Molecular Biology Commons^™

Release Of Bound Steroid From The Androgen And Estrogen Receptors Is Induced By Ddt And Its Analogs, Matthew D. Rosales, Tahyra Soto, Jacqueline I. Goodship, Ahyssa R. Cruz, Isaac A. Rodriguez, Ventura Cuba Flores, Amanda Chavez, Monica P. Solis, Esmeralda Lopez, Frank B. Dean, Evangelia Kotsikorou

School of Integrative Biological & Chemical Sciences Faculty Publications

The pesticide p,p'-DDT (DDT) and its analogs (p,p'-DDD, o,p'-DDD, and p,p'-DDE) inhibit the binding of dihydrotestosterone (DHT) to the androgen receptor (AR) and estradiol (E2) to the estrogen receptor (ERα) ligand-binding domains (LBDs), as previously reported. In this study, we introduce assays to measure the release of receptor-bound steroids. These compounds induced the release of DHT from the AR LBD and E2 from the ERα LBD. These findings suggest that DDT and its analogs may interact with a surface site on the LBD, thereby allosterically disrupting steroid binding. One potential site is binding function 3 (BF3). To explore this possibility, …

The Β2Αb Loop Determines Nad(P) Cofactor Specificity And Kinetics In Trypanosomal D-3-Hydroxybutyrate Dehydrogenases, Hideharu Hashimoto, Ian H. Mawn, William Escobar-Arrillaga, Linh Nguyen, Laura A. Madigan, Gina Antuono, Tatiana Rossy, Jorna Sojati, Anna Mienko, Erik W. Debler, Jennifer B. Palenchar

Department of Biochemistry and Molecular Biology Faculty Papers

Bacterial d-3-hydroxybutyrate dehydrogenases (HBDHs) catalyze the conversion between d-3-hydroxybutyrate and acetoacetate with NAD as the cofactor but not with NAD 2'-phosphate (NADP). However, HBDHs of the early-branched eukaryotic genus Trypanosoma utilize both NAD and NADP (T. brucei) or exclusively NADP (T. cruzi). Here we reveal that NADP specificity of T. cruzi HBDH arises from stabilization of the flexible β2αB loop by the 2'-phosphate interaction. Stabilization of this loop by a nearby C64Y mutation enables T. cruzi HBDH to use NAD in addition to NADP; thus, the Cys/Tyr residue is critical for determining cofactor specificity in trypanosomal HBDHs, suggesting that most …

Molecular And Structural Basis For Replication Initiation And Strand Separation By Human Mitochondrial Dna Polymerase Γ, Viktoriia Sokolova, Gina Buchel, S. Strock, Ashok R. Nayak, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

Defects in human mitochondrial DNA (mtDNA) replication can lead to somatic mutations associated with a range of devastating mitochondrial diseases. However, the molecular mechanisms governing the earliest steps of mtDNA replication and their fidelity remain poorly understood. Here, we found that DNA polymerase gamma (Polγ) forms stable complexes with RNA-DNA primer-template substrates, exhibiting greater stability and lower misincorporation than on DNA-primed substrates. Structural analysis revealed that Polγ interacts with the 2'-OH groups of ribose within the first four nucleotides of the primer, explaining the stability of complexes that utilize RNA primers. Although Polγ requires TWINKLE to extend RNA primers, its …

Cultivating Collaboration In Biomolviz: Key Attributes For Building A Stem Educator Community Of Practice, Pamela S. Mertz, Charmita Burch, Roderico Acevedo, Josh T. Beckham, Didem Vardar-Ulu, Kristin M. Fox, Lauren A. Genova, Rachel M. Mitton-Fry, Swati Agrawal, Daniel R. Dries, Kristen Procko

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

BioMolViz is an educational community of practice (CoP) focused on creating resources to improve biomolecular visual literacy instruction and assessment. The community of life science instructors developed in three phases, beginning with a small Core Team that emerged from a conference session and established the domain of interest for the CoP. In-person workshops, supported by short-term funding, drove the initial expansion of the community and the development of shared activities in Phase 2. This CoP was sustained through intentional choices about how members interact, collaborate, and share work. As the community matured in Phase 3, it was supported by longer-term …

Characterization Of Mettl3/14-Mediated M6a Modification In Human Transcriptome Using Nanopore Direct Rna Sequencing, Emily Kurtyan, Andrew J. Stein, Kelly J. Abdalla, Zhangerjiao Yuan, Miten Jain, Fadia Ibrahim

Department of Biochemistry and Molecular Biology Faculty Papers

Post-transcriptional RNA modifications modulate diverse aspects of RNA metabolism. N6-methyladenosine (m6A), one of the most abundant internal RNA modifications, is deposited by the core methyltransferase complex, METTL3 and METTL14. Oxford Nanopore Technologies (ONT) platform permits direct, single RNA molecule sequencing while preserving native modifications. However, without rigorous benchmarking, the accuracy and reproducibility of modification detection remain uncertain. Here, we leveraged ONT to comprehensively profile bona fide m6A modifications in cellular RNAs at single-nucleotide resolution by integrating two direct RNA sequencing chemistries (RNA002 and RNA004) with the m6Anet and Dorado modification-detection models. We independently depleted METTL3 and METTL14 in human cells …

Summer Research Internships In Agricultural Biotechnology For Off-Campus Undergraduate Students, Aaron J. Thomas

Funded Research Records

No abstract provided.

Investigation Into Molecular Bases Of Pregnancy-Associated Malaria, Nicole Pozo

Biochemistry and Molecular Biology

Plasmodium falciparum causes the most severe and deadly form of malaria and remains a major global health problem, especially in sub-Saharan Africa (Milner, 2018). The parasite infects and multiplies inside red blood cells, leading to fever, anemia, organ damage, and death if untreated (Milner, 2018; Song et al., 2022). It is especially dangerous because it avoids the immune system by changing surface proteins called Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which are encoded by more than 60 var genes. By switching between these genes, the parasite hides from immune detection and creates repeated waves of infection (Deitsch & Dzikowski, …

Rna G-Quadruplexes Function As A Tunable Switch Of Fus Phase Separation, Jenny L. Carey, Miyuki Hayashi, Emily A. Welebob, Laura R. Ganser, Huan Wang, Kerry Buckhaults, Jacquelyn A. Depierro, Zheng Shi, James Shorter, Sua Myong, Aaron R. Haeusler, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Fused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) to support essential cellular functions, but aberrant phase transitions promote toxic aggregation in neurodegenerative disease. Short RNA oligonucleotides can reverse this behavior, yet the structural determinants that govern RNA activity remain poorly defined. Here, we identify RNA G-quadruplexes (rG4s) as tunable structural motifs that potently modulate FUS LLPS. rG4 activity depends on its concentration and is modulated by rG4 length and stability: increasing repeat number switches rG4s from inhibitor to nucleator of FUS assembly, whereas chemical modifications that stabilize rG4 enhance inhibitory function and render these activities resilient to ionic perturbation. …

Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni

Biochemistry and Molecular Biology

Cryptosporidium parvum, the etiological agent of Cryptosporidiosis (diarrheal illness) represents a significant global health burden, particularly affecting immunodeficient and pediatric populations. Since the parasite has a highly reduced mitochondrion and relies on glycolysis, enzymes such as C. parvum malate dehydrogenase (CpMDH), which are believed to be indispensable for parasite viability due to their pivotal roles in NAD⁺ regeneration and redox balance, remain largely unexplored as therapeutic targets. The present study employed a multifaceted experimental and computational strategy to evaluate the inhibitory activity of two lead-like and drug-like small molecules, referred to as compound 1.8 and compound 1.5, against the cofactor …

High Mobility Group Motif Proteins’ Role In Fibrosis, Inflammation, And Vascular Injury In Systemic Sclerosis, Fabian A. Mendoza, Sonsoles Piera-Velazquez, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Systemic Sclerosis (SSc) is an idiopathic systemic autoimmune disease characterized by progressive cutaneous and systemic fibrosis, severe vasculopathy, and multiple humoral and cellular immunological alterations. The pathogenesis of SSc is highly complex and remains incompletely elucidated. The fibrotic process is a crucial component of SSc and is responsible for organ failure and high mortality. Although an increasing understanding of the fibrotic process has enabled the clinical development of antifibrotic therapeutic agents, these agents have limited clinical efficacy. Recently, the potential role of a group of transcription factors containing a High Mobility Group (HMG) motif, in the development and pathological manifestations …

Chromatin Insulators Homie And Nhomie Can Interact With Distant Copies Either Together Or Separately, With Distinct Outcomes For Enhancer-Promoter Interactions, Miki Fujioka, Wenfan Ke, Paul Schedl, James B. Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Chromatin insulators, a.k.a. boundary elements, separate regions of the chromosome with distinct chromatin characteristics, including distinct histone modifications. This activity affects gene expression by allowing chromatin domains to be stably regulated and maintained. Insulators also block enhancer-promoter interactions and, somewhat paradoxically, facilitate other interactions, particularly when they stitch together distant regions of the chromosome by pairing with specific partners. Here we explore how long-range interactions facilitated by insulator pairing are affected by the presence of two potentially competing partners. Our results show that when two partners are present, they can reduce each other's effects on distant gene expression, suggesting that …

Detection And Evaluation Of Hazardous Mercury Contamination In Various Biological Samples, Krish Italiya

Biochemistry and Molecular Biology

Mercury is a toxic environmental pollutant that threatens ecosystems and human health. This study investigates mercury contamination in Lactuca sativa (lettuce) and selected fish species, including tuna and salmon, focusing on plant responses and the limitations of X-ray fluorescence (XRF) analysis. In a controlled experiment, lettuce plants were exposed to mercury to evaluate uptake and toxicity, and XRF spectroscopy was used for quick, non-destructive elemental analysis. Results confirmed mercury accumulation in lettuce, along with visible stress symptoms such as leaf yellowing, purple pigmentation, and tissue damage. Mercury was not detected in tuna and salmon samples, likely due to concentrations below …

Structure Of Ergosteryl-Aspartate Synthase Reveals How An Entrapped Trna Is Used Like A Prosthetic Swinging Arm In The Synthesis Of Aminoacylated Sterols, Hanako Murayama, Nathaniel Yakobov, Nassira Mahmoudi, Sasha Legrosdidier, Nicolas Fournier, Solène Zuttion, Kanata Matsumoto, Michihiro Nishimura, Jingwei Ji, Bruno Senger, Laurence Huck, Howard Gamper, Yoshiaki Kise, Ralph Kleiner, Mathieu Frechin, Ya-Ming Hou, Hubert Becker, Yuzuru Itoh, Frédéric Fischer, Osamu Nureki

Department of Biochemistry and Molecular Biology Faculty Papers

Ergosteryl-3β-O-L-aspartate synthase (ErdS) catalyzes tRNA-dependent aspartylation of ergosterol, a lipid essential for fungal cell membrane integrity. However, the functional significance of ergosteryl-aspartate and the molecular mechanisms underlying its synthesis remain unclear. Here, we show that ErdS localization is highly dynamic and that Erg-Asp is required for proper hyphal growth, sporulation, and spore germination, and likely influences stress tolerance. The cryo-electron microscopy structure of ErdS revealed an unprecedented sterol-binding pocket. In addition, the structures in complex with a non-hydrolyzable Asp-N-tRNAAsp show a tRNA-guided intramolecular aminoacyl transfer mechanism between two functional domains of the enzyme. The CCA end of tRNAAsp undergoes a …

Crystal Structure Of Mouse Dxo In Complex With The Udp-N-Acetylglucosamine Cap And Molecular Mechanism For The Decapping Reactions, Najeeb Ullah, Selom K. Doamekpor, Liang Tong

Department of Biochemistry and Molecular Biology Faculty Papers

Noncanonical metabolite 5' caps have recently been identified on RNAs, and the DXO/Rai1 family of enzymes can remove these caps in eukaryotes. While the binding modes of NAD, FAD and dephospho-CoA (dpCoA) caps in the active site of mouse DXO have been determined, how DXO recognizes the UDP-glucose (UDP-Glc) and UDP-N-acetylglucosamine (UDP-GlcNAc) caps is not known. In addition, the molecular mechanism by which DXO catalyzes the decapping reactions is still poorly understood, especially the location of the water/hydroxide that attacks the scissile phosphate to initiate the decapping. Here we report the crystal structure of mouse DXO in complex with UDP-GlcNAc …

Predicting And Decoding Allosteric Binding Sites Using Protein Language Models And Structure-Based Machine Learning: An Energy Landscape-Guided Explainable Ai Framework, Kamila Riedlová, Vít Skrhák, William G. Gatlin, Max Ludwick, Lucas Turano, Marian Novotný, David Hoksza, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Computational prediction of allosteric binding sites in protein structures remains a persistent challenge, as these regulatory pockets evade detection by both sequence-based and structure-based algorithms. Both computational and physical origins of this predictive asymmetry remain insufficiently understood. In this study, we systematically examine the determinants of binding site predictability using a dual framework that integrates a fine-tuned protein language model and the structure-based method P2Rank as complementary tools probing a diverse data set of 453 human kinases, together with a physics-based interpretability layer derived from energy landscape frustration analysis. Both predictors exhibit a sharp and reproducible dichotomy on protein kinases, …

Bioinformatic Resolution Of Candidate Stress-Response Homologs In Cryptosporidium Parvum: P53-Family Vs Sestrin Identity, Freeman Tobechukwu Ezeala Mr.

Biochemistry and Molecular Biology

Cryptosporidium parvum is an apicomplexan protozoan of major public-health importance, but accurate genome annotation in this organism remains difficult because of its compact genome, deep protein divergence, and the presence of compositionally biased or low-complexity regions that can mislead similarity-based analysis.

In this thesis, I examined one such annotation problem involving a conserved Cryptosporidium stress-response candidate protein, CPATCC_0028580_t1 (833 aa). The central question was whether this protein is better interpreted as a member of the p53 family, based on similarity to p53-like DNA-binding domains (PF00870), or as a member of the Sestrin family associated with the PA26 domain.

I explored …

Evaluation Of Flt3 Inhibition With Quizartinib During Busulfan Conditioning For Hematopoietic Stem Cell Transplantation, Catherine Jankovic

Biochemistry and Molecular Biology

Hematopoietic stem cell transplantation (HSCT) is one of the only curative therapy options for many hematologic malignancies. HSCT relies on effective conditioning regimens to deplete host hematopoietic cells and enable donor engraftment. The alkylating agent Busulfan is widely used in myeloablative conditioning strategies due to its potent cytotoxic effects on hematopoietic cells and ability to clear the bone marrow. However, optimization of conditioning strategies remains an important area of investigation to improve transplant outcomes and reduce toxicity. Preliminary studies have shown that the FLT3 inhibitor Quizartinib synergizes with some chemotherapeutic agents, suggesting that targeted inhibitors may enhance conventional conditioning regimens. …

Understanding Tlr3 Immune Response Activation In Cryptosporidium Parvum And Cryspovirus Pathogenesis, Surayya Hudayberganova

Biochemistry and Molecular Biology

Cryptosporidiosis is a serious gastrointestinal illness caused by a protozoan parasite known as Cryptosporidium. It is particularly dangerous for malnourished children and those with compromised immune systems. My research focuses on the Toll-like receptor 3 (TLR3) response to the Cryptosporidium parvum infection, specifically in the presence of the parasite’s viral mutualist named cryspovirus (CSpV1). Results using research methodologies like ELISA and RT-qPCR have indicated that TLR3 expression increases during the infection process of Cryptosporidium parvum (C. parvum). Furthermore, one intriguing observation concluded during this study suggests that administering the TLR3-specific inhibitor CU-CPT4a to infected cells drastically decreased this activation. This …

Mechanistic Insights Into Enterolactone-Mediated Glut4-Dependent Glucose Uptake, Merritt Smith

Senior Honors Theses

Type 2 diabetes mellitus (T2D) is one of the leading causes of morbidity and mortality in the United States, with approximately 25% of healthcare expenditures directed toward its management and associated metabolic complications. In response to the urgent need for novel therapeutic strategies, recent research has focused on bioactive compounds derived from dietary sources. In light of that, we identified the plant lignan matairesinol (MA) and its gut-derived metabolite, enterolactone (ENL), as agents capable of enhancing glucose uptake in 3T3-L1 differentiated adipocytes. These results suggest that enterolactone may represent a promising dietary supplement for improving glycemic control in patients with …

Mitochondrial Dna Replication Is Regulated By Endoplasmic Reticulum-Mitochondrial Contact Sites, The Mitochondrial Calcium Uniporter, And Manganese, Amaia Lopez De Arbina, Angelica Zamudio-Ochoa, Mikel Muñoz-Oreja, Diego Perez-Rodriguez, Laura Mosqueira-Martín, Rebecca Lasalandra, Marina Villar-Fernandez, Uxoa Fernandez-Pelayo, Laura Rodriguez-Gomez, Seungtae Lee, Francisco Gil-Bea, Nerea Osinalde, Ainara Vallejo-Illaramendi, Dmitry Temiakov, Antonella Spinazzola, Ian Holt

Department of Biochemistry and Molecular Biology Faculty Papers

Mitochondrial DNA replication occurs at contact sites between the endoplasmic reticulum (ER) and mitochondria (ERMCS). Beyond the known role of the tubular ER protein RTN4, the factors regulating this process are poorly defined. Here, we show that repressing the ER protein ERLIN2 in human fibroblasts depletes ER-mitochondrial contact sites and inhibits mitochondrial DNA replication, as does silencing RTN4 or the ER-mitochondrial tether GRP75. GRP75 or RTN4 scarcity also decreases the level of the mitochondrial calcium uniporter (MCU), whose inhibition blocks mitochondrial DNA synthesis. Because ERMCS depletion did not diminish mitochondrial calcium, and MCU complex can transport manganese, we tested whether …

Maternal Inflammation Alters Nuclear And Mitochondrial Dna Methylation Patterns In Neonatal Brain Monocytes, Andrew Ebenezer, Jonathan Hicks, Brooke Hollander, Alexander Hone, Mona Batish, Robert Akins, Adam Marsh, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic ischemic encephalopathy (HIE) is a common birth complication that can cause death or lifelong disabling conditions like cerebral palsy, epilepsy, and autism. It is well established that maternal infection and inflammation are significant risk factors for HIE but reasons for this increase in neurological risk to the offspring remain unknown. Inflammation or infection are associated with epigenetic changes and may contribute to the increased risk of neurodevelopmental disability in exposed offspring. Here, we analyzed and compared DNA methylation patterns in brain monocytes isolated from control, maternal immune activation (MIA), and an inflammation sensitized HIE (IS-HIE) CF-1 mouse model …

Mechanistic Insights Into E. Coli Recovery From Growth Arrest, Ahmed H. Hassan, Yuko Nakano, Howard Gamper, Isao Masuda, Ludmila Vesela, Matyas Pinkas, Sathya Narayanan Nagarajan, Jonathan Dworkin, Gregor Blaha, Ya-Ming Hou, Gabriel Demo

Department of Biochemistry and Molecular Biology Faculty Papers

Bacteria survive hostile conditions by shutting down protein synthesis, but how they restart growth remains poorly understood. Here, we use an E. coli ΔrimM strain, which exhibits a prolonged growth arrest, as a model to investigate how bacteria recover from this state and restore protein synthesis. RimM is a conserved ribosome maturation factor for the 3'-major (head) domain of the 16S rRNA within the bacterial 30S subunit. The loss of RimM causes a longer delay in recovery than other 30S maturation factors, including RbfA. Cryo-EM analysis of ΔrimM ribosomes suggests a delayed recruitment of ribosomal proteins to the 30S head …

Protocol For Inducing Focal Striatal Stroke In Mice Using Photothrombosis, Bridget R. Boyle, Eileen Collyer, Andrea P. Berghella, Elena Blanco-Suarez

Department of Neuroscience Faculty Papers

Here, we present a protocol for inducing focal striatal stroke in mice using photothrombosis. We describe steps for photothrombotic striatal surgery, magnetic resonance imaging, open field behavioral assessment of stroke-induced motor deficits, and post-stroke monitoring. We then detail procedures for tissue collection and immunofluorescence. This protocol provides a standardized approach for consistently modeling striatal stroke in mice, enabling mechanistic studies and preclinical therapeutic testing.

Glioblastoma Multiforme: A Pathologic Breakdown Of One Of Neuro-Oncology's Greatest Challenges, Rosemary Westphal, Ms

Student Papers, Posters & Projects

Glioblastoma multiforme is the most common adult primary tumor with a grim median survival time of 14.6 months. It is characterized by rapid progression, diffuse infiltration, and rather poor clinical outcomes. The WHO classifies GBM as a grade 4 diffuse astrocytic tumor with distinctive histopathological features including high mitotic activity, marked cellular atypia, microvascular proliferation, and necrosis. Advances in molecular diagnostics have further classified GMB into IDH-wild type and IDH-mutant subtypes, with important therapeutic and prognostic implications. Key genetic alterations, such as EGFR amplification, PTEN loss, TP53 mutations, TERT promoter mutations, and MGMT methylations, have been identified as contributing to …

Effect Of Novel Antimicrobial Compounds On Fungal And Bacterial Pathogens, Megan Wilderman

Honors Program: Senior Projects (Public)

Antimicrobial resistance is a growing concern in medicine¹ leading to a need for the development of novel compounds. Two compounds were tested in this study, 2-hydroxyethylhydrazine (HEH) and para-nitrophenyl-isocyanide (NPIC). HEH targets phosphatidylcholine (PC) production², and NPIC targets mitochondrial function³. Choline (Cho) is a compound that bypasses the inhibition of HEH through the Kennedy pathway.² Two-fold serial dilutions were conducted in 96-well plates to test the sensitivity of different bacteria to HEH and fungi to HEH and NPIC in different media types. A choline condition was also included in the HEH dilutions to test …

Recombinant Hagfish Intermediate Filament Proteins Enable Neural Culture Substrates That Promote Neurite Extension And Reduce Oxidative Stress, Justin Jones, Kristin Durrant

Browse all Datasets

This dataset supports the production, characterization, and biological validation of a novel recombinant hagfish intermediate filament (rHIF) protein functionalized with spider silk motifs (rHIF-alpha-GRGGL). The data demonstrates a scalable bioprocess resulting in a 7.76 g/L yield, high structural alpha-helicity (77.2%), and significant support for N2a cells.

Tlr3 Mediated Type I Interferon Response In Mammalian Cell Defense Against Cryptosporidium Parvum Infection., Anjelica Matias

Biochemistry and Molecular Biology

Cryptosporidium parvum is a major cause of a diarrheal disease which affects many children in the USA as well as the rest of the world, yet the contribution of its double stranded RNA (dsRNA) viral symbiont, Cryspovirus (CSpV1) to host innate immunity remains unclear. This study investigated whether CSpV1 activates Toll Like Receptor 3 (TLR3) signaling pathways and downstream Interferon type I (IFN I) responses in mammalian intestinal epithelial cells. Confluent Human Ileocecal Colorectal Adenocarcinoma cells (HCT8) were exposed to CSpV1, and the expression levels of Tumor Necrosis Factor Receptor-Associated Factor 3 (TRAF3), Nuclear Factor-𝜅-light chain enhancer of activated B-cells …

Dna Stability In Aqueous Solutions: A Case Study On Poly A - Poly T Duplex Using Molecular Dynamics Simulations, Haripriya Chennuru

Biochemistry and Molecular Biology

This thesis relies on molecular dynamics (MD) simulations, which apply the AMBER software package to analyze the structural stability, energetics, and dynamics of Poly A - Poly T DNA duplexes. This work is mainly concerned with testing configurations of non-bonded interaction cutoffs (12 Å and 15 Å) on the Generalized Born solvation models (IGB1 and IGB2) to determine the most appropriate conditions regarding computation time and physical reliability in DNA molecular dynamics. The solvation models enable effective simulation of solvent effects, facilitating the calculation of simulation parameters to evaluate structural stability within different environmental conditions. Overall, the performance indicates that …

An Antioxidant Cocktail Of Tert-Butylhydroquinone And A Manganese Porphyrin Induces Toxic Levels Of Oxidative Stress In Cancer Cells, Sandra Tamarin, Hannah Jung, Joseph Lamorte, Laura Biesterveld, Gabriel Piñero, Grace Turchetta, Molly Myers, Rebecca Oberley-Deegan, Aimee Eggler

Student Papers, Posters & Projects

Despite significant advancement in cancer treatments, therapies with minimal toxicity to healthy cells are still limited. One targetable weakness of cancer cells is their sensitivity to oxidative stress. We find that the combination of two antioxidants—the common food additive tert-butylhydroquinone (tBHQ) and a manganese porphyrin in clinical trials, MnTnBuOE-2-PyP5+ (MnBuOE)—increases oxidative stress and causes apoptotic death in several cancer cell lines, but not in mouse primary fibroblasts. Investigating the mechanism of cell death, MnBuOE is observed to catalyze the oxidation of tBHQ, producing the electrophilic quinone tert-butylquinone (tBQ). A critical role for tBQ and its electrophilic character was revealed with …

Dapagliflozin Attenuates Cisplatin-Induced Nephrotoxicity In Rats Through Modulation Of Ros/Nf-Κb, Bcl2/Bax And Pink1/Parkin Signaling Pathways, Esraa K. Khallaf, Eman A. Ramadan, Mohey M. Elmazar, Marwa M. Safar

Pharmacy

Dapagliflozin (DPG), an anti-diabetic drug, has gained attention for its renal protective effects through multiple molecular pathways, yet its impact on mitophagy in cisplatin (CIS) nephrotoxicity remains unclear. This study aimed to examine the impact of DPG against CIS-induced nephrotoxicity in rats, targeting mainly PINK1/Parkin-mediated mitophagy and inflammatory/apoptotic pathways. Male Sprague Dawley rats received DPG (10 mg/kg; p.o) daily for 14 consecutive days and AKI was induced by a single injection of CIS (7 mg/kg; i.p) on day 10. Blood glucose, serum levels of creatinine and urea nitrogen, oxidative stress, inflammatory, apoptotic, mitophagy markers, and histological changes were assessed. DPG …