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Articles 1 - 30 of 47
Full-Text Articles in Medical Biochemistry
Isg15 Dysregulates Endoplasmic Reticulum-Mitochondrial Contacts And Calcium Homeostasis In Ataxia Telangiectasia, Oygul Mirzalieva, Ryan E. Reed, Arthur L. Haas, Meredith A. Juncker, Patrick Logarbo, Jennifer M. Klein, David Worthylake, Shyamal D. Desai
Isg15 Dysregulates Endoplasmic Reticulum-Mitochondrial Contacts And Calcium Homeostasis In Ataxia Telangiectasia, Oygul Mirzalieva, Ryan E. Reed, Arthur L. Haas, Meredith A. Juncker, Patrick Logarbo, Jennifer M. Klein, David Worthylake, Shyamal D. Desai
School of Graduate Studies Faculty Publications
Dysregulation of endoplasmic reticulum and mitochondrial (ER:Mit) contacts and mitochondrial calcium (mitCa2+) homeostasis are found in several neurodegenerative disorders, including Ataxia Telangiectasia (A-T). However, the cellular basis of these defects remains unclear. Previously, we demonstrated that the aberrantly elevated Interferon-Stimulated Gene 15 (ISG15) pathway inhibits protein polyubiquitylation, its dependent protein turnover, and mitophagy pathways in A-T. Literature indicates that silencing of mitochondrial ubiquitin ligase 1 (MUL1) stabilizes mitofusin2 (MFN2) and attenuates mitCa2+ uptake from ER to Mit (mitCa2+influx) in primary neurons. We have replicated these findings in apparently healthy fibroblasts. We hypothesized that elevated ISG15 may inhibit ubiquitin-dependent MUL1-mediated degradation …
Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan
Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan
School of Graduate Studies Faculty Publications
Neuroblastoma (NB), a pediatric cancer of sympatho-adrenal (SA) lineage, is marked by disrupted differentiation and cellular heterogeneity. INSM1, a zinc-finger transcription factor, is highly expressed in NB and developing SA tissues, where it regulates neuroendocrine differentiation, especially in chromaffin cells. We investigated INSM1's role in maintaining an undifferentiated, progenitor-like state in NB and its regulation via metabolic and epigenetic mechanisms. Transcriptomic profiling, promoter assays, and metabolic flux analysis revealed that INSM1 expression correlates with methionine cycle activity, particularly the S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio. Disruption of SAM/SAH balance altered INSM1 promoter activity and histone methylation, implicating epigenetic control in NB cell …
The Non-Coding Rna Journal Club: Highlights On Recent Papers-14, El Cheima Mhamedi, Florent Hubé, Suresh K. Alahari, Francisco J. Enguita, Barbara Pardini, Mark W. Feinberg, Laura Poliseno, Beshoy Armanios, Jing Jin, Xiao-Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, Gaetano Santulli, Stanislovas S. Jankauskas, Will S. Plewa, Simon J. Conn, Ling Yang, Patrick K. Shiu, Abhishek Kaushik, Alexander Serganov, Gentile, Giuseppe Viglietto, Nicola Amodio, Tijana Mitić, Andrea Caporali
The Non-Coding Rna Journal Club: Highlights On Recent Papers-14, El Cheima Mhamedi, Florent Hubé, Suresh K. Alahari, Francisco J. Enguita, Barbara Pardini, Mark W. Feinberg, Laura Poliseno, Beshoy Armanios, Jing Jin, Xiao-Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, Gaetano Santulli, Stanislovas S. Jankauskas, Will S. Plewa, Simon J. Conn, Ling Yang, Patrick K. Shiu, Abhishek Kaushik, Alexander Serganov, Gentile, Giuseppe Viglietto, Nicola Amodio, Tijana Mitić, Andrea Caporali
School of Graduate Studies Faculty Publications
The field of non-coding RNA research is advancing at a breathtaking pace, continually uncovering new layers of regulatory complexity and functional diversity [...].
Proteomic Analysis Of Central Amygdala Systems Regulated By Mifepristone In The Context Of Alcohol Dependence, Stephanie S. Lee, Laura Monteagudo Romero, John W. Lammons, Jennifer M. Klein, Kimberly N. Edwards, Jessie J. Guidry, Scott Edwards
Proteomic Analysis Of Central Amygdala Systems Regulated By Mifepristone In The Context Of Alcohol Dependence, Stephanie S. Lee, Laura Monteagudo Romero, John W. Lammons, Jennifer M. Klein, Kimberly N. Edwards, Jessie J. Guidry, Scott Edwards
School of Graduate Studies Faculty Publications
Alcohol use disorder (AUD) is a psychiatric disorder characterized by escalated alcohol use and the emergence of negative affective symptoms. Studies have described a dysregulation of glucocorticoid receptor (GR) signaling in the context of AUD at the levels of the hypothalamic-pituitary-adrenal (HPA) axis and central amygdala (CeA). A functional increase in CeA GR activity occurs during alcohol withdrawal in alcohol-dependent animal models, and the GR antagonist mifepristone reduces alcohol-seeking and drinking behaviors in both rodents and humans. The aims of this study were to determine differential CeA protein expression in alcohol-dependent rats and examine the effects of mifepristone treatment in …
Synthesis, Pharmacokinetic Studies, And Metabolite Analysis Of Meridianin C In Rats Using A Validated Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry Method, Liangyu Xu, Zhaogen Wu, Karna Ramachandraiah, Guihun Jiang, Guozhe Zhang
Synthesis, Pharmacokinetic Studies, And Metabolite Analysis Of Meridianin C In Rats Using A Validated Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry Method, Liangyu Xu, Zhaogen Wu, Karna Ramachandraiah, Guihun Jiang, Guozhe Zhang
School of Graduate Studies Faculty Publications
Introduction: Meridianin C (MC) is a marine-derived indole alkaloid that has demonstrated kinase inhibitory and anti-tumor activities. Despite its diverse biological properties, no previous reports have systematically evaluated the in vivo quantitative analysis of MC and its metabolites. Methods: In this study, MC was synthesized following a previously reported procedure with slight modifications. A sensitive, accurate, and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was developed to simultaneously detect MC and its five major metabolites (MC-1-N-O-GluA, MC-1-N-O-SO3H, MC-2′-N-O-GluA, MC-2′-N-O-SO3H, and MC-O-GluA-didehydration) in rat plasma. Rats received a single oral dose of MC (100 mg/kg), and pharmacokinetic analysis was …
Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari
Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari
School of Medicine Faculty Publications
The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate …
Polymorphic Α-Glucans As Structural Scaffolds In Cryptococcus Cell Walls For Chitin, Capsule, And Melanin: Insights From 13c And 1h Solid-State Nmr, Ankur Ankur, Jayasubba Reddy Yarava, Isha Gautam, Faith J. Scott, Frederic Mentink-Vigier, Christine Chrissian, Li Xie, Dibakar Roy, Ruth E. Stark, Tamara L. Doering, Ping Wang, Tuo Wang
Polymorphic Α-Glucans As Structural Scaffolds In Cryptococcus Cell Walls For Chitin, Capsule, And Melanin: Insights From 13c And 1h Solid-State Nmr, Ankur Ankur, Jayasubba Reddy Yarava, Isha Gautam, Faith J. Scott, Frederic Mentink-Vigier, Christine Chrissian, Li Xie, Dibakar Roy, Ruth E. Stark, Tamara L. Doering, Ping Wang, Tuo Wang
School of Graduate Studies Faculty Publications
Cryptococcus species are major fungal pathogens responsible for life-threatening infections in approximately a million individuals globally each year, with alarmingly high mortality rates. These fungi are distinguished by a distinctive cell wall architecture further reinforced by two virulence-associated layers, melanin and capsule, rendering them insensitive to antifungal agents targeting the cell wall, such as echinocandins. The molecular interplay between these three biomolecular layers remains poorly understood. Here we employ solid-state NMR spectroscopy to examine intact cells of both wild-type and capsule-deficient strains of C. neoformans, along with melanized cells. High-resolution 13C and 1H data revealed five distinct structural forms of …
Small Molecule Mcl-1 Inhibitor For Triple Negative Breast Cancer Therapy, Shengli Dong, Suresh K. Alahari
Small Molecule Mcl-1 Inhibitor For Triple Negative Breast Cancer Therapy, Shengli Dong, Suresh K. Alahari
School of Medicine Faculty Publications
Apoptosis is an evolutionarily conserved cell death pathway that plays a crucial role in maintaining tissue homeostasis, orchestrating organismal development, and eliminating damaged cells. Dysregulation of apoptosis can contribute to the pathogenesis of malignant tumors and neurodegenerative diseases. Anticancer drugs typically possess the capacity to induce apoptosis in tumor cells. The Bcl-2 protein family, consisting of 27 members in humans, serves as the key regulator of mitochondrial function. This family can be divided into two functional groups: anti-apoptotic proteins (e.g., Bcl-2, Bcl-xl, Mcl-1) and pro-apoptotic proteins (e.g., Bad, Bax). Mcl-1 exerts its function by binding pro-apoptotic Bcl-2 proteins thereby preventing …
Curcumin Alleviates Inflammatory Effects Of Ketamine Anesthesia In Postnatal Rats, Soroush Afshar Ghahremani, Abbas Raisi, Sohrab Minaei Beirami, Houman Kahroba, Mahnaz Mardani, Omid Dezfoulian, Vahideh Tarhriz
Curcumin Alleviates Inflammatory Effects Of Ketamine Anesthesia In Postnatal Rats, Soroush Afshar Ghahremani, Abbas Raisi, Sohrab Minaei Beirami, Houman Kahroba, Mahnaz Mardani, Omid Dezfoulian, Vahideh Tarhriz
School of Graduate Studies Faculty Publications
Curcumin has been employed in traditional medicine for over a millennium to treat various ailments, and its global use is now widespread. Chinese medicine relies heavily on curcumin as a primary element and uses it to cure infectious diseases, skin disorders, depression, and stress. It has cardioprotective, neuroprotective, and anti-diabetic properties, as well as pharmacological effects on disorders like type II diabetes, atherosclerosis, and human immunodeficiency virus replication. The anti-cancer activity of curcumin has been studied extensively with notable improvements in gastrointestinal, melanoma, urogenital, breast, and lung malignancies. We investigated the anti-inflammatory effects of curcumin on expression of tumor necrosis …
Characterizing The Monomer-Dimer Equilibrium Of Ubch8/Ube2l6: A Combined Saxs And Nmr Study, Kerem Kahraman, Scott A. Robson, Oktay Göcenler, Cansu M. Yenici, Cansu D. Tozkoparan Ceylan, Jennifer M. Klein, Volker Dötsch, Emine Sonay Elgin, Arthur L. Haas, Joshua J. Ziarek, Çağdaş Dağ
Characterizing The Monomer-Dimer Equilibrium Of Ubch8/Ube2l6: A Combined Saxs And Nmr Study, Kerem Kahraman, Scott A. Robson, Oktay Göcenler, Cansu M. Yenici, Cansu D. Tozkoparan Ceylan, Jennifer M. Klein, Volker Dötsch, Emine Sonay Elgin, Arthur L. Haas, Joshua J. Ziarek, Çağdaş Dağ
School of Medicine Faculty Publications
Interferon-stimulated gene-15 (ISG15) is an interferon-induced protein with two ubiquitin-like (Ubl) domains linked by a short peptide chain and is a conjugated protein of the ISGylation system. Similar to ubiquitin and other Ubls, ISG15 is ligated to its target proteins through a series of E1, E2, and E3 enzymes known as Uba7, Ube2L6/UbcH8, and HERC5, respectively. Ube2L6/UbcH8 plays a central role in ISGylation, underscoring it as an important drug target for boosting innate antiviral immunity. Depending on the type of conjugated protein and the ultimate target protein, E2 enzymes have been shown to function as monomers, dimers, or both. UbcH8 …
Microrna-532-3p Modulates Colorectal Cancer Cell Proliferation And Invasion Via Suppression Of Foxm1, Ketakee Mahajan, Ani V. Das, Suresh K. Alahari, Ramesh Pothuraju, S. Asha Nair
Microrna-532-3p Modulates Colorectal Cancer Cell Proliferation And Invasion Via Suppression Of Foxm1, Ketakee Mahajan, Ani V. Das, Suresh K. Alahari, Ramesh Pothuraju, S. Asha Nair
School of Graduate Studies Faculty Publications
Colorectal cancer (CRC) is a heterogeneous disease and classified into various subtypes, among which transcriptional alterations result in CRC progression, metastasis, and drug resistance. Forkhead-box M1 (FOXM1) is a proliferation-associated transcription factor which is overexpressed in CRC and the mechanisms of FOXM1 regulation have been under investigation. Previously, we showed that FOXM1 binds to promoters of certain microRNAs. Database mining led to several microRNAs that might interact with FOXM1 3’UTR. The interactions between shortlisted microRNAs and FOXM1 3’UTR were quantitated by a dual-luciferase reporter assay. MicroRNA-532-3p interacted with the 3’UTR of the FOXM1 mRNA transcript most efficiently. MicroRNA-532-3p was ectopically …
Addendum: A Small Molecule Produced By Lactobacillus Species Blocks Candida Albicans Filamentation By Inhibiting A Dyrk1-Family Kinase, Jessie Macalpine, Martin Daniel-Ivad, Zhongle Liu, Junko Yano, Nicole M. Revie, Robert T. Todd, Peter J. Stogios, Hiram Sanchez, Teresa R. O'Meara, Thomas A. Tompkins, Alexei Savchenko, Anna Selmecki, Amanda O. Veri, David R. Andes, Paul L. Fidel, Nicole Robbins, Justin Nodwell, Luke Whitesell, Leah E. Cowen
Addendum: A Small Molecule Produced By Lactobacillus Species Blocks Candida Albicans Filamentation By Inhibiting A Dyrk1-Family Kinase, Jessie Macalpine, Martin Daniel-Ivad, Zhongle Liu, Junko Yano, Nicole M. Revie, Robert T. Todd, Peter J. Stogios, Hiram Sanchez, Teresa R. O'Meara, Thomas A. Tompkins, Alexei Savchenko, Anna Selmecki, Amanda O. Veri, David R. Andes, Paul L. Fidel, Nicole Robbins, Justin Nodwell, Luke Whitesell, Leah E. Cowen
School of Dentistry Faculty Publications
No abstract provided.
Adaptative Survival Of Aspergillus Fumigatus To Echinocandins Arises From Cell Wall Remodeling Beyond Β−1,3-Glucan Synthesis Inhibition, Malitha C. Dickwella Widanage, Isha Gautam, Daipayan Sarkar, Frederic Mentink-Vigier, Josh V. Vermaas, Shi You Ding, Andrew S. Lipton, Thierry Fontaine, Jean Paul Latgé, Ping Wang, Tuo Wang
Adaptative Survival Of Aspergillus Fumigatus To Echinocandins Arises From Cell Wall Remodeling Beyond Β−1,3-Glucan Synthesis Inhibition, Malitha C. Dickwella Widanage, Isha Gautam, Daipayan Sarkar, Frederic Mentink-Vigier, Josh V. Vermaas, Shi You Ding, Andrew S. Lipton, Thierry Fontaine, Jean Paul Latgé, Ping Wang, Tuo Wang
School of Graduate Studies Faculty Publications
Antifungal echinocandins inhibit the biosynthesis of β−1,3-glucan, a major and essential polysaccharide component of the fungal cell wall. However, the efficacy of echinocandins against the pathogen Aspergillus fumigatus is limited. Here, we use solid-state nuclear magnetic resonance (ssNMR) and other techniques to show that echinocandins induce dynamic changes in the assembly of mobile and rigid polymers within the A. fumigatus cell wall. The reduction of β−1,3-glucan induced by echinocandins is accompanied by a concurrent increase in levels of chitin, chitosan, and highly polymorphic α−1,3-glucans, whose physical association with chitin maintains cell wall integrity and modulates water permeability. The rearrangement of …
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
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 …
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
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, …
Editorial: Reviews And Advances In The Molecular Mechanisms Of Breast Cancer, A. Redfern, V. Agarwal, Suresh Alahari
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 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
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
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 …
Regulation Of Tissue Factor Activity By Interaction With The First Pdz Domain Of Magi1, Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie
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 …
Coagulopathy In Severe Covid-19 Patients: Causes, Concerns And Current Treatment Regimen, Tanusree Sengupta, Arun Luiz, Chennakesavan Suganthi, Samarpan Majumder
Coagulopathy In Severe Covid-19 Patients: Causes, Concerns And Current Treatment Regimen, Tanusree Sengupta, Arun Luiz, Chennakesavan Suganthi, Samarpan Majumder
School of Graduate Studies Faculty Publications
Elevated D-dimer and fibrinogen level, mild thrombocytopenia, modest prolongation of prothrombin time, and activated partial thromboplastin time, are key indicators of coagulopathy, and have been consistently reported in severely ill COVID-19 patients. Coronavirus disease 2019 (COVID-19)-induced coagulopathy can develop serious venous and arterial thromboembolic complications. Endothelial dysfunction and hypercoagulability, triggered mostly by overproduction of inflammatory cytokines as an immune response to the infection, are the pivotal factors responsible for the above-mentioned coagulation disorder. Thus, low-molecular-weight heparin (LMWH), which has both anticoagulant and anti-inflammatory properties, has been reported to improve disease prognosis. However, there have been increasing reports of venous thromboembolic …
Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari
Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari
School of Graduate Studies Faculty Publications
Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …
Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart
Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart
School of Graduate Studies Faculty Publications
Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …
Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo
Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo
School of Medicine Faculty Publications
Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a …
Basal Expression Of Nuclear Transcription Factor, Nr4a1, Is Lower In Triple Negative Breast Cancer Compared To Other Breast Cancer Subsets, Manu Khosla, Hassan Yousefi, Celeste Wagner, Arian Lahiji, Suresh Alahari
Basal Expression Of Nuclear Transcription Factor, Nr4a1, Is Lower In Triple Negative Breast Cancer Compared To Other Breast Cancer Subsets, Manu Khosla, Hassan Yousefi, Celeste Wagner, Arian Lahiji, Suresh Alahari
School of Graduate Studies Faculty Publications
DiscoverBMB, March 25 - 28, 2023, Seattle, WA
Spdef Modulates Transcriptional Output To Regulate Multiple Pathways: Immune And Inflammatory Pathways As Potential Hubs Targeted By Spdef In Rcc 7/T Cells, A Line Of Prostate Cancer Cells Of African American Origin, Mousa Vatanmakanian, Sweaty Koul, Hari Koul
Spdef Modulates Transcriptional Output To Regulate Multiple Pathways: Immune And Inflammatory Pathways As Potential Hubs Targeted By Spdef In Rcc 7/T Cells, A Line Of Prostate Cancer Cells Of African American Origin, Mousa Vatanmakanian, Sweaty Koul, Hari Koul
School of Graduate Studies Faculty Publications
DiscoverBMB, March 25 - 28, 2023, Seattle, WA
Lkb1 Signaling And Patient Survival Outcomes In Hepatocellular Carcinoma, Khoa Nguyen, Katherine Hebert, Emily Mcconnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow
Lkb1 Signaling And Patient Survival Outcomes In Hepatocellular Carcinoma, Khoa Nguyen, Katherine Hebert, Emily Mcconnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow
School of Medicine Faculty Publications
The liver is a major organ that is involved in essential biological functions such as digestion, nutrient storage, and detoxification. Furthermore, it is one of the most metabolically active organs with active roles in regulating carbohydrate, protein, and lipid metabolism. Hepatocellular carcinoma is a cancer of the liver that is associated in settings of chronic inflammation such as viral hepatitis, repeated toxin exposure, and fatty liver disease. Furthermore, liver cancer is the most common cause of death associated with cirrhosis and is the 3rd leading cause of global cancer deaths. LKB1 signaling has been demonstrated to play a role in …
The Non-Coding Rna Journal Club: Highlights On Recent Papers—12, Patrick K.T. Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K. Distefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K. Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, André P. Gerber, He Lin, Simon J. Conn, Doha Magdy Mostafa Sleem
The Non-Coding Rna Journal Club: Highlights On Recent Papers—12, Patrick K.T. Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K. Distefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K. Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, André P. Gerber, He Lin, Simon J. Conn, Doha Magdy Mostafa Sleem
School of Graduate Studies Faculty Publications
No abstract provided.
Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija
Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija
School of Medicine Faculty Publications
Despite the suppression of human immunodeficiency virus (HIV) replication by combined antiretroviral therapy (cART), 50–60% of HIV-infected patients suffer from HIV-associated neurocognitive disorders (HAND). Studies are uncovering the role of extracellular vesicles (EVs), especially exosomes, in the central nervous system (CNS) due to HIV infection. We investigated links among circulating plasma exosomal (crExo) proteins and neuropathogenesis in simian/human immunodeficiency virus (SHIV)-infected rhesus macaques (RM) and HIV-infected and cART treated patients (Patient-Exo). Isolated EVs from SHIV-infected (SHIV-Exo) and uninfected (CTL-Exo) RM were predominantly exosomes (particle size < 150 nm). Proteomic analysis quantified 5654 proteins, of which 236 proteins (~4%) were significantly, differentially expressed (DE) between SHIV-/CTL-Exo. Interestingly, different CNS cell specific markers were abundantly expressed in crExo. Proteins involved in latent viral reactivation, neuroinflammation, neuropathology-associated interactive as well as signaling molecules were expressed at significantly higher levels in SHIV-Exo than CTL-Exo. However, proteins involved in mitochondrial biogenesis, ATP production, autophagy, endocytosis, exocytosis, and cytoskeleton organization were significantly less expressed in SHIV-Exo than CTL-Exo. Interestingly, proteins involved in oxidative stress, mitochondrial biogenesis, ATP production, and autophagy were significantly downregulated in primary human brain microvascular endothelial cells exposed with HIV+/cART+ Patient-Exo. We showed that Patient-Exo significantly increased blood–brain barrier permeability, possibly due to loss of platelet endothelial cell adhesion molecule-1 protein and actin cytoskeleton structure. Our novel findings suggest that circulating exosomal proteins expressed CNS cell markers—possibly associated with viral reactivation and neuropathogenesis—that may elucidate the etiology of HAND.
Myo1e Overexpression In Lung Adenocarcinoma Is Associated With Increased Risk Of Mortality, Ignacio Jusue-Torres, Richies Tiv, Julio C. Ricarte-Filho, Apurva Mallisetty, Leglys Contreras-Vargas, Maria Jose Godoy-Calderon, Karam Khaddour, Kathleen Kennedy, Klara Valyi-Nagy, Odile David, Martha Menchaca, Anastasia Kottorou, Angelos Koutras, Foteinos Dimitrakopoulos, Khaled M. Abdelhady, Malek Massad, Israel Rubinstein, Lawrence Feldman, John Stewart, Takeshi Shimamura, Ludmila Danilova, Alicia Hulbert
Myo1e Overexpression In Lung Adenocarcinoma Is Associated With Increased Risk Of Mortality, Ignacio Jusue-Torres, Richies Tiv, Julio C. Ricarte-Filho, Apurva Mallisetty, Leglys Contreras-Vargas, Maria Jose Godoy-Calderon, Karam Khaddour, Kathleen Kennedy, Klara Valyi-Nagy, Odile David, Martha Menchaca, Anastasia Kottorou, Angelos Koutras, Foteinos Dimitrakopoulos, Khaled M. Abdelhady, Malek Massad, Israel Rubinstein, Lawrence Feldman, John Stewart, Takeshi Shimamura, Ludmila Danilova, Alicia Hulbert
School of Medicine Faculty Publications
This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. …
Integrating Genomic Information With Tumor-Immune Microenvironment In Triple-Negative Breast Cancer, David Otohinoyi, Aditi Kuchi, Jiande Wu, Chindo Hicks
Integrating Genomic Information With Tumor-Immune Microenvironment In Triple-Negative Breast Cancer, David Otohinoyi, Aditi Kuchi, Jiande Wu, Chindo Hicks
School of Graduate Studies Faculty Publications
Background: the development and progression of triple-negative breast cancer (TNBC) is driven by somatic driver mutations and the tumor-immune microenvironment. To date, data on somatic mutations has not been leveraged and integrated with information on the immune microenvironment to elucidate the possible oncogenic interactions and their potential effects on clinical outcomes. Here, we investigated possible oncogenic interactions between somatic mutations and the tumor-immune microenvironment, and their correlation with patient survival in TNBC. Methods: We performed analysis combining data on 7,875 somatic mutated genes with information on 1,751 immune-modulated genes, using gene-expression data as the intermediate phenotype, and correlated the resulting …