Cell and Developmental Biology Commons^™

Dysregulation Of Cholesterol Metabolism And Sorafenib Drug Resistance In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard Anaya, Ana Ayala Pazzi, Manish K. Tripathi

Research Symposium

Background: Hepatocellular carcinoma (HCC) is among the most prevalent cancers and a leading cause of cancer-related deaths worldwide. Sorafenib, a multikinase inhibitor, serves as a key first-line treatment for HCC when surgical intervention is not an option. However, primary and acquired resistance to sorafenib has significantly limited its effectiveness, reducing the disease control rate. Dysregulation of numerous genes that influence cancer cell proliferation, survival, and drug resistance contributes to this challenge. Identifying the molecular drivers of sorafenib resistance remains critical to improving treatment outcomes. Several factors, including activation of oncogenic pathways (e.g., Akt/mTOR), hypoxia, cholesterol metabolism, EMT, multidrug resistance, and …

Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry

Research Symposium

Background: Our group discovered that FOXO transcription factors drive stem gene expression in cancer to promote aggressiveness. Work by our group and others demonstrated that FOXO factors universally maintain stem cells including in cancer, embryonic, hematogenic and neuronal contents. Our current efforts are delineating the molecular underpinnings by which FOXO factors halt differentiation to maintain stem cells.

In this project, we are employing myoblasts as a valuable model to examine how Foxo1 maintains stem cells. Foxo1-regulated genes in myoblasts closely parallel its targets in glioblastoma and basal breast cancer stem cells, including targets such as Leukemia Inhibitory Factor, …

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 …

5-Hydroxymethylcytosine Sequencing Of Plasma Cell-Free Dna Identifies Epigenomic Features In Prostate Cancer Patients Receiving Androgen Deprivation Therapies, Qianxia Li, Chiang-Ching Huang, Shane Huang, Yijun Tian, Jinyong Huang, Amirreza Bitaraf, Xiaowei Dong, Marja T. Nevalainen, Manishkumar Patel, Jodie Wong, Jingsong Zhang, Brandon J Manley, Jong Y. Park, Manish Kohli, Elizabeth M. Gore, Deepak Kilari, Liang Wang

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: We evaluated whether 5hmC signatures in cell-free DNA (cfDNA) are associated with treatment failure to androgen-deprivation therapies (ADT) among men with hormone-naive prostate cancer.

METHODS: We collected a total of 139 serial plasma samples from 55 prostate cancer patients receiving ADT at 3 time points including baseline (before initiating ADT, n = 55); 3 months (after initiating ADT, n = 55); and disease progression (n = 15) within 24 months or 24 months if no progression was detected (n = 14). We used selective chemical labeling sequencing to quantify 5hmC abundance across the genome and Kaplan-Meier analysis to assess …

Uncovering The Mechanisms Of Glioblastoma Relapse Prevention With Niclosamide And Camptothecin Treatment, Xiaoqian Fang, Araely Ruiz, Eunseo Yang, Brianna Morin, Kimberly Herrera-Toscano, Megan Szobody, Josue Fonseca, John-Beloved Osho, Raquel Lara

Research Symposium

Background: Glioblastoma multiforme (GBM) is the most common and lethal malignant primary brain tumor for which the development of efficacious chemotherapeutic agents remains an urgent need. In our previous studies, we demonstrated that niclosamide and camptothecin (CPT) synergistically suppressed the proliferation in human glioblastoma U87 MG cells. Recently, we observed that U87 MG cells failed to resume growth after the combined treatment was removed, a phenomenon not seen with either agent alone. We aimed to explore the sustained anti-tumor effects of niclosamide and CPT in GBM.

Methods: Human glioblastoma U87 MG cells were treated with 5 mM niclosamide, 5 mM …

The Encyclopedia Of North American Drosophilids Volume 3: Drosophilids Of The Northwest, Thomas Werner, Tessa Steenwinkel, John Jaenike

Open Access Books

The Encyclopedia of North American Drosophilids Volume 3: Drosophilids of the Northwest provides an introduction to the flies of the family Drosophilidae of the Northwest of the United States. The book strives to facilitate identification of most of the drosophilid species in this region and provides remarks on interesting aspects of their biology and suggestions for future research on them. The book is intended for researchers, teachers, and students wishing to discover the diversity of these flies.

View the 3 Volume Series of The Encyclopedia of North American Drosophilids here: https://digitalcommons.mtu.edu/fruitflies/

Access The Encyclopedia of North American Drosophilids Volume 1: …

Cargo Hitchhiking Autophagy - A Hybrid Autophagy Pathway Utilized In Yeast, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Macroautophagy is a catabolic process that maintains cellular homeostasis by recycling intracellular material through the use of double-membrane vesicles called autophagosomes. In turn, autophagosomes fuse with vacuoles (in yeast and plants) or lysosomes (in metazoans), where resident hydrolases degrade the cargo. Given the conservation of autophagy,

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 …

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.

The Role Of Non-Coding Rnas As An Innovative Therapeutic Tool For Hepatocellular Carcinoma, Nabila Mohamed Hosni El Kramani

Theses and Dissertations

Hepatocellular carcinoma (HCC) is the second lethal cancer worldwide, with over 60 million new patients added annually. Hepatitis B infection and toxins, e.g., aflatoxin, contribute to the incidence of HCC. Egypt and China show the highest prevalence of viral hepatitis and HCC in the world.

Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts larger than 200 nucleotides. These transcripts work at the transcriptional, post-transcriptional, and epigenetic levels to regulate gene expression by interacting with various biomolecules, such as RNA, DNA, and proteins. They serve essential functions in chromatin remodeling and cell survival, differentiation, and proliferation. The role and biological interactions of …

Nicotine-Driven Modulation Of Mtor Pathway In Oral Squamous Cell Carcinoma: A Cell-Specific Response To E-Cig Vapor Exposure, Kristina Vu

Annual Research Symposium

No abstract provided.

The Impact Of Electronic Cigarette Vapor And Cigarette Smoke On Oral Squamous Cell Carcinoma Invasion And Inflammation, Neha Patel

Annual Research Symposium

No abstract provided.

Comprehensive Sumo Proteomic Analyses Identify Hiv Latency-Associated Proteins In Microglia., Fergan Imbert, Dianne Langford

Rowan-Virtua School of Osteopathic Medicine Departmental Research

SUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at …

Delphi-Driven Consensus Definition For Mesenchymal Stromal Cells And Clinical Reporting Guidelines For Mesenchymal Stromal Cell-Based Therapeutics, Laurent Renesme, Kelly D. Cobey, Manoj M. Lalu, Tania M. Bubela, Raghavan Chinnadurai, John De Vos, Rod Dunbar, Dean Fergusson, Daniel Freund, Jacques Galipeau

Office of the Provost

Background aims: Despite promising results in pre-clinical studies, mesenchymal stromal cells (MSCs) face significant challenges in clinical translation. A scoping review by our group highlighted two key issues contributing to this gap: (i) lack of a clear and consensus definition for MSCs and (ii) under-reporting of critical parameters in MSC clinical studies. To address these issues, we conducted a modified Delphi study to establish and implement a consensus definition for MSCs and develop reporting guidelines for MSC clinical studies.
Methods: A steering committee of 22 international experts, including stakeholders from different MSC research fields, participated in the three Delphi rounds. …

The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker

Dissertations, Theses, and Capstone Projects

Under normoxic conditions, eukaryotes initiate translation of RNA through eIF4E recognition of the 5’ cap. However, under cellular stress, eukaryotic translation must be initiated through a 4E-independent, or “cap-independent” mechanism, involving eukaryotic initiation factor 4G (eIF4G) binding directly to the 5’ untranslated regions (5’ UTR) of the RNA. eIF4G binding then recruits the ribosome to the transcript. While this mechanism is useful for translation of apoptotic transcripts and transcripts involved in cell survival, cap-independent translation is also utilized by oncogenic RNA for tumorigenesis. Previous work by our lab and others has categorized this recruitment and initiation mechanism as either internal-ribosome-entry-site …

Staying Sane In The Membrane: Neutral Sphingomyelinase 2 As A Master Regulator Of Plasma Membrane Ceramide, Zainuddin Quadri, Erhard Bieberich

Markey Cancer Center Faculty Publications

Ceramide, a key signaling sphingolipid in the plasma membrane, plays a pivotal role in fundamental cellular processes such as adhesion, polarity, and programmed cell death. The generation of plasma membrane ceramide is largely attributed to the activity of two types of sphingomyelinases: neutral sphingomyelinase 2 (nSMase2, Smpd3) and acid sphingomyelinase (aSMase, Smpd1). While many studies have explored ceramide generation following experimental activation of these enzymes, the mechanisms governing basal or steady- state ceramide levels have remained poorly understood. Using an innovative mass spectrometry approach developed in the Canals’ lab, the team has quantified the distinct contributions of nSMase2 and aSMase …

Crosstalk Between Nnos/No And Cox-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression, Anika Patel, Shirley Tong, Moom R. Roosan, Basir Syed, Amardeep Awasthi, Richard B. Silverman, Sun Yang

Pharmacy Faculty Articles and Research

Background/Objectives: Interferon gamma (IFN-γ) in the melanoma tumor microenvironment plays opposing roles, orchestrating both pro-tumorigenic activity and anticancer immune responses. Our previous studies demonstrated the role of neuronal nitric oxide synthase (nNOS) in IFN-γ-stimulated melanoma progression. However, the underlying mechanism has not been well defined. This study determined whether the nNOS/NO and COX-2/PGE2 signaling pathways crosstalk and augment the pro-tumorigenic effects of IFN-γ in melanoma. Methods: Bioinformatic analysis of patient and cellular proteomic data was conducted to identify proteins of interest associated with IFN-γ treatment in melanoma. Changes in protein expression were determined using various analytical techniques including …

Sigma1 Inhibitor Suppression Of Adaptive Immune Resistance Mechanisms Mediated By Cancer Cell Derived Extracellular Vesicles, Paola A. Castagnino, Derick A. Haas, Luca Musante, Nathalia A. Tancler, Bach V. Tran, Rhonda Kean, Alexandra R. Steck, Luis A. Martinez, Elahe A. Mostaghel, D. Craig Hooper, Felix J. Kim

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER. Sigma1 is a unique ligand-regulated integral membrane scaffolding protein enriched in the ER of cancer cells. PD-L1 is an integral membrane glycoprotein that is translated into the ER and processed through the cellular secretory pathway. At the cell surface, PD-L1 is an immune …

Mitochondrial Mrna And The Small Subunit Rrna In Budding Yeasts Undergo 3'-End Processing At Conserved Species-Specific Elements, Michael Anikin, Michael F Henry, Viktoria Hodorova, Hristo B Houbaviy, Jozef Nosek, Dimitri G Pestov, Dmitriy A Markov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Respiration in eukaryotes depends on mitochondrial protein synthesis, which is performed by organelle-specific ribosomes translating organelle-encoded mRNAs. Although RNA maturation and stability are central events controlling mitochondrial gene expression, many of the molecular details in this pathway remain elusive. These include

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 …

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …

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 …

Investigating The Interactions Between Elm1 And Hsl7 In The Morphogenesis Checkpoint Of Saccharomyces Cerevisiae, Rachel Foster

Masters Theses & Specialist Projects

Cell shape is essential to understanding the normal regulatory processes that occur within the cell and can indicate there are abnormalities present when there is dysfunction in the cell's development, which can have broader implications regarding human disease. The morphogenesis pathway couples cell division to the timely formation of a daughter bud in Saccharomyces cerevisiae and consists of Elm1, Hsl1, Hsl7, and Swe1 proteins which interact with septins at the bud neck to provide stability for the bud and to facilitate cell division. Elm1 is needed for the recruitment of Hsl1 and subsequently Hsl7. Hsl7 will then tether Swe1 to …

The Cdk8 Kinase Module: A Novel Player In The Transcription Of Translation Initiation And Ribosomal Genes, Brittany Friedson, Stephen D Willis, Natalia Shcherbik, Alicia N Campbell, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Survival following stress is dependent upon reprogramming transcription and translation. Communication between these programs following stress is critical for adaptation but is not clearly understood. The Cdk8 kinase module (CKM) of the Mediator complex modulates the transcriptional response to various stresses. Its involvement in regulating translational machinery has yet to be elucidated, highlighting an existing gap in knowledge. Here, we report that the CKM positively regulates a subset of ribosomal protein (RP) and translation initiation factor (TIF)-encoding genes under physiological conditions in Saccharomyces cerevisiae. In mouse embryonic fibroblasts and HCT116 cells, the CKM regulates unique sets of RP and TIF …

Tight Junction Protein Impact On Sonic Hedgehog Pathway, Josh Freeman, Hudson Christensen, Dario Mizrachi

Library/Life Sciences Undergraduate Poster Competition 2025

The Sonic Hedgehog Pathway is critical for cell division and proliferation, and when disrupted, can be a major contributor to the overproliferation of cells and complications in the organism from the resultant cancers. Experimentation upon the organism Planaria Torva and A549 cells using chimera Occludin (COC)–a traditionally isolated tight junction protein having no role in the SHH pathway–has shown dramatic changes within the organism/cell signaling system, suggesting that tight-junction proteins may play a role in–or can be used to manipulate–this specific cell signaling pathway by inhibiting or activating key proteins. The possibility of a “mechanotransduction” effect by COC on SHH …

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 …

Anti-Cancer Compounds Based On Natural Imidazole Compounds, Autumn Forsythe, Victoria Hardy, Kerri L. Shelton

CSU Tower Day

We are developing a comprehensive review on imidazole-based compounds of natural origin, the most common groups of compounds, and their properties, such as the imidazole ring. The intent of this presentation is to learn about the compound’s occurrence, general/predicted properties, and advantages. The review will be a fluid development comparing imidazole derivatives of natural origin with antinociceptive/lethal properties from the last 5 years. This review would include both purely extracted products but also those modified by synthesis.

Ms Environmental Biology Capstone: Evaluating Environmental Risks And Conflicts In Golf Course Landscapes, Meredith Boos

Regis University Student Publications (comprehensive collection)

1) This review investigates the relationship between pesticide use on golf courses and in agriculture to determine whether the adverse health effects documented in agricultural settings also apply to golf course environments. While the negative health effects from agricultural pesticide use are well established, golf courses use pesticides with greater frequency and intensity, suggesting a potentially higher exposure risk for both workers and players.

2) This study proposes methods to quantify pesticide bioaccumulation on golf courses and adjacent lands. We hypothesize that areas surrounding golf courses will exhibit a spatial gradient of pesticide accumulation, increasing with proximity to treated sites …

End Epilepsy: Human And Rodent Seizures Demonstrate A Dynamic Interplay With Spreading Depolarizations, Daniel Hummel, Jacob H. Norby, Noah Ricks, John D. Rolston, Shervin Rahimpour, Juha Voipio, Andrew J. Trevelyan, Elliot H. Smith, Ryley Parrish

Library/Life Sciences Undergraduate Poster Competition 2025

Affecting more than 50 million people worldwide, Epilepsy is a condition of repeated seizures. Seizures (Sz) occur when brain cells transmit uncontrolled electrical signals, and most often terminate on their own, but how this happens is unknown. A proposed mechanism of Sz termination is a spreading depolarization (SD). A SD is a wave that travels through the brain, suppressing brain activity. Currently, the relationship between SDs and seizures is not well understood. The goal of this study was to understand how the two phenomena interact in both rodent brains, and humans. Better understanding of SDs may lead to the development …