Molecular Biology Commons^™

Inorganic Pyrophosphate Plasma Levels In Patients With Ggcx-Associated Pxe-Like Phenotypes, Qiaoli Li, Catherine Troutman, Mary Peckiconis, Tamara Wurst, Sharon Terry

Department of Biochemistry and Molecular Biology Faculty Papers

ntroduction: Pseudoxanthoma elasticum (PXE) is an autosomal recessive ectopic calcification disorder clinically affecting the skin, eyes, and vascular system. Most cases of PXE are caused by inactivating pathogenic variants in the ABCC6 gene encoding a hepatic transmembrane efflux transporter, which facilitates the extracellular release of ATP, the precursor of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Pathogenic variants in GGCX, encoding γ-glutamyl carboxylase required for activation of vitamin K-dependent coagulation factors as well as matrix Gla protein (MGP) and Gla-rich protein (GRP), two inhibitors of ectopic calcification, have also been reported to cause cutaneous changes like those seen …

Characterizing Biomolecular Structure Features Through An Innovative Elliptical Dichroism Spectrometry For Cancer Detection, Yusuf Asad, Keerthi Priya Jangili, Amara Arshad, Maliha Elma, Komila Rasuleva, Alfred Akinlalu, Tommy Gao, Umamaheswara Rao Tida, Wenjie Xia, Dali Sun

Electrical and Computer Engineering: Faculty Scholarship

This research introduces a novel method for evaluating the structural features of biomolecules, utilizing our innovative Elliptical Dichroism (ED) spectrometer specifically designed for stereochemical analysis. By integrating ED spectrometry with autocorrelation (AC) analysis, we investigate the conformational characteristics of biological molecules such as amino acids, proteins, and extracellular vesicles (EVs) induced by elliptically polarized UV absorption. Our streamlined approach offers a cost-effective and portable solution with minimal sample consumption and supports multiple working modes to efficiently characterize biomolecular structures. The insight from this new approach demonstrates potential applications in using biomolecular characterization for cancer detection.

Effects Of Microplastic Biofilms On An Anthropogenically Impacted Suburban Lake, Paris M. Velasquez

Masters Theses

Plastics have been observed in every location on the planet, and their prevalence in the environment is due in part to their strong resistance to degradation. Inland lakes are susceptible to plastic pollution by highway runoff, which contains plastic fragments of brake pads, car tires, litter, and road paint. These plastics eventually enter freshwater environments and degrade into microplastics (

The C-Terminal 4cxxc-Type Zinc Finger Domain Of Cdca7 Recognizes Hemimethylated Dna And Modulates Activities Of Chromatin Remodeling Enzyme Hells, Akeo Shinkai, Hideharu Hashimoto, Chikako Shimura, Hiroaki Fujimoto, Kei Fukuda, Naoki Horikoshi, Masaki Okano, Hitoshi Niwa, Erik W Debler, Hitoshi Kurumizaka, Yoichi Shinkai

Department of Biochemistry and Molecular Biology Faculty Papers

The chromatin-remodeling enzyme helicase lymphoid-specific (HELLS) interacts with cell division cycle-associated 7 (CDCA7) on nucleosomes and is involved in the regulation of DNA methylation in higher organisms. Mutations in these genes cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, which also results in DNA hypomethylation of satellite repeat regions. We investigated the functional domains of human CDCA7 in HELLS using several mutant CDCA7 proteins. The central region is critical for binding to HELLS, activation of ATPase, and nucleosome sliding activities of HELLS-CDCA7. The N-terminal region tends to inhibit ATPase activity. The C-terminal 4CXXC-type zinc finger domain contributes to CpG …

Predicting Mutation-Induced Allosteric Changes In Structures And Conformational Ensembles Of The Abl Kinase Using Alphafold2 Adaptations With Alanine Sequence Scanning, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Despite the success of AlphaFold2 approaches in predicting single protein structures, these methods showed intrinsic limitations in predicting multiple functional conformations of allosteric proteins and have been challenged to accurately capture the effects of single point mutations that induced significant structural changes. We examined several implementations of AlphaFold2 methods to predict conformational ensembles for state-switching mutants of the ABL kinase. The results revealed that a combination of randomized alanine sequence masking with shallow multiple sequence alignment subsampling can significantly expand the conformational diversity of the predicted structural ensembles and capture shifts in populations of the active and inactive ABL states. …

Exploring Biosignatures And Biogeochemical Processes In Lanzarote Lava Tubes: Implications For Martian Analog Research, Vera Palma, Ana Z. Miller, Francesco Sauro, Bogdan P. Onac, José M. De La Rosa, Sara Gutiérrez-Patricio, Beatriz Cubero, José A. Gonzalez-Perez, Jesus Martínez-Frías, A Teresa Caldeira

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.

Exploring Pristine Microbial Ecosystems From The Uninhabited Volcanic Selvagens Islands, Pedro N. Jiménez-Morillo, Sara Gutiérrez-Patricio, Vera Palma, Ana Teresa Caldeira, Nicasio Tomás Jiménez-Morillo, Ana Z. Miller

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.

Investigating Therapeutic Activity Of Br-Ormeloxifene (Br-Orm) Against Cervical Cancer, Mohammed Sikander, Shabnam Malik, John Apraku, Sonam Kumari, Parvez Khan, Daniel Zubieta, Hassan Mandil, Aditya Ganju, Bhavin Chauhan, Maria C. Bell, Man Mohan Singh, Sheema Khan, Murali Yallapu, Fathi T. Halaweish, Meena Jaggi, Subhash Chauhan

Research Colloquium

Aberrant activation of β-catenin signaling is strongly associated with cancer proliferation, invasion, migration, and metastasis, thus small molecules that can inhibit this pathway might have great clinical significance. Our molecular modeling studies suggest that Ormeloxifene (ORM), a triphenylethylene molecule docks with β-catenin, and its brominated analogue (Br-ORM) bind more effectively with relatively less energy (-7.6 kcal/mol) to the active site of β-catenin as compared to parent ORM. Herein, we report the synthesis and characterization of a Br-ORM by NMR and FTIR, as well as its anti-cancer potential in cervical cancer models in vitro and in vivo. Br-ORM treatment effectively …

Dissecting The Interplay Of Protein Synthesis And Degradation Pathways In Cellular Adaptation To Stress, Brittany Friedson

Theses and Dissertations

Adaptation to stress requires cells to reprogram transcription, translation, and proteolytic pathways. Although much is known about the response of each program, it remains unclear how they coordinate following stress. My studies in S. cerevisiae identified the Cdk8 kinase module (CKM) of the Mediator complex as a new player in coordinating these processes. It is well established that the CKM consists of four highly conserved proteins (cyclin C, its cognate kinase Cdk8, and two structural proteins Med12 and Med13) and predominantly represses a subset of stress responsive genes in yeast. We demonstrated for the first time that the CKM also …

Non-Redundant Roles For The Human Mrna Decapping Cofactor Paralogs Dcp1a And Dcp1b, Ivana Vukovic, Samantha M. Barnada, Jonathan W. Ruffin, Jon Karlin, Ravi Kumar Lokareddy, Gino Cingolani, Steven B. Mcmahon

Department of Medicine Faculty Papers

Eukaryotic gene expression is regulated at the transcriptional and post-transcriptional levels, with disruption of regulation contributing significantly to human diseases. The 5' m7G mRNA cap is a central node in post-transcriptional regulation, participating in both mRNA stabilization and translation efficiency. In mammals, DCP1a and DCP1b are paralogous cofactor proteins of the mRNA cap hydrolase DCP2. As lower eukaryotes have a single DCP1 cofactor, the functional advantages gained by this evolutionary divergence remain unclear. We report the first functional dissection of DCP1a and DCP1b, demonstrating that they are non-redundant cofactors of DCP2 with unique roles in decapping complex integrity and specificity. …

Engineered Nls-Chimera Downregulates Expression Of Aggregation-Prone Endogenous Fus, Miyuki Hayashi, Amandeep Girdhar, Ying-Hui Ko, Kevin Kim, Jacquelyn Depierro, Joseph R. Buchler, Nikhita Arunprakash, Aditya Bajaj, Gino Cingolani, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Importin β-superfamily nuclear import receptors (NIRs) mitigate mislocalization and aggregation of RNA-binding proteins (RBPs), like FUS and TDP-43, which are implicated in neurodegenerative diseases. NIRs potently disaggregate RBPs by recognizing their nuclear localization signal (NLS). However, disease-causing mutations in NLS compromise NIR binding and activity. Here, we define features that characterize the anti-aggregation activity of NIR and NLS. We find that high binding affinity between NIR and NLS, and optimal NLS location relative to the aggregating domain plays a role in determining NIR disaggregation activity. A designed FUS chimera (FUS_IBB), carrying the importin β binding (IBB) domain, is …

Malat1 Mediates Tet2 Loss Of Function-Driven Oncogenic Inflammation Via Rna Shielding Of Nf- Kappa B P65, Nana Adjoa Ben-Crentsil

USF Tampa Graduate Theses and Dissertations

TET2 is a dioxygenase that regulates gene expression and hematopoiesis by oxidizing 5-methylcytosine residues on DNA to 5-hydroxymethylcytosine. TET2 mutations are common genetic events in hematological disorders. For example, TET2 is the most frequently mutated gene in Chronic Myelomonocytic Leukemia and occurs in about 33% of other myeloid malignancies. It is also the second commonest mutation in clonal hematopoiesis of indeterminate potential (CHIP), a common premalignant condition in the elderly. TET2 mutations arise in founding clones and are implicated in many non-hematological sequelae seen in CHIP like atherosclerotic disease, chronic liver disease, and severe microbial infections.

The development of TET2-deficient …

Use Of Molecular Dynamics Simulations To Characterize Structural Interactions Of Protein And Drug In Antiviral Drug Discovery, Caitlin Joan Smith

All ETDs from UAB

Since 2019, the novel coronavirus SARS-CoV-2 the etiological cause of the COVID-19 pandemic has led researchers and physicians to look for effective antiviral treatments as interventions in mitigating COVID-19 disease. The severity of the disease and the limitations of current treatments have led to antiviral drug research beyond currently approved antiviral drugs. Many antivirals exist and are currently approved by the Food and Drug Administration (FDA) for other viral illnesses, yet currently only remdesivir and nirmatrelvir/ritonivir are approved for COVID-19 (October 2020, May 2023, respectively), while molnupiravir is still under emergency FDA use authorization [1, 2, 3]. Here, we have …

Combination Of 64/67cu Theranostics And Immunotherapy Targeting Fibroblast Activation Protein In Triple Negative Breast Cancer, Fnu Sharmila Sridhar

All ETDs from UAB

Triple negative breast cancer (TNBC) makes up 10-20% of breast cancer cases. Even with advancements in science, TNBC is treatment resistant due to the lack of any type of hormonal receptors on the cell surface making it difficult for targeted hormonal therapy. New research avenues have led to studies of the Tumor-microenvironment (TME) in detail. TME is a complex network of stromal cells, extracellular matrix (ECM) and cancer associated fibroblasts (CAFs) with pro-tumorigenic properties and plays a major role in tumor growth. Fibroblast activation protein (FAP) is a marker of CAF and promotes ECM remodeling through several pathways and has …

Biologic Evaluation Of 64cu & 67cu As Potential Theranostic Agents For Cancer Radiotherapy, Lakshmi Madhusoodanan

All ETDs from UAB

Immunotherapy has become a mainstay in the treatment of several types of cancer, with the potential to induce durable remission, albeit in a limited percentage of patients. More recently, radiopharmaceuticals have gained recognition in cancer treatment due to their ability to localize within cancer cells and deliver radiation, reducing adverse effects precisely. Cancer radiotherapy has the potential to synergize with immunotherapy due to its induction of immunogenic cell death (ICD), which results in distinct cellular injuries such as the formation of single-strand breaks (SSBs) and double-stranded breaks (DSBs), disruption of mitochondrial integrity, and the excessive generation of reactive oxygen species …

Determination Of Readthrough Susceptibility Among Different Schwann Cell Lines Carrying Nonsense Mutations, Trushali Vansadia

All ETDs from UAB

Neurofibromatosis Type 1 (NF1) is a genetic disorder that affects the nervous system through the formation of tumors or neurofibromas. Encoded by the NF1 gene, neurofibromin functions as a tumor suppressor by converting active GTP-Ras to inactive GDP-Ras. 20% of NF1 patients carry a genomic nonsense mutation, which generates a premature termination codon (PTC) in the NF1 mRNA, leading to the formation of a truncated neurofibromin protein. Termination at PTCs can be suppressed by the incorporation of an amino acid at the site of the PTC, also known as readthrough. Readthrough results in continued translation elongation downstream of the PTC …

A Histone Methyltransferase Contributes To Treatment Resistance In Npm1c Aml, Neha Srinivas

All ETDs from UAB

Acute myeloid leukemia (AML) is a blood cancer marked by the rapid growth of abnormal myeloid cells, driven by various genetic mutations. AML accounts for approximately 1% of all cancers and presents complicated prognosis and treatment. Menin inhibitors have shown potential in targeting AML. However, resistance to these inhibitors presents a significant clinical obstacle, as patients treated with menin inhibitors are increasingly developing resistance to the treatment. Using CRISPR-Cas9 mediated screening, we identified an epigenetic regulator contributing to resistance against menin inhibitors in AML. Utilizing knockout (KO) models of the epigenetic regulator in-vitro, ex-vivo, and in-vivo, we observed a growth …

Serum Proteomic Profile Of Subclinical Babesia Bovis Infection In Pcr-Positive Eld's Deer Using Serum Protein Electrophoresis Coupled With Lc-Ms/Ms, Vichayanee Pumpitakkul, Sittiruk Roytrakul, Narumon Phaonakrop, Gunnaporn Suriyaphol Assoc. Prof.

The Thai Journal of Veterinary Medicine

Subclinical babesiosis observed in captive Eld’s deer, which act as reservoirs for ticks, poses a risk to healthy herds. However, the knowledge of biomarkers for subclinically infected Eld’s deer and host-parasite interactions is limited. This study aimed to investigate the serum proteomic profiles and protein interactions of Babesia bovis and subclinically infected Eld’s deer, PCR-positive for B. bovis, using automated serum protein electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The findings revealed albumin and four globulin fractions: alpha-1, alpha-2, beta, and gamma globulin. Albumin protein (ALB) was consistently detected across all fractions, highlighting its role in maintaining osmotic balance …

Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich

Theses and Dissertations

A major challenge of developing collagen mimetic peptides (CMPs) by bacterial expression is to include hydroxyproline for biomedical applications. Coexpression of Prolyl-4-hydroxylase from A.mimivirus with CMPs was investigated. Additionally, four expression designs were created for potential applications in mammalian cells to utilize their natural ability of proline-hydroxylation by post-translational modification.

Predicting The Association Of Metabolites With Both Pathway Categories And Individual Pathways, Erik D. Huckvale, Hunter Moseley

Markey Cancer Center Faculty Publications

Metabolism is a network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic knowledgebases, such as the Kyoto Encyclopedia of Gene and Genomes (KEGG) contain metabolites, reactions, and pathway annotations; however, such resources are incomplete due to current limits of metabolic knowledge. To fill in missing metabolite pathway annotations, past machine learning models showed some success at predicting the KEGG Level 2 pathway category involvement of metabolites based on their …