Medicine and Health Sciences Commons^™

An Iron-Rich Subset Of Macrophages Promotes Tumor Growth Through A Bach1-Ednrb Axis, Ian W Folkert, William A Molina Arocho, Tsun Ki Jerrick To, Samir Devalaraja, Irene S Molina, Jason Shoush, Hesham Mohei, Li Zhai, Md Naushad Akhtar, Veena Kochat, Emre Arslan, Alexander J Lazar, Khalida Wani, William P Israel, Zhan Zhang, Venkata S Chaluvadi, Robert J Norgard, Ying Liu, Ashley M Fuller, Mai T Dang, Robert E Roses, Giorgos C Karakousis, John T Miura, Douglas L Fraker, T S Karin Eisinger-Mathason, M Celeste Simon, Kristy Weber, Kai Tan, Yi Fan, Kunal Rai, Malay Haldar

Faculty, Staff and Student Publications

We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional …

Longitudinal Single-Cell Profiling Reveals Molecular Heterogeneity And Tumor-Immune Evolution In Refractory Mantle Cell Lymphoma, Shaojun Zhang, Vivian Changying Jiang, Guangchun Han, Dapeng Hao, Junwei Lian, Yang Liu, Qingsong Cai, Rongjia Zhang, Joseph Mcintosh, Ruiping Wang, Minghao Dang, Enyu Dai, Yuanxin Wang, David Santos, Maria Badillo, Angela Leeming, Zhihong Chen, Kimberly Hartig, John Bigcal, Jia Zhou, Rashmi Kanagal-Shamanna, Chi Young Ok, Hun Lee, Raphael E Steiner, Jianhua Zhang, Xingzhi Song, Ranjit Nair, Sairah Ahmed, Alma Rodriquez, Selvi Thirumurthi, Preetesh Jain, Nicolaus Wagner-Bartak, Holly Hill, Krystle Nomie, Christopher Flowers, Andrew Futreal, Linghua Wang, Michael Wang

Faculty, Staff and Student Publications

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and …

Author Correction: Longitudinal Single-Cell Profiling Reveals Molecular Heterogeneity And Tumor-Immune Evolution In Refractory Mantle Cell Lymphoma, Shaojun Zhang, Vivian Changying Jiang, Guangchun Han, Dapeng Hao, Junwei Lian, Yang Liu, Qingsong Cai, Rongjia Zhang, Joseph Mcintosh, Ruiping Wang, Minghao Dang, Enyu Dai, Yuanxin Wang, David Santos, Maria Badillo, Angela Leeming, Zhihong Chen, Kimberly Hartig, John Bigcal, Jia Zhou, Rashmi Kanagal-Shamanna, Chi Young Ok, Hun Lee, Raphael E Steiner, Jianhua Zhang, Xingzhi Song, Ranjit Nair, Sairah Ahmed, Alma Rodriquez, Selvi Thirumurthi, Preetesh Jain, Nicolaus Wagner-Bartak, Holly Hill, Krystle Nomie, Christopher Flowers, Andrew Futreal, Linghua Wang, Michael Wang

Faculty, Staff and Student Publications

No abstract provided.

Conserved Signaling Modules Regulate Filamentous Growth In Fungi: A Model For Eukaryotic Cell Differentiation, Matthew D Vandermeulen, Michael C Lorenz, Paul J Cullen

Faculty, Staff and Student Publications

Eukaryotic organisms are composed of different cell types with defined shapes and functions. Specific cell types are produced by the process of cell differentiation, which is regulated by signal transduction pathways. Signaling pathways regulate cell differentiation by sensing cues and controlling the expression of target genes whose products generate cell types with specific attributes. In studying how cells differentiate, fungi have proved valuable models because of their ease of genetic manipulation and striking cell morphologies. Many fungal species undergo filamentous growth-a specialized growth pattern where cells produce elongated tube-like projections. Filamentous growth promotes expansion into new environments, including invasion into …

Variation In Air Sac Morphology And Postcranial Skeletal Pneumatization Patterns In The African Grey Parrot, Adam B. Lawson, Aracely Martinez, Brandon P. Hedrick, M. Scott Echols, Emma R. Schachner

School of Graduate Studies Faculty Publications

The anatomy of the avian lower respiratory system includes a complex interaction between air-filled pulmonary tissues, pulmonary air sacs, and much of the postcranial skeleton. Hypotheses related to the function and phylogenetic provenance of these respiratory structures have been posed based on extensive interspecific descriptions for an array of taxa. By contrast, intraspecific descriptions of anatomical variation for these features are much more limited, particularly for skeletal pneumatization, and are essential to establish a baseline for evaluating interspecific variation. To address this issue, we collected micro-computed tomography (μCT) scans of live and deceased African grey parrots (Psittacus erithacus) to assess …

Physician Perspectives About The Diagnosis And Management Of Acute Chest Syndrome, Neha Bhasin, Dana Marie Leblanc, Sean Yates, Quentin Eichbaum, An Pham, Deva Sharma, Li Zhang, Elliott P. Vichinsky, Ravi Sarode

School of Medicine Faculty Publications

Background: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). There is a lack of evidence-based laboratory and clinical risk stratification guidelines for the diagnosis and management of ACS. Study Design and Methods: To better understand physician practices for the management of ACS in the United States, we created an ACS Working Group including hematology and transfusion medicine physicians from four different SCD treatment centers in the United States. The working group created a physician survey that included physician demographics and ACS diagnostic criteria that they …

Trβ Activation Confers At2-To-At1 Cell Differentiation And Anti-Fibrosis During Lung Repair Via Klf2 And Cebpa, Xin Pan, Lan Wang, Juntang Yang, Yingge Li, Min Xu, Chenxi Liang, Lulu Liu, Zhongzheng Li, Cong Xia, Jiaojiao Pang, Mengyuan Wang, Meng Li, Saiya Guo, Peishuo Yan, Chen Ding, Ivan O Rosas, Guoying Yu

Faculty, Staff and Students Publications

Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration. Using a specific TRβ agonist, sobetirome, we demonstrate that the anti-fibrotic effects of thyroid hormone mainly rely on TRβ in mice. Cellularly, TRβ activation enhances alveolar type-2 (AT2) cell differentiation into AT1 cell and constrains AT2 cell hyperplasia. Molecularly, TRβ activation directly regulates the …

The Fundamentals Of Antiseizure Medications: A Through Z, Timothy E Welty, Jeannine M Conway, Jacquelyn Bainbridge, Kristen Park, David G Vossler, Archana A Patel, Alica Goldman

Faculty, Staff and Students Publications

Since bromides were first used in 1857 to treat epilepsy, numerous antiseizure medications (ASM) have been developed. Many of these are available for the treatment of epilepsy and status epilepticus today. With so many ASM available, questions arise as to whether all of these medications are needed and when should they be used. As precision medicine begins to play a larger role in determining targeted treatments for specific types of epilepsy, a complete understanding of various medications is needed. Additionally, access to several of these medications can be limited in the United States and are especially limited globally. All these …

Genomics Of Natural Populations: Gene Conversion Events Reveal Selected Genes Within The Inversions Of Drosophila Pseudoobscura, Stephen W Schaeffer, Stephen Richards, Zachary L Fuller

Faculty, Staff and Students Publications

When adaptive phenotypic variation or quantitative trait loci map within an inverted segment of a chromosome, researchers often despair because the suppression of crossing over will prevent the discovery of selective target genes that established the rearrangement. If an inversion polymorphism is old enough, then the accumulation of gene conversion tracts offers the promise that quantitative trait loci or selected loci within inversions can be mapped. The inversion polymorphism of Drosophila pseudoobscura is a model system to show that gene conversion analysis is a useful tool for mapping selected loci within inversions. D. pseudoobscura has over 30 different chromosomal arrangements …

Xenotransplanted Human Organoids Identify Transepithelial Zinc Transport As A Key Mediator Of Intestinal Adaptation, Maame Efua S Sampah, Vered Gazit, Deborah C Rubin, Et Al.

2020-Current year OA Pubs

Short bowel syndrome (SBS) leads to severe morbidity and mortality. Intestinal adaptation is crucial in improving outcomes. To understand the human gene pathways associated with adaptation, we perform single-cell transcriptomic analysis of human small intestinal organoids explanted from mice with experimental SBS. We show that transmembrane ion pathways, specifically the transepithelial zinc transport pathway genes SLC39A4 and SLC39A5, are upregulated in SBS. This discovery is corroborated by an external dataset, bulk RT-qPCR, and Western blots. Oral zinc supplementation is shown to improve survival and weight gain of SBS mice and increase the proliferation of intestinal crypt cells in vitro. Finally, …

An Iron-Rich Subset Of Macrophages Promotes Tumor Growth Through A Bach1-Ednrb Axis, Ian W Folkert, Mai T Dang, Et Al.

2020-Current year OA Pubs

We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional …

Human Epidemiology And Response To Sars-Cov-2 (Heros): Objectives, Design, And Enrollment Results Of A 12-City Remote Observational Surveillance Study Of Households With Children, Using Direct-To-Participant Methods, Patricia C Fulkerson, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) Study is a prospective, multicity, 6-month incidence study conducted from May 2020 to February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other National Institutes of Health-funded pediatric …

Rescue Of Scn5a Mis-Splicing Does Not Improve The Structural And Functional Heart Defects Of A Dm1 Heart Mouse Model, Larissa Nitschke, Rong-Chi Hu, Andrew N Miller, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant multisystemic disorder for which cardiac features, including conduction delays and arrhythmias, are the second leading cause of disease mortality. DM1 is caused by expanded CTG repeats in the 3' untranslated region of the DMPK gene. Transcription of the expanded DMPK allele produces mRNAs containing long tracts of CUG repeats, which sequester the Muscleblind-Like family of RNA binding proteins, leading to their loss-of-function and the dysregulation of alternative splicing. A well-characterized mis-regulated splicing event in the DM1 heart is the increased inclusion of SCN5A exon 6A rather than the mutually exclusive exon …

Cryo-Em Analysis Of Pseudomonas Phage Pa193 Structural Components, Stephano M. Iglesias, Chun-Feng Hou, Johnny Reid, Evan Schauer, Renae Geier, Angela Soriaga, Lucy Sim, Lucy Gao, Julian Whitelegge, Pierre Kyme, Deborah Birx, Sebastien Lemire, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193. We used bioinformatics, proteomics, and cryogenic electron microscopy single particle analysis to identify, annotate, and build atomic models for 21 distinct structural polypeptide chains forming the icosahedral capsid, neck, contractile tail, and baseplate. We identified a putative scaffolding protein stabilizing the interior of the capsid 5-fold …

Plasma Proteomic Biomarkers In Alzheimer's Disease And Cardiovascular Disease: A Longitudinal Study, Laurie A. Theeke, Ying Liu, Silas Wang, Xingguang Luo, R Osvaldo Navia, Danqing Xiao, Chun Xu, Kesheng Wang

Health & Biomedical Sciences Faculty Publications

The co-occurrence of Alzheimer's disease (AD) and cardiovascular diseases (CVDs) in older adults highlights the necessity for the exploration of potential shared risk factors. A total of 566 adults were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 111 individuals with AD, 383 with mild cognitive impairment (MCI), and 410 with CVD. The multivariable linear mixed model (LMM) was used to investigate the associations of AD and CVD with longitudinal changes in 146 plasma proteomic biomarkers (measured at baseline and the 12-month follow-up). The LMM showed that 48 biomarkers were linked to AD and 46 to CVD ( …

Finding The Right Mentor & Maintaining The Relationship Through Key Conversations, Adebisi Alli, Ankita Sagar, Eliza Lo Chin, Paulina Awuah-Saadiq, Susan Thompson Hingle

Journal of Wellness

No abstract provided.

Pilot Study To Evaluate Effectiveness Of Concurrent Hpv Vaccination At Time Of Treatment For Vin 2+, Cin 2+, Vain 2+ In Immunocompromised Individuals, Sara Lever Md

Dept. of Obstetrics & Gynecology Resident Research Day

No abstract provided.

Effects Of Race And Socioeconomic Factors On Detection Of Gynecological Cancer: State-Wide Analysis, Caitlin Witt Md

Dept. of Obstetrics & Gynecology Resident Research Day

No abstract provided.

Enhancing Obgyn Residency Training Through Pudendal Nerve Block Simulation, Allison Lazenby Md

Dept. of Obstetrics & Gynecology Resident Research Day

No abstract provided.

Duration, Cost, And Escalation Of Care Events For Physical Therapy Management Of Low Back Pain In Service Members With Limb Loss, Brittney M. Gunterstockman, Brad D. Hendershot, Joseph Kakyomya, Charity G. Patterson, Christopher L. Dearth, Shawn Farrokhi

Physical Therapy Faculty Articles and Research

Introduction Physical therapy (PT) is recommended as a primary treatment for low back pain (LBP), a common and impactful musculoskeletal condition after limb loss. The purpose of this brief report is to report the duration and cost of PT care, and subsequent escalation of care events, for LBP in service members with and without limb loss. Materials and Methods This was a retrospective cohort, descriptive study. Service members with and without limb loss (matched) who received PT for LBP at a military treatment facility from 2015 to 2017 were included. Duration of PT care, number of PT visits, and escalation …

Maternal Cortisol Concentration Is Associated With Reduced Brain Activation To Infant Cry And More Intrusive Parenting Behavior, Andrew Erhart, Sarah Enos Watamura, Aviva K. Olsavsky, Alexander J. Dufford, Rebekah C. Tribble, Tom Yeh, Pilyoung Kim

Psychology: Faculty Scholarship

Previous research indicates that maternal cortisol function and maternal brain response to infant are each in turn related to variations in parenting behavior. However, little is known about how maternal cortisol and maternal brain function are associated, thus studying these two mechanisms together may improve our understanding of how maternal cortisol assessed during interactions with own infant is associated with brain response to infant cry. First-time mothers (N = 59) of infants aged 3-4 months old were recruited to participate. Mothers' cortisol concentration was measured during a naturalistic interaction with their infant and their behavior was coded for two parenting …

Increased Myositis And Possible Myocarditis In Melanoma Patients Treated With Immune Checkpoint Inhibitors In The Covid-19 Era, Allison L. Gradone, Vincent T Ma, Alexi Vasbinder, Leslie A Fecher, Sarah Yentz, Salim S Hayek, Christopher D Lao

Department of Medical Oncology Faculty Papers

BACKGROUND: Immune checkpoint inhibitor (ICI)-mediated myocarditis results in significant morbidity and mortality. At our institution, we noted an increased incidence of ICI-mediated myocarditis cases, leading to further investigation in our database of advanced melanoma patients treated with ICI therapy.

METHODS: A single-center, retrospective cohort analysis of patients with advanced melanoma identified cases of ICI-mediated myocarditis and myositis.

RESULTS: 366 patients with advanced melanoma received a dose of ICI from September 2014 to October 2019. Of these patients, there were 0 cases of ICI-mediated myocarditis (0%, 95% CI 0%-1.0%) and 2 cases of ICI-mediated myositis (0.55%, 95% CI 0.07%-1.96%). From November …

Sars-Cov-2 Vaccine Improved Hemostasis Of A Patient With Protein S Deficiency: A Case Report, Mohammad A. Mohammad, Alaa Malik, Lekha Thangada, Diana Polanía-Villanueva, Jovanny Zabaleta, Rinku Majumder

School of Medicine Faculty Publications

A 16-year-old patient, while an infant, incurred right-sided hemiparesis and had difficulty breast feeding. She was later diagnosed with a neonatal stroke and her genetic testing showed a missense mutation in her PROS1 (Protein S) gene. Both her grandfather and father, but not her mother, had hereditary Protein S (PS) deficiency. The patient was not prescribed any mediation due to her young age but was frequently checked by her physician. The patient’s plasma was first collected at the age of 13, and the isolated plasma from the patient and her father were analyzed by aPTT, thrombin generation, and enzyme-linked immunosorbent …

Effect Of Nano2, A Donor Of Nitric Oxide, On Glucose Mediated Oxidative Stress In Pancreaticb-Cells, Kazi Nazrul Islam, Rahib K. Islam, Mohammod B. Rashid, Branson Smith, Safa K. Islam

School of Medicine Faculty Publications

Annual Meeting of the Endocrine Society, ENDO 2024, June 1 - 4, 2024, Boston, MA

Multiregional Transcriptomic Profiling Provides Improved Prognostic Insight In Localized Non-Small Cell Lung Cancer, Chenyang Li, Thinh T Nguyen, Jian-Rong Li, Xingzhi Song, Junya Fujimoto, Latasha Little, Curtis Gumb, Chi-Wan B Chow, Ignacio I Wistuba, Andrew P Futreal, Jianhua Zhang, Shawna M Hubert, John V Heymach, Jia Wu, Christopher I Amos, Jianjun Zhang, Chao Cheng

Faculty, Staff and Student Publications

Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels. At the gene level, the maximal expression of hazardous genes (expression negatively associated with survival) but the minimal expression of protective genes (expression positively associated with …

25-Hydroxycholesterol Promotes Brain Cytokine Production And Leukocyte Infiltration In A Mouse Model Of Lipopolysaccharide-Induced Neuroinflammation, Johnathan Romero, Danira Toral-Rios, Jinsheng Yu, Steven M Paul, Anil G Cashikar

2020-Current year OA Pubs

Neuroinflammation has been implicated in the pathogenesis of several neurologic and psychiatric disorders. Microglia are key drivers of neuroinflammation and, in response to different inflammatory stimuli, overexpress a proinflammatory signature of genes. Among these, Ch25h is a gene overexpressed in brain tissue from Alzheimer's disease as well as various mouse models of neuroinflammation. Ch25h encodes cholesterol 25-hydroxylase, an enzyme upregulated in activated microglia under conditions of neuroinflammation, that hydroxylates cholesterol to form 25-hydroxycholesterol (25HC). 25HC can be further metabolized to 7α,25-dihydroxycholesterol, which is a potent chemoattractant of leukocytes. We have previously shown that 25HC increases the production and secretion of …

Genetic And Clinical Correlates Of Two Neuroanatomical Ai Dimensions In The Alzheimer's Disease Continuum, Junhao Wen, Aristeidis Sotiras, Daniel S Marcus, Pamela Lamontagne, Tammie L Benzinger, John C Morris, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is associated with heterogeneous atrophy patterns. We employed a semi-supervised representation learning technique known as Surreal-GAN, through which we identified two latent dimensional representations of brain atrophy in symptomatic mild cognitive impairment (MCI) and AD patients: the "diffuse-AD" (R1) dimension shows widespread brain atrophy, and the "MTL-AD" (R2) dimension displays focal medial temporal lobe (MTL) atrophy. Critically, only R2 was associated with widely known sporadic AD genetic risk factors (e.g., APOE ε4) in MCI and AD patients at baseline. We then independently detected the presence of the two dimensions in the early stages by deploying the trained …

Machine Learning And Bayesian Network Analyses Identifies Associations With Insomnia In A National Sample Of 31,285 Treatment-Seeking College Students, Adam Calderon, Seung Yeon Baik, Matthew H S Ng, Ellen E Fitzsimmons-Craft, Daniel Eisenberg, Denise E Wilfley, C Barr Taylor, Michelle G Newman

2020-Current year OA Pubs

BACKGROUND: A better understanding of the relationships between insomnia and anxiety, mood, eating, and alcohol-use disorders is needed given its prevalence among young adults. Supervised machine learning provides the ability to evaluate which mental disorder is most associated with heightened insomnia among U.S. college students. Combined with Bayesian network analysis, probable directional relationships between insomnia and interacting symptoms may be illuminated.

METHODS: The current exploratory analyses utilized a national sample of college students across 26 U.S. colleges and universities collected during population-level screening before entering a randomized controlled trial. We used a 4-step statistical approach: (1) at the disorder level, …

Holistic Review In Health Professions Education Program Admissions: A Concept Analysis, Andrea N. Bowens

Internet Journal of Allied Health Sciences and Practice

Purpose: Health professions education programs often use holistic reviews to promote a more diverse student body, leading to a more diverse healthcare workforce. Although many organizations and educational institutions advocate for holistic reviews of applicants, there are inconsistencies in the literature as to what this practice entails. Thus, the purpose of this concept analysis was to identify the defining attributes of holistic reviews and provide an operational definition. Methods: Walker and Avant’s description of a concept analysis served as a guide for this review. This systematic process included an analysis of current literature, legal proceedings, and organizational documents; identification of …

Who Moved My Cheese?, Cheryl J. Hill

Internet Journal of Allied Health Sciences and Practice

No abstract provided.