Genetic Phenomena Commons^™

Archival Single-Cell Genomics Reveals Persistent Subclones During Dcis Progression, Kaile Wang, Tapsi Kumar, Junke Wang, Darlan Conterno Minussi, Emi Sei, Jianzhuo Li, Tuan M Tran, Aatish Thennavan, Min Hu, Anna K Casasent, Zhenna Xiao, Shanshan Bai, Lei Yang, Lorraine M King, Vandna Shah, Petra Kristel, Carolien L Van Der Borden, Jeffrey R Marks, Yuehui Zhao, Amado J Zurita, Ana Aparicio, Brian Chapin, Jie Ye, Jianjun Zhang, Don L Gibbons, Ellinor Sawyer, Alastair M Thompson, Andrew Futreal, E Shelley Hwang, Jelle Wesseling, Esther H Lips, Nicholas E Navin

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary …

Pan-Cancer Analysis Of Post-Translational Modifications Reveals Shared Patterns Of Protein Regulation, Yifat Geffen, Shankara Anand, Yo Akiyama, Tomer M Yaron, Yizhe Song, Jared L Johnson, Akshay Govindan, Özgün Babur, Yize Li, Emily Huntsman, Liang-Bo Wang, Chet Birger, David I Heiman, Qing Zhang, Mendy Miller, Yosef E Maruvka, Nicholas J Haradhvala, Anna Calinawan, Saveliy Belkin, Alexander Kerelsky, Karl R Clauser, Karsten Krug, Shankha Satpathy, Samuel H Payne, D R Mani, Michael A Gillette, Saravana M Dhanasekaran, Mathangi Thiagarajan, Mehdi Mesri, Henry Rodriguez, Ana I Robles, Steven A Carr, Alexander J Lazar, François Aguet, Lewis C Cantley, Li Ding, Gad Getz, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology in both normal and cancer cells. Advances in mass spectrometry enable high-throughput, accurate, and sensitive measurement of PTM levels to better understand their role, prevalence, and crosstalk. Here, we analyze the largest collection of proteogenomics data from 1,110 patients with PTM profiles across 11 cancer types (10 from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns of changes in protein acetylation and phosphorylation involved in hallmark cancer processes. These patterns revealed subsets of tumors, from different cancer types, including those with …

Pan-Cancer Proteogenomics Connects Oncogenic Drivers To Functional States, Yize Li, Eduard Porta-Pardo, Collin Tokheim, Matthew H Bailey, Tomer M Yaron, Vasileios Stathias, Yifat Geffen, Kathleen J Imbach, Song Cao, Shankara Anand, Yo Akiyama, Wenke Liu, Matthew A Wyczalkowski, Yizhe Song, Erik P Storrs, Michael C Wendl, Wubing Zhang, Mustafa Sibai, Victoria Ruiz-Serra, Wen-Wei Liang, Nadezhda V Terekhanova, Fernanda Martins Rodrigues, Karl R Clauser, David I Heiman, Qing Zhang, Francois Aguet, Anna P Calinawan, Saravana M Dhanasekaran, Chet Birger, Shankha Satpathy, Daniel Cui Zhou, Liang-Bo Wang, Jessika Baral, Jared L Johnson, Emily M Huntsman, Pietro Pugliese, Antonio Colaprico, Antonio Iavarone, Milan G Chheda, Christopher J Ricketts, David Fenyö, Samuel H Payne, Henry Rodriguez, Ana I Robles, Michael A Gillette, Chandan Kumar-Sinha, Alexander J Lazar, Lewis C Cantley, Gad Getz, Li Ding

Faculty, Staff and Student Publications

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of …

Wearable Biosensor With Molecularly Imprinted Conductive Polymer Structure To Detect Lentivirus In Aerosol, Jaskirat Singh Batra, Ting-Yen Chi, Mo-Fan Huang, Dandan Zhu, Zheyuan Chen, Dung-Fang Lee, Jun Kameoka

Faculty, Staff and Student Publications

The coronavirus disease (COVID-19) pandemic has increased pressure to develop low-cost, compact, user-friendly, and ubiquitous virus sensors for monitoring infection outbreaks in communities and preventing economic damage resulting from city lockdowns. As proof of concept, we developed a wearable paper-based virus sensor based on a molecular imprinting technique, using a conductive polyaniline (PANI) polymer to detect the lentivirus as a test sample. This sensor detected the lentivirus with a 4181 TU/mL detection limit in liquid and 0.33% to 2.90% detection efficiency in aerosols at distances ranging from 30 cm to 60 cm. For fabrication, a mixture of a PANI monomer …

Mapping The Evolution Of T Cell States During Response And Resistance To Adoptive Cellular Therapy, Pavan Bachireddy, Elham Azizi, Cassandra Burdziak, Vinhkhang N Nguyen, Christina S Ennis, Katie Maurer, Cameron Y Park, Zi-Ning Choo, Shuqiang Li, Satyen H Gohil, Neil G Ruthen, Zhongqi Ge, Derin B Keskin, Nicoletta Cieri, Kenneth J Livak, Haesook T Kim, Donna S Neuberg, Robert J Soiffer, Jerome Ritz, Edwin P Alyea, Dana Pe'er, Catherine J Wu

Faculty, Staff and Student Publications

No abstract provided.

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

Bicuspid Aortic Valve And Thoracic Aortic Disease: Further Evidence Of Clinically Silent But Deadly Risk To Family Members Of Affected Individuals, Siddharth K Prakash, Hector I Michelena, Dianna M Milewicz

Faculty, Staff and Student Publications

No abstract provided.

Triple-Negative Breast Tumors Are Dependent On Mutant P53 For Growth And Survival, Denada Dibra, Sydney M Moyer, Adel K El-Naggar, Yuan Qi, Xiaoping Su, Guillermina Lozano

Faculty, Staff and Student Publications

The TP53 tumor suppressor gene is mutated early in the majority of patients with triple-negative breast cancer (TNBC). The most frequent TP53 alterations are missense mutations that contribute to tumor aggressiveness. We developed an autochthonous somatic K14-Cre driven TNBC mouse model with p53R172H and p53R245W mutations in which mutant p53 can be toggled on and off genetically while leaving the tumor microenvironment intact and wild-type for p53. These mice develop TNBCs with a median latency of 1 y. Deletion of mutant p53R172H or p53R245W in vivo in these tumors blunts their tumor growth and significantly extends survival of mice. Downstream …

Pirtobrutinib In Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma, Michael L Wang, Wojciech Jurczak, Pier Luigi Zinzani, Toby A Eyre, Chan Y Cheah, Chaitra S Ujjani, Youngil Koh, Koji Izutsu, James N Gerson, Ian Flinn, Benoit Tessoulin, Alvaro J Alencar, Shuo Ma, David Lewis, Ewa Lech-Maranda, Joanna Rhodes, Krish Patel, Kami Maddocks, Nicole Lamanna, Yucai Wang, Constantine S Tam, Talha Munir, Hirokazu Nagai, Francisco Hernandez-Ilizaliturri, Anita Kumar, Timothy S Fenske, John F Seymour, Andrew D Zelenetz, Binoj Nair, Donald E Tsai, Minna Balbas, Richard A Walgren, Paolo Abada, Chunxiao Wang, Junjie Zhao, Anthony R Mato, Nirav N Shah

Faculty, Staff and Student Publications

Purpose: Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated mantle-cell lymphoma (MCL), a population with poor prognosis.

Methods: Patients with cBTKi pretreated relapsed/refractory (R/R) MCL received pirtobrutinib monotherapy in a multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529). Efficacy was assessed in the first 90 consecutively enrolled patients who met criteria for inclusion in the primary efficacy cohort. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR) and safety. …

Incidence Of Resting-State Functional Connectivity To Secondary Language Areas And Contralateral Language Areas In Patients With Brain Tumors, Angela L Young, Suprateek Kundu, Karthik K Tappa, Ping Hou, Ho-Ling Liu, Vinodh A Kumar

Faculty, Staff and Student Publications

Purpose: Secondary language areas, including the pre-supplementary motor area (pre-SMA), dorsolateral prefrontal cortex (DLPFC), and the visual word form area (VWFA) play important roles in speech, but have been under-evaluated in the realm of resting-state (rs)-fMRI. The purpose of this study is to determine the incidence that secondary language areas and contralateral language areas can be localized using seed-based correlation (SBC) rs-fMRI.

Methods: We retrospectively reviewed 40 rs-fMRIs for functional connectivity (FC) to secondary language areas in cases where FC to Broca's or Wernicke's area near tumor in the left hemisphere were successfully generated using SBC analysis. Logistical regression was …

The Interplay Between H3k36 Methylation And Dna Methylation In Cancer, Jiameng Dan, Zeling Du, Jinghong Zhang, Taiping Chen

Faculty, Staff and Student Publications

No abstract provided.

The Pyrimidinosome: Orchestrating Pyrimidine Biosynthesis And Ferroptosis Defense, Boyi Gan

Faculty, Staff and Student Publications

A recent study by Yang et al.1 uncovers the pyrimidinosome, a multienzyme complex where enzymes from different subcellular compartments collaborate to enable efficient pyrimidine biosynthesis and ferroptosis defense, highlighting the remarkable adaptability of cellular metabolism and new therapeutic opportunities.

Labeling Piezo2 Activity In The Peripheral Nervous System, Nicholas W Villarino, Yasmeen M F Hamed, Britya Ghosh, Adrienne E Dubin, Amanda H Lewis, Max A Odem, Meaghan C Loud, Yu Wang, M Rocio Servin-Vences, Ardem Patapoutian, Kara L Marshall

Duncan NRI Faculty and Staff Publications

Sensory neurons detect mechanical forces from both the environment and internal organs to regulate physiology. PIEZO2 is a mechanosensory ion channel critical for touch, proprioception, and bladder stretch sensation, yet its broad expression in sensory neurons suggests it has undiscovered physiological roles. To fully understand mechanosensory physiology, we must know where and when PIEZO2-expressing neurons detect force. The fluorescent styryl dye FM 1-43 was previously shown to label sensory neurons. Surprisingly, we find that the vast majority of FM 1-43 somatosensory neuron labeling in mice in vivo is dependent on PIEZO2 activity within the peripheral nerve endings. We illustrate the …

Spatial Organization Of The Mouse Retina At Single Cell Resolution By Merfish, Jongsu Choi, Jin Li, Salma Ferdous, Qingnan Liang, Jeffrey R Moffitt, Rui Chen

Faculty, Staff and Students Publications

The visual signal processing in the retina requires the precise organization of diverse neuronal types working in concert. While single-cell omics studies have identified more than 120 different neuronal subtypes in the mouse retina, little is known about their spatial organization. Here, we generated the single-cell spatial atlas of the mouse retina using multiplexed error-robust fluorescence in situ hybridization (MERFISH). We profiled over 390,000 cells and identified all major cell types and nearly all subtypes through the integration with reference single-cell RNA sequencing (scRNA-seq) data. Our spatial atlas allowed simultaneous examination of nearly all cell subtypes in the retina, revealing …

Loss Of Syncrip Unleashes Apobec-Driven Mutagenesis, Tumor Heterogeneity, And Ar-Targeted Therapy Resistance In Prostate Cancer, Xiaoling Li, Yunguan Wang, Su Deng, Guanghui Zhu, Choushi Wang, Nickolas A Johnson, Zeda Zhang, Carla Rodriguez Tirado, Yaru Xu, Lauren A Metang, Julisa Gonzalez, Atreyi Mukherji, Jianfeng Ye, Yuqiu Yang, Wei Peng, Yitao Tang, Mia Hofstad, Zhiqun Xie, Heewon Yoon, Liping Chen, Xihui Liu, Sujun Chen, Hong Zhu, Douglas Strand, Han Liang, Ganesh Raj, Housheng Hansen He, Joshua T Mendell, Bo Li, Tao Wang, Ping Mu

Faculty, Staff and Student Publications

Tumor mutational burden and heterogeneity has been suggested to fuel resistance to many targeted therapies. The cytosine deaminase APOBEC proteins have been implicated in the mutational signatures of more than 70% of human cancers. However, the mechanism underlying how cancer cells hijack the APOBEC mediated mutagenesis machinery to promote tumor heterogeneity, and thereby foster therapy resistance remains unclear. We identify SYNCRIP as an endogenous molecular brake which suppresses APOBEC-driven mutagenesis in prostate cancer (PCa). Overactivated APOBEC3B, in SYNCRIP-deficient PCa cells, is a key mutator, representing the molecular source of driver mutations in some frequently mutated genes in PCa, including FOXA1, …

Multifocal And Multicentric Glioblastoma: Imaging Signature, Molecular Characterization, Patterns Of Spread, And Treatment, Maguy Farhat, Gregory N Fuller, Max Wintermark, Caroline Chung, Vinodh A Kumar, Melissa Chen

Faculty, Staff and Student Publications

Multifocal and multicentric glioblastoma (GBM) or collectively, m-GBM, is an imaging diagnosis present in up to 34% of patients with GBM. Compared to unifocal disease, patients with m-GBM have worse outcomes owing to the enhanced aggressive nature of the disease and its resistance to currently available treatments. To improve the understanding of its complex behavior, many associations have been established between the radiologic findings of m-GBM and its gross histology, genetic composition, and patterns of spread. Additionally, the holistic knowledge of the exact mechanisms of m-GBM genesis and progression is crucial for identifying potential targets permitting enhanced diagnosis and treatment. …

Genetic Control Of Mrna Splicing As A Potential Mechanism For Incomplete Penetrance Of Rare Coding Variants, Jonah Einson, Dafni Glinos, Eric Boerwinkle, Peter Castaldi, Dawood Darbar, Mariza De Andrade, Patrick Ellinor, Myriam Fornage, Stacey Gabriel, Soren Germer, Richard Gibbs, Craig P Hersh, Jill Johnsen, Robert Kaplan, Barbara A Konkle, Charles Kooperberg, Rami Nassir, Ruth J F Loos, Deborah A Meyers, Braxton D Mitchell, Bruce Psaty, Ramachandran S Vasan, Stephen S Rich, Michael Rienstra, Jerome I Rotter, Aabida Saferali, Moore Benjamin Shoemaker, Edwin Silverman, Albert Vernon Smith, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium; Pejman Mohammadi, Pejman Mohammadi, Stephane E Castel, Ivan Iossifov, Tuuli Lappalainen

Faculty, Staff and Student Publications

Exonic variants present some of the strongest links between genotype and phenotype. However, these variants can have significant inter-individual pathogenicity differences, known as variable penetrance. In this study, we propose a model where genetically controlled mRNA splicing modulates the pathogenicity of exonic variants. By first cataloging exonic inclusion from RNA-sequencing data in GTEx V8, we find that pathogenic alleles are depleted on highly included exons. Using a large-scale phased whole genome sequencing data from the TOPMed consortium, we observe that this effect may be driven by common splice-regulatory genetic variants, and that natural selection acts on haplotype configurations that reduce …

A Dimensional Approach To Discrepancy In Parenting Styles In Russian Families, Marina A Zhukova, Nan Li, Vitalii Zhukov, Elena L Grigorenko

Faculty, Staff and Students Publications

We investigated the magnitude and direction of differences in parenting styles as they relate to children's mental health problems, as assessed using the CBCL. The sample consisted of 306 families residing in a large industrial city in Russia. We aimed to expand the cross-cultural literature on parenting styles by assessing a sample of Russian families and analyzing how agreement versus disagreement between self-reported and partner-reported parenting styles related to children's mental health problems. The findings suggested that both congruence and incongruence between parenting styles could be associated with children's mental health problems. When parents agreed about high warmth and matched …

Successful Treatment Of Non-Langerhans Cell Histiocytosis With The Mek Inhibitor Trametinib: A Multicenter Analysis, Ashley Aaroe, Razelle Kurzrock, Gaurav Goyal, Aaron M Goodman, Harsh Patel, Gordon Ruan, Gary Ulaner, Jason Young, Ziyi Li, Derek Dustin, Ronald S Go, Eli L Diamond, Filip Janku

Faculty, Staff and Student Publications

Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are rare non-Langerhans cell histiocytoses (non-LCHs), for which therapeutic options are limited. MAPK pathway activation through BRAFV600E mutation or other genomic alterations is a histiocytosis hallmark and correlates with a favorable response to BRAF inhibitors and the MEK inhibitor cobimetinib. However, there has been no systematic evaluation of alternative MEK inhibitors. To assess the efficacy and safety of the MEK inhibitor trametinib, we retrospectively analyzed the outcomes of 26 adult patients (17 with ECD, 5 with ECD/RDD, 3 with RDD, and 1 with ECD/LCH) treated with orally administered trametinib at 4 major US …

Traf3-Ewsr1 Signaling Axis Acts As A Checkpoint On Germinal Center Responses, Yanchuan Li, Lele Zhu, Chun-Jung Ko, Jin-Young Yang, Hongjiao Wang, Ganiraju Manyam, Jing Wang, Xuhong Cheng, Shuli Zhao, Zuliang Jie

Faculty, Staff and Student Publications

The formation of germinal centers (GCs) is crucial for humoral immunity and vaccine efficacy. Constant stimulation through microbiota drives the formation of constitutive GCs in Peyer's patches (PPs), which generate B cells that produce antibodies against gut antigens derived from commensal bacteria and infectious pathogens. However, the molecular mechanism that regulates this persistent process is poorly understood. We report that Ewing Sarcoma Breakpoint Region 1 (EWSR1) is a brake to constitutive GC generation and immunoglobulin G (IgG) production in PPs, vaccination-induced GC formation, and IgG responses. Mechanistically, EWSR1 suppresses Bcl6 upregulation after antigen encounter, thereby negatively regulating induced GC B …

Psilocybin-Assisted Psychotherapy For Cancer-Related Anxiety And Depression, Dan Yaniv, Lois Michelle Ramondetta, Lorenzo Cohen, Moran Amit

Faculty, Staff and Student Publications

No abstract provided.

Metabolic Liver Cancer: Associations Of Rare And Common Germline Variants In One-Carbon Metabolism And Dna Methylation Genes, Samuel O Antwi, Michael Heckman, Launia White, Irene Yan, Vivekananda Sarangi, Kimberly P Lauer, Joseph Reddy, Fowsiyo Ahmed, Swathi Veliginti, Ellis D Mejías Febres, Rikita I Hatia, Ping Chang, Laura Izquierdo-Sanchez, Loreto Boix, Angela Rojas, Jesus M Banales, Maria Reig, Per Stål, Manuel Romero Gómez, Amit G Singal, Donghui Li, Manal M Hassan, Lewis R Roberts, Tushar Patel

Faculty, Staff and Student Publications

Animal studies implicate one-carbon metabolism and DNA methylation genes in hepatocellular carcinoma (HCC) development in the setting of metabolic perturbations. Using human samples, we investigated the associations between common and rare variants in these closely related biochemical pathways and risk for metabolic HCC development in a multicenter international study. We performed targeted exome sequencing of 64 genes among 556 metabolic HCC cases and 643 cancer-free controls with metabolic conditions. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple comparisons. Gene-burden tests were used for rare variant associations. Analyses were performed in …

Piezo2 In Somatosensory Neurons Controls Gastrointestinal Transit, M Rocio Servin-Vences, Ruby M Lam, Alize Koolen, Yu Wang, Dimah N Saade, Meaghan Loud, Halil Kacmaz, Suzanne Frausto, Yunxiao Zhang, Arthur Beyder, Kara L Marshall, Carsten G Bönnemann, Alexander T Chesler, Ardem Patapoutian

Duncan NRI Faculty and Staff Publications

The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence of food and help digestion by mechanically breaking down and propelling gut content. Mechanical sensing in the gut is thought to be essential for regulating motility; however, the identity of the neuronal populations, the molecules involved, and the functional consequences of this sensation are unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel sensation and motility. Piezo2 in mouse dorsal root, but not nodose ganglia is required to sense gut content, and this activity slows down food transit rates in …

Safety And Efficacy Of Immune Checkpoint Inhibitors In Patients With Cancer And Viral Hepatitis: The Md Anderson Cancer Center Experience, Mirella Nardo, Bulent Yilmaz, Blessie Elizabeth Nelson, Harrys A Torres, Lan Sun Wang, Bruno Palma Granwehr, Juhee Song, Hanna R F Dalla Pria, Van A Trinh, Isabella C Glitza Oliva, Sapna P Patel, Nizar M Tannir, Ahmed Omar Kaseb, Mehmet Altan, Sunyoung S Lee, Ethan Miller, Hao Zhang, Bettzy A Stephen, Aung Naing

Faculty, Staff and Student Publications

Background: Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment.

Materials and methods: We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019.

Results: Of the 1076 patients screened, we identified 33 with concurrent hepatitis. …

Beyond The Exome: What’S Next In Diagnostic Testing For Mendelian Conditions, Monica H Wojcik, Chloe M Reuter, Shruti Marwaha, Medhat Mahmoud, Michael H Duyzend, Hayk Barseghyan, Bo Yuan, Philip M Boone, Emily E Groopman, Emmanuèle C Délot, Deepti Jain, Alba Sanchis-Juan, Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium, Lea M Starita, Michael Talkowski, Stephen B Montgomery, Michael J Bamshad, Jessica X Chong, Matthew T Wheeler, Seth I Berger, Anne O'Donnell-Luria, Fritz J Sedlazeck, Danny E Miller

Faculty, Staff and Student Publications

Despite advances in clinical genetic testing, including the introduction of exome sequencing (ES), more than 50% of individuals with a suspected Mendelian condition lack a precise molecular diagnosis. Clinical evaluation is increasingly undertaken by specialists outside of clinical genetics, often occurring in a tiered fashion and typically ending after ES. The current diagnostic rate reflects multiple factors, including technical limitations, incomplete understanding of variant pathogenicity, missing genotype-phenotype associations, complex gene-environment interactions, and reporting differences between clinical labs. Maintaining a clear understanding of the rapidly evolving landscape of diagnostic tests beyond ES, and their limitations, presents a challenge for non-genetics professionals. …

The Case For Expanding Visual Assessments During Spaceflight, Ethan Waisberg, Joshua Ong, Mouayad Masalkhi, Nasif Zaman, Sharif Amit Kamran, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Spaceflight associated neuro-ocular syndrome (SANS) is one of the potential barriers to human long-duration spaceflight (LDSF), including a manned mission to Mars. While a large barrier, the pathophysiology of SANS is not well understood, and functional and structural findings from SANS continue to be further characterized. Currently on the International Space Station (ISS), scheduled visual assessments are static visual acuity, Amsler grid, and a self-reported survey. Additional visual assessments may help the understanding of this neuro-ophthalmic phenomenon, as well as the effects of spaceflight of overall ocular health. In this paper, a case is made for expanding scheduled visual assessments …

The Collaborative National Quality And Efficacy Registry For Scleroderma: Association Of Medication Use On Gastrointestinal Tract Symptoms In Early Disease And The Importance Of Tobacco Cessation, Sarah Luebker, Tracy M Frech, Shervin Assassi, Jessica K Gordon, Elana J Bernstein, Virginia D Steen, Ami A Shah, Laura K Hummers, Carrie Richardson, Dinesh Khanna, Flavia V Castelino, Lorinda Chung, Faye N Hant, Victoria K Shanmugam, John M Vanburen, Jessica Alvey, Monica Harding, Nora Sandorfi

Faculty, Staff and Student Publications

Objectives: Systemic Sclerosis (SSc) is frequently associated with gastrointestinal tract (GIT) involvement. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative study collecting longitudinal follow up data on SSc patients with less than 5-years disease duration enrolled at Scleroderma centres of excellence. This manuscript presents the GIT natural history and outcomes in relation to other scleroderma manifestations and medication exposures.

Methods: CONQUER participants that had completed a minimum of two serial Scleroderma Clinical Trials Consortium GIT Questionnaires (GIT 2.0) were included in this analysis. Patients were categorised by total GIT 2.0 severity at baseline, and by category …

Real-Time 3-D Video Reconstruction For Guidance Of Transventricular Neurosurgery, Prasad Vagdargi, Ali Uneri, Xiaoxuan Zhang, Craig K Jones, Pengwei Wu, Runze Han, Alejandro Sisniega, Junghoon Lee, Patrick Helm, Mark Luciano, William S Anderson, Gregory D Hager, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

Neuroendoscopic approach to deep-brain targets imparts deformation of the ventricles and adjacent parenchyma, limiting the accuracy of conventional neuronavigation. We report a method for 3D endoscopic reconstruction and registration via simultaneous localization and mapping (SLAM) for real-time guidance with or without robotic assistance. The aim is to permit augmented video overlay of structures registered from preoperative or intraoperative 3D images within and beyond the endoscopic field of view for more accurate targeting in the presence of deep-brain deformation. Phantom studies were performed to evaluate geometric accuracy and uncertainty in distinct scenarios of limited data (feature sparsity and scene occlusion), demonstrating …

Cerebellar Dysfunction As A Source Of Dystonic Phenotypes In Mice, Amanda M Brown, Meike E Van Der Heijden, H A Jinnah, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

There is now a substantial amount of compelling evidence demonstrating that the cerebellum may be a central locus in dystonia pathogenesis. Studies using spontaneous genetic mutations in rats and mice, engineered genetic alleles in mice, shRNA knockdown in mice, and conditional genetic silencing of fast neurotransmission in mice have all uncovered a common set of behavioral and electrophysiological defects that point to cerebellar cortical and cerebellar nuclei dysfunction as a source of dystonic phenotypes. Here, we revisit the Ptf1aCre/+;Vglut2flox/flox mutant mouse to define fundamental phenotypes and measures that are valuable for testing the cellular, circuit, and …