Medical Sciences Commons^™

Unexpected Biliary Duct Dilation, A Wise Decision-Making Case., Mario A. Trujillo, Mathew R. Peynado, Muhammad Ali Siddiqui, Laura P. Ackerman

Research Colloquium

Background: Common bile duct dilation is expected in certain healthy populations with specific factors like age or post procedure status. When a size larger than expected is found in an acute setting further investigation is required. In the setting of acute abdominal pain in a patient with past medical history of cholelithiasis, the study protocol for patients with more than expected enlarged common bile duct and no apparently underlying disease in the biliary tree is not well elucidated.

Case: A 68-year-old female with past medical history but not limited to cholelithiasis, hypertension, type 2 diabetes mellitus, end stage renal …

Can Zinc Reduce The Disease Burden Of Diabetes Mellitus?, Ronald Shaju, Rahnuma Ahmad, Mohammed S. Razzaque

Research Colloquium

Background: Diabetes mellitus is a prevalent chronic metabolic disorder characterized by hyperglycemia. Traditionally, this disease is managed with medication and dietary modifications. However, recent studies have shown the potential role of zinc in diabetes management. We explained the complex interplay between zinc deficiency, impaired glucose metabolism, and the progression of diabetes to elucidate the potential therapeutic benefits of zinc supplementation.

Methods: A comprehensive literature search using databases such as Google Scholar, PubMed, and Scopus was conducted to identify relevant studies published between November 2023 and February 2024. Keywords such as ‘zinc in diabetes mellitus,’ ‘zinc supplementation,’ ‘zinc deficiency,’ and ‘diabetic …

Microglia In Post-Mortem Hippocampal Brain Tissue Of Male And Female Neonates After Hie, Kassandra M. Pulido, Angela N. Viaene, Amelia J. Eisch, Danielle G. Barber

Research Colloquium

Background: Hypoxic-ischemic encephalopathy (HIE) is the second-leading cause of neonatal morbidity and mortality worldwide. There are sex differences in the pathophysiology of HIE, particularly in microglia, which are critical in the immune response. Prior work highlights microglial aggregation in the hippocampus of human infants as a marker for HIE, but it is unknown whether this differs by sex.

Aim: We compare the microglial response in post-mortem hippocampal tissue from male and female neonates diagnosed with HIE vs. Controls who expired from other causes.

Methods: Using a retrospective cohort design, we reviewed medical records of neonates with hippocampal tissue in the …

Houston, We Have A Problem: Diagnostic Difficulties In The Aids Patient With Tuberculosis Infection, Hector D. Preciado, Maria E. Torres, Muhammad A. Siddiqui, Liza Salloum, Lee Gelpi, Jose E. Campo Maldonado

Research Colloquium

Background: Tuberculosis (TB) is the leading cause of infectious death worldwide with 1.5 million deaths annually and nearly 1/4th of the world’s population (1.7 billion) infected with latent tuberculosis infection (LTBI) in 2014. Its diagnosis conventionally relies on tuberculin skin testing (TST), and Interferon-Gamma Release Assay (IGRA) which relies on the production of Interferon Gamma (IFN-y) in response to Mycobacterium tuberculosis (MTB) specific antigens. IGRA is a useful tool for detecting latent TB disease, and can be used as an adjunct for the diagnosis of active TB cases. Increases in IFN-y levels might support the diagnosis of a new TB …

Comorbidity Of Mood Disorders And Upper Airway Resistance Syndrome: A Case Report, Abhishekh Pokhrel, Alexa Lissete Zarate, Alcides Amador

Research Colloquium

Background: The comorbidity of mood disorders and Upper Airway Resistance Syndrome (UARS) presents a significant challenge, especially in pediatric populations. UARS, characterized by increased upper airway resistance during sleep, often leads to disrupted sleep and daytime symptoms such as fatigue and cognitive impairment. Studies estimate UARS affects 15-30% of patients undergoing polysomnography for suspected sleep-disordered breathing. Mood & Anxiety Disorders are prevalent in patients with sleep-disordered breathing, with higher rates than in the general population.

Case Presentation: 16-year-old female, with psychiatric history of Bipolar II Disorder current episode depressed, ADHD, and Other Specified Anxiety Disorder presents for a follow-up. Since …

Unraveling Dilated Cardiomyopathy Linked To An Enigmatic Mybpc3 Variant, Khiem D. Ngo, Carlos Alejos, Jennifer Rojas, Sobia Memon, James Stone

Research Colloquium

Background: Non-ischemic cardiomyopathy (NICM), can arise from various causes, including hemodynamic pathology, infections, immunologic abnormalities, toxic injuries, and genetic factors. Determining the prevalence of NICM is challenging due to varying definitions and diagnostic criteria, selection bias, and geographic variation. MYBPC3 is the primary gene known to cause restrictive cardiomyopathy, dilated cardiomyopathy, and left ventricular non-compaction. This gene encodes cMyBP-C, a structural protein of the heart muscle that interacts with actin, myosin, and titin to maintain sarcomeric integrity. While loss-of-function mutations are common, MYBPC3 missense variants of uncertain significance (VUS) are also prevalent. Individuals with MYBPC3 missense VUS predicted to disrupt …

Investigating The Determinants Of Frailty: The Intersection Of Genetics And Environment In Mexican Americans From South Texas, Natasha Garcia-Rodriguez, Vincent P. Diego, Marcio Almeida, Jacob Galan, Sandra Laston, Joanne E. Curran, Tom Howard, Eron Manusov, John Blangero, Sarah Williams-Blangero

Research Colloquium

Background: The projected worldwide population of people aged 65 and over is anticipated to hit 1.6 billion by 2050. Frailty, marked by increased susceptibility to adverse health outcomes, mortality, and decreased health-related quality of life (HrQoL), poses significant challenges to an aging population. The Frailty Index (FI), is the ratio of the number of accumulated health deficits to the total number of deficits considered, is used to predict frailty.

Methods: Utilizing data from the Mexican American Family Study, we investigated the heritability and gene-environment (GxE) interactions influencing frailty in 1,029 Mexican American participants. We calculated the FI using 34 variables, …

Pulmonary Fibrosis As A Presentation Of Short Telomere Syndrome: Case Report, Roy Kondapavuluru, Jian Garcia Cruz, Sreejith Pillai, Andres Suarez Parraga

Research Colloquium

Introduction: Short telomere syndrome (STS), also known as accelerated aging syndrome, is an inheritable gene mutation resulting in decreased telomere length causing high cell turnover of organ systems such as skin, bone marrow, liver, hair, lungs, and immune system. Due to diverse clinical manifestations, STS poses a diagnostic challenge, with bone marrow failure and idiopathic pulmonary fibrosis being frequent manifestations. The inherited form of STS demonstrates genetic anticipation occurring at an earlier age with more severe manifestations in the affected progeny. We present a rare case of inherited STS in a young patient with severe pulmonary fibrosis.

Case Presentation: A …

Pre-Hospital Stroke Time Intervals In The Rio Grande Valley, Kelsey Baker, Elio E. Garcia Sosa

Research Colloquium

Background and Introduction: Stroke continues to be a significant cause of mortality in the United States. Despite advancements in acute stroke treatments such as thrombolytic therapy and endovascular procedures, many patients remain unable to benefit from these interventions due to delays in receiving treatment. Healthcare professionals have made substantial efforts to improve 'door to needle' times, the interval between a patient's arrival at the hospital and the administration of thrombolytic therapy, yielding promising outcomes. However, a critical gap persists: the time interval from the onset of stroke symptoms to when patients actually present at a healthcare facility. This study aims …

Unveiling The Impact Of Phosphate On Skeletal Muscle Dysfunction In Chronic Kidney Disease, Hiram Garcia, Sowmya Duddu, Erik Hinojosa, Model Zerfu, Nathaniel L. Alvarez, Mohammad Razzaque, Alex Zuo

Research Colloquium

Background: Chronic Kidney Disease (CKD) is characterized by progressive decline in renal function that ultimately culminates in the inability of the kidneys to effectively maintain homeostasis. The kidneys are a key regulator of phosphate, with other organs assisting in regulation including the skeletal system. In CKD, reduced kidney function leads to hyperphosphatemia. While its impact on the skeletal system is moderately studied, its effects on skeletal muscle are less reviewed. In our literature review, we aim to describe the effects of phosphate in the context of patients who have CKD while providing clinical context for this deserving population. We describe …

Systemic Biology Approach Linking Type 2 Diabetes And Depression In A Rio Grande Valley Family Study Population, Cameron B. Caldwell, Eron Manusov, Vincent P. Diego, Ana C. Leandro, Sandra Laston, John Blangero, Sarah Williams-Blangero, Marcio Almeida

Research Colloquium

Background: Type 2 diabetes and depression are major public health concerns that disproportionally impact Mexican Americans. Prevalence of T2D and depression have been estimated as high as 30% and 40%, respectively in Mexican American populations along the Texas-Mexico border. While the interaction between these two phenotypes is well documented, the underlying genetic basis of this interaction remains unclear. Our aims for this project were to identify genes co-expressed in type 2 diabetes and depression to dissect the interaction correlations between both conditions by means of a functional gene expression correlation network.

Methods: A total of 528 Mexican American participants from …

Role Of Customized Visual And Multifactorial Interventions In Preventing Falls Among Individuals With Visual Impairment In South India, Ramya S

Theses and Dissertations

Falls are the second leading cause of unintentional injuries and extensively studied among the elderly. Hence, intervention studies for falls prevention are restricted to the elderly with or without visual impairment (VI). Even among studies with VI, strategies for treatable VI are widely explored. Hence this study aimed to understand falls and interventions that may reduce falls in all the age groups especially among those with untreatable VI.

This mixed methods study included identification of subjects aged ≥ 18 years with VI from clinical records of Medical Research Foundation, Chennai and details of previous history of falls were enquired over …

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 …

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 …

1-Year Outcomes Of Resolute Onyx Zotarolimus-Eluting Stent For Symptomatic Intracranial Atherosclerotic Disease: A Multicenter Propensity Score-Matched Comparison With Stenting Versus Aggressive Medical Management For Preventing Recurrent Stroke In Intracranial Stenosis Trial, Saisree Ravi, Ibrahim A Bhatti, Ravi S Nunna, Syed Khalid, Wondwossen G Tekle, Omar Tanweer, Jan-Karl Burkhardt, Pascal M Jabbour, Stavropoula I Tjoumakaris, Nabeel A Herial, Adnan H Siddiqui, Ramesh Grandhi, Adnan I Qureshi, Farhan Siddiq, Ameer E Hassan

Faculty, Staff and Students Publications

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is one of the most prevalent causes of stroke across the world. Endovascular treatment has gained prominence but remains a challenge with unfavorable results. Recent literature has demonstrated that the Resolute Onyx Zotarolimus-Eluting Stent (RO-ZES) is a technically safe option with low complication rates along with 30-day outcomes associated with intracranial stent placement for ICAD with RO-ZES compared to results from the Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. Here, we aim to compare outcomes at one year with the SAMMPRIS trial with a multicenter longitudinal study.

MATERIALS …

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. …

The Effect Of Intravenous Thrombolysis In Stroke Patients With Unsuccessful Thrombectomy, Sameh Samir Elawady, Rahim Abo Kasem, Hidetoshi Matsukawa, Conor Cunningham, Mohamed Mahdi Sowlat, Noah Lee Nawabi, Atakan Orscelik, Joshua M Venegas, Julio Isidor, Hasna Loulida, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Brian Howard, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Ramesh Grandhi, Roberto Crosa, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Ergun Daglioglu, Richard Williamson, Pedro Navia, Peter Kan, Reade De Leacy, Shakeel Chowdhry, David J Altschul, Alejandro M Spiotta, Sami Al Kasab

Faculty, Staff and Students Publications

BACKGROUND: The benefit of intravenous thrombolysis (IVT) is well established. We aim to study the benefits of IVT in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) who underwent unsuccessful mechanical thrombectomy (MT).

METHODS: We included AIS patients who underwent MT for anterior circulation LVO with failed recanalization (modified treatment in cerebral ischemia [mTICI] score ≤ 2A). Patients who received IVT prior to MT were compared to those who received MT alone. Propensity score matching using demographic, clinical, radiographic and procedural variables was used to match patients with and without IVT. The primary outcome was favorable 90-day good …

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 …

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 …

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. …

Barriers And Opportunities In Pancreatic Cancer Immunotherapy, Yixin Ju, Dongzhi Xu, Miao-Miao Liao, Yutong Sun, Wen-Dai Bao, Fan Yao, Li Ma

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) presents a fatal clinical challenge characterized by a dismal 5-year overall survival rate, primarily due to the lack of early diagnosis and limited therapeutic efficacy. Immunotherapy, a proven success in multiple cancers, has yet to demonstrate significant benefits in PDAC. Recent studies have revealed the immunosuppressive characteristics of the PDAC tumor microenvironment (TME), including immune cells with suppressive properties, desmoplastic stroma, microbiome influences, and PDAC-specific signaling pathways. In this article, we review recent advances in understanding the immunosuppressive TME of PDAC, TME differences among various mouse models of pancreatic cancer, and the mechanisms underlying resistance to …

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 …

Zeolite-Promoted Platinum Catalyst For Efficient Reduction Of Nitrogen Oxides With Hydrogen, Shaohua Xie, Liping Liu, Yuejin Li, Kailong Ye, Daekun Kim, Xing Zhang, Hongliang Xin, Lu Ma, Steven N Ehrlich, Fudong Liu

Faculty, Staff and Student Publications

Internal combustion engine fueled by carbon-free hydrogen (H2-ICE) offers a promising alternative for sustainable transportation. Herein, we report a facile and universal strategy through the physical mixing of Pt catalyst with zeolites to significantly improve the catalytic performance in the selective catalytic reduction of nitrogen oxides (NOx) with H2 (H2-SCR), a process aiming at NOx removal from H2-ICE. Via the physical mixing of Pt/TiO2 with Y zeolite (Pt/TiO2 + Y), a remarkable enhancement of NOx reduction activity and N2 selectivity was simultaneously achieved. The incorporation of Y zeolite effectively captured the in-situ generated water, fostering a water-rich environment surrounding the …

Mesenchymal Stromal Cells Protect Combined Oncolytic And Helper-Dependent Adenoviruses From Humoral Immunity, Ada Irmak Özcan, Arianexys Aquino Lόpez, Alexandra N Wolff, Audrey Ma, Amanda Rosewell Shaw, Masataka Suzuki, Malcolm K Brenner, Mary K Mckenna

Faculty, Staff and Students Publications

Systemic delivery of oncolytic and immunomodulatory adenoviruses may be required for optimal effects on human malignancies. Mesenchymal stromal cells (MSCs) can serve as delivery systems for cancer therapeutics due to their ability to transport and shield these agents while homing to tumors. We now use MSCs to deliver a clinically validated binary oncolytic and helper-dependent adenovirus combination (CAdVEC) to tumor cells. We show successful oncolysis and helper-dependent virus function in tumor cells even in the presence of plasma from adenovirus-seropositive donors. In both two- and three-dimensional cultures, CAdVEC function is eliminated even at high dilutions of seropositive plasma but is …

Assessing The Adequacy Of A Prediction Model, Abhaya Indrayan, Sakshi Mishra Ms

COBRA Preprint Series

No abstract provided.

Use Of Web-Based Surveys To Collect Long-Term Pediatric Outcomes In Patients With Twin-Twin Transfusion Syndrome Treated With Fetoscopic Laser Photocoagulation: Observational Study, Eric Bergh, Kimberly Rennie, Jimmy Espinoza, Anthony Johnson, Ramesha Papanna

Faculty, Staff and Student Publications

Background: In the United States, patients with monochorionic diamniotic twins who undergo in utero fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS) may travel great distances for care. After delivery, many parents cannot return to study sites for formal pediatric evaluation due to geographic location and cost.

Objective: The aim of this study was to collect long-term pediatric outcomes in patients who underwent FLP for TTTS.

Methods: We assessed the feasibility of using a web-based survey designed in REDCap (Research Electronic Data Capture; Vanderbilt University) to collect parent-reported outcomes in children treated for TTTS at a single center during …

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. …

Bacteroides Ovatus Alleviates Dysbiotic Microbiota-Induced Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C Stinson, Mohamed A Jamal, Miriam R Ortega, Christopher A Sanchez, Saira S Ahmed, Jennifer L Karmouch, Chia-Chi Chang, Ivonne I Flores, Lauren K Mcdaniel, Alexandria N Brown, Rawan K El-Himri, Valerie A Chapa, Lin Tan, Bao Q Tran, Yao Xiao, Christopher Fan, Dung Pham, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Israel K Glover, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Katherine Y King, Robert A Britton, Pavan Reddy, Matthew C Wong, Nadim J Ajami, Jennifer A Wargo, Samuel Shelburne, Pablo C Okhuysen, Chen Liu, Stephanie W Fowler, Margaret E Conner, Zoe Katsamakis, Natalie Smith, Marina Burgos Da Silva, Doris M Ponce, Jonathan U Peled, Marcel R M Van Den Brink, Christine B Peterson, Gabriela Rondon, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Philip L Lorenzi, Rohtesh S Mehta, Eric C Martens, Amin M Alousi, Robert R Jenq

Faculty, Staff and Student Publications

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects …

Immunoactive Signatures Of Circulating Trna- And Rrna-Derived Rnas In Chronic Obstructive Pulmonary Disease, Megumi Shigematsu, Takuya Kawamura, Deepak Deshpande, Yohei Kirino

Computational Medicine Center Faculty Papers

Chronic obstructive pulmonary disease (COPD) is the most prevalent lung disease, and macrophages play a central role in the inflammatory response in COPD. We here report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma from patients with COPD. While circulating sncRNAs are increasingly recognized for their regulatory roles and biomarker potential in various diseases, the conventional RNA sequencing (RNA-seq) method cannot fully capture these circulating sncRNAs due to their heterogeneous terminal structures. By pre-treating the plasma RNAs with T4 polynucleotide kinase, which converts all RNAs to those with RNA-seq susceptible ends (5′-phosphate and 3′-hydroxyl), we comprehensively sequenced …

Prospective Characterization Of Early Symptom Onset And Progression In Young Pediatric Patients With Variants In The G La Gene Across 5 Years: Longitudinal Data From The Fabry Moppet Study, D A Laney, M F Houde, A L Foley, D S Peck, A M Atherton, L P Manwaring, D K Grange, Bryce Heese, M D Holida, A L Quillin, R Vinson, C Auray-Blais, R J Hopkin

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This prospective, longitudinal study was designed to determine the natural history of Fabry disease (FD) in early pediatric patients across the disease spectrum.

METHODS: In this observational study of children under 5 years of age with variants in the GLA gene, prospective phenotypic and urinary biomarker data were collected annually over 5 years.

RESULTS: The study population included 40 participants (35 male, 5 female) with GLA variants including 15 with classic pathogenic variants (CFD), 6 with nonclassic pathogenic variants (NFD), and 19 with a variant of uncertain significance. The most common first symptoms reported were in participants with CFD …