Medical Sciences Commons^™

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 …

The Mapk Homolog, Smk1, Promotes Assembly Of The Glucan Layer Of The Spore Wall In S. Cerevisiae, Julia Y. Lee-Soety, Gwendolyn Resch, Abhimannyu Rimal, Erica S. Johnson, Jonathan Benway, Edward Winter

Department of Biochemistry and Molecular Biology Faculty Papers

Smk1 is a MAPK homolog in the yeast Saccharomyces cerevisiae that controls the postmeiotic program of spore wall assembly. During this program, haploid cells are surrounded by a layer of mannan and then a layer of glucan. These inner layers of the spore wall resemble the vegetative cell wall. Next, the outer layers consisting of chitin/chitosan and then dityrosine are assembled. The outer layers are spore-specific and provide protection against environmental stressors. Smk1 is required for the proper assembly of spore walls. However, the protective properties of the outer layers have limited our understanding of how Smk1 controls this morphogenetic …

Identification And Characterization Of Cannabichromene's Major Metabolite Following Incubation With Human Liver Microsomes, Alexandra M Ward, Touraj Shokati, Jost Klawitter, Jelena Klawitter, Vu Nguyen, Laura Kozell, Atheir I Abbas, David Jones, Uwe Christians

Faculty, Staff and Student Publications

Cannabichromene (CBC) is a minor cannabinoid within the array of over 120 cannabinoids identified in the Cannabis sativa plant. While CBC does not comprise a significant portion of whole plant material, it is available to the public in a purified and highly concentrated form. As minor cannabinoids become more popular due to their potential therapeutic properties, it becomes crucial to elucidate their metabolism in humans. Therefore, the goal of this was study to identify the major CBC phase I-oxidized metabolite generated in vitro following incubation with human liver microsomes. The novel metabolite structure was identified as 2′-hydroxycannabicitran using gas chromatography–mass …

Cyp3a Mediates An Unusual C(Sp2)-C(Sp3) Bond Cleavage Via Ipso-Addition Of Oxygen In Drug Metabolism, Xuan Qin, Yong Wang, Qiuji Ye, John M Hakenjos, Jin Wang, Mingxing Teng, Lei Guo, Zhi Tan, Damian W Young, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Mammalian cytochrome P450 drug-metabolizing enzymes rarely cleave carbon–carbon (C-C) bonds and the mechanisms of such cleavages are largely unknown. We identified two unusual cleavages of non-polar, unstrained C(sp2)-C(sp3) bonds in the FDA-approved tyrosine kinase inhibitor pexidartinib that are mediated by CYP3A4/5, the major human phase I drug metabolizing enzymes. Using a synthetic ketone, we rule out the Baeyer-Villiger oxidation mechanism that is commonly invoked to address P450-mediated C-C bond cleavages. Our studies in 18O2 and H218O enriched systems reveal two unusual distinct mechanisms of C-C bond cleavage: one bond is cleaved by CYP3A-mediated ipso-addition of oxygen to a C(sp2) …

E6 Inhibtion-Mediated Combinatorial Therapy For Hpv+ Hnscc, Sonia Whang

Loma Linda University Electronic Theses, Dissertations & Projects

High-risk human papillomaviruses (HPV) are the causative agents of virtually all cases of cervical cancer and up to 80% of head and neck squamous cell carcinoma (HNSCC). Current treatment options include chemo- and radiotherapy, though the effectiveness of these therapies is limited by the viral oncoprotein E6, which disrupts apoptotic pathways by binding to and accelerating the degradation of molecules such as p53 and caspase- 8. Our hypothesis was that inhibiting E6 and rescuing the apoptotic mediators would increase the effectiveness of apoptotic agents. The aims of this study were to first, develop an HPV+ HNSCC xenograft model to test …

Abnormal Morphology And Synaptogenic Signaling In Astrocytes Following Prenatal Opioid Exposure, Ethan B. Niebergall, Daron Weekley, Anna Mazur, Nathan A. Olszewski, Kayla M. Deschepper, N. Radant, Aishwarya S. Vijay

Biomedical Sciences

In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and …

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 …

Serine Deamination By Human Serine Racemase Synergizes With Antibiotics To Curtail The Replication Of Chlamydia Trachomatis, Patricia D. Mott, Arnold H. Zea, Jamiya Lewis, Oygul Mirzalieva, Ashok A. Aiyar

School of Medicine Faculty Publications

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates …

Sex And Age Differences In Near-Infrared Spectroscopy Responses And The Resulting Influences On Cognition, Miranda K. Traylor

Graduate Theses and Dissertations (2019 - present)

Vascular dysfunction is the earliest known marker of neurodegeneration. However, limited research has been conducted to determine if changes in peripheral vascular function track differences in brain health. Therefore, the purpose was to determine if previously reported sex differences in near-infrared spectroscopy (NIRS) vascular occlusion test (VOT) parameters persist across the lifespan and if these differences track age- and sex-related differences in a cognitive task. Ninety-nine healthy, cognitively intact adults (50 women, 49 men) across the adult lifespan (19-81 yrs) were used for analysis. The combination of NIRS-VOT was used to quantify microvascular function. Cognition was defined as the time …

A Combination Of Generated Hydrogen Sulfide And Nitric Oxide Activity Has A Potentiated Protectant Effect Against Cisplatin Induced Nephrotoxicity, Faria Khurshid, Javeid Iqbal, Fiaz Ud Din Ahmad, Arslan Hussain Lodhi, Abdul Malik, Suhail Akhtar, Azmat Ali Khan, Marvi Imam Bux, Mohammed Younis

Biomedical Sciences Faculty Publications

Aim: Hydrogen sulfide and nitricoxide possess cytoprotective activity and in vivo, they are generated from exogenous sodium hydrosulfide and L-arginine respectively. Cisplatin is a major chemotherapeutic agent used to treat cancer and has a high incidence of nephrotoxicity as a side effect. The study aim was to explore the effects of NaHS and L-arginine or their combination on cisplatin induced nephrotoxicity in rats. Methods: Wistar Kyoto rats were given a single intraperitoneal dose of cisplatin (5 mg/kg) followed either by NaHS (56 μmol/kg, i. p.), L-arginine (1.25 g/L in drinking water) or their combination daily for 28-days. Post-mortem plasma, urine …

Exploration Of The Activity, Delivery And Activation Of Androgen Receptor Potential Indane Scaffold Antagonists For Prostate Cancer Treatment, Shengxin Zhang, Gemma K Kinsella, Tao Zhang, James Curtin

Other resources

Androgen receptor (AR)-targeted therapy remains the gold standard strategy for the treatment of advanced prostate cancer. Several compounds of Indane derivatives have been reported to exhibit significant AR antagonist capabilities, starting at a concentration as low as 0.1 μM. However, an anti-prostate cancer lead molecule derived from Indane-related scaffold remains elusive. The project will investigate the interaction of novel bioactive indane scaffolds as androgen receptor antagonists through in silico and in vitro screening to complete the hit-to-lead, while also investigating potential drug delivery and drug activation/sensitisation mechanisms using a combination of colloid nanomaterial and cold atmospheric plasma to target AR-independent, …

Hammerhead-Type Fxr Agonists Induce An Enhancer Rna Fincor That Ameliorates Nonalcoholic Steatohepatitis In Mice, Jinjing Chen, Ruoyu Wang, Feng Xiong, Hao Sun, Byron Kemper, Wenbo Li, Jongsook Kemper

Faculty, Staff and Student Publications

The nuclear receptor, farnesoid X receptor (FXR/NR1H4), is increasingly recognized as a promising drug target for metabolic diseases, including nonalcoholic steatohepatitis (NASH). Protein-coding genes regulated by FXR are well known, but whether FXR also acts through regulation of long non-coding RNAs (lncRNAs), which vastly outnumber protein-coding genes, remains unknown. Utilizing RNA-seq and global run-on sequencing (GRO-seq) analyses in mouse liver, we found that FXR activation affects the expression of many RNA transcripts from chromatin regions bearing enhancer features. Among these we discovered a previously unannotated liver-enriched enhancer-derived lncRNA (eRNA), termed FXR-induced non-coding RNA (

Nanocavity-Mediated Purcell Enhancement Of Er In Tio2 Thin Films Grown Via Atomic Layer Deposition, Cheng Ji, Michael T Solomon, Gregory D Grant, Koichi Tanaka, Muchuan Hua, Jianguo Wen, Sagar Kumar Seth, Connor P Horn, Ignas Masiulionis, Manish Kumar Singh, Sean E Sullivan, F Joseph Heremans, David D Awschalom, Supratik Guha, Alan M Dibos

Faculty, Staff and Student Publications

The use of trivalent erbium (Er3+), typically embedded as an atomic defect in the solid-state, has widespread adoption as a dopant in telecommunication devices and shows promise as a spin-based quantum memory for quantum communication. In particular, its natural telecom C-band optical transition and spin-photon interface make it an ideal candidate for integration into existing optical fiber networks without the need for quantum frequency conversion. However, successful scaling requires a host material with few intrinsic nuclear spins, compatibility with semiconductor foundry processes, and straightforward integration with silicon photonics. Here, we present Er-doped titanium dioxide (TiO2) thin film growth on silicon …

Ai Is A Viable Alternative To High Throughput Screening: A 318-Target Study, Izhar Wallach, Denzil Bernard, Kong Nguyen, Gregory Ho, Adrian Morrison, Adrian Stecula, Andreana Rosnik, Ann Marie O’Sullivan, Aram Davtyan, Ben Samudio, Bill Thomas, Brad Worley, Brittany Butler, Christian Laggner, Desiree Thayer, Ehsan Moharreri, Greg Friedland, Ha Truong, Henry Van Den Bedem, Ho Leung Ng, Kate Stafford, Krishna Sarangapani, Kyle Giesler, Lien Ngo, Michael Mysinger, Mostafa Ahmed, Nicholas J. Anthis, Niel Henriksen, Arthur L. Haas, Et Al

School of Medicine Faculty Publications

High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, …

Hedgehog Signaling And Congenital Disorders; The Case Of Anencephaly And Polydactyly, Joshua Towery

First-Year Research Immersion (FRI) Scholarship

The Hedgehog pathway is a fundamental signaling pathway in the human body; involved in carcinogenesis, stem cell maintenance, as well as limb patterning in embryonic development. Originally discovered in drosophila, their initial discovery, and subsequent analysis revealed many novel pieces of information about the mechanisms inside the human body, as many core components of the signaling pathway are carried over from fruit flies to humans. Because of the key roles hedgehog signaling plays in human development, dysfunction and mutations in the pathway can be detrimental. This review will focus on two congenital birth defects thought to be caused by hedgehog …

Combined Ion Beam Irradiation Platform And 3d Fluorescence Microscope For Cellular Cancer Research, Andrew D Harken, Naresh T Deoli, Citlali Perez Campos, Brian Ponnaiya, Guy Garty, Grace S Lee, Malte J Casper, Shikhar Dhingra, Wenze Li, Gary W Johnson, Sally A Amundson, Peter W Grabham, Elizabeth M C Hillman, David J Brenner

Faculty, Staff and Student Publications

To improve particle radiotherapy, we need a better understanding of the biology of radiation effects, particularly in heavy ion radiation therapy, where global responses are observed despite energy deposition in only a subset of cells. Here, we integrated a high-speed swept confocally-aligned planar excitation (SCAPE) microscope into a focused ion beam irradiation platform to allow real-time 3D structural and functional imaging of living biological samples during and after irradiation. We demonstrate dynamic imaging of the acute effects of irradiation on 3D cultures of U87 human glioblastoma cells, revealing characteristic changes in cellular movement and intracellular calcium signaling following ionizing irradiation.

Cyclophilin A Supports Translation Of Intrinsically Disordered Proteins And Affects Haematopoietic Stem Cell Ageing, Laure Maneix, Polina Iakova, Charles G Lee, Shannon E Moree, Xuan Lu, Gandhar K Datar, Cedric T Hill, Eric Spooner, Jordon C K King, David B Sykes, Borja Saez, Bruno Di Stefano, Xi Chen, Daniela S Krause, Ergun Sahin, Francis T F Tsai, Margaret A Goodell, Bradford C Berk, David T Scadden, André Catic

Faculty, Staff and Students Publications

Loss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found that proteins with intrinsically disordered regions (IDRs) are frequent PPIA substrates. IDRs facilitate interactions with other proteins or nucleic acids and can trigger liquid-liquid phase separation. Over 20% of PPIA substrates are involved in the formation of supramolecular membrane-less organelles. PPIA affects regulators of stress granules (PABPC1), P-bodies (DDX6) and nucleoli (NPM1) to promote phase separation and increase cellular stress resistance. …

Unraveling Sorafenib Resistance In Hepatocellular Carcinoma: Exploring Key Facets, Dennis Kwabiah, Kyle Doxtater, Yamile Abuchard, Sophia Leslie, Ricardo Pequeno Bracho, Shaibir Hussain, Manish K. Tripathi

Research Symposium

Hepatocellular carcinoma (HCC) stands as the prevalent form of primary liver cancer worldwide, diagnosing over half a million new cases annually. Surgical interventions like hepatectomy and liver transplantation offer a potential cure for early-stage HCC. However, the prognosis for advanced stages remains grim due to drug resistance, particularly with high refractoriness rates. Sorafenib, a tyrosine kinase inhibitor, is an approved treatment for advanced HCC. Despite its use, the overall survival extension for these patients remains limited due to the drug's ineffectiveness, and the mechanism behind advanced HCC's resistance to sorafenib remains elusive. TCGA analysis of HCC patient cohorts reveals elevated …

Utility Of Peripheral Protein Biomarkers For The Prediction Of Incident Interstitial Features: A Multicentre Retrospective Cohort Study, Samuel Ash, Tracy J Doyle, Bina Choi, Ruben San Jose Estepar, Victor Castro, Nicholas Enzer, Ravi Kalhan, Gabrielle Liu, Russell Bowler, David O Wilson, Raul San Jose Estepar, Ivan O Rosas, George R Washko

Faculty, Staff and Students Publications

INTRODUCTION/RATIONALE: Protein biomarkers may help enable the prediction of incident interstitial features on chest CT.

METHODS: We identified which protein biomarkers in a cohort of smokers (COPDGene) differed between those with and without objectively measured interstitial features at baseline using a univariate screen (t-test false discovery rate, FDR p

RESULTS: In COPDGene, 1305 biomarkers were available and 20 differed between those with and without interstitial features at baseline. Of these, 11 were associated with feature progression over a mean of 5.5 years of follow-up, and of these 4 were available in PLuSS, (angiopoietin-2, matrix metalloproteinase 7, macrophage inflammatory protein 1 …

Biomechanical Analysis Of The Maxillary Sinus Floor Membrane During Internal Sinus Floor Elevation With Implants At Different Angles Of The Maxillary Sinus Angles, Yinxin Deng, Ruihong Ma, Yilin He, Shujia Yu, Shiyu Cao, Kang Gao, Yiping Dou, Pan Ma

Faculty, Staff and Student Publications

OBJECTIVE: This study analyzed and compared the biomechanical properties of maxillary sinus floor mucosa with implants at three different maxillary sinus angles during a modified internal sinus floor elevation procedure.

METHODS: 3D reconstruction of the implant, maxillary sinus bone, and membrane were performed. The maxillary sinus model was set at three different angles. Two internal maxillary sinus elevation models were established, and finite element analysis was used to simulate the modified maxillary sinus elevation process. The implant was elevated to 10 mm at three maxillary sinus angles when the maxillary sinus floor membrane was separated by 0 and 4 mm. …

Editorial: Reviews And Advances In The Molecular Mechanisms Of Breast Cancer, A. Redfern, V. Agarwal, Suresh Alahari

School of Medicine Faculty Publications

No abstract provided.

The Effects Of Curcumin On Erα, P53, And P21 In The Mcf-7 Breast Cancer Cell Line, Samantha E. Pfiffner, Mia Morse, Erin Hallman, Kaylin Whittaker, Aisha Zanib, Sumi Dinda Ph.D.

Medical Student Research Symposium

Curcumin is a golden-yellow flavonoid compound derived from the turmeric plant root that has been used in Chinese and Indian medicine for centuries. Curcumin has been shown to have antioxidant and anti-inflammatory properties, and because of this, has been gaining traction in the field of cancer research. Breast cancer is the most commonly diagnosed cancer in women, and is the second leading cause of cancer death in women, next to lung cancer. Because of the prevalence and mortality of breast cancer, possible therapeutics must be investigated. Due to the beneficial properties of curcumin and pervasiveness of breast cancer, we have …

Hif Expression In Clear-Cell Renal Cell Carcinoma (Ccrcc) Tumors Of Adults With And Without Obstructive Sleep Apnea (Osa), Olivia Heppell, Carlos Guerra Londono, Nilesh Gupta

Medical Student Research Symposium

Introduction: Upregulation of hypoxia-inducible factors (HIF) is an important pathological feature shared by clear cell renal cell carcinoma (ccRCC) and obstructive sleep apnea (OSA). However, it is unclear whether OSA alters the pathogenesis of ccRCC via HIF expression.

Methods: A retrospective cohort of adults undergoing nephrectomy for ccRCC was identified electronically (IRB#16040-1). The diagnosis of OSA was established with preoperative STOP-BANG scores or polysomnography. A consecutive sample of 20 individuals with and 20 without OSA was selected. Clinical characteristics and pathology results were reviewed. Resected tumor sections were immunohistochemically stained for HIF-1& HIF-2 at antibody dilutions of 1:150. Intensity and …

The Optimization Of A Natural Language Processing Approach For The Automatic Detection Of Alzheimer’S Disease Using Gpt Embeddings, Benjamin S. Runde, Ajit Alapati, Nicolas G. Bazan

School of Medicine Faculty Publications

The development of noninvasive and cost-effective methods of detecting Alzheimer’s disease (AD) is essential for its early prevention and mitigation. We optimize the detection of AD using natural language processing (NLP) of spontaneous speech through the use of audio enhancement techniques and novel transcription methodologies. Specifically, we utilized Boll Spectral Subtraction to improve audio fidelity and created transcriptions using state-of-the-art AI services—locally-based Wav2Vec and Whisper, alongside cloud-based IBM Cloud and Rev AI—evaluating their performance against traditional manual transcription methods. Support Vector Machine (SVM) classifiers were then trained and tested using GPT-based embeddings of transcriptions. Our findings revealed that AI-based transcriptions …

Phenolic Acids Prevent Sex-Steroid Deficiency-Induced Bone Loss And Bone Marrow Adipogenesis In Mice, Perry C. Caviness, Oxana P. Lazarenko, Michael L. Blackburn, Jennifer F. Chen, Christopher E. Randolph, Jovanny Zabaleta, Fenghuang Zhan, Jin Ran Chen

School of Medicine Faculty Publications

Phenolic acids, such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA), can be produced from microbiome digestion of polyphenols. Previously it was found that HA and 3-3-PPA facilitate bone formation and suppress bone resorption. However, the mechanism of action by which HA and 3-3-PPA protect bone from degeneration is currently unknown. In this report, we present that HA and 3-3-PPA suppression of bone resorption is able to ameliorate bone loss in an ovariectomy (OVX) osteopenic mouse model though not to the extent of Zoledronic acid (ZA). HA and 3-3-PPA treatments were shown to significantly decrease bone marrow adipocyte-like cell …

A Mutation In F-Actin Polymerization Factor Suppresses The Distal Arthrogryposis Type 5 Piezo2 Pathogenic Variant In Caenorhabditis Elegans, Xiaofei Bai, Harold E Smith, Luis O Romero, Briar Bell, Valeria Vásquez, Andy Golden

Faculty, Staff and Student Publications

The mechanosensitive PIEZO channel family has been linked to over 26 disorders and diseases. Although progress has been made in understanding these channels at the structural and functional levels, the underlying mechanisms of PIEZO-associated diseases remain elusive. In this study, we engineered four PIEZO-based disease models using CRISPR/Cas9 gene editing. We performed an unbiased chemical mutagen-based genetic suppressor screen to identify putative suppressors of a conserved gain-of-function variant pezo-1[R2405P] that in human PIEZO2 causes distal arthrogryposis type 5 (DA5; p. R2718P). Electrophysiological analyses indicate that pezo-1(R2405P) is a gain-of-function allele. Using genomic mapping and whole-genome sequencing approaches, we identified a …

Efficacy Of Supplemental Ultrasound-Guided Pericapsular Nerve Group (Peng) Block Combined With Lateral Femoral Cutaneous Nerve Block In Patients Receiving Local Infiltration Analgesia After Hip Fracture Surgery: A Prospective Randomized Controlled Trial, Seung-Hee Yoo, Min-Jin Lee, Min-Hyouk Beak, Won-Joong Kim

Faculty, Staff and Student Publications

No abstract provided.

Transcription Factor Bach1 In Cancer: Roles, Mechanisms, And Prospects For Targeted Therapy, Dian Hu, Zerui Zhang, Xiangyuan Luo, Siwen Li, Junqing Jiang, Jiaqian Zhang, Zhangfan Wu, Yijun Wang, Mengyu Sun, Xiaoping Chen, Bixiang Zhang, Xiao Xu, Shuai Wang, Shengjun Xu, Yufei Wang, Wenjie Huang, Limin Xia

Faculty, Staff and Student Publications

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status …

Bispecific Bcma/Cd24 Car-T Cells Control Multiple Myeloma Growth, Fumou Sun, Yan Cheng, Visanu Wanchai, Wancheng Guo, David Mery, Hongwei Xu, Dongzheng Gai, Eric Siegel, Clyde Bailey, Cody Ashby, Samer Al Hadidi, Carolina Schinke, Sharmilan Thanendrarajan, Yupo Ma, Qing Yi, Robert Z Orlowski, Maurizio Zangari, Frits Van Rhee, Siegfried Janz, Gail Bishop, Guido Tricot, John D Shaughnessy, Fenghuang Zhan

Faculty, Staff and Student Publications

Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T cell treatment of myeloma are rare. One potential reason is that a small subset of minimal residual myeloma cells seeds relapse. Residual myeloma cells following BCMA-CAR-T-mediated treatment show less-differentiated features and express stem-like genes, including CD24. CD24-positive myeloma cells represent a large fraction of residual myeloma cells after BCMA-CAR-T therapy. In this work, we develop CD24-CAR-T cells and test their ability to eliminate myeloma cells. We find that CD24-CAR-T cells …

Regulation Of Tissue Factor Activity By Interaction With The First Pdz Domain Of Magi1, Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie

School of Medicine Faculty Publications

Background; Tissue factor (TF) activity is stringently regulated through processes termed encryption. Post-translational modification of TF and its interactions with various protein and lipid moieties allows for a multi-step de-encryption of TF and procoagulant activation. Membrane-associated guanylate kinase-with inverted configuration (MAGI) proteins are known to regulate the localisation and activity of a number of proteins including cell-surface receptors. Methods; The interaction of TF with MAGI1 protein was examined as a means of regulating TF activity. MDA-MB-231 cell line was used which express TF and MAGI1, and respond well to protease activated receptor (PAR)2 activation. Proximity ligation assay (PLA), co-immunoprecipitation and …