Anatomy Commons^™

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

Anaplastic Large Cell Lymphoma In Children And Adolescents, Eric J. Lowe, Wilhelm Woessmann

Department of Pediatrics Faculty Publications

Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) accounts for >95% of ALCL cases in children and adolescents. The first description of ALCL as a CD30-positive lymphoma in 1985 was followed by the detection of chromosomal translocations involving the ALK gene at chromosome 2p23. The pathogenesis of ALK-positive ALCL is based on signalling from the constitutive active ALK kinase. The clinical characteristics, therapy regimens and outcome data were reported in the 1990s and 2000s. Different chemotherapy regimens led to astonishingly similar long-term event-free survival rates of 70%, independent of the drugs, doses and duration of therapy. Additionally, patients with relapsed …

Cellular And Molecular Mechanisms Of Lung Regeneration, Repair, And Fibrosis, Volume Ii, Yong Qiu, Xiao Xiao Tang, Shigeyuki Shichino, Prem Prakash Kushwaha, Yan Y. Sanders, Remo Castro Russo, Chunheng Mo

Department of Biomedical and Translational Sciences Faculty Publications

[Introduction] Organ fibrosis represents a substantial a major contributor to global disease burden, implicated in over 30% of cases leading to disability-associated and fatal conditions. Among these conditions, idiopathic pulmonary fibrosis (IPF) stands as a progressive and frequently fatal interstitial lung disease characterized by aberrant extracellular matrix deposition and parenchymal scarring. The prognosis for IPF patients is poor, with a median survival time of just 3–5 years (Bhattacharya and Ramachandran, 2023; Lederer and Martinez, 2018, Ma et al., 2024, Wei et al., 2024). Current FDA-approved therapeutics, Pirfenidone and Nintedanib, demonstrate capacity to attenuate functional decline in pulmonary fibrosis but remain …

The Central Role For Troponin C Amino-Terminal ⍺-Helix In Vertebrate Thin Filiment Ca²⁺-Activation, Yun Shi, Lauren A. Blackwell, Ryan K. Schroy, B. Max Cleland, Cristina M. Risi, Michelle S. Parvatiyar, Jose R. Pinto, Vitold E. Galkin, P. Bryant Chase

Department of Biomedical and Translational Sciences Faculty Publications

Troponin C (TnC) is the Ca²⁺-sensing subunit of troponin that is responsible for activating thin filaments in striated muscle, and, in turn, for regulating the systolic and diastolic contractile function of cardiac muscle. The secondary structure of vertebrate TnC is mainly composed of α-helices, with nine helices named sequentially, starting from the amino terminus, from N to A–H. The N-helix is a 12-residue-long α-helix located at the extreme amino terminus of the protein and is the only helical structure that does not participate in forming Ca²⁺-binding EF-hands. Evolutionarily, the N-helix is found only in TnC from mammalian species and most …

Epigenetic Regulation In Fibrosis, Qingping Wei, Xiaoru Hu, Yan Sanders

Department of Biomedical and Translational Sciences Faculty Publications

[Introduction] Fibrosis is one of the pathological conditions underlying the progression of numerous chronic diseases, and it contributes substantially to morbidity and mortality worldwide. Increasing amounts of evidence indicate that epigenetic mechanisms—including DNA methylation, histone modifications, RNA modifications, and non-coding RNAs—play pivotal roles in epithelial cell injury and maladaptive tissue repair, inflammatory cell and fibroblast activation, and extracellular matrix remodeling and accumulation. Compared to genetic alterations, epigenetic changes are relatively reversible, positioning them as promising therapeutic targets. The articles collected in this Research Topic highlight recent advances in understanding how epigenetic regulation shapes fibrotic processes across multiple organ systems and …

Deletion Of Chop In Beta Cell Protects Mice From Cardiovascular Complications In Type 2 Diabetes: Evidence From A Pre-Clinical Mouse Model, Balaji Srinivas, Kiran Alluri, Nour-Eddine Rhaleb, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Introduction

Cardiovascular complications are the leading cause of morbidity and mortality in patients with type 2 diabetes (T2D), which is recognized as a major independent risk factor for coronary artery disease, stroke, peripheral vascular disease, and heart failure. The interrelationship between metabolic dysfunction and cardiovascular disease is complex and multifactorial, involving hyperglycemia, insulin resistance, inflammation, and oxidative stress. Evidence indicates that endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR) contribute to metabolic dysregulation and vascular dysfunction. However, the specific role of beta cell-derived UPR mediators, particularly C/EBP homologous protein (CHOP), in coordinating this interorgan axis between …

Phenotype Specific Nuclear Lamina Remodeling In Hipsc Derived Cardiomyocytes Bearing Tnnt2 Sarcomeric Variants, Isabella Leite Coscarella, Olalekan H. Usman, Lili Wang, Maicon Landim-Vieira, Lillian Wirstiuk, Amber N. Brown, Diego A. R. Zorio, Brian K. Washburn, Cynthia Vied, Bjorn C. Knollmann, Christopher Solís, Vitold E. Galkin, P. Bryant Chase, J. Travis Hinson, Jerome Irianto, Jose Renato Pinto

Department of Biomedical and Translational Sciences Faculty Publications

[Summary] Cardiomyocytes endure physical stress from the myocardium environment while generating their own mechanical strains. The force generated by sarcomeres is transmitted both longitudinally to adjacent sarcomeres and laterally to the cytoskeleton via intermediate filaments. This mechanical stimulus impacts other organelles, including the nucleus, thus playing a vital role in sensing and signaling nuclear adaptations. However, there is limited understanding of how changes in cardiac contractility affect nuclear mechanics. Here, we sought to investigate the effects of hyper- and hypo-contractility in nuclei of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) bearing TNNT2 pathogenic variants associated with hypertrophic (HCM) or dilated …

Left Ventricular Assist Device Destination Therapy: A Journey To Home And Beyond, Mian Z. Munir, Marissa C. Galicia-Castillo, Mia Achitoov, Amin Yehya

Department of Medicine Faculty Publications

[Case] Mr H is a 74-year-old man with history of end-stage heart failure (ESHF) secondary to hereditary transthyretin cardiac amyloidosis. Our patient underwent placement of a HeartMate II (Abbott) left ventricular assist device (LVAD) as destination therapy (DT) at an outside hospital and later came to us (Sentara Heart Hospital) for continued management because he resided in the area. Over a 2-year period, the patient experienced multiple hospital admissions for acute heart failure (HF) exacerbations, delirium, and recurrent low-flow alarms. During his last hospitalization, the palliative medicine team was consulted to facilitate goals-of-care discussions with the patient and his family, …

The Pre-Polarization And Concentration Of Cells Near Micro-Electrodes Using Ac Electric Fields Enhances The Electrical Cell Lysis In A Sessile Drop, Kishor Kaphle, Dharmakeerthi Nawarathna

Electrical & Computer Engineering Faculty Publications

Cell lysis is the starting step of many biomedical assays. Electric field-based cell lysis is widely used in many applications, including point-of-care (POC) applications, because it provides an easy one-step solution. Many electric field-based lysis methods utilize micro-electrodes to apply short electric pulses across cells. Unfortunately, these cell lysis devices produce relatively low cell lysis efficiency as electric fields do not reach a significant portion of cells in the sample. Additionally, the utility of syringe pumps for flow cells in and out of the microfluidics channel causes cell loss and low throughput cell lysis. To address these critical issues, we …

Enhancing Bone Regeneration Using Kaempferol As An Osteoprotective Compound: Signaling Mechanisms, Delivery Strategies, And Potential Applications, Mojdeh Salehi Namini, Sanam Mohandesnezhad, Sadaf Mohandesnezhad, Vahid Mansouri, Lobat Tayebi, Nima Beheshtizadeh

Electrical & Computer Engineering Faculty Publications

Various plants, including fruits, vegetables, and spices, contain kaempferol, a bioflavonoid compound with diverse medicinal effects, such as antioxidant, antibacterial, and anti-inflammatory characteristics. Furthermore, this compound exhibits multiple health-promoting properties, including osteoprotection and osteogenesis, primarily by modulating various cell-signaling pathways. This review aims to illustrate the medical advantages of kaempferol and its role in regulating bone metabolism through cell signaling mechanisms. Numerous studies have demonstrated the bone-protective properties of kaempferol and its encapsulated form. Further research is needed to clarify the optimal dosages, toxicity, safety, and other potential mechanisms of action. This review demonstrates that several signaling pathways, including nuclear …

Categorizing Clinical Response To Mepolizumab For Patients With Chronic Rhinosinusitis With Nasal Polyps: Synapse Trial, Claire Hopkins, Larry Borish, Jared Silver, Peter Howarth, Robert Chan, Priya Dsilva, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

[Introduction] Chronic rhinosinusitis with nasal polyps (CRSwNP) can substantially affect quality of life (QoL), and is often challenging to manage.¹ First-line treatment for the management of CRSwNP involves intranasal corticosteroids, with short courses of systemic corticosteroids (SCS) for exacerbations, and sinus surgery for uncontrolled disease.² Biologics targeting type 2 inflammation (eg, dupilumab, omalizumab, and mepolizumab) have become a treatment option for refractory CRSwNP. With the advent of disease-modifying treatments such as biologics, control, defined as patients reporting no/low-symptom levels, has increasingly become the treatment goal for CRSwNP.³ However, the optimal use of biologics for symptom control in individual patients remains …

Acute Exacerbations Of Chronic Rhinosinusitis, Robert M. Frederick, Kent Lam, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

Purpose of Review

We aim to highlight recent advancements on the evolving chronic rhinosinusitis (CRS) phenotype: acute exacerbations of chronic rhinosinusitis (AECRS). We focused on studies that expanded the current understanding of its pathophysiology, patient characteristics, and disease burden.

Recent findings

Defining AECRS has been a topic of discussion for many years. A recent regulatory definition of AECRS in the literature incorporates a > 3 day requirement of worsened symptoms and an escalation of treatment. It is important not to rely on patient-reported rescue medication frequency as it was recently demonstrated these are only obtained for 1/3 of reported AECRS episodes. …

Biomechanics Of The Atherosclerotic Lipidome: (Un)Expected Statin Interactions And Membrane Remodelling, Ethan M. Fong

Pomona Senior Theses

Statins interact with lipid membranes in ways that shape their pharmacokinetics, off-target effects, and pleiotropic actions, yet these interactions' mechanical and biophysical consequences remain poorly understood. This thesis employs a combination of surface plasmon resonance (SPR), quartz crystal microbalance with dissipation monitoring (QCM-D), and rheological modelling to characterize how representative statins intercalate within biomimetic supported lipid bilayers (SLBs) of healthy and diseased composition. SPR reveals that lipophilic statins exhibit higher apparent affinities and slower dissociation kinetics, especially in cholesterol- and anionic lipid-rich membranes. QCM-D analyses demonstrate that statins alter membrane mass, dissipation, and interfacial stiffness in a statin- and membrane-dependent …

Caveolin-Mediated Endocytosis: Bacterial Pathogen Exploitation And Host-Pathogen Interaction, Dibyasri Barman, Rishi Drolia

Biological Sciences Faculty Publications

Within mammalian cells, diverse endocytic mechanisms, including phagocytosis, pinocytosis, and receptor-mediated endocytosis, serve as gateways exploited by many bacterial pathogens and toxins. Among these, caveolae-mediated endocytosis is characterized by lipid-rich caveolae and dimeric caveolin proteins. Caveolae are specialized microdomains on cell surfaces that impact cell signaling. Caveolin proteins facilitate the creation of caveolae and have three members in vertebrates: caveolin-1, caveolin-2, and caveolin-3. Many bacterial pathogens hijack caveolin machinery to invade host cells. For example, the Gram-positive facultative model intracellular bacterial pathogen Listeria monocytogenes exploits caveolin-mediated endocytosis for efficient cellular entry, translocation across the intestinal barrier, and cell–cell spread. Caveolin …

Dengue Virus Modulates Critical Cell Cycle Regulatory Proteins In Human Megakaryocyte Cells, Swarnendu Basak, Shovan Dutta, Supreet Khanal, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Suppression of human megakaryocytes by dengue virus (DENV) infection significantly reduces the platelet count that eventually leads to thrombocytopenia, severe dengue and death. To understand DENV interactions with megakaryocytes, we investigated the cell cycle in leukemic human megakaryocytic in vitro cell line (MEG-01 cells). Megakaryocytes are known for complex endomitotic cell cycle leading to their polyploidy state. Our study shows that DENV uses these polyploid cells for its replication. Understanding the modulation of DENV-mediated cell cycle regulation in megakaryocytes is therefore highly important. We show that DENV2 (serotype 2) infection significantly modulates cell cycle signaling. Our protein profile microarray data …

Magnetization Transfer Ratio In The Typically Developing Pediatric Spinal Cord: Normative Data And Age Correlation, Sara Naghizadeh Kashani, Iswarya Vel, Zahra Sadeghi Adl, Shiva Shahrampour, Devon Middleton, Mahdi Alizadeh, Laura Krisa, Scott Faro, Slimane Tounekti, Julien Cohen-Adad, Feroze Mohamed

Department of Radiology Faculty Papers

BACKGROUND AND PURPOSE: This study presents automated atlas-based magnetization transfer (MT) measurements of the typically developing pediatric cervical spinal cord (SC). We report normative MT ratio (MTR) values from the whole cervical cord white matter (WM) and WM tracts, examining variations with age, sex, height, and weight.

METHODS: MT scans of 33 healthy females (mean age = 12.8) and 22 males (mean age = 13.09) were acquired from the cervical SC (C2-C7) using a 3.0 T MRI. Data were processed using the SC Toolbox, segmented, and registered to the PAM50 template. Affine and non-rigid transformations co-registered the PAM50 WM atlas …

Major Adverse Cardiovascular Events Are Less Frequent In Psoriasis Patients Starting Glp-1ra Compared To Controls: An Observable Retrospective Cohort Study, Ana Ormaza Vera, Marla F. Osorlo, Madison Olexson, June Choi, Chunghwan Ro, Clinton Enos

Department Dermatology Faculty Publications

Background: Psoriasis is an independent risk factor for major adverse cardiovascular events (MACE). We have previously shown that psoriasis patients with dyslipidemia have an increased incidence of MACE despite treatment with a biologic and a statin. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown to reduce MACE in patients with type 2 diabetes and obesity, comorbidities that commonly co-occur with psoriasis. However, the association between GLP-1RA and the incidence of MACE among patients with psoriasis remains unknown.

Methods: We conducted a retrospective cohort study from 2014-2024 using a large, multi-center, electronic health record network (TriNetX). Patients aged 18-90 who started GLP-1RA …

40 Years Passing By In (A) “Heartbeat”, Christopher Janney

Monsoon: South Asian Studies Association Journal

This article outlines the forty-year history go Christopher Janney’s iconic performance work “HeartBeat.” Trained as an architect and jazz musician, Janney combines these two disciplines to create large interactive light/sound installations and performances. On the one hand, he attempts to make architecture more like music, more “alive” using real-time sensing devices as on his “Harmonic Convergence” installation on the Miami International Airport. On the other hand, he attempts to make music more like architecture, more physical more visual. In his “HeartBeat” performance, a dancer wears a heartbeat device that amplifies his/her heartbeat in “real time.” Over this pulse, live musicians …

Yoga Sūtra Book Four And The Yogabindu, Christopher Key Chapple

Monsoon: South Asian Studies Association Journal

Four themes from the fourth pāda of Patañjali’s Yoga Sūtra are examined here: karma (IV:2-13), individuality (IV:16), humility (IV:20-22), and freedom (IV:29-34). Affirmations and variant interpretations of these four are provided from Haribhadra Virahāṅka’s Yogabindu, most likely composed a century or two later.

Collective Karma: From The Yogasūtra To Taylor Swift, Zoë Slatoff

Monsoon: South Asian Studies Association Journal

The Indian knowledge traditions speak at length about karma, which is divided into three categories—accumulated (saṃcita), ripe (prārabdha), and future (kriyamāṇa). While much is said about our individual karma and how it affects our repeated reincarnation in cyclic existence, how does this affect others and how do others affect us? In other words, as this paper explores, what is our reciprocal and collective karma?