Cell Biology Commons^™

Uca1 As A Key Regulator Of The Warburg Effect During Anoikis Resistance In Colorectal Cancer Metastasis, Ricardo Pequeno Bracho, Salique Hassan Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Subhash Chauhan, Bilal Hafeez, Tamer Oraby, Manish K. Tripathi

Research Symposium

Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality in the United States. While localized CRC has a 90% five-year survival rate, this drops sharply to 14% upon metastasis. Metastasis occurs in approximately 40–50% of CRC cases and requires cancer cells to acquire anoikis resistance—a critical adaptation allowing survival after detachment from the extracellular matrix, enabling migration and colonization of secondary sites. Understanding the molecular mechanisms driving anoikis resistance, particularly those linked to altered glucose metabolism, is essential for developing targeted therapies for metastatic CRC.

Cancer cells frequently exhibit the Warburg Effect, a metabolic adaptation favoring glycolysis over …

Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …

The Correlation Between Temporomandibular Disorder (Tmd) And Vitamin D Deficiency, Iris Kim, Claudia Freitas

Annual Research Symposium

No abstract provided.

Hiv Associated Epigenetic Trends And Chronic Diseases: Insights Into The Hidden Burden Of Chronic Infection, Courtney G. Wallace, Zachary Capriotti, Zachary Klase

Kimmel Cancer Center Faculty Papers

Human Immunodeficiency Virus (HIV) remains a major health challenge despite dramatic advances in treatment and prevention. People living with HIV (PLWH) continue to experience high rates of non-AIDS comorbidities, including cardiovascular, renal, pulmonary, oncologic, and neurocognitive disorders. These conditions persist under viral suppression, underscoring the lasting biological impact of infection. Epigenetic dysregulation has emerged as a key driver of these outcomes. HIV integration, viral proteins, chronic inflammation, and ART exposure have all been reported to alter DNA methylation, histone modifications, transcription factor networks, and noncoding RNA regulation. These changes extend beyond infected cells, reprogramming uninfected immune and tissue compartments. Long-lived …

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …

An In Vivo Study Of Lns8801, A Gper Agonist, In A Spontaneous Melanoma-Prone Mouse Model, Tgs., Christina Marinaro, John Sauer, Christopher A Natale, Todd Ridky, Suzie Chen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Melanoma is the most aggressive and deadly form of skin cancer that arises from the transformation of melanocytes, the pigment producing cells of the skin. In the year 2024 there will be approximately 10,000 new cases of melanoma diagnosed and approximately 8,000 deaths attributed to melanoma in the United States. In this study we treated a group of male and female transgenic mice that spontaneously develop metastatic melanoma, TGS, with a G-protein-coupled estrogen receptor agonist LNS8801 to assess the efficacy on disease progression. A second group of male and female TGS mice was also exposed to UVB irradiation to mimic …

Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta

Graduate Theses/Dissertations

In 2020, 10 million deaths were attributed to cancer, with multidrug resistance being responsible for over 90% of deaths in cancer patients receiving treatment. This study utilized the model organism Tetrahymena thermophila to study how cells become resistant to Ultraviolet Radiation (UV) radiation, a process similar to multidrug resistance, specifically focusing on the nucleotide excision repair and ubiquitin shuttle protein Rad23. The National Cancer Institute documented 30-60% of cancers tested had a mutation in RAD23. Knockdown of RAD23 in Tetrahymena thermophila demonstrated a UV resistance phenotype with decreased nucleotide excision repair and differential expression of proteins active within caspase-independent …

Early Host Defense Against Virus Infections, Søren R. Paludan, Thomas Pradeu, Andreas Pichlmair, K. Brad Wray, Jacob Giehm Mikkelsen, David Olagnier, Trine H. Mogensen

Presidential Fellows Articles and Research

Early host defense eliminates many viruses before infections are established while clearing others so they remain subclinical or cause only mild disease. The field of immunology has been shaped by broad concepts, including the pattern recognition theory that currently dominates innate immunology. Focusing on early host responses to virus infections, we analyze the literature to build a working hypothesis for the principles that govern the early line of cellular antiviral defense. Aiming to ultimately arrive at a criteria-based theory with strong explanatory power, we propose that both controlling infection and limiting inflammation are key drivers for the early cellular antiviral …

Single-Molecule Studies Reveal The Off-Pathway Early Paused State Intermediates As A Target Of Streptolydigin Inhibition Of Rna Polymerase And Its Dramatic Enhancement By Gre Factors, Anatolii Arseniev, Mikhail Panfilov, Georgii Pobegalov, Alina Potyseva, Polina Pavlinova, Maria Yakunina, Jookyung Lee, Sergei Borukhov, Konstantin Severinov, Mikhail Khodorkovskii

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Antibiotic streptolydigin (Stl) inhibits bacterial transcription by blocking the trigger loop folding in the active center of RNA polymerase (RNAP), which is essential for catalysis. We use acoustic force spectroscopy to characterize the dynamics of transcription elongation in ternary elongation complexes (ECs) of RNAP in the presence of Stl at a single-molecule level. We found that Stl induces long-lived stochastic pauses while the instantaneous velocity of transcription between the pauses is unaffected. Stl enhances the short-lived pauses associated with an off-pathway early paused state intermediates of the RNAP nucleotide addition cycle. Unexpectedly, we found that transcript cleavage factors GreA and …

Sk609, A Novel Dopamine D3 Receptor Agonist And Norepinephrine Transporter Blocker With Putative Pro-Cognitive Actions, Does Not Induce Psychostimulant-Like Increases In Risky Choice During Probabilistic Discounting, Christopher P. Knapp, Brooke Fallon, Sandhya Kortagere, Barry D. Waterhouse, Stan B Floresco, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

RATIONALE: Psychostimulants, such as amphetamine (AMPH) and methylphenidate (MPH), non-selectively elevate extracellular concentrations of the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), and are common pharmacological strategies used to improve prefrontal cortex (PFC)-dependent cognitive dysfunction. However, this approach can be problematic given AMPH has been shown to increase preference for risky choices in a rodent assay of risk/reward decision making. SK609 is a novel NE reuptake blocker that selectively activates DA D3 receptors without affinity for the DA transporter. SK609 has been shown to improve cognitive performance without increasing psychostimulant-like spontaneous locomotor activity, suggesting SK609 may benefit neurocognitive function without …

Elucidating The Mechanism Of Interleukin-17a Signaling In The Pathogenesis Of West Nile Virus, Farzana Nazneen

Dissertations

West Nile Virus (WNV), a neurotropic flavivirus transmitted by mosquitoes, is a leading cause of viral encephalitis in the United States and remains a significant public health concern. Unfortunately, no vaccine or therapeutic intervention is available against WNV infection. Previous studies, including ours, demonstrated that interleukin-17A (IL-17A) signaling increases the cytotoxic potential of CD8⁺ T cells to facilitate WNV and parasite clearance; however, the molecular mechanism is not understood. IL-17 receptor C (IL-17RC) is an obligatory co-receptor with IL-17 receptor A (IL-17RA) for signaling induced by IL-17A, IL-17A/F, and IL-17F. In this study, we found that IL-17RC deficient ( …

Ecological And Pathological Applications Of The Heat Shock Response, Taylor Rae Stanley

Theses and Dissertations

The heat shock response (HSR) is a cytoprotective stress response pathway that regulates cellular proteostasis. The HSR is an evolutionarily conserved pathway that is essential for normal cellular functioning. Here, we explore the broad ecological and pathological impacts of the HSR. In an ecological context, we perform gene level analysis of the transcriptomes of two closely related sunfish. We found that the more invasive bluegill sunfish has gene expansions in two HSR gene families, the HSP70 family and the HSP90 family compared to the redear sunfish. These gene expansions were also observed in several other teleost fish species and were …

Apoa2 Increases Cholesterol Efflux Capacity To Plasma Hdl By Displacing The C-Terminus Of Resident Apoa1, Snigdha Sarkar, Jamie Morris, Youngki You, Hannah Sexmith, Scott E. Street, Stephanie M. Thibert, Isaac K. Attah, Chelsea M. Hutchinson Bunch, Irina V. Novikova, James E. Evans, Amy S. Shah, Scott M. Gordon, Jere P. Segrest, Karin E. Bornfeldt, Tomas Vaisar, Jay W. Heinecke, W. Sean Davidson, John T. Melchior

Saha Cardiovascular Research Center Faculty Publications

Abstract The ability of high-density lipoprotein (HDL) to promote cellular cholesterol efflux is a more robust predictor of cardiovascular disease protection than HDL-cholesterol levels in plasma. Previously, we found that lipidated HDL containing both apolipoprotein A-I (APOA1) and A-II (APOA2) promotes cholesterol efflux via the ATP-binding cassette transporter (ABCA1). In the current study, we directly added purified, lipid-free APOA2 to human plasma and found a dose-dependent increase in whole plasma cholesterol efflux capacity. APOA2 likewise increased the cholesterol efflux capacity of isolated HDL with the maximum effect occurring when equal masses of APOA1 and APOA2 coexisted on the particles. Follow-up …

Untargeted Lipidomics Reveals Novel Hdl Metabotypes And Lipid-Clinical Correlates, Peer W. F. Karmaus, Scott M. Gordon, Marcus Y. Chen, Alison A. Motsinger-Reif, Rodney W. Snyder, Timothy R. Fennell, Suramya Waidyanatha, Reshan A. Fernando, Alan T. Remaley, Michael B. Fessler

Saha Cardiovascular Research Center Faculty Publications

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein …

Mechanisms Of Extracellular Vesicle Uptake And Implications For The Design Of Cancer Therapeutics, Stephanie R Jackson Cullison, Joseph P Flemming, Kubra Karagoz, Peter J Wermuth, Mỹ G Mahoney

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as …

Effects Of Cadherin Mediated Contact Normalization On Oncogenic Src Kinase Mediated Gene Expression And Protein Phosphorylation, Rachel E Nicoletto, Cayla J Holdcraft, Ariel C Yin, Edward P Retzbach, Stephanie A Sheehan, Amanda A Greenspan, Christopher M Laugier, Jason Trama, Caifeng Zhao, Haiyan Zheng, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called "contact normalization", to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a β-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. β-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to …

Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios

PANDION: The Osprey Journal of Research and Ideas

Maintaining glucose homeostasis is extremely important to remain in good health and prevent disease. This homeostasis is achieved via the regulation of hepatic metabolic pathways like gluconeogenesis and glycogenesis by insulin, which is expressed during high blood glucose. Insulin is responsible for facilitating the uptake of glucose into other tissues from the blood, as well as signaling whether to stimulate or slow glucose metabolism in the liver. Hyperglycemia is one of the main effects of diabetes, a disease characterized by the body’s inability to produce or respond to insulin. Without insulin, hepatic glucose output continues and blood glucose accumulates, causing …

Genetics Of Mdh In Humans, Adam Haberman, Celeste N. Peterson

Biology: Faculty Scholarship

Malate dehydrogenase (MDH) performs key roles in metabolism, but little is known about its function specifically in human health and disease. In this minireview, we describe the incomplete state of our knowledge of human MDH genetics. Humans have three MDH genes with a total of four validated isoforms. MDH1 and MDH2 are widely expressed, while MDH1B is only expressed in a small subset of tissues. Many mutations in MDH1 and MDH2 have been identified in patients, but only a few have been studied to determine what symptoms they cause. MDH1 has been associated with cancer and a neurodevelopmental disorder. MDH2 …

Aging-Related Changes In The Mechanical Properties Of Single Cells, Amarnath Singam, Chandrabali Bhattacharya, Seungman Park

Mechanical Engineering Faculty Research

Mechanical properties, along with biochemical and molecular properties, play crucial roles in governing cellular function and homeostasis. Cellular mechanics are influenced by various factors, including physiological and pathological states, making them potential biomarkers for diseases and aging. While several methods such as AFM, particle-tracking microrheology, optical tweezers/stretching, magnetic tweezers/twisting cytometry, microfluidics, and micropipette aspiration have been widely utilized to measure the mechanical properties of single cells, our understanding of how aging affects these properties remains limited. To fill this knowledge gap, we provide a brief overview of the commonly used methods to measure single-cell mechanical properties. We then delve into …

Distinct Expression Patterns Of Hedgehog Signaling Components In Mouse Gustatory System During Postnatal Tongue Development And Adult Homeostasis, Archana Kumari, Nicole E Franks, Libo Li, Gabrielle Audu, Sarah Liskowicz, John D Johnson, Charlotte M Mistretta, Benjamin L Allen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The Hedgehog (HH) pathway regulates embryonic development of anterior tongue taste fungiform papilla (FP) and the posterior circumvallate (CVP) and foliate (FOP) taste papillae. HH signaling also mediates taste organ maintenance and regeneration in adults. However, there are knowledge gaps in HH pathway component expression during postnatal taste organ differentiation and maturation. Importantly, the HH transcriptional effectors GLI1, GLI2 and GLI3 have not been investigated in early postnatal stages; the HH receptors PTCH1, GAS1, CDON and HHIP, required to either drive HH pathway activation or antagonism, also remain unexplored. Using lacZ reporter mouse models, we mapped expression of the HH …

Rewiring The Sex-Determination Pathway During The Evolution Of Self-Fertility., Yongquan Shen, Shin-Yi Lin, Jonathan Harbin, Richa Amin, Allison Vassalotti, Joseph Romanowski, Emily Schmidt, Alexis Tierney, Ronald E Ellis

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show …

Maackia Amurensis Seed Lectin (Masl) And Soluble Human Podoplanin (Shpdpn) Sequence Analysis And Effects On Human Oral Squamous Cell Carcinoma (Oscc) Cell Migration And Viability, Ariel C Yin, Cayla J Holdcraft, Eamonn J Brace, Tyler J Hellmig, Sayan Basu, Saumil Parikh, Katarzyna Jachimowska, Evelyne Kalyoussef, Dylan Roden, Soly Baredes, Eugenio M Capitle, David I Suster, Alan J Shienbaum, Caifeng Zhao, Haiyan Zheng, Kevin Balcaen, Simon Devos, Jurgen Haustraete, Mahnaz Fatahzadeh, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, …

Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate …

Intra-Accumbens Microinfusion Of The Dopamine D3 Receptor Partial Agonist (±)Vk4-40 Does Not Affect Basal Locomotion In Mice, Yeonwoo Sim, Nicole M. Hinds, Amy Hauck Newman, Daniel F. Manvich

Rowan-Virtua Research Day

The opioid epidemic remains a pressing public health crisis, prompting the search for alternative pharmacotherapies for Opioid Use Disorder (OUD). This study explores the potential of the dopamine D3 receptor (D3R) partial agonist, (±)VK4-40, as a novel treatment option. We investigated the impact of intra-nucleus accumbens (NAc) microinfusion of VK4-40 on basal locomotion in mice. Results indicate that VK4-40 did not significantly alter basal locomotion, suggesting that its therapeutic effects may not be mediated through disruptions in generalized motor function. Future research will focus on elucidating the neuropharmacological mechanisms underlying VK4-40's therapeutic actions and exploring its effects on psychostimulant-induced hyperlocomotion. …

Loss Of Tumor Suppressor Tmem127 Drives Ret-Mediated Transformation Through Disrupted Membrane Dynamics, Timothy J Walker, Eduardo Reyes-Alvarez, Brandy D Hyndman, Michael G Sugiyama, Larissa C B Oliveira, Aisha N Rekab, Mathieu J F Crupi, Rebecca Cabral-Dias, Qianjin Guo, Patricia L M Dahia, Douglas S Richardson, Costin N Antonescu, Lois M Mulligan

Faculty, Staff and Student Publications

Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumor pheochromocytoma (PCC) can be caused by activating mutations of the rearranged during transfection (RET) receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumor suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and …

Investigating Optimal Laboratory Growth Conditions Of Gracilibacillus Halotolerans In Media Supplemented With Salt, Isaac Young

Annual Research Symposium

As interest continues to grow in the field of persister cells and their morphology, there arises an ever-evolving desire to further understand specific strains of bacteria that exemplify the qualities of seemingly anomalous survival regardless of anti-bacterial treatment. In the case of the Gracilibacillus halotolerans, a halotolerant extremophile extracted from the Great Salt Lake with known persistent characteristics, uncovering its optimal growth conditions was essential for future investigations. Identifying the optimal salinity for the growth of G. halotolerans will allow us to standardize our growth methods, uncover several mechanisms of saline tolerance, and add to future investigations of persistence with …

Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …

Prenatal Androgen Exposure Reduces Ovarian Function, Marlee Weets

All Master's Theses

Polycystic ovary syndrome (PCOS) is the most common reproductive and endocrine disorder, being the leading cause of infertility for females of reproductive age. The etiology of PCOS is not fully known, although it is hypothesized that there is a genetic, epigenetic, and environmental component to the disease. One of the environmental influences that can cause an abnormal reproductive phenotype similar to PCOS is prenatal exposure to excess androgens (male sex hormones). Previous studies have shown that prenatal exposure to androgens in mice can cause a PCOS-like ovarian phenotype similar to people with PCOS. To examine how prenatal androgen exposure causes …