Digital Commons Network^™

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna

Faculty, Staff and Student Publications

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …

G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse

Faculty, Staff and Student Publications

Background: Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.

Methods: Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the …

Enhancing Motor Function In Individuals With Lower Limb Amputation Through Peerbased Learning Of Balance And Fall Recovery Skills, Zoe Castle, Jer Ja Chuang, Jewel Granados, Danna Shaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Purpose: Lower limb amputation (LLA) is a devastating condition that is becoming more prevalent in the United States. We examined the effects of peer-based action observation learning on the brain activation and the eyetracking pattern in individuals with LLA.

Methods: Fourteen individuals with LLA (51.9±12.6 years, 4 females, 9 with transfemoral amputations) were asked to learn a balance task through observing the movements demonstrated by individuals with LLA or persons with intact limbs. Electroencephalogram (EEG) signals, visual attention time, and peak saccade velocity were recorded when participants watched the demonstration videos. Power spectral density (PSD) was used to analyze the …

Acute Kidney Injury Triggers Hypoxemia By Lung Intravascular Neutrophil Retention That Reduces Capillary Blood Flow, Yohei Komaru, Liang Ning, Carine Lama, Anusha Suresh, Eirini Kefaloyianni, Mark J. Miller, Shinichi Kawana, Hailey M Shepherd, Wenjun Li, Daniel Kreisel, Andreas Herrlich

2020-Current year OA Pubs

Sterile acute kidney injury (AKI) is common in the clinic and frequently associated with unexplained hypoxemia that does not improve with dialysis. AKI induces remote lung inflammation with neutrophil recruitment in mice and humans, but which cellular cues establish neutrophilic inflammation and how it contributes to hypoxemia is not known. Here we report that AKI induced rapid intravascular neutrophil retention in lung alveolar capillaries without extravasation into tissue or alveoli, causing hypoxemia by reducing lung capillary blood flow in the absence of substantial lung interstitial or alveolar edema. In contrast to direct ischemic lung injury, lung neutrophil recruitment during remote …

Label-Free Multimodal Optical Biopsy Reveals Biomolecular And Morphological Features Of Diabetic Kidney Tissue In 2d And 3d, Anthony A Fung, Zhi Li, Craig Boote, Petar Markov, Joseph P Gaut, Sanjay Jain, Lingyan Shi

2020-Current year OA Pubs

Kidney disease, the ninth leading cause of death in the United States, suffers from poor diagnostic efficiency (10%). Traditional biopsies use molecular reagents to enhance diagnostic power but are limited by overlapping spatial and chromatic signals, product quality variability, and additional processing. To address these challenges without disrupting routine diagnostics, we implement label-free imaging modalities-stimulated Raman scattering (SRS), second harmonic generation (SHG), and two-photon fluorescence (TPF)-within a single setup. We identify morphological, lipidomic, and metabolic biomarkers in control and diabetic kidney samples at subcellular resolution. Label-free Stimulated Raman Histology (SRH) reveals distinct collagen morphology, mesangial-glomerular volumes, lipid saturation, redox status, …

Maintenance Of Graft Tissue-Resident Foxp3+ Cells Is Necessary For Lung Transplant Tolerance In Mice, Wenjun Li, Yuriko Terada, Yun Zhu Bai, Yuhei Yokoyama, Hailey M. Shepherd, Junedh M. Amrute, Amit I. Bery, Zhiyi Liu, Jason M. Gauthier, Marina Terekhova, Jon H. Ritter, Varun Puri, Ramsey R. Hachem, Maxim N. Artyomov, Kory J. Lavine, Ruben G. Nava, Andrew E. Gelman, Daniel Kreisel, Et Al.

2020-Current year OA Pubs

Mechanisms that mediate allograft tolerance differ between organs. We have previously shown that Foxp3+ T cell-enriched bronchus-associated lymphoid tissue (BALT) is induced in tolerant murine lung allografts and that these Foxp3+ cells suppress alloimmune responses locally and systemically. Here, we demonstrated that Foxp3+ cells that reside in tolerant lung allografts differed phenotypically and transcriptionally from those in the periphery and were clonally expanded. Using a mouse lung retransplant model, we showed that recipient Foxp3+ cells were continuously recruited to the BALT within tolerant allografts. We identified distinguishing features of graft-resident and newly recruited Foxp3+ cells and showed that graft-infiltrating Foxp3+ …

Divergent Dna Methylation Dynamics In Marsupial And Eutherian Embryos, Bryony J. Leeke, Wazeer Varsally, Sugako Ogushi, Jasmin Zohren, Sergio Menchero, Aurélien Courtois, Daniel M. Snell, Aurélie Teissandier, Obah Ojarikre, John L. Vandeberg

School of Medicine Publications

Based on seminal work in placental species (eutherians)1,2,3,4,5,6,7,8,9,10, a paradigm of mammalian development has emerged wherein the genome-wide erasure of parental DNA methylation is required for embryogenesis. Whether such DNA methylation reprogramming is, in fact, conserved in other mammals is unknown. Here, to resolve this point, we generated base-resolution DNA methylation maps in gametes, embryos and adult tissues of a marsupial, the opossum Monodelphis domestica, revealing variations from the eutherian-derived model. The difference in DNA methylation level between oocytes …

A Theory-Based Examination Of Factors Influencing Caregivers’ Intentions To Disclose Sickle Cell Trait Status To Their Children, Christine A. Chaba

WUSM Theses and Dissertations – All Programs

Sickle cell trait (SCT), the heterozygous form of sickle cell disease, has significant implications for health and reproductive decision-making. Timely disclosure of SCT status to children by their caregivers is critical for promoting genetic awareness and supporting informed reproductive choices. However, many caregivers delay or avoid this conversation. This study examined the psychosocial and behavioral factors influencing caregivers’ intentions to disclose SCT status to their children, guided by the Theory of Planned Behavior and the Theory of Regret Regulation. A descriptive, cross-sectional study was conducted with 78 caregivers of Children with SCT, who completed an online survey. The study addressed …

Targeting The Beiging Of Muscle-Associated Adipose Tissue To Promote Muscle Regeneration, Jacob C. Parson

WUSM Theses and Dissertations – All Programs

The expansion of intra-muscular adipose tissue (IMAT) between myofibers and epi-muscular adipose tissue (EMAT) outside of the muscle boundary accompanies numerous pathologies including diabetes, muscular dystrophy, and aging. IMAT and EMAT are anatomically juxtaposed to myofibers. Some evidence supports that IMAT and EMAT impede muscle function. This is potentially due to paracrine factors that are secreted by IMAT/EMAT. Different adipose depots can be classified in numerous ways including where they are located anatomically as well as the factors in which they secrete. Unlike classical white fat, adipose depots classified as brown or beige, noted by the marker uncoupling protein-1 (UCP-1) …

Identifying Distinct Subgroups With Severe Pain In Sickle Cell Disease: A Cluster Analysis Of The Grndad Multi-Center Registry, Martha O. Kenney, Samuel Wilson, Morgan Rosser, Sophie Lanzkron, Julie Kanter, Susan Padrino, Payal Desai, Deepa Manwani, Alice Cohen, Stephanie Guarino, Ward Hagar, Joshua Field, Jane Little

Department of Medicine Faculty Papers

Sickle cell disease (SCD) affects millions of individuals worldwide, and is characterized by both acute, episodic pain and chronic, persistent pain. Despite the significant burden of the disease, clinicians continue to face significant challenges in treating SCD pain due to variability in pain experiences. The objectives of this study were (1) to identify distinct pain subgroups based on demographic and biopsychosocial characteristics and (2) to evaluate the relationship between the subgroups and pain impact - a SCD-disease specific measure of pain interference. To achieve these objectives, we performed a hierarchical cluster analysis on a cross-sectional sample of adults with SCD …

A Phase I Dose-Escalation Study Of The Hif-2 Alpha Inhibitor Dff332 In Patients With Advanced Clear-Cell Renal Cell Carcinoma, Sumanta K Pal, Joel Picus, Et Al.

2020-Current year OA Pubs

PURPOSE: Mutations or silencing of the von Hippel-Lindau tumor suppressor gene accumulate hypoxia-inducible factors (HIF). HIF-2α is implicated in the oncogenesis of ∼50% of patients with clear-cell renal cell carcinoma (ccRCC) but has been considered "undruggable." DFF332, an orally administered novel allosteric inhibitor of HIF-2α, showed dose-dependent antitumor efficacy in preclinical models of ccRCC.

PATIENTS AND METHODS: This first-in-human study evaluated the safety, tolerability, antitumor activity, pharmacokinetics, and pharmacodynamics of DFF332 in patients with heavily pretreated advanced ccRCC. Preliminary data from the dose escalation of DFF332 monotherapy, administered orally at 50 or 100 mg weekly or 25, 50, 100, or …

The Identification Of Xpr1 As A Voltage- And Phosphate-Activated Phosphate-Permeable Ion Channel, Hongjiang Wu, Liang Sun, Tong Huo, Theodore G Wensel, Frank T Horrigan, Zhao Wang

Faculty, Staff and Students Publications

Maintaining a balance of inorganic phosphate (Pi) is vital for cellular functionality. Proper phosphate levels are managed through Pi import and export; and the processes governing Pi export remain the least understood. Xenotropic and Polytropic retrovirus Receptor 1 (XPR1) has been identified as the only known Pi export protein in mammals. In this study, we introduce the cryogenic electron microscopy structure of human XPR1 (hXPR1), unveiling a structural arrangement distinct from that of any known ion transporter. Our structural results suggest that hXPR1 may operate as an ion channel, a hypothesis supported by patch clamp recordings revealing hXPR1's voltage- and …

Early Hematopoietic Differentiation Of An Inducible Pluripotent Stem Cell Model Of Infant Lymphoblastic Leukemia, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Priyanka Kumar, Jay L. Vivian, John M. Perry

Research Days

This abstract describes our work regarding the differentiation of human inducible pluripotent stem cells into hematopoietic stem and progenitor cells as the groundwork for the development of a genomics driven inducible pluripotent stem cell model of KMT2A rearranged infant acute lymphoblastic leukemia.

Multi-Omic Analysis Of Kmt2a-Rearranged Pediatric Acute Myeloid Leukemia Reveals Novel Pathways Of Interest, Trenton Edwards, Irina Pushel, Thomas Gremminger, Lisa Lansdon, Byunggil Yoo, Michaella Rekowski, Michael Washburn, Midhat Farooqi

Research Days

Objectives/Goals

Acute Myeloid Leukemia (AML) is the second most common leukemia among pediatric populations. Approximately 15% of pediatric AML cases have KMT2A gene rearrangements (KMT2A-r), which carry a worse prognosis. Our goal is to better characterize the biologic landscape of KMT2A-r pediatric AML. We hypothesize that a multi-omic approach will reveal mechanisms underlying the aggressive nature of KMT2A-r AML.

Methods/Study Population

This study makes use of deidentified peripheral blood and/or bone marrow samples banked in the Children’s Mercy Tumor Bank Biorepository. For this study, we used samples at diagnosis and remission from four KMT2A-r pediatric AML …

“Restless And Uneasy…Thin And Stretched”: The Ring, The Ringbearers, And Bodies In Psychological Crisis In Tolkien’S The Lord Of The Rings., Sara Brown

Journal of Tolkien Research

The attachment that Tolkien’s Ring-bearers have for the Ring, a twisted and perverted form of love, is sterile and barren; it leaves those affected unable to settle and form fruitful, loving relationships with others, an effect that Tolkien referred to as a “Ring-restlessness.” Gollum, Bilbo, and Frodo all suffer, to their own degree, from the psychological crisis caused by the Ring that renders them uneasy and agitated. This paper examines this crisis through a psychological lens, exploring how the Ringbearers are living in discord with their true selves, and struggling with the meaninglessness of life that the Ring leaves behind.

Perceiving The Perceiver: “Viewing” Sauron Through The Gestalt Theory Of Perception, Cameron Bourquein

Journal of Tolkien Research

This paper uses Gestalt theory, the Gestalt laws of perception, and the reception theory of Wolfgang Iser to elucidate the character “Sauron” as he appears in The Lord of the Rings, The Rings of Power, and Tolkien’s wider legendarium. It argues firstly that Sauron’s high degree of indeterminacy and ambiguity suggests he can be read as a gestalt entity, one the reader creates by mentally constructing a whole from (seemingly) disparate parts. Building on the semiotics work of Nagy (2013), it argues that Sauron in The Lord of the Rings can be read as gestalt across the spatial, …

Fears And Pains And Rages: The Psychology Of Gandalf's Anger, Nicholas Birns

Journal of Tolkien Research

We are used to seeing emotions in Tolkien as coded morally. Lust or possessiveness is evil whereas care and forbearance are good. There are some emotions, though, that cross these moral boundaries and one of these is anger Moreover, anger in Tolkien is very coded in terms of gender, as it is nearly always male rage. After examining the cases of Saruman and Wormtongue (angry because the world will not cooperate with their plans) and Thingol (angry because he realizes he has just postponed his doom rather than staved it off), we will examine the case of Gandalf. Gandalf is …

Impact Of Diagnosis To Treatment Interval On Outcomes In Patients With Newly Diagnosed Marginal Zone Lymphoma - A Us Multisite Study, Narendranath Epperla, Geoffrey Shouse, Natalie Grover, Pallawi Torka, Kaitlin Annunzio, Marcus Watkins, Andrea Anampa-Guzmán, Beth Christian, Colin Thomas, Md, Stefan Barta, Praveen Geethakumari, Reem Karmali, Nancy Bartlett, Adam Olszewski

Department of Medicine Faculty Papers

Diagnosis-to-treatment interval (DTI) is an important prognostic factor in patients with newly diagnosed aggressive lymphomas, however the impact of DTI on outcomes in marginal zone lymphoma (MZL) is unknown. In this multicenter retrospective cohort study, we included adult patients with MZL who received first-line immunochemotherapy within 120 days of diagnosis at 10 US medical centers. Patients who received treatment within 60 days from their diagnosis were classified into the short DTI group and those who received treatment beyond 60 days into long DTI group. The primary objective was progression-free survival (PFS), while secondary objectives included overall survival (OS) and cumulative …

Causes Of Death Among Us Medical Residents, Nicholas A. Yaghmour, William E. Bynum, Frederic W. Hafferty, Karen D. Könings, Thomas Richter, Timothy P. Brigham, Thomas J. Nasca

Division of Nephrology Faculty Papers

IMPORTANCE: From 2000 to 2014, the leading causes of medical resident death in the United States were neoplastic diseases and suicide.

OBJECTIVE: To examine whether US medical resident rates of death have changed since 2014 and whether causes of resident death differ by specialty.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, residents and fellows who were enrolled in Accreditation Council for Graduate Medical Education (ACGME)-accredited training programs and who died from January 2015 to December 2021 were submitted to the National Death Index to obtain causes of death. These decedents were compared with residents and fellows who died between …

Chronic Inflammatory Pain And Chronic Thc Vapor Inhalation Alter Midbrain Neuronal Activity, Leslie K. Kelley, Nicholas W. Gilpin, Jason W. Middleton

School of Medicine Faculty Publications

In an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic delta-9 tetrahydrocannabinol (THC) vapor inhalation effects on intrinsic and synaptic properties of ventrolateral periaqueductal gray (vlPAG) neurons in male and female rats treated with complete Freund's adjuvant (CFA). We report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically …

Structural And Molecular Basis Of Pcna-Activated Fan1 Nuclease Function In Dna Repair, F. Li, A. S. Phadte, M. Bhatia, S. Barndt, A.R. Monte Carlo, Iii, C.F.D. Hou, R. Yang, S. Strock, A. Pluciennik

Department of Biochemistry and Molecular Biology Faculty Papers

FAN1 is a DNA dependent nuclease whose proper function is essential for maintaining human health. For example, a genetic variant in FAN1, Arg507 to His hastens onset of Huntington's disease, a repeat expansion disorder for which there is no cure. How the Arg507His mutation affects FAN1 structure and enzymatic function is unknown. Using cryo-EM and biochemistry, we have discovered that FAN1 arginine 507 is critical for its interaction with PCNA, and mutation of Arg507 to His attenuates assembly of the FAN1-PCNA complex on a disease-relevant extrahelical DNA extrusions formed within DNA repeats. This mutation concomitantly abolishes PCNA-FAN1-dependent cleavage of such …

Multifaceted Roles Of Epac Signaling In Renal Functions, Oleh Pochynyuk, Kyrylo Pyrshev, Xiaodong Cheng

The Brown Foundation: Institute of Molecular Medicine

3',5'-cyclic adenosine monophosphate (cAMP) is a fundamental secondary messenger capable of rapidly amplifying and propagating cellular signals in response to various extracellular stimuli. cAMP plays a significant role in hormone-mediated regulation of renal fluid and electrolyte balance. Impaired signaling of cAMP has been linked to a variety of pathological ramifications in the kidneys. This review explores the physiological functions of exchange proteins directly activated by cAMP (Epac) in renal water balance and the regulation of solute transport in the renal tubule. Additionally, the involvement of Epac signaling in renal pathologies such as acute kidney injury, chronic kidney disease, and polycystic …

Clinical And Fundamental Research Progressions On Tumor-Infiltrating Lymphocytes Therapy In Cancer, Jiandong Hu, Mengli Jin, Weihong Feng, Barbara Nassif-Rausseo, Alexandre Reuben, Chunhua Ma, Gregory Lizee, Fenge Li

Faculty, Staff and Student Publications

Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy-encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy-has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form of treatment elicits substantial antigen-specific immune responses, enhances or restores anti-tumor immunity, thereby facilitating the control and destruction of tumor cells, and yielding durable responses across a range of cancers, which can lead to the eradication of tumor lesions and the prevention of recurrence. Tumor-infiltrating lymphocytes (TILs), a subset of ACT, are characterized by their heterogeneity and …

Forward Genetic Screen In Zebrafish Identifies New Fungal Regulators That Limit Host-Protective Candida-Innate Immune Interaction, Bailey A Blair, Emma Bragdon, Gursimran Dhillon, Nnamdi Baker, Lena Stasiak, Mya Muthig, Pedro Miramon, Michael C Lorenz, Robert T Wheeler

Faculty, Staff and Student Publications

Candida is one of the most frequent causes of bloodstream infections, and our first line of defense against these invasive infections is the innate immune system. The early immune response is critical in controlling Candida albicans infection, but C. albicans has several strategies to evade host immune attack. Phagocytosis of C. albicans blocks hyphal growth, limiting host damage and virulence, but how C. albicans limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131 C. albicans mutants for altered …

Autophagy Is Required For The Therapeutic Effects Of The Nad+ Precursor Nicotinamide In Obesity-Related Heart Failure With Preserved Ejection Fraction, Mahmoud Abdellatif, Moydul Islam, Abhinav Diwan, Et Al.

2020-Current year OA Pubs

No abstract provided.

Genome-Wide Allele-Specific Expression In Multi-Tissue Samples From Healthy Male Baboons Reveals The Transcriptional Complexity Of Mammals, Ramesh Ramasamy, Muthuswamy Raveendran, R Alan Harris, Hiep D Le, Ludovic S Mure, Giorgia Benegiamo, Ouria Dkhissi-Benyahya, Howard Cooper, Jeffrey Rogers, Satchidananda Panda

Faculty, Staff and Students Publications

Allele-specific expression (ASE) is pivotal in understanding the genetic underpinnings of phenotypic variation within species, differences in disease susceptibility, and responses to environmental factors. We processed 11 different tissue types collected from 12 age-matched healthy olive baboons (Papio anubis) for genome-wide ASE analysis. By sequencing their genomes at a minimum depth of 30×, we identified over 16 million single-nucleotide variants (SNVs). We also generated long-read sequencing data, enabling the phasing of all variants present within the coding regions of 96.5% of assayable protein-coding genes as a single haplotype block. Given the extensive heterozygosity of baboons relative to humans, we could …

Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional θ-waves. The resemblances between θ-oscillons and the conventional θ-waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled …

The Genestar Manual For Biospecimen Collection Biobanking And Omics Data Generation From Commercial Space Missions, Aparna Krishnavajhala, Marie-Claude Gingras, Emmanuel Urquieta, Hsu Chao, Dilrukshi Bandaranaike, Yi Chen, Sravya Bhamidipati, Viktoriya Korchina, S Michelle Griffin, Michal M Masternak, Hannah Moreno, Javid Mohammed, Mullai Murugan, Jennifer E Posey, Jimmy H Wu, Donna Muzny, Richard A Gibbs, Harsha Doddapaneni

Faculty, Staff and Students Publications

The surge in commercial and civilian spaceflight enables the systematic and longitudinal, large-scale biospecimen collection to understand the prospective effects of space travel on human health. The Genomics and Space Medicine (Space Omics) project at BCM-HGSC involves a comprehensive biospecimen collection plan from commercial/private space flight participants. The manuscript addresses the critical gaps in the biospecimen collection process including details of the informed consent process, a provision for subjects to obtain custom CLIA-WGS reports, a data dictionary and a LIMS enabled biobank. The manuscript also discusses the biospecimens collection, processing methodologies and nucleic acid suitability for Omics data generation. Results …

Role Of Systemic Therapy In Localized Renal Cell Carcinoma: Where Do We Stand And Where Are We Heading?, Deepa Raghavan, Viktoriya Gibatova, Nikhil Vojjala, Nagaishwarya Moka, Aihua Edward Yen

Faculty, Staff and Students Publications

The effectiveness of immunotherapy and targeted therapy has been well established in metastatic renal cell cancer (mRCC). These therapies demonstrated higher overall response rates and led to prolonged survival. In contrast, in localized RCC, conventional treatment is either partial or complete nephrectomy. While surgery is a curative option in early stages, high recurrence rates remain a concern, with survival rates ranging from 53% to 85%, depending on the initial stage at the time of diagnosis. Given favorable outcomes with systemic therapies in the metastatic setting, there has also been an increased interest in utilizing these therapies for the localized stage …

Spatial Epigenomic Niches Underlie Glioblastoma Cell State Plasticity, Sam Kint, Subhi Talal Younes, Shuozhen Bao, Gretchen Long, David Wouters, Erin Stephenson, Xing Lou, Mei Zhong, Di Zhang, Graham Su, Archibald Enninful, Mingyu Yang, Huey-Miin Chen, Katrina Ellestad, Colleen Anderson, Jennifer Moliterno, John Kelly, Jennifer A Chan, Alejandro Sifrim, Jiangbing Zhou, Ana Nikolic, Rong Fan, Marco Gallo

Faculty, Staff and Students Publications

IDH-wildtype glioblastoma (GBM) is an aggressive brain tumor with poor survival and few therapeutic options. Transcriptionally-defined cell states coexist in GBM and occupy defined regions of the tumor. Evidence indicates that GBM cell states are plastic, but it remains unclear if they are determined by the underlying epigenetic state and/or by microenvironmental factors. Here, we present spatially-resolved epigenomic profiling of human GBM tissues that implicate chromatin structure as a key enabler of cell plasticity. We report two epigenetically-defined and spatially-nested tumor niches. Each niche activates short-range molecular signals to maintain its own state and, surprisingly, long-range signals to reinforce …