Digital Commons Network^™

Targeting Ribosome Biogenesis For Pancreatic Cancer Treatment, Carlos Perez Iii

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related death in the United States. Currently, PanCa is one of the recalcitrant cancers that has very limited therapeutic options available for its treatment. The current standard care of PanCa is gemcitabine (GEM) alone or in combination with FOLFIRINOX, nab-paclitaxel, erlotinib, or 5-FU PanCa, which often show poor response. Therefore, new treatment strategies are required for the prevention and treatment of cancer. Ribosome biogenesis process is dysregulated in most of the cancer types of results in production of more ribosomes and synthesis of oncoproteins which lead to the induction, progression, …

The Bulletin: Sidney Kimmel Medical College At Thomas Jefferson University, Volume 71, Issue 2, Summer 2022

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

This issue includes:

• 4 - Dean's Column
• 8 - Time Capsule - Dr. Marion Siegman
• 11 - A Message from Elizabeth A. Dale
• 14 - ICYMI (In Case You Missed It)
• 18 - At the Intersection of Health and Design
• 20 - Discovery - A Path Toward Digital Equity
• 26 - Mark L. Tykocinski Takes the Helm as President of Thomas Jefferson University
• 28 - Student Profile - Kayla Holston
• 30 - Faculty Profile - Stephen D. Silberstein, MD
• 34 - Alumni Profile - Mahesh Krishnan, MD ’94
• 36 - Class Notes
• 42 - Reimagine
• 43 - Bookshelf
• 44- In …

Mratbn72: Familiar And Unfamiliar Features Of A New Rat Genome Reference Assembly, Tristan V De Jong, Hao Chen, Wesley A Brashear, Kelli J Kochan, Andrew E Hillhouse, Yaming Zhu, Isha S Dhande, Elizabeth A Hudson, Mary H Sumlut, Melissa L Smith, Theodore S Kalbfleisch, Peter A Doris

The Brown Foundation: Institute of Molecular Medicine

Rat genomic tools have been slower to emerge than for those of humans and mice and have remained less thorough and comprehensive. The arrival of a new and improved rat reference genome, mRatBN7.2, in late 2020 is a welcome event. This assembly, like predecessor rat reference assemblies, is derived from an inbred Brown Norway rat. In this "user" survey we hope to provide other users of this assembly some insight into its characteristics and some assessment of its improvements as well as a few caveats that arise from the unique aspects of this assembly. mRatBN7.2 was generated by the Wellcome …

Promoting Best Practice In Cancer Care In Sub Saharan Africa, Karishma Sharma, Shahin Sayed, Mansoor Saleh

Internal Medicine, East Africa

Promoting best practice in the management of a cancer patient is rooted in the application of new knowledge derived through various sources including population science, laboratory advances, and translational research. Ultimately, the impact of these advances depends on their application at the patient’s bedside. A close collaboration between the oncologist and the pathologist is critical in underwriting progress in the management of the cancer patient. Recent advancements have shown that more granular characteristics of the tumor and themicroenvironment are defining determinants when it comes to disease course and overall outcome. Whereas, histologic features and basic immunohistochemical characterization were previously adequate …

Maternal Obesity, Pregnancy Weight Gain, And Birth Weight And Risk Of Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Minjae Lee, Timothy Zaki, Ezra Burstein, Barbara A Cohn

Faculty, Staff and Student Publications

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect on cancer in adulthood. We examined associations of maternal obesity, pregnancy weight gain, and birth weight and CRC in adult offspring.

Design: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California (N=18 751 live births among 14 507 mothers). Clinical information was abstracted from mothers' medical records 6 months prior to pregnancy through delivery. Diagnoses of …

Covid-19 Vaccines In India: Judicial Blind Spots In Upholding The Right To Health, Kajal Bhardwaj, Veena Johari

Socio-Legal Review

The COVID-19 pandemic brought to the forefront the intrinsic link between health and human rights and exposed the conflict between public health measures and individual rights and liberties. These conflicts are apparent in the context of COVID-19 vaccines as well. Vaccines were fast-tracked, given emergency approval and produced and distributed by a few manufacturers with the help of the government and multiple agencies, to control the COVID-19 pandemic. However, the lack of transparency in regulation, the formulation of arbitrary policies, unfair pricing, unequal procurement, restricted and discriminatory distribution, lack of informed consent and lack of accountability for adverse events following …

Child Sexual Abuse Cases In India And Judicial Officers’ Perceptions And Experiences Of Pocso-Related Special Training, Shailesh Kumar

Socio-Legal Review

Stakeholder training has been considered essential to tackle the problem of poor engagement with child sexual abuse (‘CSA’) victims in the pre-trial and trial stages of the criminal process. Be it stakeholder attitudes and behaviour towards the CSA victims and the accused involved in CSA cases or stakeholders’ procedural practices, more and improved training has been repeatedly emphasised. It is, therefore, pivotal to investigate what kind of special training is imparted to stakeholders under the Protection of Children from Sexual Offences (‘POCSO’) Act, 2012, as well as the challenges and limitations to such training. Also important is to analyse and …

Otulin's Novel Regulatory Mechanisms In Genotoxic And Inflammatory Nf-Kb Signaling, Mingqi Li

Theses and Dissertations (ETD)

Triple negative breast cancer (TNBC) is aggressive but cannot be treated with hormone therapy or molecular therapy due to the lack of a target. Chemotherapy is a systemic treatment that works by attacking rapidly growing cells, which is initially more effective for TNBC patients than those individuals with the hormone receptor-positive breast cancer. However, patients with TNBC tend to develop resistance to chemo drugs, called chemoresistance. After years of effort, the signaling pathways involved in TNBC chemoresistance are gradually revealed, including the nuclear factor-kappa B (NF-kB) pathway. Transcription factor NF-kB is widely involved in cancer development and progression, and its …

Biofeedback Technologies As Extended Cognition: A Philosophical Analysis, Haesoo Park

Student Publications

Every year technologies become more sophisticated and more accessible. Some have become a seamless extension of mind, so much so that they are better understood no longer as tools, but as integral parts of how our mind works. Biofeedback devices are examples of such technologies that are increasingly used in institutional contexts and for personal use. They offer a presumed scientific and objective basis for life decisions and behavioral health interventions, as well as a promise of new forms of self-knowledge. Yet in the very design of biofeedback technologies are cultural and institutional values that are rarely critically appraised. This …

Federal Court Rules That North Carolina Violated The Constitution And Title Vii By Excluding Coverage For Gender Transition From Its Public Employee Health Plan, Arthur S. Leonard

Other Publications

No abstract provided.

Soil Quality Indicators And Vegetation Responses Following Ecological Restoration Thinning Of Ponderosa Pine On Three Soil Parent Material Types Under Grazing And Non-Grazing In Northern Arizona, Christopher Macdonald

Electronic Theses and Dissertations

This research was performed in a northern Arizona ponderosa pine (Pinus ponderosa P. & C., Lawson) forest. The objectives were to a) increase understanding of long-term vegetation responses to ecological restoration treatments on three soils types, with and without grazing, b) evaluate the responses soil physical, chemical, and biological properties to restoration treatments, with and without grazing, c) determine the utility of measured soil quality indicators to informing risks to sustainable soils management in southwestern ponderosa pine forests.

There were no significant differences in soil bulk density by soil type, treatment type, or grazing treatment. No significant differences …

Volume 31, Number 2, Summer 2022, Office Of Communications, Illinois Wesleyan University

Illinois Wesleyan University Magazine, 2018-present

VOLUME 31 | NUMBER 2 | Summer 2022

ON OUR COVER: Dr. Nurman Noor ’08 showcased his culinary skills as an eventual runner-up in The Great Australian Bake Off. Photo courtesy of Foxtel Publicity.

14 Baked with Love Dr. Nurman Noor ’08 may be a general practitioner by trade, but a passion for baking earned him a spot in the TV series The Great Australian Bake Off, where he won scores of fans with his likable personality, raw vulnerability and mouth-watering creations.

18 Breaking Through Angela (Tomazin) Hesemann ’09 found herself laid off at the outset of the COVID-19 pandemic, …

The Impact Of Steam-Flaked Rye Replacing Steam-Flaked Corn On Performance And Carcass Characteristics Of Yearling Steers And The Effect Of Exogenous Megasphaera Elsdenii Administration Techniques On Ruminal Fermentation And Blood Parameters In An Acidosis Challenge Model, Samantha K. Wagner

Department of Animal Science: Dissertations, Theses, and Student Research

A feedlot study was conducted to evaluate the effects of replacing steam-flaked corn (SFC) with steam-flaked rye (SFR) in the diets of yearling steers (Exp. 1). A separate study was conducted to evaluate the effects of three different administration techniques of Megasphaera elsdenii NCIMB 41125 on rumen fermentation and blood parameters in an acidosis challenge model (Exp. 2). In Exp. 1, SFC was replaced with SFR to create four different treatments, each differing in the ratio of SFC:SFR. The four treatments were 0:100, 25:75, 50:50, and 100:0 SFR:SFC (as a percentage of the grain inclusion). Increasing inclusions of SFR resulted …

Research Data Management Practices And Impacts On Long-Term Data Sustainability: An Institutional Exploration, Sarah Elaine Bratt

Dissertations - ALL

With the 'data deluge' leading to an institutionalized research environment for data management, U.S. academic faculty have increasingly faced pressure to deposit research data into open online data repositories, which, in turn, is engendering a new set of practices to adapt formal mandates to local circumstances. When these practices involve reorganizing workflows to align the goals of local and institutional stakeholders, we might call them 'data articulations.' This dissertation uses interviews to establish a grounded understanding of the data articulations behind deposit in 3 studies: (1) a phenomenological study of genomics faculty data management practices; (2) a grounded theory study …

Evaluation Of The Energetic Factors In Crystalline Pharmaceuticals Using Solid-State Density Functional Theory And Low-Frequency Vibrational Spectroscopy, Margaret P. Davis

Dissertations - ALL

Due to the importance of maintaining stable and effective pharmaceutical solid doses, it is critical to study the variety of solid forms that active pharmaceutical ingredients can adopt including polymorphs, hydrates, and cocrystals. In this work, low-frequency vibrational spectroscopies and rigorous quantum mechanical simulations are combined to provide a new technique for characterizing and investigating pharmaceutically relevant polymorphs, hydrates, and cocrystals as well as a series of model cocrystals. Low-frequency spectra in the sub-200 cm-1 range provide not only unique and characteristic spectra for all of the systems explored here but, along with X-ray structural parameters, they offer a way …

Uv- And Visible-Light Photopatterning Of Molecular Gradients Using The Thiol–Yne Click Reaction, Mark Mitmoen, Ofer Kedem

Chemistry Faculty Research and Publications

The rational design of chemical coatings is used to control surface interactions with small molecules, biomolecules, nanoparticles, and liquids as well as optical and other properties. Specifically, micropatterned surface coatings have been used in a wide variety of applications, including biosensing, cell growth assays, multiplexed biomolecule interaction arrays, and responsive surfaces. Here, a maskless photopatterning process is studied, using the photocatalyzed thiol–yne “click” reaction to create both binary and gradient patterns on thiolated surfaces. Nearly defect-free patterns are produced by first coating glass surfaces with mercaptopropylsilatrane, a silanizing agent that forms smoother self-assembled monolayers than the commonly used 3-mercaptopropyltrimethoxysilane. Photopatterning …

Crispr Detection Of Circulating Cell-Free Mycobacterium Tuberculosis Dna In Adults And Children, Including Children With Hiv: A Molecular Diagnostics Study, Zhen Huang, Sylvia M Lacourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa, Lisa M Cranmer, Irene Njuguna, Dalton C Wamalwa, Elizabeth Maleche-Obimbo, Donald G Catanzaro, Christopher J Lyon, Grace John-Stewart, Andrew Dinardo, Anna M Mandalakas, Bo Ning, Tony Y Hu

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.

METHODS: In this molecular diagnostics study we analysed archived serum from two patient populations evaluated for tuberculosis in Eswatini and Kenya to detect Mtb-cfDNA, analysing serum from all individuals who had both sufficient serum volumes and clear diagnostic results. …

Understanding The Priorities And Practices Of Rural Science Teachers: Implications For Designing Professional Learning, Kerri Wingert, Jennifer Jacobs, William Lindsay, Abraham S. Lo, Cari F. Herrmann-Abell, William R. Penuel

The Rural Educator

In order to design professional learning that supports rural science teachers to effectively implement standards-based “five-dimensional” (5D) instructional and assessment practices, a critical first step is to elicit their perspectives, prior experiences, concerns, and interests. Based on survey data from 87 rural science teachers in Colorado, along with focus group sessions with 18 of those teachers, this article investigates teachers’ perspectives on what makes rural science teaching unique, the degree to which they use 5D science instruction, their curricular and assessment resources, and their professional learning experiences and preferences. Overall, rural science teachers in Colorado reported using rich practices for …

The Impact Of Racial Trauma: A Crucial Conversation In Rural Education, Tameka O. Grimes, Shannon K. Roosma

The Rural Educator

Coinciding with the COVID-19 pandemic and the resulting global health crisis, George Floyd's murder was broadcast on social media and popular news (The Marshall Project, 2021). While COVID-19 reports demonstrated the ways Communities of Color and rural communities were disproportionately disadvantaged in the U.S. healthcare system (Artiga et al., 2020; Centers for Disease Control and Prevention, 2021; Dandachi et al., 2021; Fortuna et al., 2020), marches and rallies for Black Lives Matter became emblematic of social discord and civic demand for social justice to upend a racist law enforcement and judicial system (Rickford, 2016). These recent examples of systemic racism …

Sources Of 7-Ketocholesterol, Metabolism And Inactivation Strategies: Food And Biomedical Applications, Imen Ghzaiel, Khouloud Sassi, Amira Zarrouk, Shubhrima Ghosh, Irundika H.K. Dias, Thomas Nury, Mohamed Ksila, Soukaina Essadek, Mounia Tahri Joutey, Fatiha Brahmi, Wafa Mihoubi, Sandrine Rup-Jacques, Mohammad Samadi, Leila Rezig, Smail Meziane, Taoufik Ghrairi, Olfa Masmoudi-Kouki, Sonia Hammami, Boubker Nasser, Mohamed Hammami, Yuqin Wang, William J. Griffiths, Anne Vejux, Gérard Lizard

Research Outputs: 2025-Present

7-Ketocholesterol (or 7-oxocholesterol) is an oxysterol essentially formed by cholesterol autoxidation. It is often found at enhanced levels in the body fluids and/or target tissues of patients with age-related diseases (cardiovascular, neuronal, and ocular diseases) as well as in subjects concerned with civilization diseases (type 2 diabetes, bowel diseases, and metabolic syndrome). The involvement of increased 7-ketocholesterol levels in the pathophysiology of these diseases is widely suspected. Indeed, 7-ketocholesterol at elevated concentrations is a powerful inducer of oxidative stress, inflammation, and cellular degeneration which are common features of all these diseases. It is important to better know the origin of …

Pirtobrutinib Inhibits Wild-Type And Mutant Bruton’S Tyrosine Kinase-Mediated Signaling In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells.

We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide preserves CD23.CAR T cells in vitro effector functions in terms of antigen-specific cytotoxicity, cytokine release and proliferation. Overall, lenalidomide …

Urgent Cytoreduction For Newly Diagnosed Acute Myeloid Leukemia Patients Allows Acquisition Of Pretreatment Genomic Data And Enrollment On Investigational Clinical Trials, Kunhwa Kim, Marina Konopleva, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Guilin Tang, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Caitlin R Rausch, Musa Yilmaz, Koji Sasaki, Nicholas J Short, Nitin Jain, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Newly diagnosed acute myeloid leukemia is often deemed a medical emergency, requiring urgent treatment. This is in contradiction with the need for accurate cytogenetic and molecular data, which is not immediately available, to select optimal therapy. We hypothesized that cytoreduction with hydroxyurea or cytarabine would enable urgent disease control and provide a bridge to clinical trial enrollment. We analyzed three prospective frontline clinical trials that allowed the use of cytoreduction before treatment initiation. Among 274 patients with a median age of 62 (range, 18-89), there was no significant difference in short- and long-term outcome and safety among patients who did …

Stalled Replication Fork Protection Limits Cgas-Sting And P-Body-Dependent Innate Immune Signalling, Ahmed Emam, Xiao Wu, Shengfeng Xu, Longqiang Wang, Shichang Liu, Bin Wang

Faculty, Staff and Student Publications

Protection of stalled replication forks is crucial for cells to respond to replication stress and maintain genome stability. Genome instability and replication stress have been linked to immune activation. Here we show that Abro1 and FANCD2 protect replication forks, which is linked with the restriction of innate immune responses. We reveal that stalled replication fork degradation induced by Abro1 or FANCD2 deficiency leads to accumulation of cytosolic single-stranded DNA and activation of a cGAS-STING-dependent innate immune response that is dependent on DNA2 nuclease. We further show that the increased cytosolic single-stranded DNA contains ribosomal DNA that can bind to cGAS. …

Redirecting Host Preexisting Influenza A Virus Immunity For Cancer Immunotherapy, Bharat K R Chaganty, Songbo Qiu, Yang Lu, Gabriel Lopez-Berestein, Bulent Ozpolat, Zhen Fan

Faculty, Staff and Student Publications

We tested the concept that host preexisting influenza A virus immunity can be redirected to inhibit tumor growth and metastasis through systemic administration of influenza A virus-related peptides to targeted tumors. Mice infected with influenza A virus strain A/Puerto Rico/8/34 (PR8) were used as a model of a host with preexisting viral immunity. The extent to which preexisting influenza A immunity in PR8-immunized mice can be redirected to inhibit tumor growth and metastasis was first examined by ectopic expression of influenza A nucleoprotein (NP) and hemagglutinin (HA) in syngeneic mammary tumor cells via lentiviral transduction. Then, the feasibility of implementing …

Haploidentical Versus Matched Unrelated Versus Matched Sibling Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide, Rohtesh S Mehta, Rima M Saliba, Sassine Ghanem, Amin M Alousi, Gabriela Rondon, Paolo Anderlini, Gheath Al-Atrash, Qaiser Bashir, Chitra M Hosing, Jin S Im, Partow Kebriaei, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Betul Oran, Uday R Popat, Muzaffar H Qazilbash, Jeremy Ramdial, Neeraj Saini, Samer A Srour, Richard E Champlin, Katayoun Rezvani, Elizabeth J Shpall

Faculty, Staff and Student Publications

With the use of post-transplantation cyclophosphamide (PTCy), the outcomes of mismatched related donor hematopoietic cell transplantation (HCT) are now approaching those of matched donor HCT. Here we compared haploidentical donor HCT versus HLA-matched unrelated donor (MUD) HCT and HLA-identical sibling donor (MSD) HCT in a cohort in which all patients received PTCy for graft-versus-host disease (GVHD) prophylaxis. We included 661 patients (275 haploidentical, 246 MUD, and 140 MSD HCT). The most common diagnoses were acute myelogenous leukemia and myelodysplastic syndrome. In multivariate analysis, the haploidentical group was found to have significantly higher nonrelapse mortality (NRM) (hazard ratio [HR], 3.2; 95% …

Frailty Repels The Knife: The Impact Of Frailty Index On Surgical Intervention And Outcomes, Katelyn F Handley, Anil K Sood, Graziela Zibetti Dal Molin, Shannon N Westin, Larissa A Meyer, Bryan Fellman, Pamela T Soliman, Robert L Coleman, Nicole D Fleming

Faculty, Staff and Student Publications

Objective: To assess the impact of frailty in patients with ovarian cancer on surgical procedures and outcomes.

Methods: A retrospective review of patients with stage II-IV ovarian cancer from April 2013 to September 2017 was performed. Patients were triaged by laparoscopy to determine primary resectability. The adjusted modified frailty index score (amFI) was calculated and amFI ≥2 classified as high frailty. Clinical outcomes, progression free survival (PFS) and overall survival (OS) were estimated.

Results: 592 patients met inclusion criteria; amFI of 0, 1 and ≥ 2 was noted in 57%, 29%, and 14%, respectively. Patients with high frailty were less …

Hap40 Is A Conserved Central Regulator Of Huntingtin And A Potential Modulator Of Huntington’S Disease Pathogenesis, Shiyu Xu, Gang Li, Xin Ye, Dongsheng Chen, Zhihua Chen, Zhen Xu, Moretti Daniele, Sara Tambone, Alessandra Ceccacci, Licia Tomei, Lili Ye, Yue Yu, Amanda Solbach, Stephen M Farmer, Erin Furr Stimming, George Mcallister, Deanna M Marchionini, Sheng Zhang

Faculty, Staff and Student Publications

Perturbation of huntingtin (HTT)'s physiological function is one postulated pathogenic factor in Huntington's disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT's conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, …

Prospecting Cellular Gold Nanoparticle Biomineralization As A Viable Alternative To Prefabricated Gold Nanoparticles, Aaron S Schwartz-Duval, Konstantin V Sokolov

Faculty, Staff and Student Publications

Gold nanoparticles (GNPs) have shown considerable potential in a vast number of biomedical applications. However, currently there are no clinically approved injectable GNP formulations. Conversely, gold salts have been used in the clinic for nearly a century. Further, there is evidence of GNP formation in patients treated with gold salts (i.e., chrysiasis). Recent reports evaluating this phenomenon in human cells and in murine models indicate that the use of gold ions for in situ formation of theranostic GNPs could greatly improve the delivery within dense biological tissues, increase efficiency of intracellular gold uptake, and specificity of GNP formation within cancer …

Functional Genomic Analysis Of Epithelioid Sarcoma Reveals Distinct Proximal And Distal Subtype Biology, Samuel V Rasmussen, Jia Xiang Jin, Lissett R Bickford, Andrew D Woods, Felix Sahm, Kenneth A Crawford, Kiyo Nagamori, Hiroaki Goto, Keila E Torres, Angelo Sidoni, Erin R Rudzinski, Khin Thway, Robin L Jones, Alessio Ciulli, Hollis Wright, Melvin Lathara, Ganapati Srinivasa, Kavya Kannan, Paul H Huang, Thomas G P Grünewald, Noah E Berlow, Charles Keller

Faculty, Staff and Student Publications

Background: Metastatic epithelioid sarcoma (EPS) remains a largely unmet clinical need in children, adolescents and young adults despite the advent of EZH2 inhibitor tazemetostat.

Methods: In order to realise consistently effective drug therapies, a functional genomics approach was used to identify key signalling pathway vulnerabilities in a spectrum of EPS patient samples. EPS biopsies/surgical resections and cell lines were studied by next-generation DNA exome and RNA deep sequencing, then EPS cell cultures were tested against a panel of chemical probes to discover signalling pathway targets with the most significant contributions to EPS tumour cell maintenance.

Results: Other biologically inspired functional …

Leveraging Single-Cell Sequencing To Unravel Intratumour Heterogeneity And Tumour Evolution In Human Cancers, Amy L Bowes, Maxime Tarabichi, Nischalan Pillay, Peter Van Loo

Faculty, Staff and Student Publications

Intratumour heterogeneity (ITH) and tumour evolution are well-documented phenomena in human cancers. While the advent of next-generation sequencing technologies has facilitated the large-scale capture of genomic data, the field of single-cell genomics is nascent but rapidly advancing and generating many new insights into the complex molecular mechanisms of tumour biology. In this review, we provide an overview of current single-cell DNA sequencing technologies, exploring how recent methodological advancements have enumerated new insights into ITH and tumour evolution. Areas highlighted include the potential power of single-cell genome sequencing studies to explore evolutionary dynamics contributing to tumourigenesis through to progression, metastasis, and …