vanegas-Riddick
Evaluating The Effects Of Akt Knockdown And Everolimus Treatment On Ewing Sarcoma, Arisha Arif, Alfie Barcenez, Nicole Vanegas-Riddick
Posters - 2026
The purpose of this study is to use the gene AKT1, due to the interest in AKT1’s role in cancer cell proliferation, and the drug Everolimus, to determine if combined targeted therapy works as a more efficient therapeutic approach. We hypothesize that the knockdown of AKT1 will increase the sensitivity of Ewing sarcoma cells to Everolimus, resulting in reduced proliferation and/or survival compared to drug treatment alone. This would suggest that AKT1 normally protects cells from drug-induced stress. Ewing Sarcoma has been connected to chromosomal translocations and most common in pediatric patients. It is most often treated with chemotherapy and …
Sirna Knockdown Of Rptor Alters Gene Expression In Ewing Sarcoma Cells, Sergio Cipriano, David Leavitt, Michael Oliva, Liam Valdez
Sirna Knockdown Of Rptor Alters Gene Expression In Ewing Sarcoma Cells, Sergio Cipriano, David Leavitt, Michael Oliva, Liam Valdez
Posters - 2026
Ewing sarcoma is a highly aggressive cancer that primarily affects children and young adults. Although treatment options exist, many patients do not respond effectively, showing the need for improved targeted therapies¹. RPTOR is a key in mTORC1 complex which regulates cell growth, proliferation, and survival². LY2874455 is a selective pan-FGFR inhibitor that targets growth factor signaling pathways involved in tumor progression³, and FGFR signaling interacts with pathways such as mTOR, making it a potential target for combination therapies. We hypothesized that silencing RPTOR in Ewing sarcoma cells would disrupt mTOR signaling and alter expression of genes linked to cell survival …
Polθ Activity Modulates Sensitivity To Standard Therapies In Dnmt3a-Deficient Leukemia, Bac Viet Le, Umeshkumar Vekariya, Monika M. Toma, Margaret Nieborowska-Skorska, Marie-Christine Caron, Malgorzata Gozdecka, Zayd Haydar, Martin Walsh, Jayashri Ghosh, Elaine Vaughan-Williams, Paulina Podszywalow-Bartnicka, Anna-Mariya Kukuyan, Sylwia Ziolkowska, Jessica Atkins, Emir Hadzijusufovic, Gurushankar Chandramouly, Reza Nejati, Katarzyna Piwocka, Richard T. Pomerantz, George S. Vassiliou, Brian J.P. Huntly, Peter Valent, Mariusz Wasik, Alfonso Bellacosa, Jean-Yves Masson, Gaorav P. Gupta, Grant A. Challen, Tomasz Skorski
Polθ Activity Modulates Sensitivity To Standard Therapies In Dnmt3a-Deficient Leukemia, Bac Viet Le, Umeshkumar Vekariya, Monika M. Toma, Margaret Nieborowska-Skorska, Marie-Christine Caron, Malgorzata Gozdecka, Zayd Haydar, Martin Walsh, Jayashri Ghosh, Elaine Vaughan-Williams, Paulina Podszywalow-Bartnicka, Anna-Mariya Kukuyan, Sylwia Ziolkowska, Jessica Atkins, Emir Hadzijusufovic, Gurushankar Chandramouly, Reza Nejati, Katarzyna Piwocka, Richard T. Pomerantz, George S. Vassiliou, Brian J.P. Huntly, Peter Valent, Mariusz Wasik, Alfonso Bellacosa, Jean-Yves Masson, Gaorav P. Gupta, Grant A. Challen, Tomasz Skorski
Department of Biochemistry and Molecular Biology Faculty Papers
Myeloid malignancies carrying somatic DNMT3A mutations (DNMT3Amut) are refractory to standard therapy. DNMT3Amut leukemia cells accumulate toxic DNA double-strand breaks (DSBs) and stalled replication forks, rendering them dependent on DNA damage response (DDR). We report here that DNA polymerase theta (Polθ), a key element in DSB repair by end-joining (Polθ-mediated end-joining [TMEJ]) and in fork restarting, promotes survival and proliferation of DNMT3Amut leukemia cells. Polθ is overexpressed in DNMT3Amut leukemia cells due to abrogation of PARP1 PARylation-dependent UBE2O E3 ligase-mediated ubiquitination and proteasomal degradation of Polθ. In addition, PARP1-mediated recruitment of the SMARCAD1-MSH2/MSH3 repressive complex to DSBs is diminished in …
Evaluating Novel Targeted Combination Therapies For Gastrointestinal Cancers, Joseph A. Goode
Evaluating Novel Targeted Combination Therapies For Gastrointestinal Cancers, Joseph A. Goode
Graduate Studies Theses and Dissertations 2026
Gastrointestinal (GI) cancers remain among the leading causes of cancer-related mortality worldwide, with therapeutic resistance continuing to limit the effectiveness of current treatments. Three complementary studies were conducted to identify therapeutic vulnerabilities and evaluate novel combination strategies in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). First, dual inhibition of fibroblast growth factor receptor 4 (FGFR4) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling was investigated in PDAC models. A combination of targeted drug treatments reduced viability, clonogenic survival, migration, and suppressed signaling pathways involved in translational control. This supported a functional interaction between FGFR4 and PI3K-mTOR co-activation in …
Molecular Pathway Dysregulation In Chronic Liver Disease: Metabolic And Mechanotransductive Drivers Of Hepatic Pathophysiology, Samantha Harvat
Molecular Pathway Dysregulation In Chronic Liver Disease: Metabolic And Mechanotransductive Drivers Of Hepatic Pathophysiology, Samantha Harvat
Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research
Metabolic dysfunction–associated steatotic liver disease (MASLD) represents a rapidly growing cause of chronic liver injury, yet the molecular interactions linking metabolic stress, inflammation, fibrosis, and hepatocellular carcinoma (HCC) remain incompletely defined. This thesis integrates transcriptomic analyses across multiple GEO datasets to identify coordinated metabolic, inflammatory, and mechanotransductive pathways that collectively drive disease progression.
Analysis of human liver biopsy datasets (GSE126848 and GSE89632) revealed consistent suppression of glycolysis, β-oxidation, and oxidative phosphorylation across MASLD and MASH samples, accompanied by modest compensatory TCA cycle activation. These alterations reflect impaired metabolic flexibility, mitochondrial stress, and increased ROS susceptibility. Concurrently, cytokine-network enrichment demonstrated activation …
Blood-Based Clinical Markers For Early Dementia Detection: Insights From Ad-Detect-Cohort, Benard Aliwa, Jasmit Shah, Olivera Nesic Taylor,, Samuel Nguku, Juzar Hooker, Dilraj Sokhi, Sylvia Mbugua, Litha Musili, Rachel Maina, Harrison Kaleli, Levi Muyela, Anne Njoki Gitere, Anne Nyambura, Zul Merali, Karen Blackmon, Chinedu Momoh
Blood-Based Clinical Markers For Early Dementia Detection: Insights From Ad-Detect-Cohort, Benard Aliwa, Jasmit Shah, Olivera Nesic Taylor,, Samuel Nguku, Juzar Hooker, Dilraj Sokhi, Sylvia Mbugua, Litha Musili, Rachel Maina, Harrison Kaleli, Levi Muyela, Anne Njoki Gitere, Anne Nyambura, Zul Merali, Karen Blackmon, Chinedu Momoh
Brain and Mind Institute
Background: Over 55 million people worldwide live with dementia, with more than60% residing in low- and middle-income countries. Alzheimer’s disease, the mostcommon form of dementia, accounts for 60–70% of cases. Early and accurate diagnosisremains a global challenge, necessitating novel approaches to mitigate the diseaseburden. Biomarkers hold significant promise in improving diagnostic accuracy andpredicting disease progression. Validated biomarkers for the preclinical stages ofdementia are crucial for advancing diagnosis and therapeutic strategies. We aimedto identify potential clinical markers for early dementia detection and assess theirpredictive accuracy in identifying high-risk individuals.
Method: We analyzed blood samples from dementia cases (n = 30) and …
Mitochondria-Mediated Epigenetic Transfer Between Chondrosarcoma And Wild-Type Cells, Caleb C. J. Wyckoff
Mitochondria-Mediated Epigenetic Transfer Between Chondrosarcoma And Wild-Type Cells, Caleb C. J. Wyckoff
Biomedical Sciences Theses & Dissertations
Glioblastoma (GB), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), cholangiocarcinoma, and chondrosarcoma (CS) cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme exhibits transformation of alpha-ketoglutarate (αKG) into the oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers. Mitochondrial-mediated transfer between cancer cells and recipient cells is a significant event that impacts the physiology of the receiving cell, specifically the epigenetic landscape. Previous experiments indicating increased DNA methylation in mesenchymal stem cells exposed to IDH1 or IDH2 conditioned medium underscore the potential role of D2HG to alter methylation states. Additionally, the presence of …
Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu
Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu
Mako: NSU Undergraduate Student Journal
Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …
Advanced Interactions Of Directed Energy With Retinal Pigment Epithelial Cells And Their Photochemical And Photothermal Responses, Jin B. Ha
Theses & Dissertations
Excess optical radiation can injure the retina through either rapid heat deposition (photothermal damage) or cumulative photo‑oxidative stress (photochemical damage), yet current laser‑safety limits treat these mechanisms as independent. To test that assumption, this dissertation integrated systematic wavelength, duration and temperature‑controlled laser exposures with live/dead fluorescence imaging in a melanin‑loaded hTERT‑RPE1 monolayer model. First, concurrent 447 nm (blue) and 2 µm (infra‑red) beams delivered for 200 s demonstrated a strong thermal–photochemical synergy: each beam alone was sub‑threshold (≤25 % lethality) but together produced 100 % RPE death without exceeding 50 °C, proving that modest heating markedly lowers the photon dose …
In Silico Prediction Of Cytotoxic T-Cell Epitopes From Helicobacter Pylori Virulence Factors Using An Immunoinformatics Approach, Demy Valerie Chacon, Kiana Alika Co, Daphne Noreen Enriquez, Aubrey Love Labarda, Reanne Eden Manongsong, Edward Kevin B. Bragais
In Silico Prediction Of Cytotoxic T-Cell Epitopes From Helicobacter Pylori Virulence Factors Using An Immunoinformatics Approach, Demy Valerie Chacon, Kiana Alika Co, Daphne Noreen Enriquez, Aubrey Love Labarda, Reanne Eden Manongsong, Edward Kevin B. Bragais
Biology Faculty Publications
Background: Helicobacter pylori infects approximately half of the global population, leading to gastric and duodenal ulcers. Despite the availability of antibiotics, challenges such as patient reluctance, high treatment costs, and antibiotic resistance limit their effectiveness, making vaccination a promising alternative. This study used immunoinformatics to identify candidate epitopes for a multiepitope vaccine construct against H. pylori.
Material and methods: The protein variability server was utilized for conservation analysis. The epitopes were screened for antigenicity, allergenicity, toxicity, cross-reactivity, and population coverage. Selected epitopes were docked with their corresponding human leukocyte antigen (HLA) alleles, and thermodynamic quantities were determined. Five virulence …
A Cancer Education Needs Assessment: Informing Middle-Aged Female Patients About The Relationships Between Obesity And Women’S Health Concerns In The Reproductive System, Breast, And Endometrial Health, Batul Mirza
MUSC Theses and Dissertations
Obesity significantly impacts women’s health, particularly among middle-aged women, by increasing the risk of hormone-sensitive cancers such as breast, endometrial, and reproductive system cancers. This study examines the educational needs of this demographic group regarding obesity-related cancer risks and explores effective intervention strategies. Obesity-induced mechanisms – hormonal imbalances, chronic inflammation, and insulin resistance – drive cancer susceptibility, emphasizing the need for targeted health education. The study employs a qualitative design, which includes interviews with subject matter experts (SMEs) and surveys of middle-aged women. The goal is to assess awareness, perceived barriers, and preferred learning methods. Findings suggest that with many …
Why Acromegaly Dies: A Systematic Review, Isam Noori Salman, Safaa Ehssan Atta, Baydaa Ahmed Abed, Noor Ulhuda G. Mohammed
Why Acromegaly Dies: A Systematic Review, Isam Noori Salman, Safaa Ehssan Atta, Baydaa Ahmed Abed, Noor Ulhuda G. Mohammed
Maaen Journal for Medical Sciences
Acromegaly is a rare endocrine clinical syndrome characterized by long-term elevated production of growth hormone (GH) due to a pituitary adenoma tumor. The main problem of acromegaly patients (AC-PTs) is prolonged elevated GH concentration, which leads to increased insulin-like growth factor 1 (IGF-1) production, causing the characteristic tissue and bone overgrowth. The appearance of diabetes in AC-PTs was linked with the high risks of cardiovascular morbidity, indicating that individuals with both conditions face heightened health challenges. Acromegaly typically has a higher cancer incidence rather than the general population. Without early diagnosis and effective treatment, excess GH can have widespread systemic …
Cholestasis And Fluid Flow Are Biomechanic Regulators Of Cholangiocarcinoma Progression, Andrew Oleksijew
Cholestasis And Fluid Flow Are Biomechanic Regulators Of Cholangiocarcinoma Progression, Andrew Oleksijew
Theses & Dissertations
Cholestasis, altered or absent bile flow, is associated with poor survival in patients with cholangiocarcinoma, an aggressive cancer of the biliary epithelium. Changes in bile flow often result in stricture or obstruction. Experimental cholestasis promoted tumor growth and progression. However, studies are needed that directly assess the mechanical interaction between bile flow, or bile shear stress, and cholangiocarcinoma signaling. We hypothesized that cholestasis and absent bile shear stress activated cancer signaling and increased aggressive cellular behaviors such as proliferation and migration. Fluid shear stress approximating bile flow was applied by orbital culture plate method and compared to identical static culture …
Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse
Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse
Dissertations and Theses (Open Access)
Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.
Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …
Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim
Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim
Open Access Theses & Dissertations
In-situ coagulation is a common clinical feature of pancreatic ductal adenocarcinoma (PDAC) that presents a highly thrombotic and crosslinked insoluble fibrin (x-fibrin)-laden tumor stroma (FibTS). However, the specific impact of FibTS on immune cells behavior remains largely unexplored in this poorly infiltrated tumor. We aimed to elucidate how FibTS in PDAC regulates immune cell infiltration, polarization, and crosstalk that favors immunosuppressive microenvironment and tumor growth. We characterized human PDAC tissues by multiplex immunostaining and checked the spatial distribution of immune cells based on the presence of x-fibrin. We investigated how FibTS influences the infiltration of tumor-associated macrophage (TAM) and T-cell …
Jak1 V658f Drives Oncogenic Transformation Via Transcriptional Reprogramming Independent Of Y598 Phosphorylation And Canonical Jak-Stat Signaling, Omar Javier Rodriguez Moncivais
Jak1 V658f Drives Oncogenic Transformation Via Transcriptional Reprogramming Independent Of Y598 Phosphorylation And Canonical Jak-Stat Signaling, Omar Javier Rodriguez Moncivais
Open Access Theses & Dissertations
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and complex malignancy that accounts for 15% of pediatric acute lymphoblastic leukemia (ALL) cases in the United States. Tyrosine kinases control critical cellular processes, including the development, survival, and activation of T cells, and are established drivers of leukemia.Tyrosine kinases involved in hematological disorders include receptor tyrosine kinases and non-receptor tyrosine kinases family members such as SRC, ABL, FAK, and Janus kinases (JAKs). This study primarily focused on JAK1 gain-of-function (GoF) mutations. These mutations are recognized as hyperactivating mutations, maintaining kinase activity of JAKs on and essentially keeping downstream signaling effectors, like …
Molecular Subtyping Of Hypertensive Disorders Of Pregnancy, Michal Elovitz, Elaine Gee, Nathaniel Delaney-Busch, Alison Moe, Mitsu Reddy, Arkady Khodursky, Johnny La, Ilma Abbas, Kay Mekaru, Hunter Collins, Farooq Siddiqui, Rory Nolan, Rupsa Boelig, Daniel Kiefer, Pamela Simmons, George Saade, Antonio Saad, Ebony Carter, Thomas Mcelrath, Stephen Quake, Mark Depristo, Carrie Haverty, Manfred Lee, Eugeni Namsaraev, Vincenzo Berghella, Ai-Ris Collier, Antonia Frolova, Esther Park-Hwang, Luis Pacheco, Elizabeth Sutton, Maneesh Jain, Kara Rood, William A Grobman, Joseph Biggio, Cynthia Gyamfi-Bannerman, Arun Jeyabalan, Morten Rasmussen
Molecular Subtyping Of Hypertensive Disorders Of Pregnancy, Michal Elovitz, Elaine Gee, Nathaniel Delaney-Busch, Alison Moe, Mitsu Reddy, Arkady Khodursky, Johnny La, Ilma Abbas, Kay Mekaru, Hunter Collins, Farooq Siddiqui, Rory Nolan, Rupsa Boelig, Daniel Kiefer, Pamela Simmons, George Saade, Antonio Saad, Ebony Carter, Thomas Mcelrath, Stephen Quake, Mark Depristo, Carrie Haverty, Manfred Lee, Eugeni Namsaraev, Vincenzo Berghella, Ai-Ris Collier, Antonia Frolova, Esther Park-Hwang, Luis Pacheco, Elizabeth Sutton, Maneesh Jain, Kara Rood, William A Grobman, Joseph Biggio, Cynthia Gyamfi-Bannerman, Arun Jeyabalan, Morten Rasmussen
Department of Obstetrics and Gynecology Faculty Papers
Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. …
Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes
Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes
Open Access Theses & Dissertations
C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …
Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr.
Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr.
Markey Cancer Center Faculty Publications
Steroid receptors are ligand-induced transcription factors that have broad functions among all living animal species, ranging from control of sex differences, body weight, stress responses, and many others. Their binding to coregulator proteins is regulated by corepressors and coactivators that interchange upon stimulation with a ligand. Coregulator proteins are an imperative and understudied aspect of steroid receptor signaling. Here, we discuss steroid receptor basics from protein domain structures that allow them to interact with coregulators and other proteins, their essential functions as transcription factors, and other elemental protein–protein interactions. We deliberate about the mechanisms that coregulators control in steroid receptor …
Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.
Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.
Markey Cancer Center Faculty Publications
The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSRe5- 8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSRe5- 8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble …
Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka
Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka
Markey Cancer Center Faculty Publications
Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting …
Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley
Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley
Markey Cancer Center Faculty Publications
Background/Objectives: Pathway annotations of non-macromolecular (relatively small) biomolecules facilitate biological and biomedical interpretation of metabolomics datasets. However, low pathway annotation levels of detected biomolecules hinder this type of interpretation. Thus, predicting the pathway involvement of detected but unannotated biomolecules has a high potential to improve metabolomics data analysis and omics integration. Past publications have only made use of the Kyoto Encyclopedia of Genes and Genomes-derived datasets to develop machine learning models to predict pathway involvement. However, to our knowledge, the Reactome knowledgebase has not been utilized to develop these types of predictive models.
Methods: We created a dataset ready for …
Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li
Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li
Markey Cancer Center Faculty Publications
Introduction: Septic patients have low levels of high-density lipoproteins (HDLs), which is a risk factor. Replenishing HDLs with synthetic HDLs (sHDLs) has shown promise as a therapy for sepsis. This study aimed to develop a computational approach to design and test new types of sHDLs for sepsis treatment. Methods: We used a three-step computational approach to design sHDL nanoparticles based on the structure of HDLs and their binding to endotoxins. We tested the efficacy of these sHDLs in two sepsis mouse models—cecal ligation and puncture (CLP)-induced and P. aeruginosa-induced sepsis models—and assessed their impact on inflammatory signaling in cells. Results: …
Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu
Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu
Markey Cancer Center Faculty Publications
Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …
Use Of Synthetic Water-Soluble Kcc2 To Modulate Chloride Homeostasis In Cultured Dopamine-Neuron-Like Cells, Mason Terry, Andrew Payne, Dario Mizrachi
Use Of Synthetic Water-Soluble Kcc2 To Modulate Chloride Homeostasis In Cultured Dopamine-Neuron-Like Cells, Mason Terry, Andrew Payne, Dario Mizrachi
Annual Research Symposium
No abstract provided.