Open Access. Powered by Scholars. Published by Universities.®

Digital Commons Network™

Open Access. Powered by Scholars. Published by Universities.®

Medical Specialties

Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 4771 - 4800 of 25839

Full-Text Articles in Entire DC Network

Loss Of P53 And Smad4 Induces Adenosquamous Subtype Pancreatic Cancer In The Absence Of An Oncogenic Kras Mutation, Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen Sep 2024

Loss Of P53 And Smad4 Induces Adenosquamous Subtype Pancreatic Cancer In The Absence Of An Oncogenic Kras Mutation, Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT. The Trp53

Go to article

Perfusion-Weighted Imaging With Dynamic Contrast Enhancement (Pwi/Dce) Morphologic, Qualitative, Semiquantitative, And Radiomics Features Predicting Undifferentiated Pleomorphic Sarcoma (Ups) Treatment Response, R F Valenzuela, E Duran-Sierra, M Canjirathinkal, B Amini, K E Torres, R S Benjamin, J Ma, W L Wang, K P Hwang, R J Stafford, C Wu, A M Zarzour, A J Bishop, S Lo, J E Madewell, R Kumar, W A Murphy, C M Costelloe Sep 2024

Perfusion-Weighted Imaging With Dynamic Contrast Enhancement (Pwi/Dce) Morphologic, Qualitative, Semiquantitative, And Radiomics Features Predicting Undifferentiated Pleomorphic Sarcoma (Ups) Treatment Response, R F Valenzuela, E Duran-Sierra, M Canjirathinkal, B Amini, K E Torres, R S Benjamin, J Ma, W L Wang, K P Hwang, R J Stafford, C Wu, A M Zarzour, A J Bishop, S Lo, J E Madewell, R Kumar, W A Murphy, C M Costelloe

Faculty, Staff and Student Publications

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from …

Go to article

Detecting Altered Hepatic Lipid Oxidation By Mri In An Animal Model Of Masld, Marc Mcleod, Mario C Chang, Anna Rushin, Mukundan Ragavan, Rohit Mahar, Gaurav Sharma, Arshee Badar, Anthony Giacalone, Max E Glanz, Vinay R Malut, Dalton Graham, Nishanth E Sunny, James A Bankson, Kenneth Cusi, Matthew E Merritt Sep 2024

Detecting Altered Hepatic Lipid Oxidation By Mri In An Animal Model Of Masld, Marc Mcleod, Mario C Chang, Anna Rushin, Mukundan Ragavan, Rohit Mahar, Gaurav Sharma, Arshee Badar, Anthony Giacalone, Max E Glanz, Vinay R Malut, Dalton Graham, Nishanth E Sunny, James A Bankson, Kenneth Cusi, Matthew E Merritt

Faculty, Staff and Student Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of MASLD/MASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we develop a method for estimating hepatic β-oxidation from the metabolism of [D

Go to article

Gut Phageome In Mexican Americans: A Population At High Risk For Metabolic Dysfunction-Associated Steatotic Liver Disease And Diabetes, Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta Sep 2024

Gut Phageome In Mexican Americans: A Population At High Risk For Metabolic Dysfunction-Associated Steatotic Liver Disease And Diabetes, Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta

Faculty, Staff and Student Publications

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of …

Go to article

The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy Through Tfeb, Mckenna Losby, Matthew Hayes, Aurore Valfort, Danesh H Sopariwala, Ryan Sanders, John K Walker, Weiyi Xu, Vihang A Narkar, Lilei Zhang, Cyrielle Billon, Thomas P Burris Sep 2024

The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy Through Tfeb, Mckenna Losby, Matthew Hayes, Aurore Valfort, Danesh H Sopariwala, Ryan Sanders, John K Walker, Weiyi Xu, Vihang A Narkar, Lilei Zhang, Cyrielle Billon, Thomas P Burris

Faculty, Staff and Students Publications

Autophagy is an essential self-degradative and recycling mechanism that maintains cellular homeostasis. Estrogen receptor-related orphan receptors (ERRs) are fundamental in regulating cardiac metabolism and function. Previously, we showed that ERR agonists improve cardiac function in models of heart failure and induce autophagy. Here, we characterized a mechanism by which ERRs induce the autophagy pathway in cardiomyocytes. Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome pathway and has been shown to be crucial regulator of genes that control autophagy. We discovered that TFEB is a direct ERR target gene whose expression is induced by ERR agonists. Activation of …

Go to article

Creb-Binding Protein/P300 Bromodomain Inhibition Reduces Neutrophil Accumulation And Activates Antitumor Immunity In Triple-Negative Breast Cancer, Xueying Yuan, Xiaoxin Hao, Hilda L Chan, Na Zhao, Diego A Pedroza, Fengshuo Liu, Kang Le, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Michael J Soth, Philip Jones, Xiang Hf Zhang, Jeffrey M Rosen Sep 2024

Creb-Binding Protein/P300 Bromodomain Inhibition Reduces Neutrophil Accumulation And Activates Antitumor Immunity In Triple-Negative Breast Cancer, Xueying Yuan, Xiaoxin Hao, Hilda L Chan, Na Zhao, Diego A Pedroza, Fengshuo Liu, Kang Le, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Michael J Soth, Philip Jones, Xiang Hf Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB-binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing …

Go to article

Vglut2-Based Glutamatergic Signaling In Central Noradrenergic Neurons Is Dispensable For Normal Breathing And Chemosensory Reflexes, Yuan Chang, Savannah Lusk, Andersen Chang, Christopher S Ward, Russell S Ray Sep 2024

Vglut2-Based Glutamatergic Signaling In Central Noradrenergic Neurons Is Dispensable For Normal Breathing And Chemosensory Reflexes, Yuan Chang, Savannah Lusk, Andersen Chang, Christopher S Ward, Russell S Ray

Faculty, Staff and Students Publications

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. …

Go to article

Cortisol And Alpha-Synuclein Stability In Saliva Under Varying Storage And Handling Conditions, Mo Zheng, Sujata Srikanth, Jeremiah Carpenter, Delphine Dean Sep 2024

Cortisol And Alpha-Synuclein Stability In Saliva Under Varying Storage And Handling Conditions, Mo Zheng, Sujata Srikanth, Jeremiah Carpenter, Delphine Dean

Journal of the South Carolina Academy of Science

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments and non-motor symptoms, significantly impacting patients' quality of life. Currently, cerebrospinal fluid (CSF) is the primary biofluid used for PD biomarker studies, notably α-synuclein, despite the invasive nature of lumbar puncture procedures. Recent work has shown that some of these PD biomarkers have been measured in saliva. As an alternative to CSF, saliva can be non-invasively self-collected by patients repeatedly over time to monitor biomarker levels. However, the stability of these biomarkers in saliva needs to be evaluated before saliva can be considered for patient self-collection studies. Therefore, …

Go to article

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 Sep 2024

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 …

Go to article

Knee Osteoarthritis: Disease Burden, Available Treatments, And Emerging Options, Michael Langworthy, Vinod Dasa, Andrew I. Spitzer Sep 2024

Knee Osteoarthritis: Disease Burden, Available Treatments, And Emerging Options, Michael Langworthy, Vinod Dasa, Andrew I. Spitzer

School of Medicine Faculty Publications

Osteoarthritis (OA) is a prevalent condition that affects nearly 528 million people worldwide, including 23% of the global population aged ⩾40, and is characterized by progressive damage to articular cartilage, which often leads to substantial pain, stiffness, and reduced mobility for affected patients. Pain related to OA is a barrier to maintaining physical activity and a leading cause of disability, accounting for 2.4% of all years lived with disability globally, reducing the ability to work in 66% of US patients with OA and increasing absenteeism in 21% of US patients with OA. The joint most commonly involved in OA is …

Go to article

Loss Of Hd-Ptp Function Results In Lipodystrophy, Defective Cellular Signaling And Altered Lipid Homeostasis, Destiny F Schultz, Brian A Davies, Johanna A Payne, Cole P Martin, Annabel Y Minard, Bennett G Childs, Cheng Zhang, Karthik B Jeganathan, Ines Sturmlechner, Thomas A White, Alain De Bruin, Liesbeth Harkema, Huiqin Chen, Michael A Davies, Sarah Jachim, Nathan K Lebrasseur, Robert C Piper, Hu Li, Darren J Baker, Jan Van Deursen, Daniel D Billadeau, David J Katzmann Sep 2024

Loss Of Hd-Ptp Function Results In Lipodystrophy, Defective Cellular Signaling And Altered Lipid Homeostasis, Destiny F Schultz, Brian A Davies, Johanna A Payne, Cole P Martin, Annabel Y Minard, Bennett G Childs, Cheng Zhang, Karthik B Jeganathan, Ines Sturmlechner, Thomas A White, Alain De Bruin, Liesbeth Harkema, Huiqin Chen, Michael A Davies, Sarah Jachim, Nathan K Lebrasseur, Robert C Piper, Hu Li, Darren J Baker, Jan Van Deursen, Daniel D Billadeau, David J Katzmann

Faculty, Staff and Student Publications

His domain protein tyrosine phosphatase (HD-PTP; also known as PTPN23) facilitates function of the endosomal sorting complexes required for transport (ESCRTs) during multivesicular body (MVB) formation. To uncover its role in physiological homeostasis, embryonic lethality caused by a complete lack of HD-PTP was bypassed through generation of hypomorphic mice expressing reduced protein, resulting in animals that are viable into adulthood. These mice exhibited marked lipodystrophy and decreased receptor-mediated signaling within white adipose tissue (WAT), involving multiple prominent pathways including RAS/MAPK, phosphoinositide 3-kinase (PI3K)/AKT and receptor tyrosine kinases (RTKs), such as EGFR. EGFR signaling was dissected in vitro to assess the …

Go to article

Longitudinal Intravascular Antibody Labeling Identified Regulatory T Cell Recruitment As A Therapeutic Target In A Mouse Model Of Lung Cancer, Sean-Luc Shanahan, Nikesh Kunder, Charles Inaku, Natalie B Hagan, Grace Gibbons, Nicolas Mathey-Andrews, Gayathri Anandappa, Shawn Soares, Kristen E Pauken, Tyler Jacks, Jason M Schenkel Sep 2024

Longitudinal Intravascular Antibody Labeling Identified Regulatory T Cell Recruitment As A Therapeutic Target In A Mouse Model Of Lung Cancer, Sean-Luc Shanahan, Nikesh Kunder, Charles Inaku, Natalie B Hagan, Grace Gibbons, Nicolas Mathey-Andrews, Gayathri Anandappa, Shawn Soares, Kristen E Pauken, Tyler Jacks, Jason M Schenkel

Faculty, Staff and Student Publications

Anticancer immunity is predicated on leukocyte migration into tumors. Once recruited, leukocytes undergo substantial reprogramming to adapt to the tumor microenvironment. A major challenge in the field is distinguishing recently recruited from resident leukocytes in tumors. In this study, we developed an intravascular Ab technique to label circulating mouse leukocytes before they migrate to tissues, providing unprecedented insight into the kinetics of recruitment. This approach unveiled the substantial role of leukocyte migration in tumor progression using a preclinical mouse model of lung adenocarcinoma. Regulatory T cells (Tregs), critical mediators of immunosuppression, were continuously and rapidly recruited into tumors throughout cancer …

Go to article

Phototaxis Is A Satiety-Dependent Behavioral Sequence In Hydra Vulgaris, Soonyoung Kim, Krishna N Badhiwala, Guillaume Duret, Jacob T Robinson Sep 2024

Phototaxis Is A Satiety-Dependent Behavioral Sequence In Hydra Vulgaris, Soonyoung Kim, Krishna N Badhiwala, Guillaume Duret, Jacob T Robinson

Faculty, Staff and Students Publications

Understanding how internal states such as satiety are connected to animal behavior is a fundamental question in neuroscience. Hydra vulgaris, a freshwater cnidarian with only 12 neuronal cell types, serves as a tractable model system for studying state-dependent behaviors. We found that starved hydras consistently move towards light, while fed hydras do not. By modeling this behavior as a set of three sequences of head orientation, jump distance and jump rate, we demonstrate that the satiety state only affects the rate of the animal jumping to a new position, while the orientation and jump distance are unaffected. These findings yield …

Go to article

A Novel Non-Invasive Murine Model Of Neonatal Hypoxic-Ischemic Encephalopathy Demonstrates Developmental Delay And Motor Deficits With Activation Of Inflammatory Pathways In Monocytes, Elise A Lemanski, Bailey A Collins, Andrew T Ebenezer, Sudha Anilkumar, Victoria A Langdon, Qi Zheng, Shanshan Ding, Karl Royden Franke, Jaclyn M Schwarz, Elizabeth Wright-Jin Sep 2024

A Novel Non-Invasive Murine Model Of Neonatal Hypoxic-Ischemic Encephalopathy Demonstrates Developmental Delay And Motor Deficits With Activation Of Inflammatory Pathways In Monocytes, Elise A Lemanski, Bailey A Collins, Andrew T Ebenezer, Sudha Anilkumar, Victoria A Langdon, Qi Zheng, Shanshan Ding, Karl Royden Franke, Jaclyn M Schwarz, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. …

Go to article

Hif-2Α-Dependent Induction Of Mir-29a Restrains Th1 Activity During T Cell Dependent Colitis, Agnieszka K Czopik, Eóin N Mcnamee, Victoria Vaughn, Xiangsheng Huang, In Hyuk Bang, Trent Clark, Yanyu Wang, Wei Ruan, Tom Nguyen, Joanne C Masterson, Eunyoung Tak, Sandra Frank, Colm B Collins, Howard Li, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Mark E Gerich, Glenn T Furuta, Xiaoyi Yuan, Anil K Sood, Edwin F De Zoeten, Holger K Eltzschig Sep 2024

Hif-2Α-Dependent Induction Of Mir-29a Restrains Th1 Activity During T Cell Dependent Colitis, Agnieszka K Czopik, Eóin N Mcnamee, Victoria Vaughn, Xiangsheng Huang, In Hyuk Bang, Trent Clark, Yanyu Wang, Wei Ruan, Tom Nguyen, Joanne C Masterson, Eunyoung Tak, Sandra Frank, Colm B Collins, Howard Li, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Mark E Gerich, Glenn T Furuta, Xiaoyi Yuan, Anil K Sood, Edwin F De Zoeten, Holger K Eltzschig

Faculty, Staff and Student Publications

Metabolic imbalance leading to inflammatory hypoxia and stabilization of hypoxia-inducible transcription factors (HIFs) is a hallmark of inflammatory bowel diseases. We hypothesize that HIF could be stabilized in CD4+ T cells during intestinal inflammation and alter the functional responses of T cells via regulation of microRNAs. Our assays reveal markedly increased T cell-intrinsic hypoxia and stabilization of HIF protein during experimental colitis. microRNA screen in primary CD4+ T cells points us towards miR-29a and our subsequent studies identify a selective role for HIF-2α in CD4-cell-intrinsic induction of miR-29a during hypoxia. Mice with T cell-intrinsic HIF-2α deletion display elevated T-bet (target …

Go to article

Spatially Fractionated Grid Radiation Potentiates Immune-Mediated Tumor Control, Rebecca A Bekker, Nina Obertopp, Gage Redler, José Penagaricano, Jimmy J Caudell, Kosj Yamoah, Shari Pilon-Thomas, Eduardo G Moros, Heiko Enderling Sep 2024

Spatially Fractionated Grid Radiation Potentiates Immune-Mediated Tumor Control, Rebecca A Bekker, Nina Obertopp, Gage Redler, José Penagaricano, Jimmy J Caudell, Kosj Yamoah, Shari Pilon-Thomas, Eduardo G Moros, Heiko Enderling

Faculty, Staff and Student Publications

Background: Tumor-immune interactions shape a developing tumor and its tumor immune microenvironment (TIME) resulting in either well-infiltrated, immunologically inflamed tumor beds, or immune deserts with low levels of infiltration. The pre-treatment immune make-up of the TIME is associated with treatment outcome; immunologically inflamed tumors generally exhibit better responses to radio- and immunotherapy than non-inflamed tumors. However, radiotherapy is known to induce opposing immunological consequences, resulting in both immunostimulatory and inhibitory responses. In fact, it is thought that the radiation-induced tumoricidal immune response is curtailed by subsequent applications of radiation. It is thus conceivable that spatially fractionated radiotherapy (SFRT), administered through …

Go to article

Minimally Invasive Therapies For Knee Osteoarthritis, Uchenna Osuala, Megan H Goh, Arian Mansur, John B Smirniotopoulos, Arielle Scott, Christine Vassell, Bardia Yousefi, Neil K Jain, Alan A Sag, Allison Lax, Kevin W Park, Alexander Kheradi, Marc Sapoval, Jafar Golzarian, Peiman Habibollahi, Osman Ahmed, Shamar Young, Nariman Nezami Sep 2024

Minimally Invasive Therapies For Knee Osteoarthritis, Uchenna Osuala, Megan H Goh, Arian Mansur, John B Smirniotopoulos, Arielle Scott, Christine Vassell, Bardia Yousefi, Neil K Jain, Alan A Sag, Allison Lax, Kevin W Park, Alexander Kheradi, Marc Sapoval, Jafar Golzarian, Peiman Habibollahi, Osman Ahmed, Shamar Young, Nariman Nezami

Faculty, Staff and Student Publications

Knee osteoarthritis (KOA) is a musculoskeletal disorder characterized by articular cartilage degeneration and chronic inflammation, affecting one in five people over 40 years old. The purpose of this study was to provide an overview of traditional and novel minimally invasive treatment options and role of artificial intelligence (AI) to streamline the diagnostic process of KOA. This literature review provides insights into the mechanisms of action, efficacy, complications, technical approaches, and recommendations to intra-articular injections (corticosteroids, hyaluronic acid, and plate rich plasma), genicular artery embolization (GAE), and genicular nerve ablation (GNA). Overall, there is mixed evidence to support the efficacy of …

Go to article

Impact And Characterization Of Serial Structural Variations Across Humans And Great Apes, Wolfram Höps, Tobias Rausch, Michael Jendrusch, Jan O Korbel, Fritz J Sedlazeck Sep 2024

Impact And Characterization Of Serial Structural Variations Across Humans And Great Apes, Wolfram Höps, Tobias Rausch, Michael Jendrusch, Jan O Korbel, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Modern sequencing technology enables the systematic detection of complex structural variation (SV) across genomes. However, extensive DNA rearrangements arising through a series of mutations, a phenomenon we refer to as serial SV (sSV), remain underexplored, posing a challenge for SV discovery. Here, we present NAHRwhals ( https://github.com/WHops/NAHRwhals ), a method to infer repeat-mediated series of SVs in long-read genomic assemblies. Applying NAHRwhals to haplotype-resolved human genomes from 28 individuals reveals 37 sSV loci of various length and complexity. These sSVs explain otherwise cryptic variation in medically relevant regions such as the TPSAB1 gene, 8p23.1, 22q11 and Sotos syndrome regions. Comparisons …

Go to article

Targeting Ribosome Biogenesis Is A Novel Approach For The Management Of Pancreatic Cancer, Mudassier Ahmad, Haider Ahsan, Carlos Perez, Muhammad Bangash, Andrew Massey, Emmanuel Anning, Manish Tripathi, Dae Kim, Subhash C. Chauhan, Bilal Bin Hafeez Sep 2024

Targeting Ribosome Biogenesis Is A Novel Approach For The Management Of Pancreatic Cancer, Mudassier Ahmad, Haider Ahsan, Carlos Perez, Muhammad Bangash, Andrew Massey, Emmanuel Anning, Manish Tripathi, Dae Kim, Subhash C. Chauhan, Bilal Bin Hafeez

Research Colloquium

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related deaths in the United States with limited therapeutic options available. Gemcitabine, a deoxycytidine nucleoside analog is currently considered the most effective therapy for PanCa. However, it shows only a marginal survival benefit of six months. Aberrant ribosome biogenesis occurs in most tumor types. We observed that PanCa cells are addicted to ribosome biogenesis, which supports their highly aggressive metastatic phenotypes. Thus, strategically targeting ribosome biogenesis process could be one of the ideal strategies for the prevention and treatment of PanCa. In this study, we elucidated the molecular mechanisms of POLR1A …

Go to article

Obsessive Compulsive Disorder And Other Specified Anxiety Disorder In An 8-Year-Old Post-Respiratory Infection: A Case Report, Michael Tran, Alcides Amador, Sofia Camacho Bermudez Sep 2024

Obsessive Compulsive Disorder And Other Specified Anxiety Disorder In An 8-Year-Old Post-Respiratory Infection: A Case Report, Michael Tran, Alcides Amador, Sofia Camacho Bermudez

Research Colloquium

Background: This case report presents the diagnosis and management of Obsessive Compulsive Disorder (OCD) and Other Specified Anxiety Disorders in an 8-year-old male. The importance lies in the development of psychiatric symptoms after multiple respiratory infections and the subsequent diagnosis of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). It highlights a potential connection between infections and psychiatric manifestations in pediatric patients. PANDAS is an immune-mediated neuropsychiatric disorder that occurs after a Group A Strep (GAS) infection, characterized by the sudden onset or worsening of obsessive-compulsive disorder and tic disorder. While pathophysiology is not fully understood, evidence indicates that …

Go to article

Mouse Monocytes Express Cd127 By Immune Cells, Not Lps, Reza Yazdani, Mozhde Askari, Amir Moghadam-Ahmadi, Gholamreza Azizi, Bogoljub Ciric, Alexandra Boehm, Guang-Xian Zhang, Mohamad Rostami Sep 2024

Mouse Monocytes Express Cd127 By Immune Cells, Not Lps, Reza Yazdani, Mozhde Askari, Amir Moghadam-Ahmadi, Gholamreza Azizi, Bogoljub Ciric, Alexandra Boehm, Guang-Xian Zhang, Mohamad Rostami

Department of Neurology Faculty Papers

The essential role of interleukin 7 (IL-7) signaling via its receptor (IL-7Rα; CD127) in T cell development and function has been well documented. However, CD127 expression and function in myeloid cells, including monocytes, are less clear, especially in mice. In the present study we report an inducible CD127 expression in mouse monocytes/macrophages. This induction is dependent on the presence of other immune cells, highlighting that regulation of CD127 expression on monocytes differs in mice and humans. We demonstrate that CD127 is functional, as IL-7 downregulated its expression. We also saw decreased CD127 expression during inflammation in vivo. Overall, upregulation …

Go to article

Characterization Of Dna Damage Repair Pathway Utilization In High-Grade Serous Ovarian Cancers Yields Rational Therapeutic Approaches, Erika Nakatsuka, Lijun Tan, Brianna Cunneen, Caroline Foster, Yu Leo Lei, Karen Mclean Sep 2024

Characterization Of Dna Damage Repair Pathway Utilization In High-Grade Serous Ovarian Cancers Yields Rational Therapeutic Approaches, Erika Nakatsuka, Lijun Tan, Brianna Cunneen, Caroline Foster, Yu Leo Lei, Karen Mclean

Faculty, Staff and Student Publications

While poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have improved the prognosis of ovarian high-grade serous carcinoma (HGSC) tumors that are homologous recombination (HR) deficient (HRD), new therapeutic strategies are needed for tumors that are HR proficient (HRP) because they demonstrate greater resistance to current treatments and thus have poorer clinical outcomes. Additionally, clinical precautionary statements regarding potential risks associated with PARPi, such as myelodysplastic syndrome, highlight the need for combinatorial approaches that can lessen the dose and duration of PARPi treatment to reduce toxicities. Here, we evaluated DNA double-strand damage repair pathways in HRD and HRP ovarian cancer cell lines …

Go to article

Expanding The Crispr Base Editing Toolbox In Drosophila Melanogaster, Michael Clark, Christina Nguyen, Hung Nguyen, Aidan Tay, Samuel J Beach, Maciej Maselko, Víctor López Del Amo Sep 2024

Expanding The Crispr Base Editing Toolbox In Drosophila Melanogaster, Michael Clark, Christina Nguyen, Hung Nguyen, Aidan Tay, Samuel J Beach, Maciej Maselko, Víctor López Del Amo

Faculty, Staff and Student Publications

CRISPR base editors can introduce point mutations into DNA precisely, and cytosine base editors (CBEs) catalyze C to T transitions. While CBEs have been thoroughly explored in cell culture and organisms such as mice, little is known about DNA base editing in insects. In this study, we evaluated germline editing rates of three different CBEs expressed under actin (ubiquitous) or nanos (germline) promoters utilizing Drosophila melanogaster. The original Rattus norvegicus-derived cytosine deaminase APOBEC1 (rAPO-1) displayed high base editing rates (~99%) with undetectable indel formation. Additionally, we show that base editors can be used for generating male sterility and female lethality. …

Go to article

Synthesis And Optimization Of Small Molecule Inhibitors Of Prostate Specific Antigen, Jeffery A Erickson, Ravikumar Jimmidi, Prashanth Anamthathmakula, Xuan Qin, Jian Wang, Leyi Gong, Jaehyeon Park, Gary Koolpe, Caitlin Tan, Martin M Matzuk, Feng Li, Srinivas Chamakuri, Wipawee Winuthayanon Sep 2024

Synthesis And Optimization Of Small Molecule Inhibitors Of Prostate Specific Antigen, Jeffery A Erickson, Ravikumar Jimmidi, Prashanth Anamthathmakula, Xuan Qin, Jian Wang, Leyi Gong, Jaehyeon Park, Gary Koolpe, Caitlin Tan, Martin M Matzuk, Feng Li, Srinivas Chamakuri, Wipawee Winuthayanon

Faculty, Staff and Students Publications

Semen liquefaction is a postejaculation process that transforms semen from a gel-like (coagulated) form to a water-like consistency (liquefied). This process is primarily regulated by serine proteases from the prostate gland, most prominently, prostate-specific antigen (PSA; KLK3). Inhibiting PSA activity has the potential to impede liquefaction of human semen, presenting a promising target for nonhormonal contraception in the female reproductive tract. This study employed triazole B1 as a starting compound. Through systematic design, synthesis, and optimization, we identified compound 20 (CDD-3290) as a 216 nM inhibitor of PSA with better stability in media than triazole B1. Further, we also evaluated …

Go to article

Evaluation Of High-Affinity Monoclonal Antibodies And Antibody-Drug Conjugates By Homogenous Time-Resolved Fret, Harmon Greenway, Jin Wang Sep 2024

Evaluation Of High-Affinity Monoclonal Antibodies And Antibody-Drug Conjugates By Homogenous Time-Resolved Fret, Harmon Greenway, Jin Wang

Faculty, Staff and Students Publications

The rapid growth of therapeutic monoclonal antibodies demands greater accessibility to scalable methods of evaluating antigen binding. Homogenous TR-FRET is ideal for preliminary screening but has not been reported to assay these interactions due to their high-affinity and complex solution-phase kinetics. Here we report the development of a competition assay to rank-order the relative affinities of these drugs for a common antigen. The assay is compatible with automation, requires no modification of the analytes, and measures affinities as low as single-digit picomolar. We further demonstrate applications to inform the development of antibody-drug conjugates. The assay may aid discovery and manufacturing …

Go to article

Context-Aware Single-Cell Multiomics Approach Identifies Cell-Type-Specific Lung Cancer Susceptibility Genes, Erping Long, Jinhu Yin, Ju Hye Shin, Yuyan Li, Bolun Li, Alexander Kane, Harsh Patel, Xinti Sun, Cong Wang, Thong Luong, Jun Xia, Younghun Han, Jinyoung Byun, Tongwu Zhang, Wei Zhao, Maria Teresa Landi, Nathaniel Rothman, Qing Lan, Yoon Soo Chang, Fulong Yu, Christopher I Amos, Jianxin Shi, Jin Gu Lee, Eun Young Kim, Jiyeon Choi Sep 2024

Context-Aware Single-Cell Multiomics Approach Identifies Cell-Type-Specific Lung Cancer Susceptibility Genes, Erping Long, Jinhu Yin, Ju Hye Shin, Yuyan Li, Bolun Li, Alexander Kane, Harsh Patel, Xinti Sun, Cong Wang, Thong Luong, Jun Xia, Younghun Han, Jinyoung Byun, Tongwu Zhang, Wei Zhao, Maria Teresa Landi, Nathaniel Rothman, Qing Lan, Yoon Soo Chang, Fulong Yu, Christopher I Amos, Jianxin Shi, Jin Gu Lee, Eun Young Kim, Jiyeon Choi

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, underlying mechanisms and target genes are largely unknown, as most risk-associated variants might regulate gene expression in a context-specific manner. Here, we generate a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Identified candidate cis-regulatory elements (cCREs) are largely cell type-specific, with 37% detected in one cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs combined with transcription factor footprinting prioritize the variants for 68% of the GWAS loci. …

Go to article

Role Of Poly(A)-Binding Protein Cytoplasmic 1, A Trna-Derived Rna Fragment-Bound Protein, In Respiratory Syncytial Virus Infection, Devin V Davis, Eun-Jin Choi, Deena Ismail, Miranda L Hernandez, Jong Min Choi, Ke Zhang, Kashish Khatkar, Sung Yun Jung, Wenzhe Wu, Xiaoyong Bao Sep 2024

Role Of Poly(A)-Binding Protein Cytoplasmic 1, A Trna-Derived Rna Fragment-Bound Protein, In Respiratory Syncytial Virus Infection, Devin V Davis, Eun-Jin Choi, Deena Ismail, Miranda L Hernandez, Jong Min Choi, Ke Zhang, Kashish Khatkar, Sung Yun Jung, Wenzhe Wu, Xiaoyong Bao

Faculty, Staff and Students Publications

Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections (LRTI) across all demographics, with increasing mortality and morbidity among high-risk groups such as infants under two years old, the elderly, and immunocompromised individuals. Although newly approved vaccines and treatments have substantially reduced RSV hospitalizations, accessibility remains limited, and response to treatment varies. This underscores the importance of comprehensive studies on host-RSV interactions. tRNA-derived RNA fragments (tRFs) are recently discovered non-coding RNAs, notable for their regulatory roles in diseases, including viral infections. Our prior work demonstrated that RSV infection induces tRFs, primarily derived from the 5'-end of …

Go to article

Persistent Tailoring Of Msc Activation Through Genetic Priming, Michael A Beauregard, Guy C Bedford, Daniel A Brenner, Leonardo D Sanchez Solis, Tomoki Nishiguchi, Abhimanyu, Santiago Carrero Longlax, Barun Mahata, Omid Veiseh, Pamela L Wenzel, Andrew R Dinardo, Isaac B Hilton, Michael R Diehl Sep 2024

Persistent Tailoring Of Msc Activation Through Genetic Priming, Michael A Beauregard, Guy C Bedford, Daniel A Brenner, Leonardo D Sanchez Solis, Tomoki Nishiguchi, Abhimanyu, Santiago Carrero Longlax, Barun Mahata, Omid Veiseh, Pamela L Wenzel, Andrew R Dinardo, Isaac B Hilton, Michael R Diehl

Faculty, Staff and Student Publications

Mesenchymal stem/stromal cells (MSCs) are an attractive platform for cell therapy due to their safety profile and unique ability to secrete broad arrays of immunomodulatory and regenerative molecules. Yet, MSCs are well known to require preconditioning or priming to boost their therapeutic efficacy. Current priming methods offer limited control over MSC activation, yield transient effects, and often induce the expression of pro-inflammatory effectors that can potentiate immunogenicity. Here, we describe a genetic priming method that can both selectively and sustainably boost MSC potency via the controlled expression of the inflammatory-stimulus-responsive transcription factor interferon response factor 1 (IRF1). MSCs engineered to …

Go to article

Batf Is A Major Driver Of Nk Cell Epigenetic Reprogramming And Dysfunction In Aml, Bijender Kumar, Anand Singh, Rafet Basar, Nadima Uprety, Ye Li, Huihui Fan, Ana Karen Nunez Cortes, Mecit Kaplan, Sunil Acharya, Hila Shaim, Anna C Xu, Manrong Wu, Emily Ensley, Dexing Fang, Pinaki P Banerjee, Luciana Melo Garcia, Silvia Tiberti, Paul Lin, Hind Rafei, Maliha Nuzhat Munir, Madison Moore, Mayra Shanley, Mayela Mendt, Lucila N Kerbauy, Bin Liu, Alexander Biederstädt, Elif Gokdemir, Susmita Ghosh, Kiran Kundu, Francia Reyes-Silva, Xin Ru Jiang, Xinhai Wan, April L Gilbert, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Patrick Zhang, Enli Liu, Luis Muniz-Feliciano, Gary M Deyter, Abhinav K Jain, Juan Jose Rodriguez-Sevilla, Simona Colla, Guillermo Garcia-Manero, Elizabeth J Shpall, Ken Chen, Hussein A Abbas, Kunal Rai, Katayoun Rezvani, May Daher Sep 2024

Batf Is A Major Driver Of Nk Cell Epigenetic Reprogramming And Dysfunction In Aml, Bijender Kumar, Anand Singh, Rafet Basar, Nadima Uprety, Ye Li, Huihui Fan, Ana Karen Nunez Cortes, Mecit Kaplan, Sunil Acharya, Hila Shaim, Anna C Xu, Manrong Wu, Emily Ensley, Dexing Fang, Pinaki P Banerjee, Luciana Melo Garcia, Silvia Tiberti, Paul Lin, Hind Rafei, Maliha Nuzhat Munir, Madison Moore, Mayra Shanley, Mayela Mendt, Lucila N Kerbauy, Bin Liu, Alexander Biederstädt, Elif Gokdemir, Susmita Ghosh, Kiran Kundu, Francia Reyes-Silva, Xin Ru Jiang, Xinhai Wan, April L Gilbert, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Patrick Zhang, Enli Liu, Luis Muniz-Feliciano, Gary M Deyter, Abhinav K Jain, Juan Jose Rodriguez-Sevilla, Simona Colla, Guillermo Garcia-Manero, Elizabeth J Shpall, Ken Chen, Hussein A Abbas, Kunal Rai, Katayoun Rezvani, May Daher

Faculty, Staff and Student Publications

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) belong to a continuous disease spectrum of myeloid malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients with myeloid malignancies display global dysfunction with impaired killing capacity, altered metabolism and exhausted phenotype at the single cell transcriptomic and proteomic levels. In this study we identified that this dysfunction was mediated through a crosstalk between NK cells and myeloid blasts necessitating cell-cell contact. NK cell dysfunction could be prevented by targeting the αvβ integrin/TGF-β/SMAD pathway but, once established, was persistent due to profound epigenetic reprogramming. …

Go to article

Targeting Prmt3 Impairs Methylation And Oligomerization Of Hsp60 To Boost Anti-Tumor Immunity By Activating Cgas/Sting Signaling, Yunxing Shi, Zongfeng Wu, Shaoru Liu, Dinglan Zuo, Yi Niu, Yuxiong Qiu, Liang Qiao, Wei He, Jiliang Qiu, Yunfei Yuan, Guocan Wang, Binkui Li Sep 2024

Targeting Prmt3 Impairs Methylation And Oligomerization Of Hsp60 To Boost Anti-Tumor Immunity By Activating Cgas/Sting Signaling, Yunxing Shi, Zongfeng Wu, Shaoru Liu, Dinglan Zuo, Yi Niu, Yuxiong Qiu, Liang Qiao, Wei He, Jiliang Qiu, Yunfei Yuan, Guocan Wang, Binkui Li

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) has emerged as a promising therapeutic option for hepatocellular carcinoma (HCC), but resistance to ICB occurs and patient responses vary. Here, we uncover protein arginine methyltransferase 3 (PRMT3) as a driver for immunotherapy resistance in HCC. We show that PRMT3 expression is induced by ICB-activated T cells via an interferon-gamma (IFNγ)-STAT1 signaling pathway, and higher PRMT3 expression levels correlate with reduced numbers of tumor-infiltrating CD8+ T cells and poorer response to ICB. Genetic depletion or pharmacological inhibition of PRMT3 elicits an influx of T cells into tumors and reduces tumor size in HCC mouse models. Mechanistically, …

Go to article

First Prev Next Last