Cell and Developmental Biology Commons^™

Impact Of Zar1l Expression On Drug Response In Breast Cancer Cells, Maryam M. Gerges, Smita Misra

Student Scholar Symposium

Breast cancer (BC) is the most common cancer in women worldwide and the second leading cause of cancer-related deaths among females. BC arises from the uncontrolled proliferation of breast epithelial cells. A crucial gene associated with BC is the Breast Cancer Susceptibility Gene 2 (BRCA2), a tumor suppressor that aids in DNA repair. Proper BRCA2 function helps prevent BC. Our lab studied the cell cycle-dependent expression of BRCA2 revealing that its promoter exhibits bi-directional activity. During cell division, forward activity transcribes BRCA2, while in the resting phase, reverse activity transcribes ZAR2 (Zygote Arrest 1 Like). ZAR2, an RNA-binding protein with …

Pediatric Glioblastoma Molecular Mechanisms, Ariana Trabachino, Joshua Owens

Student Scholar Symposium

Powerpoint presentation

Functionality Of The Ryanodine Receptor Type 1 (Ryr1) In The Development Of Malignant Hyperthermia (Mh), Cesar Medina, Joshua Owens

Student Scholar Symposium

Malignant Hyperthermia (MH) is a rare but potentially lethal pharmacogenetic disorder, affecting roughly 1 in 30,000 children and 1 in 100,000 adults undergoing surgery. MH can be triggered by agents used for general anesthesia. These may include volatile anesthetics such as sevoflurane, isoflurane, desflurane, halothane or depolarizing neuromuscular blockers such as succinylcholine. Upon administration of a trigger, an MH susceptible (MHS) patient can develop a hypermetabolic state during the intraoperative or postoperative periods. If not treated quickly, an MH episode could result in organ dysfunction or death. The primary mechanisms involved in the development of an MH crisis include the …

Effects Of Valerobetaine In Fatty-Acid Induced Breast Cancer Cell Proliferation, Carolyn Tran, Maryam Mina, Diyar Fadhil

Student Scholar Symposium

Breast cancer is the second leading cause of cancer deaths among women with 287,500 new cases of invasive breast cancer and 43,250 deaths reported in 2022. In fact, 75% of these deaths aren’t from the initial tumor but due to the spread of breast cancer tumors to other sites, also known as metastases. Breast cancer occurs when breast tissue cells mutate and proliferate uncontrollably, resulting in a lump or mass. In breast cancer, the origin of proliferation, or the primary site, for cancer cells is mostly within the milk ducts. Then, tumor cells can start migrating away from its primary …

Investigating Carnitine-Dependent Mechanisms Of Valerobetaine In Breast Cancer Migration Inhibition, Audrey Birdwell

Student Scholar Symposium

Breast cancer accounts for approximately 297,500 cases annually in the United States, leading to over 43,000 fatalities. These deaths occur due to cancer's ability to bypass the normal cell cycle, proliferating uncontrollably and metastasizing throughout the body. Notably, over 75% of breast cancer-related deaths are attributed to metastases. The hallmark of altered cellular metabolism enables cancer cells to enhance fat metabolism alongside glycolysis, driving increased tumor aggressiveness and higher metastatic rates. Currently, no FDA-approved drugs directly target metastases or prevent migrating cancer cells. Consequently, inhibiting fat metabolism presents a potential strategy to reduce metastases and cancer cell migration; however, existing …

Her2 Amplification In Breast Cancer And Its Treatment Options, Emerald Cole, Zoe Grace Brigance

Student Scholar Symposium

Breast cancer affects approximately 2.3 million women worldwide, causing an estimated 670,000 deaths in 2022. Among its subtypes, 15-20% exhibit overexpression of Human Epidermal Growth Factor Receptor 2 (HER2), a tyrosine kinase receptor that drives tumor aggressiveness. HER2 activates the PI3K and RAS/RAF/MAPK pathways, promoting uncontrolled cell growth, proliferation, and survival. In HER2+ breast cancer, gene amplification leads to excess HER2 protein production, resulting in persistent signaling and unchecked tumor progression. However, this dependency on HER2 presents a key therapeutic opportunity. Trastuzumab, an anti-HER2 monoclonal antibody, inhibits HER2 signaling and enhances immune-mediated cancer cell destruction. When combined with Lapatinib, chemotherapy, …

Microrna-Mediated Regulation Of The Parkinson's Disease-Associated Gene, Lrrk2, Peyton B. Hanser, Pavithra Madamarandawala, Wendy Olivas

Undergraduate Research Symposium

Parkinson’s Disease (PD) is an age-related neurodegenerative disease. LRRK2 is one of the main PD-associated genes, as both familial mutations and its abnormal overexpression are associated with PD progression. However, underlying molecular mechanisms leading to LRRK2 abnormal overexpression are not well understood. MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate target messenger RNAs (mRNAs) by binding to a specific sequence in their 3’ UTRs (untranslated regions at the ends of mRNAs) and blocking translation of the mRNA. Previous studies have identified miR-205 as one regulator of LRRK2. However, the LRRK2 3’ UTR has many other computationally-predicted miRNA …

The Cytotoxicity And Anti-Inflammatory Properties Of 1’S-1’-Acetoxychavicol Acetate (Aca) On Oral Cells, Nur Umairah Atiqah Sabri, Nor Syazwani Muhammad Zahidan, Zulfahmi Said, Siti Noor Adnalizawati Adnan, Normaliza Ab Malik

Journal of Dentistry Indonesia

Objective: Mouthwash is widely used to maintain oral health by reducing the prevalence of pathogenic microbiomes. Nonetheless, chlorhexidine, a common active ingredient, is associated with side effects including teeth staining, mucosal peeling, mouth and tongue numbness. This has prompted interest in natural alternatives. This study aimed to identify the cytotoxicity and anti-inflammatory properties of 1’S-1’-acetoxychavicol acetate (ACA) isolated from Alpinia conchigera rhizome against human primary gingival fibroblast and keratinocyte (HPGF and HPGK). Methods: Cytotoxicity of ACA (1.57 mg/mL) against HPGF and HPGK was assessed using the MTT assay. Meanwhile, the anti-inflammatory property of ACA was analyzed based on …

Role Of Cellular Stress Responses In Innate Immune Defense Against Acute Respiratory Infections, Amit Sharma

LSU Doctoral Dissertations

The endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1α (IRE1α) is an important regulator of innate immune cells. However, its role in pulmonary innate host defenses remains poorly understood. This dissertation elucidates the dual, context-dependent role of IRE1α in host defense against methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. We demonstrate IRE1α’s function as both a detrimental mediator of acute pathology and an essential facilitator of innate immune memory. Our work revealed that acute IRE1α activation during primary MRSA infection is detrimental. In lungs and alveolar macrophages (AMs), IRE1α is activated in response to MRSA infection. Consequently, IRE1α activation triggers a hyperinflammatory …

Evaluating The Sna1 Gene Using Crispr Mediated Knockdown In Ewing Sarcoma Cells, Rosanna Jees, Sonia Cerrillo, Terry Jo Shackleford

Mechanisms of Disease

Ewing sarcoma is a pediatric cancer with limited therapeutic options and poor long-term survival. CRISPR–Cas9–mediated gene editing provides a powerful tool for investigating tumor molecular behavior and identifying potential therapeutic targets. In this study, we worked with CRISPR–Cas9 in Ewing sarcoma ES8 cells to evaluate the roles of the transcription factors SNAI1 and SNAI2, both implicated in epithelial–mesenchymal transition and cancer progression. Using guide RNAs targeting each gene, we assessed proliferation, apoptosis, migration, and long-term survival through Incucyte live-cell imaging and colony-formation assays. Knockout of SNAI1 resulted in decreased cell proliferation and reduced migratory capacity compared with controls, suggesting a …

Effects Of Ptk2 Knockdown On Key Cellular Processes In Es8 Cells, Adrian Cruz, Emiliano Rueda, Dylan Andrews, Terry Jo Shackleford

Mechanisms of Disease

Ewing sarcoma is an aggressive form of pediatric cancer characterized by rapid growth and metastatic potential, with limited treatment options available. PTK2 is a key regulator of many pathways involved in tumor behavior, including integrin-mediated adhesion, survival, and migration. This research lab investigated how CRISPR-Cas9 knockdown of PTK2 can affect cellular processes in ES8 Ewing sarcoma cells. To assess the effectiveness of reducing PTK2 expression, we utilized live-cell imaging, wound-healing assays, measurements of caspase activity, colony formation, and qRT-PCR. Our results showed that incomplete knockdown decreased cell proliferation and colony formation, while also increasing apoptotic activity. Additionally, migratory ability was …

How Cxcr4 Knockdown Affects Tumorigenic Properties In Es8 Cells, Gabriella Galdeano, Damon James, Terry Jo Shackleford

Mechanisms of Disease

C-X-C chemokine receptor type 4 (CXCR4) is a seven-transmembrane G-protein–coupled receptor (GPCR). When activated by its ligand SDF-1 (CXCL12), CXCR4 triggers signaling pathways that promote cell survival, proliferation, angiogenesis, and chemotaxis. Many cancers exploit the CXCR4/SDF-1 axis to support tumor growth and metastasis. Ewing sarcoma (ES8) is an aggressive pediatric bone and soft-tissue cancer, and elevated CXCR4 signaling has been linked to increased migration and metastatic behavior. ES8 cells, a well-established ES8 cell line, provided a model to study how CXCR4contributes to tumor progression. CRISPR-Cas9 genome editing was used to knock down CXCR4 in ES8 cells, delivered through lipid-based transfection. …

Investigating The Role Of Twist1 In Cancer Progression Using Crispr Knockdown, Abby Guerrero, Sofia Perez, Terry J. Shackleford

Mechanisms of Disease

TWIST1 is a transcription factor that plays a critical role in epithelial-mesenchymal transition (EMT), a process that promotes cancer cell migration, invasion, and metastasis. This study investigates the functional role of TWIST1 in cancer progression by using CRISPR/Cas9-mediated knockdown to examine its effects on apoptosis, proliferation, migration, and invasion. TWIST1 was knocked down in cancer cell lines using CRISPR/Cas9 assay. Knockdown efficiency and changes in genes were confirmed by qRT-PCR. Functional assays included caspase assays for apoptosis, MTT assays for proliferation, wound-healing assays for migration, Matrigel invasion assays, and colony formation assays to assess long-term growth and invasive potential. Across …

Itgb1 Knockdown Alters Apoptosis And Proliferation In Ewing Sarcoma Cells, Aditi Kumar, Magdalena Saad, Terry J. Shackleford

Mechanisms of Disease

Integrin beta 1 (ITGB1) is an adhesion receptor that link cells to the extracellular matrix and regulates pathways involved in survival, proliferation, and migration. In order to understand its role in Ewing Sarcoma, we applied CRISPR-Cas9 with two guide RNAs to knock down ITGB1 in ES8 cells. We then assessed changes in cell growth, death, movement, and gene expression using Incucyte live-cell imaging, colony formation assays, wound healing assays, and qRT-PCR. qRT-PCR showed partial ITGB1 reduction, with ITGB1_gRNA2 producing the strongest decrease. ITGB1_gRNA2 also led to a small increase in caspase activity and a 20-30% increase in proliferation at the …

Elucidating The Mechanism Of Neprilysin-Regulated Triple-Negative Breast Cancer Invasion, Kai Lam, Ellie Griner

Student Scholar Symposium

Triple-negative breast cancer (TNBC) is a highly invasive and difficult-to-target form of cancer. It is characterized by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor 2 receptors, making current targeted therapies ineffective and leaving chemotherapy as the primary treatment option. Previous studies in this lab have linked reduced expression of neprilysin (NEP), a membrane-bound protease that cleaves and inactivates mitogenic peptides, to a highly invasive phenotype in TNBC. Our data indicates that while NEP promotes phosphoinositol 3-kinase (PI3K) signaling, it simultaneously inhibits cellular invasion. Here, we begin to explain a possible mechanism behind the anti-invasive role …

Δ-Valerobetaine As A Novel Inhibitor Of Breast Cancer Cell Migration: Hinders Cellular Migration Of Mcf-7 Cells Through Reducing Atp Concentrations And Fak Activation, Braxton Ivie, Lincoln Brown, Bryson Lovorn

Student Scholar Symposium

δ-valerobetaine as a Novel Inhibitor of Breast Cancer Cell Migration: Hinders Cellular Migration of MCF-7 Cells Through Reducing ATP Concentrations and FAK Activation

Lincoln Brown, Braxton Ivie, Bryson Lovorn, Joshua Owens

Based on female breast cancer diagnoses from 2014-2020, the CDC reports that the 5-year relative survival rate for local and regional breast cancers was 98.9% and 86.3%, respectively, while the survival rate for metastasized cancers was reportedly 32.4%. These discrepancies in survival highlight an increased mortality rate when cancer metastasizes. Interestingly, aggressive tumors have been shown to metabolize fats at higher rates than low-metastatic tumors. Recently, our group has …

Epidemiology, Presentation, And Diagnosis Of Type 2 Diabetes Mellitus In Children And Adolescents, Bisher Alsabbagh, Whard Alsabbagh

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

The prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents has increased substantially over recent decades, paralleling rising rates of pediatric obesity and metabolic risk. Youth-onset T2DM is characterized by significant insulin resistance accompanied by an inadequate compensatory insulin response, resulting in progressive hyperglycemia and early beta-cell dysfunction. Incidence varies widely among racial and ethnic groups, with the highest rates observed in non-Hispanic Black, Hispanic, Native American, Asian American, and Pacific Islander youth. Risk factors include obesity, family history, high-risk ethnicity, pubertal insulin resistance, prenatal metabolic exposures, and comorbid conditions such as polycystic ovary syndrome. Clinical presentation ranges …

Increased Intermembrane Space [Ca2+] Drives Mitochondrial Structural Damage In Cpvt, Shanna Hamilton, Radmila Terentyeva, Roland Veress, Fruzsina Perger, Zuzana Nichtova, Mark Bannister, Jinxi Wang, Sage Quiggle, Rachel Battershell, Matthew Gorr, Sandor Györke, Bum-Rak Choi, Christopher George, Andriy Belevych, György Csordás, Dmitry Terentyev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Mitochondrial dysfunction caused by abnormally high RyR2 (ryanodine receptor) activity is a common finding in cardiovascular diseases. Mechanisms linking RyR2 gain of function with mitochondrial remodeling remain elusive. We hypothesized that RyR2 hyperactivity in cardiac disease increases [Ca 2+ ] in the mitochondrial intermembrane space (IMS) and activates the Ca 2+ -sensitive protease calpain, driving remodeling of mitochondrial cristae architecture through cleavage of structural protein OPA1 (optic atrophy protein 1).

METHODS: We generated a highly arrhythmogenic rat model of catecholaminergic polymorphic ventricular tachycardia, induced by RyR2 gain-of-function mutation S2236L(Ser2336Leu)(+/-) . We created a new biosensor to measure IMS-[Ca2+ ] …

Protein-Protein Interaction–Interfering Peptide Rescues Dysregulated Nmda Receptor Signaling, Robert E. Featherstone, Hongbin Li, Ameet S. Sengar, Karin E. Borgmann-Winter, Olya Melnychenko, Lindsey M. Crown, Ray L. Gifford, Felix Amirfathi, Anamika Banerjee, Aivi Tran, Krishna Parekh, Margaret Heller, Wenyu Zhang, Robert J. Gallop, Adam D. Marc, Pragya Komal, Michael W. Salter, Steven J. Siegel, Chang-Gyu Hahn

Farber Institute for Neuroscience Faculty Papers

The complex and heterogeneous genetic architecture of neuropsychiatric illnesses compels us to look beyond individual risk genes for therapeutic strategies and target the interactive dynamics and convergence of their protein products. A mechanistic substrate for convergence of synaptic neuropsychiatric risk genes are protein-protein interactions (PPIs) in the N-methyl-D-aspartate receptor (NMDAR) complex. NMDAR hypofunction in schizophrenia is associated with hypoactivity of Src kinase, resulting from convergent alterations in PPIs of Src with its partners. Of these, the association of Src with PSD-95, which inhibits the activity of this kinase in the NMDAR complex, is known to be increased in schizophrenia. Here, …

Neurogenesis And Functional Recovery Of Murine Retinal Ganglion Cells After Glaucoma Induction Following Treatment With Pnu-282987, Samantha Luzadre

Masters Theses

Experiments were performed to demonstrate electrical recovery in glaucoma-induced adult mice after neurogenesis of retinal ganglion cells (RGCs). Newly derived RGCs were induced following eye drop treatment with a selective alpha7 nicotinic acetylcholine receptor agonist, PNU-282987. Both sexes of transgenic (RlbpCre-ER (CRE⁺) and Rosa-tdTomato (tdTomato⁺)) adult mice were utilized to trace newly generated RGCs originating from Müller glia (MG). Experimental mice were injected with hypertonic saline into the episcleral vein of anesthetized mice to significantly increase intraocular pressure (IOP) and induce glaucoma-like conditions. One month after the injection and after significant death of RGCs occurred, mice …