Digital Commons Network^™

A New Era Of Morphological Investigations: Reviewing Methods For Comparative Anatomical Studies, K. L. Ford, J. S. Albert, A. P. Summers, B. P. Hedrick, E. R. Schachner, A. S. Jones, K. Evans, P. Chakrabarty

School of Medicine Faculty Publications

The increased use of imaging technology in biological research has drastically altered morphological studies in recent decades and allowed for the preservation of important collection specimens alongside detailed visualization of bony and soft-tissue structures. Despite the benefits associated with these newer imaging techniques, there remains a need for more "tra- ditional"methods of morphological examination in many comparative studies. In this paper, we describe the costs and benefits of the various methods of visualizing, examining, and comparing morphological structures. There are significant differences not only in the costs associated with these different methods (monetary, time, equipment, and software), but also in …

Comparison Of Efficacy And Inflammatory Response To Thermoconjunctivoplasty Performed With Cautery Or Pulsed 1460 Nm Laser, Lauren Nakhleh, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Conjunctivochalasis is a degenerative condition of the conjunctiva that disrupts tear distribution and causes irritation. Thermoreduction of the redundant conjunctiva is required if symptoms are not relieved with medical therapy. Near-infrared laser treatment is a more controlled method to shrink the conjunctiva than thermocautery. This study compared tissue shrinkage, histology, and postoperative inflammation in thermoconjunctivoplasty performed on the mouse conjunctiva using either thermocautery or pulsed 1460 nm near-infrared laser irradiation. Three sets of experiments were performed on female C57BL/6J mice (

Random Forest Model Reveals The Interaction Between N6-Methyladenosine Modifications And Rna-Binding Proteins, Chao Cheng

Faculty, Staff and Students Publications

RNA-binding proteins (RBPs) have critical roles in N6-methyladenosine (m6A) modification process. We designed a Random Forest (RF) model to systematically analyze the interaction among RBPs and m6A modifications by integrating the binding signals from hundreds of RBPs. Accurate prediction of m6A sites demonstrated significant connections between RBP bindings and m6A modifications. The relative importance of different RBPs from the model provided a quantitative metric to evaluate their interactions with m6A modifications. Redundancy analysis showed that several RBPs may have similar binding patterns with m6A sites. The RF model exhibited fairly high prediction accuracy across cell lines, suggesting a conservative RBP …

Cyanobacteria And Algal-Based Biological Life Support System (Blss) And Planetary Surface Atmospheric Revitalizing Bioreactor Brief Concept Review, Aly Alrabaa, Jeffrey A Jones

Faculty, Staff and Students Publications

Exploring austere environments required a reimagining of resource acquisition and utilization. Cyanobacterial in situ resources utilization (ISRU) and biological life support system (BLSS) bioreactors have been proposed to allow crewed space missions to extend beyond the temporal boundaries that current vehicle mass capacities allow. Many cyanobacteria and other microscopic organisms evolved during a period of Earth's history that was marked by very harsh conditions, requiring robust biochemical systems to ensure survival. Some species work wonderfully in a bioweathering capacity (siderophilic), and others are widely used for their nutritional power (non-siderophilic). Playing to each of their strengths and having them grow …

Hervs And Cancer-A Comprehensive Review Of The Relationship Of Human Endogenous Retroviruses And Human Cancers, Erik Stricker, Erin C Peckham-Gregory, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Genomic instability and genetic mutations can lead to exhibition of several cancer hallmarks in affected cells such as sustained proliferative signaling, evasion of growth suppression, activated invasion, deregulation of cellular energetics, and avoidance of immune destruction. Similar biological changes have been observed to be a result of pathogenic viruses and, in some cases, have been linked to virus-induced cancers. Human endogenous retroviruses (HERVs), once external pathogens, now occupy more than 8% of the human genome, representing the merge of genomic and external factors. In this review, we outline all reported effects of HERVs on cancer development and discuss the HERV …

A Differentiation Roadmap Of Murine Placentation At Single-Cell Resolution, Xiangxiang Jiang, Yue Wang, Zhenyu Xiao, Long Yan, Shanshan Guo, Hao Wu, Xiaoyin Lu, Hongmei Wang

Faculty, Staff and Student Publications

The placenta is one of the most important yet least understood organs. Due to the limitations of conventional research approaches, we are still far from a comprehensive understanding of mouse placentation, especially regarding the differentiation of trophoblast lineages at the early developmental stage. To decipher cell compositions and developmental processes, we systematically profile the single-cell transcriptomes of trophoblast cells from extraembryonic tissues (embryonic day 7.5 (E7.5) and E8.5) and placentae (E9.5-E14.5) at one-day intervals. We identify distinct trophoblast cell types during mouse placentation, including unreported progenitor cells and intermediate precursor cells. An updated differentiation roadmap of mouse trophoblast lineages is …

Ferroptosis Hijacking By Mycobacterium Tuberculosis, Boyi Gan

Faculty, Staff and Student Publications

A recent study from Nature Communications reveals that Mycobacterium tuberculosis can hijack epigenetic machinery in host cells and induce host cell ferroptosis, which promotes pathogen pathogenicity and spread. These findings also suggest new therapeutic strategies to treat tuberculosis.

Protocols For Single-Cell Rna-Seq And Spatial Gene Expression Integration And Interactive Visualization, Surbhi Sona, Matthew Bradley, Angela H Ting

Faculty, Staff and Student Publications

There is a wealth of software that utilizes single-cell RNA-seq (scRNA-seq) data to deconvolve spatial transcriptomic spots, which currently are not yet at single-cell resolution. Here we provide protocols for implementing Seurat and Giotto packages to elucidate cell-type distribution in our example human ureter scRNA-seq dataset. We also describe how to create a stand-alone interactive web application using Seurat libraries to visualize and share our results. For complete details on the use and execution of this protocol, please refer to Fink et al. (2022).

A Mast Cell-Thermoregulatory Neuron Circuit Axis Regulates Hypothermia In Anaphylaxis, Chunjing Bao, Ouyang Chen, Huaxin Sheng, Jeffrey Zhang, Yikai Luo, Han Liang, Ru-Rong Ji, Soman N Abraham

Faculty, Staff and Student Publications

IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an extensive systemic release of MC mediators. Through precipitating vasodilatation and vascular leakage, these mediators are believed to trigger a sharp drop in blood pressure in humans and in core body temperature in animals. We report that the IgE/MC-mediated drop in body temperature in mice associated with anaphylaxis also requires the body's thermoregulatory neural circuit. This circuit is activated when granule-borne chymase from MCs is deposited on proximal TRPV1+ …

The Association Between Medication Use In Older Women With Early-Stage Operable Primary Breast Cancer And Decision Regarding Primary Treatment

Faculty, Staff and Student Publications

Background: Polypharmacy is one factor contributing to increased mortality, hospitalization, and adverse drug reactions in older adults. The aim of this study was to measure the prevalence of polypharmacy in a cohort of older women with early-stage operable primary breast cancer and the relationship of polypharmacy to primary treatment decision and functional status.

Methods: A total of 139 patients with a new diagnosis of early-stage operable primary breast cancer proven histologically were recruited as part of a prospective study. The average age was 77 years. Assessment using a cancer-specific Comprehensive Geriatric Assessment (CGA) tool was conducted within 6 weeks of …

Opa1 Disease-Causing Mutants Have Domain-Specific Effects On Mitochondrial Ultrastructure And Fusion, Benjamín Cartes-Saavedra, Daniel Lagos, Josefa Macuada, Duxan Arancibia, Florence Burté, Marcela K. Sjöberg-Herrera, María Estela Andrés, Rita Horvath, Patrick Yu-Wai-Man, György Hajnóczky, Verónica Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Inner mitochondrial membrane fusion and cristae shape depend on optic atrophy protein 1, OPA1. Mutations in OPA1 lead to autosomal dominant optic atrophy (ADOA), an important cause of inherited blindness. The Guanosin Triphosphatase (GTPase) and GTPase effector domains (GEDs) of OPA1 are essential for mitochondrial fusion; yet, their specific roles remain elusive. Intriguingly, patients carrying OPA1 GTPase mutations have a higher risk of developing more severe multisystemic symptoms in addition to optic atrophy, suggesting pathogenic contributions for the GTPase and GED domains, respectively. We studied OPA1 GTPase and GED mutations to understand their domain-specific contribution to protein function by analyzing …

Esrage-Expressing Ohsv Enhances Anti-Tumor Efficacy By Inhibition Of Endothelial Cell Activation, Jessica Swanner, Ji Seon Shim, Kimberly A Rivera-Caraballo, Karina Vázquez-Arreguín, Bangxing Hong, Tae Jin Lee, Balveen Kaur, Ji Young Yoo

Faculty, Staff and Student Publications

High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that plays an important role in inflammation and tumorigenesis. Receptor for advanced glycation end products (RAGE) is one of the major receptors to which extracellular HMGB1 binds to mediate its activity. RAGE is highly expressed on the endothelial cells (ECs) and regulates endothelial permeability during inflammation. Here, we introduced the endogenous secretory form of RAGE (esRAGE) as a decoy receptor for RAGE ligands into an oncolytic herpes simplex virus 1 (oHSV) (OVesRAGE), which, upon release, can function to block RAGE signaling. OVesRAGE significantly decreased phosphorylation of MEK1/2 and …

Animal Models And Their Role In Imaging-Assisted Co-Clinical Trials, Donna M Peehl, Cristian T Badea, Thomas L Chenevert, Heike E Daldrup-Link, Li Ding, A Mcgarry Houghton, John Kurhanewicz, Michael T Lewis, Shunqiang Li, Gary D Luker, Cynthia X Ma, H Charles Manning, Yvonne M Mowery, Peter J O'Dwyer, Robia G Pautler, Mark A Rosen, Raheleh Roudi, Brian D Ross, Kooresh I Shoghi, Renuka Sriram, Moshe Talpaz, Richard L Wahl, Rong Zhou

Faculty, Staff and Student Publications

The availability of high-fidelity animal models for oncology research has grown enormously in recent years, enabling preclinical studies relevant to prevention, diagnosis, and treatment of cancer to be undertaken. This has led to increased opportunities to conduct co-clinical trials, which are studies on patients that are carried out parallel to or sequentially with animal models of cancer that mirror the biology of the patients' tumors. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are considered to be the models that best represent human disease and have high translational value. Notably, one element of co-clinical trials that still needs significant …

How Erastin Assassinates Cells By Ferroptosis Revealed, Boyi Gan

Faculty, Staff and Student Publications

No abstract provided.

The Pathogenesis Of Covid-19: Hypercoagulation And D-Dimer In Thrombotic Complications, Leonid Dubey, Halyna Lytvyn, Olha Dorosh, Nataliya Dubey, Olena Kozlova, Michal Pruc, Nina Kubikowska, Lukasz Szarpak, Kavita Batra, Francesco Chirico, Gabriella Nucera, Svitlana Doan, Uljana Shevtsiv

School of Medicine Faculty Research

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a new coronavirus disease (COVID-19), which is highly contagious and its pathogenesis has not been fully elucidated. In COVID-19, the inflammation and blood coagulation systems are excessively activated. SARS-CoV- 2 damages endothelial cells and pneumocytes, which leads to disruption of hemostasis in SARS. Thromboembolism is the main cause of mortality in patients with COVID-19. Clots, including pulmonary embolism (PE) and deep vein thrombosis (DVT), ranging from minor to fatal complications of the SARS-CoV-2 infection are known. Individuals with pre-existing diseases are more susceptible to the development of blood clots and poor outcomes. …

Preclinical Perspectives On The Mechanisms Underlying The Therapeutic Actions Of Psilocybin In Psychiatric Disorders, Andreas B. Wulff, Charles D. Nichols, Scott M. Thompson

School of Medicine Faculty Publications

Psychedelic compounds have shown extraordinary potential in treating a wide range of neuropsychiatric disorders. Psilocybin, for example, has now been shown in several clinical trials to induce a rapid (within days) and persistent (3–12 months) improvement in human treatment-resistant depression and other neuropsychiatric conditions. Here we review the preclinical models and experimental approaches that have been used to study the neurobiological actions of psychedelic drugs. We further summarize the insights these studies have provided into the possible mechanisms underlying the induction of their therapeutic actions, including the receptors to which psychedelics bind and the second messenger signaling cascades that they …

Daily Posture Behavior Patterns Derived From Multitime-Scale Topic Models Using Wearable Triaxial Acceleration For Assessment Of Concern About Falling, Changhong Wang, Yu Wang, Haitao Zhao, Guanzheng Liu, Bijan Najafi

Center on Aging Staff Publications

Concern about falling is prevalent in older population. This condition would cause a series of adverse physical and psychological consequences for older adults' health. Traditional assessment of concern about falling is relied on self-reported questionnaires and thus is too subjective. Therefore, we proposed a novel multi-time-scale topic modelling approach to quantitatively evaluate concern about falling by analyzing triaxial acceleration signals collected from a wearable pendent sensor. Different posture segments were firstly recognized to extract their corresponding feature subsets. Then, each selected feature related to concern about falling was clustered into discrete levels as feature letters of artificial words in different …

Fresh Produce As A Potential Vector And Reservoir For Human Bacterial Pathogens: Revealing The Ambiguity Of Interaction And Transmission, Ahmed Esmael, Rashad R. Al-Hindi, Raed S. Albiheyri, Mona G. Alharbi, Amani A. R. Filimban, Mazen S. Alseghayer, Abdulaziz M. Almaneea, Meshari Ahmed Alhadlaq, Jumaa Ayubu, Addisu D. Teklemariam

Nebraska Center for Virology: Faculty Publications

The consumer demand for fresh produce (vegetables and fruits) has considerably increased since the 1980s for more nutritious foods and healthier life practices, particularly in developed countries. Currently, several foodborne outbreaks have been linked to fresh produce. The global rise in fresh produce associated with human infections may be due to the use of wastewater or any contaminated water for the cultivation of fruits and vegetables, the firm attachment of the foodborne pathogens on the plant surface, and the internalization of these agents deep inside the tissue of the plant, poor disinfection practices and human consumption of raw fresh produce. …

The Alpha7 Integrin Subunit In Astrocytes Promotes Endothelial Blood-Brain Barrier Integrity, Zhihua Chen, Jack R Kelly, John E Morales, Raymond C Sun, Arpan De, Joseph H Mccarty

Faculty, Staff and Student Publications

The blood-brain barrier (BBB) is a vascular endothelial cell boundary that partitions the circulation from the central nervous system to promote normal brain health. We have a limited understanding of how the BBB is formed during development and maintained in adulthood. We used quantitative transcriptional profiling to investigate whether specific adhesion molecules are involved in BBB functions, with an emphasis on understanding how astrocytes interact with endothelial cells. Our results reveal a striking enrichment of multiple genes encoding laminin subunits as well as the laminin receptor gene Itga7, which encodes the alpha7 integrin subunit, in astrocytes. Genetic ablation of Itga7 …

Sequential Targeting Of Retinoblastoma And Dna Synthesis Pathways Is A Therapeutic Strategy For Sarcomas That Can Be Monitored In Real Time, Tuyen Duong Thanh Nguyen, Yan Wang, Tuyen N Bui, Rossana Lazcano, Davis R Ingram, Varshini Vakulabharanam, Marc A Pina, Cansu Karakas, Mi Li, Nicole M Kettner, Neeta Somaiah, Peter J Hougton, Osama Mawlawi, Alexander J Lazar, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective 2-step sequential combination …

Sequential Targeting Of Retinoblastoma And Dna Synthesis Pathways Is A Therapeutic Strategy For Sarcomas That Can Be Monitored In Real Time, Tuyen Duong Thanh Nguyen, Yan Wang, Tuyen N Bui, Rossana Lazcano, Davis R Ingram, Varshini Vakulabharanam, Marc A Pina, Cansu Karakas, Mi Li, Nicole M Kettner, Neeta Somaiah, Peter J Hougton, Osama Mawlawi, Alexander J Lazar, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell-cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1,043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective two-step sequential combination strategy …

Kdm6a Loss Triggers An Epigenetic Switch That Disrupts Urothelial Differentiation And Drives Cell Proliferation In Bladder Cancer, Hong Qiu, Vladimir Makarov, Jennifer K Bolzenius, Angela Halstead, Yvonne Parker, Gopakumar V Iyer, Daniel Kim, Varna Thayaparan, Daniel J Lindner, Georges-Pascal Haber, Angela H Ting, Bing Ren, Timothy A Chan, Vivek Arora, David B Solit, Byron H Lee

Faculty, Staff and Student Publications

Disruption of KDM6A, a histone lysine demethylase, is one of the most common somatic alternations in bladder cancer. Insights into how KDM6A mutations affect the epigenetic landscape to promote carcinogenesis could help reveal potential new treatment approaches. Here, we demonstrated that KDM6A loss triggers an epigenetic switch that disrupts urothelial differentiation and induces a neoplastic state characterized by increased cell proliferation. In bladder cancer cells with intact KDM6A, FOXA1 interacted with KDM6A to activate genes instructing urothelial differentiation. KDM6A-deficient cells displayed simultaneous loss of FOXA1 target binding and genome-wide redistribution of the bZIP transcription factor ATF3, which in turn repressed …

Safety Of Nivolumab Added To Chemoradiation Therapy Platforms For Intermediate And High-Risk Locoregionally Advanced Head And Neck Squamous Cell Carcinoma: Rtog Foundation 3504, Maura L Gillison, Robert L Ferris, Jonathan Harris, A Dimitrios Colevas, Loren K Mell, Richard C Jordan, Minh-Tam Truong, Claudia Kirsch, Arnab Chakravarti, Dukagjin M Blakaj, David A Clump, James P Ohr, John F Deeken, Michael F Gensheimer, Nabil F Saba, Jennifer A Dorth, David I Rosenthal, Rom S Leidner, Randall J Kimple, Mitchell Machtay, Walter J Curran, Pedro Torres-Saavedra, Quynh Thu Le

Faculty, Staff and Student Publications

PURPOSE: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown.

METHODS AND MATERIALS: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting …

Acute Acat1/Soat1 Blockade Increases Mam Cholesterol And Strengthens Er-Mitochondria Connectivity., Taylor C Harned, Radu V Stan, Ze Cao, Rajarshi Chakrabarti, Henry N Higgs, Catherine C Y Chang, Ta Yuan Chang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cholesterol is a key component of all mammalian cell membranes. Disruptions in cholesterol metabolism have been observed in the context of various diseases, including neurodegenerative disorders such as Alzheimer's disease (AD). The genetic and pharmacological blockade of acyl-CoA:cholesterol acyltransferase 1/sterol O-acyltransferase 1 (ACAT1/SOAT1), a cholesterol storage enzyme found on the endoplasmic reticulum (ER) and enriched at the mitochondria-associated ER membrane (MAM), has been shown to reduce amyloid pathology and rescue cognitive deficits in mouse models of AD. Additionally, blocking ACAT1/SOAT1 activity stimulates autophagy and lysosomal biogenesis; however, the exact molecular connection between the ACAT1/SOAT1 blockade and these observed benefits remain …

Tsks Localizes To Nuage In Spermatids And Regulates Cytoplasmic Elimination During Spermiation, Taichi Noda, Akane Morohoshi, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Spermatozoa have a streamlined shape to swim through the oviduct to fertilize oocytes. To become svelte spermatozoa, spermatid cytoplasm must be eliminated in several steps including sperm release, which is part of spermiation. Although this process has been well observed, the molecular mechanisms that underlie it remain unclear. In male germ cells, there are membraneless organelles called nuage, which are observed by electron microscopy in various forms of dense material. Reticulated body (RB) and chromatoid body remnant (CR) are two types of nuage in spermatids, but the functions of both are unknown. Using CRISPR/Cas9 technology, we deleted the entire coding …

In Vivo Functional Characterization Of Egfr Variants Identifies Novel Drivers Of Glioblastoma, Estefania Luna-Figueroa, Alexis Cervantes, Rachel Curry, Carrie A Mohila, Ganesh Rao, Ali Jalali, Gordon B Mills, Kenneth L Scott, Benjamin Deneen

Faculty, Staff and Students Publications

BACKGROUND: Glioblastoma is the most common and aggressive primary brain tumor. Large-scale sequencing initiatives have cataloged its mutational landscape in hopes of elucidating mechanisms driving this deadly disease. However, a major bottleneck in harnessing this data for new therapies is deciphering "driver" and "passenger" events amongst the vast volume of information.

METHODS: We utilized an autochthonous, in vivo screening approach to identify driver, EGFR variants. RNA-Seq identified unique molecular signatures of mouse gliomas across these variants, which only differ by a single amino acid change. In particular, we identified alterations to lipid metabolism, which we further validated through an unbiased …

Human Schistosomiasis Vaccines As Next Generation Control Tools

Faculty, Staff and Students Publications

No abstract provided.

Hypermitotic Meningiomas Harbor Dna Methylation Subgroups With Distinct Biological And Clinical Features, James C Bayley, Akdes S Harmanci, Sybren L N Maas, Sandro Santagata, Tiemo Klisch, Arie Perry, Wenya Linda Bi, Felix Sahm, Akash J Patel, Stephen T Magill, David R Raleigh

Faculty, Staff and Students Publications

BACKGROUND: Meningiomas, the most common primary intracranial tumors, can be separated into 3 DNA methylation groups with distinct biological drivers, clinical outcomes, and therapeutic vulnerabilities. Alternative meningioma grouping schemes using copy number variants, gene expression profiles, somatic short variants, or integrated molecular models have been proposed. These data suggest meningioma DNA methylation groups may harbor subgroups unifying contrasting theories of meningioma biology.

METHODS: A total of 565 meningioma DNA methylation profiles from patients with comprehensive clinical follow-up at independent discovery (n = 200) or validation (n = 365) institutions were reanalyzed and classified into Merlin-intact, Immune-enriched, or Hypermitotic DNA methylation …

Enzalutamide-Induced Signatures Revealed By Epigenetic Plasticity Using Single-Cell Multi-Omics Sequencing In Prostate Cancer, Huihui Fan, Jinze Li, Astrid M Manuel, Zhongming Zhao

Faculty, Staff and Student Publications

Prostate cancer is morphologically and molecularly heterogeneous, which poses obstacles for early diagnosis and treatment. Advancements in understanding the heterogeneity of prostate cancer will help navigate through these challenges and ultimately benefit patients. In this study, we integrated single-cell sequencing for transposase-accessible chromatin and whole transcriptome in prostate cancer cell lines, aiming to decode the epigenetic plasticity upon enzalutamide (ENZ) treatment. By comparing the cell populations representing early-treatment response or resistance to the initial tumor cells, we identified seven signature gene sets; they present consistent trends of chromatin closing co-occurred with down-regulated genes during early response and chromatin opening with …

Renal Cell Carcinoma Unclassified With Medullary Phenotype In A Patient With Neurofibromatosis Type 2, Sanila Sarkar, Whitney Throckmorton, Racheal Bingham, Pavlos Msaouel, Giannicola Genovese, Priya Rao, Cynthia E Herzog

Faculty, Staff and Student Publications

We present, to our knowledge, the first reported case of germline neurofibromatosis Type 2 (NF2) associated with renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) with somatic loss by immunohistochemistry of the SMARCB1 tumor suppressor gene located centromeric to NF2 on chromosome 22q. Our patient is a 15-year-old with germline neurofibromatosis Type 2 (NF2) confirmed by pathogenic mutation of c.-854-??46+??deletion. Her NF2 history is positive for a right optic nerve sheath meningioma, CNIII schwannoma requiring radiation therapy and post gross total resection of right frontotemporal anaplastic meningioma followed by radiation. At age 15 she developed new onset weight loss and …