Medical Cell Biology Commons^™

Invasion And Metastasis In Cancer: Molecular Insights And Therapeutic Targets, Yongxing Li, Fengshuo Liu, Qingjin Cai, Lijun Deng, Qin Ouyang, Xiang H-F Zhang, Ji Zheng

Faculty, Staff and Students Publications

The progression of malignant tumors leads to the development of secondary tumors in various organs, including bones, the brain, liver, and lungs. This metastatic process severely impacts the prognosis of patients, significantly affecting their quality of life and survival rates. Research efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management strategies. Consequently, a comprehensive understanding of the biological foundations of tumor metastasis, identification of pivotal signaling pathways, and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic tumors. However, current research is …

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

Annual Research Symposium

No abstract provided.

Mir-125a-3p And Its Targets: Promising Biomarkers For Ovarian, Liver, And Breast Cancers, Offering A Beacon Of Hope For More Effective Diagnosis And Treatment Strategies, Eman Kamaleldien Anwer

Theses and Dissertations

Cancer is a worldwide health problem with various genetic and epigenetic alterations, resulting in disease heterogeneity. Effective diagnostic, therapeutic, and monitoring markers have been determined recently; however, new diagnostic, prognostic, and therapeutic markers are needed. MicroRNAs (miRNA), short non-coding RNAs, have a highlighted role in cancer progression, migration, and programmed cell death. Our study aims to investigate the significance of miR-125a-3p and its downstream targets in breast (BRCA), hepatocellular (HCC), and ovarian (OVCA) malignancies and their possibility as diagnostic biomarkers and targets for therapeutic agents. Bioinformatics and online tools were used to determine the miRNA-predicted downstream targets, analyze GEO datasets, …

In-Silico Modeling And Characterization Of Kcc2 Protein Interaction With A Small Molecule Direct Agonist Identifies Potential Binding Sites For Modulating Behaviors Associated With Substances Of Abuse, William Hai Dang Ho, Alfred Amendolara, Kenyon Mitchell, Jaden Miner, Ruth Northcott, Braxton Bingham, Andrew J. Payne

Annual Research Symposium

Purpose

KCC2 is a potassium-chloride cotransporter that plays a critical role in neuronal function by regulating GABAergic signaling via chloride gradients. Maintaining this concentration gradient is crucial for balancing excitation and inhibition in the brain. While KCC2 dysregulation has been implicated in epilepsy and seizures, recent studies suggest that KCC2 inhibition results in phenotypes mirroring those seen in chronic opioid dependence. As such, increasing evidence support KCC2 being a potential therapeutic target for modulating behaviors associated with substances of abuse. Currently, only a few direct small molecule agonists against KCC2 have been reported, and no definitive active site on the …

Machine Learning-Enhanced Surface-Enhanced Spectroscopic Detection Of Polycyclic Aromatic Hydrocarbons In The Human Placenta, Oara Neumann, Yilong Ju, Andres B Sanchez-Alvarado, Guodong Zhou, Weiwu Jiang, Bhagavatula Moorthy, Melissa A Suter, Ankit Patel, Peter Nordlander, Naomi J Halas

Faculty, Staff and Students Publications

The detection and identification of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, polycyclic aromatic compounds (PACs), are essential for environmental and health monitoring, for assessing toxicological exposure and their associated health risks. PAHs/PACs are the most dangerous chemicals found in tobacco smoke, and cigarette use during pregnancy can convey these molecules to the developing fetus through the placenta. This exposure is associated with many negative health outcomes, from premature birth to sudden infant death syndrome and adverse neurodevelopmental disorders. This study demonstrates the use of surface-enhanced Raman and surface-enhanced infrared absorption spectroscopies for direct detection of PAHs/PACs in human placental …

Plasma Micrornas To Select Optimal Patients For Antibody Production From Anti-Addiction Vaccines, Thomas R Kosten, Amrit Koirala, David A Nielsen, Coreen B Domingo, Ynhi T Thomas, Preethi H Gunaratne, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Cocaine and illicit amphetamines (disguised as “Adderall”) are being laced with fentanyl and producing accidental and intentional fatal overdoses. Vaccines can prevent these overdoses, but 33% of humans generate insufficient anti-drug antibody (AB) levels. Plasma microRNAs (miRs) can be used to predict non-responders. We have plasma stored from 152 cocaine vaccine trial participants following three vaccinations over 9 weeks and examined miRs as potential response biomarkers. Methods: We compared 2517 miRs before anti-cocaine vaccination in participants with the highest (n = 25) to the lowest (n = 23) antibody levels. False Discovery Rates (FDRs) were applied to identify differentially …

Author Correction: Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao

Faculty, Staff and Students Publications

Correction to: Nature Communications 10.1038/s41467-024-55134-9, published online 30 December 2024

In the version of the article initially published, there were errors in Fig. 3d, where in the x-axis labels now reading “GPP-shRNA1, GPP-shRNA2, GPP-shRNA3…,” the second and third labels were duplicates of the first. The figure is amended in the HTML and PDF versions of the article.

Anatomy And Variations Of The Carina And Its Cartilaginous Makeup: A Cadaveric Study, Chung Yoh Kim, Kristen Rizzuto, Daniel Tahan, Devendra Shekhawat, Rarinthorn Samrid, Yoko Tabira, Stephen J. Bordes, Joe Iwanaga, R. Shane Tubbs

School of Medicine Faculty Publications

Purpose: The carina, located at the bifurcation of the trachea, has been regarded as a part of the trachea. Although clinically useful as an anatomical landmark, studies of its detailed morphology are lacking in the literature. Methods: The distal trachea and left and right main bronchi were harvested from 32 cadavers and the carina studied using microsurgical dissection, endoscopy, micro-CT, and histology. Results: The right bronchial cartilages were most commonly involved in forming the carina (72.41%), and the left bronchial cartilages were the second most commonly involved (37.93%). The carinal cartilages were slightly deviated to the left of midline in …

Cardiac Surgical Bleeding, Transfusion, And Quality Metrics: Joint Consensus Statement By The Enhanced Recovery After Surgery Cardiac Society And Society For The Advancement Of Patient Blood Management, Rawn Salenger, Rakesh C Arora, Arthur Bracey, Mario D'Oria, Daniel T Engelman, Caroline Evans, Michael C Grant, Serdar Gunaydin, Vicki Morton, Sherri Ozawa, Prakash A Patel, Jacob Raphael, Todd K Rosengart, Linda Shore-Lesserson, Pierre Tibi, Aryeh Shander

Faculty, Staff and Students Publications

Background: Excessive perioperative bleeding is associated with major complications in cardiac surgery, resulting in increased morbidity, mortality, and cost.

Methods: An international expert panel was convened to develop consensus statements on the control of bleeding and management of transfusion and to suggest key quality metrics for cardiac surgical bleeding. The panel reviewed relevant literature from the previous 10 years and used a modified RAND Delphi methodology to achieve consensus.

Results: The panel developed 30 consensus statements in 8 categories, including prioritizing control of bleeding, prechest closure checklists, and the need for additional quality indicators beyond reexploration rate, such as time …

Virus-Specific T-Cell Therapy For The Management Of Viral Infections In The Immunocompromised, Kiriakos Koukoulias, Penelope Georgia Papayanni, Ann Marie Leen, Spyridoula Vasileiou

Faculty, Staff and Students Publications

Background: Immunocompromised individuals are at major risk for severe infectious complications. This is particularly relevant in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT) - a treatment modality that has proven curative for a range of malignant and nonmalignant hematological diseases. However, transplant-associated immune suppression leaves patients susceptible to infectious complications from viruses such as cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and BK virus (BKV). While pharmacological agents are available to prevent and/or treat some of these viruses, they can be associated with significant toxicities and are often ineffective. To circumvent these issues, several groups have explored the …

Hypoxia Signaling In The Adipose Tissue, Phu M Huynh, Fenfen Wang, Yu A An

Faculty, Staff and Student Publications

Obesity per se is rapidly emerging all over the planet and further accounts for many other life-threatening conditions, such as diabetes, cardiovascular diseases, and cancers. Decreased oxygen supply or increased relative oxygen consumption in the adipose tissue results in adipose tissue hypoxia, which is a hallmark of obesity. This review aims to provide an up-to-date overview of the hypoxia signaling in the adipose tissue. First, we summarize literature evidence to demonstrate that hypoxia is regularly observed during adipose tissue remodeling in humans and rodent models with obesity. Next, we discuss how hypoxia-inducible factors (HIFs) are regulated and how adipose tissues …

Trmt1l-Catalyzed M22g27 On Tyrosine Trna Is Required For Efficient Mrna Translation And Cell Survival Under Oxidative Stress, Sseu-Pei Hwang, Han Liao, Katherine Barondeau, Xinyi Han, Cassandra Herbert, Hunter Mcconie, Amirtha Shekar, Dimitri G Pestov, Patrick A Limbach, Jeffrey T Chang, Catherine Denicourt

Faculty, Staff and Student Publications

tRNA modifications are critical for several aspects of their functions, including decoding, folding, and stability. Using a multifaceted approach encompassing eCLIP-seq and nanopore tRNA-seq, we show that the human tRNA methyltransferase TRMT1L interacts with the component of the Rix1 ribosome biogenesis complex and binds to the 28S rRNA as well as to a subset of tRNAs. Mechanistically, we demonstrate that TRMT1L is responsible for catalyzing N2,N2-dimethylguanosine (m22G) solely at position 27 of tRNA-Tyr-GUA. Surprisingly, TRMT1L depletion also impaired the deposition of 3-(3-amino-3-carboxypropyl) uridine (acp3U) and dihydrouridine on tRNA-Tyr-GUA, Cys-GCA, and Ala-CGC. TRMT1L knockout cells have a marked decrease in tRNA-Tyr-GUA …

Dna Methylation Profiling At Base-Pair Resolution Reveals Unique Epigenetic Features Of Early-Onset Colorectal Cancer In Underrepresented Populations, Jason Sheng Li, Karen Riggins, Li Yang, Chaorong Chen, Patricia Castro, Wedad Alfarkh, Neda Zarrin-Khameh, Michael E Scheurer, Chad J Creighton, Benjamin Musher, Wei Li, Lanlan Shen

Faculty, Staff and Students Publications

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients.

RESULTS: We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top …

Nkapl Facilitates Transcription Pause-Release And Bridges Elongation To Initiation During Meiosis Exit, Zhenlong Kang, Chen Xu, Shuai Lu, Jie Gong, Ruoyu Yan, Gan Luo, Yuanyuan Wang, Qing He, Yifei Wu, Yitong Yan, Baomei Qian, Shenglin Han, Zhiwen Bu, Jinwen Zhang, Xian Xia, Liang Chen, Zhibin Hu, Mingyan Lin, Zheng Sun, Yayun Gu, Lan Ye

Faculty, Staff and Students Publications

Transcription elongation, especially RNA polymerase II (Pol II) pause-release, is less studied than transcription initiation in regulating gene expression during meiosis. It is also unclear how transcription elongation interplays with transcription initiation. Here, we show that depletion of NKAPL, a testis-specific protein distantly related to RNA splicing factors, causes male infertility in mice by blocking the meiotic exit and downregulating haploid genes. NKAPL binds to promoter-associated nascent transcripts and co-localizes with DNA-RNA hybrid R-loop structures at GAA-rich loci to enhance R-loop formation and facilitate Pol II pause-release. NKAPL depletion prolongs Pol II pauses and stalls the SOX30/HDAC3 transcription initiation complex …

Exosomal Galectin-3 Promotes Peritoneal Metastases In Gastric Adenocarcinoma Via Microenvironment Alterations, Yibo Fan, Shumei Song, Melissa Pool Pizzi, Gengyi Zou, Jody V Vykoukal, Katsuhiro Yoshimura, Jiankang Jin, George A Calin, Rebecca E Waters, Qiong Gan, Linghua Wang, Samir Hanash, Shilpa S Dhar, Jaffer A Ajani

Faculty, Staff and Student Publications

Peritoneal carcinomatosis (PC) in gastric adenocarcinoma (GAC) is the most common metastatic site and leads to a short median survival. Exosomes have been shown to remodel the microenvironment, facilitating tumor metastases. However, the functional component in GAC cell-derived exosomes that remodel the landscape in the peritoneal cavity remains unclear. To address this, we performed in-depth proteomic profiling of ascites-derived exosomes from patients with PC, and we found that Galectin-3 was highly enriched in exosomes derived from malignant ascites. exosomal Galectin-3 was the crucial regulator of PC. Blockage of exosomal Galectin-3 significantly inhibited tumor metastases and prolonged overall survival. Exosomal Galectin-3 …

Pharmacological Or Genetic Inhibition Of Ltcc Promotes Cardiomyocyte Proliferation Through Inhibition Of Calcineurin Activity, Lynn A C Devilée, Abou Bakr M Salama, Jessica M Miller, Janice D Reid, Qinghui Ou, Nourhan M Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K Rosengart, Douglas Andres, Jonathan Satin, Tamer M A Mohamed, James E Hudson, Riham R E Abouleisa

Faculty, Staff and Students Publications

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle …

Molecular Dynamics At Immune Synapse Lipid Rafts Influence The Cytolytic Behavior Of Car T Cells, Ahmed Z Gad, Jessica S Morris, Lea Godret-Miertschin, Melisa J Montalvo, Sybrina S Kerr, Harrison Berger, Jessica C H Lee, Amr M Saadeldin, Mohammad H Abu-Arja, Shuo Xu, Spyridoula Vasileiou, Rebecca M Brock, Kristen Fousek, Mohamed F Sheha, Madhuwanti Srinivasan, Yongshuai Li, Arash Saeedi, Kandice R Levental, Ann M Leen, Maksim Mamonkin, Alexandre Carisey, Navin Varadarajan, Meenakshi Hegde, Sujith K Joseph, Ilya Levental, Malini Mukherjee, Nabil Ahmed

Faculty, Staff and Students Publications

Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART. We reasoned that molecular dynamics at the CART immune synapse (CARIS) could explain differences in their tumor rejection kinetics. We observed that CD28.ζ-CART engaged in brief highly lethal CARIS and mastered serial killing, whereas 4-1BB.ζ-CART formed lengthy CARIS and relied on robust expansion and cooperative killing. We analyzed CARIS membrane lipid rafts (mLRs) and found that, upon tumor engagement, CD28.ζ-CAR molecules rapidly but transiently translocated into mLRs, mobilizing the microtubular organizing center and lytic granules …

Fluorescence Lifetime Sorting Reveals Tunable Enzyme Interactions Within Cytoplasmic Condensates, Leyla E Fahim, Joshua M Marcus, Noah D Powell, Zachary A Ralston, Katherine Walgamotte, Eleonora Perego, Giuseppe Vicidomini, Alessandro Rossetta, Jason E Lee

Faculty, Staff and Students Publications

Ribonucleoprotein (RNP) condensates partition RNA and protein into multiple liquid phases. The multiphasic feature of condensate-enriched components creates experimental challenges for distinguishing membraneless condensate functions from the surrounding dilute phase. We combined fluorescence lifetime imaging microscopy (FLIM) with phasor plot filtering and segmentation to resolve condensates from the dilute phase. Condensate-specific lifetimes were used to track protein-protein interactions by measuring FLIM-Förster resonance energy transfer (FRET). We used condensate FLIM-FRET to evaluate whether mRNA decapping complex subunits can form decapping-competent interactions within P-bodies. Condensate FLIM-FRET revealed the presence of core subunit interactions within P-bodies under basal conditions and the disruption of …

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 …

Development Of The Mechanoresponsive Pericellular Matrix Of Chondrons, Donghee Lee, Sydney E. Greer, Andrew T. Dudley

Journal Articles: Genetics, Cell Biology & Anatomy

Physical properties of cartilage are conferred by the composition and ultrastructure of the extracellular matrix. This study focuses on the development of the pericellular matrix (PCM), a domain that directly contacts the chondrocyte and is a key regulator of biomechanical and biochemical signaling. Using three-dimensional cell culture, microfluidic cell compression platforms, and genetic mouse models, we demonstrated that collagen VI is initially assembled at the cell surface and then displaced to form a shell at the PCM-territorial matrix boundary. Cell surface-bound hyaluronan is crucial for the assembly process, and hyaluronan-aggrecan complexes drive displacement. Integrin adhesion is not required early but …