Genetic Phenomena Commons^™

Novel Biomarker Discovery In Multiple Sclerosis, Manisha Gangasani

Honors Theses

Multiple Sclerosis (MS) is a chronic neuroinflammatory disorder affecting the brain, spinal cord, and optic nerve. Patients experience cognitive, motor, autonomic, and emotional symptoms that often overlap with other neurological conditions, making early diagnosis challenging. Current diagnostic criteria require evidence of lesions with dissemination in time and space. Racial disparities in MS outcomes are well documented, with Black individuals often exhibiting greater disease severity, higher relapse rates, and increased disability compared to White individuals. These differences likely reflect a combination of genetic, biological, environmental, and healthcare access factors, underscoring the need to improve early diagnosis and reduce inequities in care. …

Epigenetic Activation Of Ebv Bglf4 Determines Antiviral-Based Regimen Response In Ebv+Cns Lymphoproliferative Disease, Christoph Weigel, Haley Klimaszewski, Fode Tounkara, Selamawit Addissie, Sarah Schlotter, Betsy Pray, James Dugan, Bradley Haverkos, Lynda Villagomez, Mark Lustberg, Pierluigi Porcu, Timothy Voorhees, Richard Ambinder, Shannon Kenney, Joyce Fingeroth, Henri-Jacques Delecluse, Michael Caligiuri, Lapo Alinari, Ginny Bumgardner, Christopher Oakes, Robert Baiocchi

Kimmel Cancer Center Faculty Papers

Epstein-Barr virus (EBV)–associated primary central nervous system lymphoproliferative diseases (EBV+PCNSL) are aggressive conditions with poor prognoses. We previously reported durable responses in patients with PCNSL who were treated with the antivirals ganciclovir and azidothymidine, plus rituximab and dexamethasone (GARD). Responses were associated with the detection of the lytic viral protein kinases, BGLF4 and BXLF1. These antiviral activating kinases are associated with lytic EBV, however, the mechanism for expression in latently infected EBV+CNSL is unknown. Expanding on previous work, we provide long-term clinical outcome data (N = 24) and show that RNA expression analysis in CNSL tissue biopsies (n = 12) …

Immune-Mediated Necrotizing Myopathy In Association With Statin Exposure, Charlie E. Babcock, Phebie Rossi, Jennifer Hasvold

Aesculapius Journal (Health Sciences & Medicine)

Statins are first-line therapy for hyperlipidemia and are widely prescribed in primary care. Although generally safe, they carry rare but serious risks that must be considered on an individual basis. One such complication is immune-mediated necrotizing myopathy (IMNM), an autoimmune condition characterized by persistent muscle weakness and elevated creatine kinase (CK) despite discontinuation of the statin. We describe an 87-year-old man with a history of atorvastatin intolerance who was reinitiated on the medication five years later. Shortly thereafter, he developed progressive weakness, recurrent hospitalizations, and ultimately was diagnosed with IMNM confirmed by biopsy and HMG-CoA reductase antibodies. Despite treatment with …

Sexually Dimorphic Effects Of Gpnmb Modulation On Vertebral Bone Mass Regulation And Intravertebral Disc Health, Hakem Altawil, Fayez Safadi

Williams Honors College, Honors Research Projects

Osteoporosis and vertebral degeneration are major contributors to musculoskeletal morbidity, yet the molecular mechanisms regulating vertebral bone and intervertebral disc (IVD) homeostasis remain incompletely understood. GPNMB (osteoactivin) has been identified as a regulator of bone remodeling, though its role in spine health is unclear. This study evaluated the effects of GPNMB deficiency on lumbar vertebral bone microarchitecture and IVD integrity in a sex-dependent context.

Six-month-old male and female wild-type (WT) and GPNMB knockout (KO) mice were analyzed using micro–computed tomography (µCT) of lumbar vertebrae (L4–L6) and histological assessment of the L5–L6 IVD. KO males exhibited increased bone volume fraction, bone …

The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …

Long Covid Incidence Across Sars-Cov-2 Lineages And Identification Of Conserved Spike Targets For Multivalent Vaccines, Grace J. Kim, Md Ashad Alam, Judy S. Crabtree, Rebecca Rose, Susanna L. Lamers, San Chu, Ronald Horswell, Daniel Fort, Lucio Miele

School of Graduate Studies Faculty Publications

Background: Long COVID remains poorly characterized at the genomic level. The primary aim of this study was to examine the relationship between viral sequences and the incidence of Long COVID at a tertiary care center in Louisiana between April 2020 and December 2022. A secondary aim was analysis of the Spike protein to identify conserved regions for multivalent vaccine targets. Method: To estimate Long COVID incidence across variants, we linked 4,789 SARS-CoV-2 sequences to 3,090 de-identified patient electronic health record information. The base population was defined as any patient with an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) …

Radiogenomic Profiling Of Prostate Tumors Prior To External Beam Radiotherapy Converges On A Transcriptomic Signature Of Tgf-Β Activity Driving Tumor Recurrence, Anson T. Ku, Uma Shankavaram, Shana Y. Trostel, Hong Zhang, Sumeyra Kartal, Houssein A. Sater, Stephanie A. Harmon, Nicole V. Carrabba, Yang Liu, Hyunnam Ryu, James A. Proudfoot, Boon Hao Hong, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke, Mack Roach, Howard M. Sandler, Stephanie L. Pugh, Kenneth L. Zeitzer, Lucas C. Mendez, Nirav S. Kapadia, William A. Hall, Anand B. Desai, Radka S. Stoyanova, Alan Pollack, Elai Davicioni, Melvin L. K. Chua, Baris Turkbey, Adam G. Sowalsky, Deborah E. Citrin

Einstein Health Papers

PURPOSE: Clinical risk grouping based on PSA, tumor grade, and disease extent guides treatment intensity for localized prostate cancer. However, many patients with intermediate- or high-risk disease treated with external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) still develop biochemical recurrence (BCR). Early identification of patients at high risk for BCR could enable personalized treatment strategies.

EXPERIMENTAL DESIGN: We prospectively enrolled 29 patients with intermediate- or high-risk prostate cancer undergoing EBRT and ADT. Pretreatment biopsies (n = 60) underwent whole-transcriptome microarray and whole-exome sequencing. Patients received multiparametric MRI at baseline and 6 months after treatment, with a median follow-up …

Genomic Ascertainment Of Chek2 -Related Cancer Predisposition, Sunyoung Kim, Jung Kim, Mark Ramos, Jeremy Haley, Diane Smelser, H. Shanker Rao, Uyenlinh L. Mirshahi, Katherine L. Nathanson, Barry I. Graubard, Hormuzd A. Katki, David Carey, Douglas R. Stewart

School of Graduate Studies Faculty Publications

Importance: There is clear evidence that deleterious germline variants in CHEK2 increase risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers. Objective: To quantify the prevalence of as well as cancer risk and survival associated with CHEK2 germline pathogenic and likely pathogenic variants using genomic ascertainment. Design, Setting, and Participants: This case-control study used 2 electronic health record-linked and exome-sequenced biobanks: UK Biobank (n = 469765) and Geisinger MyCode (adults only; n = 167050). Variants were classified according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Cases …

Identification Of Predictive Pretreatment Biomarkers For Neoadjuvant Chemotherapy Response In Latino Invasive Breast Cancer Patients, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos A. Orozco, Sandra Diaz-Casas, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba L. Combita

School of Medicine Faculty Publications

Background: Breast cancer (BC) exhibits significant heterogeneity in incidence and mortality worldwide. Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced BC; however, its efficacy varies by subtype. This study examined the gene expression profiles associated with NAC response in Colombian women with invasive BC. Methods: RNA sequencing of pre-treatment tissues from 58 patients (29 responders and 29 non-responders) identified differentially expressed genes (DEGs) for each molecular subtype, and prognostic performance was evaluated using risk scores. Results: Functional enrichment analysis highlighted the immune system pathways in non-responders. Changes in cytokine target activity and immune cell populations were analyzed to …

Liver-Directed Base Editing Of Abcc6 Prevents Ectopic Calcification In A Variant-Humanized Mouse Model Of Pseudoxanthoma Elasticum, Lauren C. Testa, Dora Obiri-Yeboah, Hooda Said, Ping Qu, Michael A. Levine, Mohamad-Gabriel Alameh, Kiran Musunuru, Qiaoli Li, Xiao Wang

Department of Biochemistry and Molecular Biology Faculty Papers

Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disorder characterized by ectopic calcification of elastic fibers throughout the skin, retina, and arteries. It is caused by pathogenic variants in ABCC6 , which encodes a transmembrane transporter that primarily localizes to hepatocytes. Loss of ABCC6 function in hepatocytes leads to systemic deficiency of inorganic pyrophosphate (PPi), a potent inhibitor of calcification; such depletion of PPi from the circulation is responsible for multisystemic ectopic calcification seen in PXE. Therefore, liver-targeted variant correction by genome editing and subsequent restoration of systemic PPi may offer a one-and-done therapeutic approach for PXE. The ABCC6 …

Immunogenomic Diversity Of Triple-Negative Breast Cancers In Obese And Non-Obese Black And White Women, Fokhrul Hossain, Denise Danos, Jovanny Zabaleta, Xiao-Cheng Wu, Luis Del Valle, Chindo Hicks, Jiande Wu, Jerneja Tomsic, Susan Neuhausen, Yuan Chun Ding, Kavitha Mukund, Zahra Mesrizadeh, Shankar Subramaniam, Augusto Ochoa, Victoria Seewaldt, Lucio Miele

School of Medicine Faculty Publications

Racial disparities in incidence and outcomes of triple-negative breast cancer (TNBC) have been attributed to ancestry, socioeconomic factors and/or obesity. We studied 253 TNBCs from 128 Black and 125 White women. Arms were balanced for age, AJCC stage, histological grade and molecular subtypes, and differed significantly in BMI distribution, obesity, and Area Deprivation Index. We examined survival rates, whole-transcriptome RNASeq and genetic ancestry. In our sample, Black race or obesity were not intrinsically predictive of poor outcomes. TNBC molecular portraits varied with stage and biological aggressiveness, irrespective of race. We identified a novel group of TNBCs with a distinctive luminal-like …

Her3 Promotes Triple-Negative Breast Cancer Progression By Upregulating Phf8 Via Mir-34b-5p-Dependent Mechanism, Hui Lyu, Cong Cong Tan, Yakun Wu, Margaret E. Larsen, Qingzhao Yu, Guobin Kang, Charles Wood, Shou Ching Tang, Bolin Liu

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with limited targeted treatment options and poor clinical outcomes. HER3 has recently emerged as a promising therapeutic target, with HER3-directed antibody–drug conjugates advancing to Phase III clinical trials for non-small cell lung cancer. However, the downstream molecular mechanisms by which HER3 promotes TNBC progression remain poorly defined. In this study, we uncovered a previously unrecognized HER3/miR-34b-5p/PHF8 signaling axis that drives TNBC cell proliferation and tumor growth. Mechanistically, HER3 activation suppresses the tumor-suppressive microRNA miR-34b-5p, resulting in the upregulation of the histone demethylase PHF8 (KDM7B), which in …

Human Kallikrein 2: A Novel Lineage-Specific Surface Target In Prostate Cancer, Fei Shen, Ryan Smith, Theresa Mcdevitt, Krista Menard, Shaozhou Tian, Gerald Chu, Ruchi Chaudhary, Jennifer Mccann, Halley Oyer, Sherry C. Wang, Steven Max, Peter Francis, William K. Kelly, Charles G. Drake

Kimmel Cancer Center Faculty Papers

PURPOSE: Targeted therapies for metastatic prostate cancer are limited, highlighting the need for novel drug targets and mechanisms of action (MoA). Human kallikrein 2 (KLK2) is a prostate-specific antigen expressed across the prostate cancer disease continuum. However, it was not recognized as a therapeutic target for prostate cancer in the past due to limited evidence of its cell surface expression. In this study, we systematically characterized KLK2 expression in prostate cancer, confirmed its cell surface expression, and demonstrated the preclinical efficacy of three KLK2-targeting therapeutics with distinct MoA.

EXPERIMENTAL DESIGN: The KLK2 expression profile in different stages of prostate cancer …

Genomic Profiling Of Intraocular Leiomyomas Reveals Recurrent Copy Number Alterations, Vivian Tang, Yubai Chou, Cuyan Demirkesen, Michele M. Bloomer, Joseph B. Crawford, Ahmet M. Sarici, Carol L. Shields, Ralph C. Eagle Jr., Codrin E. Iacob, Walter P. Devine, Tatyana Milman, Melike Pekmezci

Wills Eye Hospital Papers

PURPOSE: Leiomyomas are benign smooth muscle tumors that commonly present in the uterus, soft tissue, skin, and gastrointestinal tract but in rare cases can also arise within the eye. Notably, intraocular leiomyomas often show slightly different histopathologic and immunohistochemical features, referred to as mesectodermal morphology, given their presumed neural crest origin. Genetic and cytogenetic alterations of intraocular leiomyomas, as well as their association with various clinical and histopathologic features, have not been previously studied.

METHODS: We identified eight patients diagnosed with intraocular leiomyoma and performed targeted next-generation sequencing, whole transcriptome RNA sequencing, and chromosomal copy number analysis on those with …

Runx2 Cooperates With Srebp1 To Rewire Cancer Metabolism And Promote Aggressiveness, Emanuele Vitale, Mila Gugnoni, Veronica Manicardi, Silvia Muccioli, Federica Torricelli, Benedetta Donati, Simonetta Piana, Gloria Manzotti, Elisa Salviato, Francesca Reggiani, Cristian Ascione, Rebecca Vezzani, Moira Ragazzi, Mattia Forcato, Oriana Romano, Silvio Bicciato, Aaron Goldman, Marco Tigano, Alessia Ciarrocchi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Embryonic Transcription Factors (TFs) are often reactivated in cancer, driving developmental gene programs that support phenotypic plasticity. Metabolic adaptation fuels this plasticity by supplying energy and molecular building blocks for growth. RUNX2, the master regulator of bone morphogenesis, is ectopically expressed in epithelial cancer, promoting metastasis through trans-differentiation processes like Epithelial-to-Mesenchymal Transition (EMT) and osteomimicry. By combining omics data with functional validation, we demonstrated that RUNX2 drives cancer cell metabolic rewiring by repressing mitochondrial respiration while promoting anabolic processes. We showed that RUNX2 upregulates key genes of lipid biosynthesis by regulating and cooperating with SREBP1. In vivo expression analysis in …

Overview Of Exosomal Non-Coding Rnas In Cardiovascular Disease Using High Throughput Sequencing, Mortaza Eivazi, Leila Abkhooie, Kamran Hosseini, Parnia Mobasheran, Tahereh Ebrahimi, Vahideh Tarhriz, Eric Lazartigues

School of Graduate Studies Faculty Publications

Non-coding RNAs including miRNAs, long-ncRNAs, and circular RNAs play crucial roles in cell-to-cell communication and epigenetic regulation. They control gene expression at multiple levels, including transcriptional, post-transcriptional, and translational, thereby influencing associated signaling pathways. Encapsulated within exosomes, micro-vesicles, and apoptotic bodies, ncRNAs can be transported between cells while being protected from harsh environmental conditions. Studies have shown various expression patterns across different cell types and in various physiological and pathological states. However, the precise correlations and extent of their contribution to diseases are still under investigation. Recent studies have reported the involvement of extracellular vesicle-associated ncRNAs in the pathogenesis of …

Setdb1 Is Critically Required For Uveal Melanoma Growth And Represents A Promising Therapeutic Target, Imène Krossa, Céline Pisibon, Yann Cheli, Karine Bille, Mélanie Dalmasso, Sabah Hamadat, Chrystel Husser, Marie Irondelle, Julien Cherfils-Vicini, Frédéric Soysouvanh, Sacha Nahon-Esteve, Arnaud Martel, Sandra Lassalle, Jean-Pierre Caujolle, Célia Maschi, Stéphanie Baillif, Dan Hasson, Saul Carcamo, Andrerw E. Aplin, Irwin Davidson, Emily Bernstein, Valeria Naim, Robert Ballotti, Corine Bertolotto, Thomas Strub

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, we conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin regulators. We revealed that the lysine methyltransferase, SETDB1, plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 deficiency induces a DNA damage response, senescence-like state and growth arrest. Knockdown of SETDB1 is associated with a decreased expression of genes related to replication and cell cycle. Moreover, deficiency in CDC6, an essential regulator of DNA replication, phenocopies SETDB1 inhibition. Using a pre-clinical model, we further demonstrated that anti-SETDB1 therapy impairs …

Fine Mapping Regulatory Variants By Characterizing Native Cpg Methylation With Nanopore Long-Read Sequencing, Yijun Tian, Shannon K. Mcdonnell, Lang Wu, Nicholas B. Larson, Liang Wang

School of Medicine Faculty Publications

5-Methylcytosine (5mC) is the most common DNA modification in the human genome. Bisulfite conversion combined with short-read sequencing captures this modification at single-nucleotide resolution but introduces PCR duplication bias and limits co-methylation analysis between distant cytosines. To resolve these limitations, we used nanopore long-read sequencing to profile human methylation and performed long-range co-methylation analysis with native DNA modification information. We analyzed the nanopore demo data in the adaptive sampling sequencing targeting the CpG islands and applied the linkage disequilibrium (LD) R to identified methylation haplotype blocks (MHBs). We found that the cancer genome exhibited significantly smaller MHBs, higher CpG density, …

Molecular Determinants Of Neoadjuvant Chemotherapy Resistance In Breast Cancer: An Analysis Of Gene Expression And Tumor Microenvironment, Hedda Michelle Guevara-Nieto, Carlos A. Orozco-Castaño, Rafael Parra-Medina, Jenny Nathaly Poveda-Garavito, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba Lucia Combita

School of Graduate Studies Faculty Publications

Neoadjuvant chemotherapy (NAC) is a critical component of breast cancer treatment, but the molecular mechanisms underlying resistance remain poorly understood. This study aimed to identify transcriptomic changes associated with NAC resistance across four breast cancer subtypes: Luminal A, Luminal B/HER2-positive, Luminal B/HER2-negative, and Triple-Negative Breast Cancer (TNBC). RNA-seq analysis was performed on paired pre- and post-NAC breast cancer samples from 32 nonresponders. Differentially expressed genes (DEGs) were identified, and functional enrichment analyses were conducted. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Tumor microenvironment (TME) infiltration was estimated using deconvolution algorithms. The results revealed distinct gene expression profiles …

A Social Media Campaign And Web-Based Survey About Prostate Cancer Genetics: Mixed Methods Study, Amy Leader, Stacy Loeb, Preethi Selvan, Ashley Hunter, Rebecca Hartman, Scott Keith, Veda Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline genetic variants are important for prostate cancer (PCa) management and hereditary cancer risk assessment, but testing is underused. Furthermore, patients are often unaware of the genetic connections to PCa. Social media is increasingly serving as a source of awareness for health information and a method to gather data from a large population.

OBJECTIVE: There were three objectives: to (1) create and test social media messages related to PCa genetics and genetic testing, (2) determine which social media message was most engaging, and (3) assess knowledge of and attitudes toward PCa genetic testing through an online survey using the …

Organism-Specific Sequence Motifs Link Ribosomal Rnas To Brain Disorders, Isidore Rigoutsos, Stepan Nersisyan, Eric Londin, Iliza Nazeraj, Bonnie Dong, Anastasios Vourekas, Phillipe Loher

Computational Medicine Center Faculty Papers

We report that in humans, mice, fruit flies, and worms, the ribosomal RNAs and the transcribed spacers of 45S are densely packed with organism-specific sequence motifs that are primarily shared with nervous system genes. The human ribosomal RNAs and 45S spacers contain 1,723 such motifs. Specific combinations of these motifs are predominantly found in 3,430 human nervous system genes, of which 1,046 are genes associated with brain disorders, including autism spectrum disorder and schizophrenia. The sequences of the 1,723 motifs and their locations in the introns and exons of nervous system genes are unique to primates. Experimental evidence indicates that …

Neuronal Activity-Dependent Gene Dysregulation In C9orf72 I3neuronal Models Of Als/Ftd Pathogenesis, Layla T. Ghaffari, Emily A. Welebob, Sarah E. Bond Newton, Ashley V. Boehringer, Kelly L. Cyliax, Piera Pasinelli, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9ORF72 (C9) gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE-induced pluripotent stem cell-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization or a blockade of K⁺ channels, followed by RNA sequencing, induces …

Corticobasal Syndrome With Mixed Pathology In The Absence Of Grn Mutation: A Clinico-Pathological Case Of Ftld-Tdp With Coexisting Alzheimer’S And Lewy Body Pathology, Hugo Zamarron, David Irwin, Jeffery Phillips, Edward Lee, Matthew Tisdall, Corey Mcmillan

Research Colloquium

Background: Corticobasal syndrome (CBS) is a neurodegenerative disorder characterized by often asymmetric fronto-pariteal and extra-pyramidal features that is traditionally associated with tauopathy, but pathological findings are heterogenous, including other forms of frontotemporal lobar degeneration (FTLD) and mixed pathologies of aging. We present clinical, radiographic, and histopathologic features of asymmetry in a unique patient with CBS and underlying FTLD with TDP-43 pathology (FTLD-TDP), co-occurring with other age-related pathologies.

Case Presentation: A 76-year-old man presented with progressive cognitive and motor dysfunction including asymmetric parkinsonism, left-sided dystonia and rigidity, apraxia, visuospatial impairment, and a subtle social disorder including apathy and social withdrawal. The …

Integrated Mirna-Mrna Analyses Of Triple-Negative Breast Cancer In Black And White Patients With Or Without Obesity, Fokhrul Hossain, Martha I. Gonzalez-Ramirez, Jone Garai, Diana Polania-Villanueva, Li Li, Farzeen Nafees, Md Manirujjaman, Bolin Liu, Samarpan Majumder, Xiao Cheng Wu, Chindo Hicks, Luis Del Valle, Denise Danos, Augusto Ochoa, Lucio Miele, Jovanny Zabaleta

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer. miRNAs play an essential role in TNBC pathogenesis and prognosis. Obesity is linked with an increased risk for several cancers, including breast cancer. Obesity is also related to the dysregulation of miRNA expression in adipose tissues. However, there is limited knowledge about race- and obesity-specific differential miRNA expression in TNBC. We performed miRNA sequencing of 48 samples (24 tumor and 24 adjacent non-tumor tissues) and RNA sequencing of 24 tumors samples from Black (AA) and White (EA) TNBC patients with or without obesity. We identified 55 miRNAs exclusively …

Bard1: A Friend Or Foe In Pancreatic Ductal Adenocarcinoma?, Lily Zekavat, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid malignancy with poor overall prognosis and limited response to standard treatments. Growing interest in the modulation of DNA repair mechanisms, including the homologous recombination (HR) repair pathway, has opened new avenues for therapeutic development. BARD1 (BRCA1-Associated RING Domain 1) plays a complex role in tumor biology, functioning either as a tumor suppressor or as an oncogenic driver, depending on isoform expression, cellular context, and regulatory environment. In this review, we examine the dual roles of BARD1, focusing on its regulation and paradoxical activities in PDAC. We summarize evidence that BARD1 and BARD1 …

The Brescia International Multidisciplinary Consensus Guidelines On The Optimal Pathology Assessment And Multidisciplinary Pathways Of Non-Pancreatic Neoplasms In And Around The Ampulla Of Vater (Peripan), Mohammad Abu Hilal, Bas A Uijterwijk, Daniël H L Lemmers, Boris V Janssen, Marc G Besselink, Denise Bianchi, Arantza Fariña, Noriyoshi Fukushima, Anthony J Gill, Seung-Mo Hong, Alyssa Krasinskas, Claudio Luchini, Laura Melocchi, Giulio Rossi, Aldo Scarpa, Olca Basturk, Deyali Chatterjee, Angela Chou, Irene Esposito, Roger Feakins, Bas Groot Koerkamp, Ralph H Hruban, Stefano La Rosa, Chanjuan Shi, Aatur Singhi, Joanne Verheij, Huamin Wang, Sergio Alfieri, Fabio Ausania, Adnan Alseidi, Marco J Bruno, Ugo Boggi, Claudio Bnà, Christos Dervenis, Massimo Falconi, Michele Ghidini, Jakob W Kist, Giovanni Marchegiani, Michele Milella, Roberto Salvia, Ajith Siriwardena, Hanneke Wilmink, Alberto Zaniboni, Shaimaa Al-Janabi, Maia Blomhoff Holm, Eva Roos, Naoki Sano, In Hye Song, Zeynep Tarcan, Gianpaolo Balzano, Isabella Frigerio, Alfredo Guglielmi, Giuseppe Malleo, Horacio Asbun, Volkan Adsay, Caroline Verbeke

Faculty, Staff and Student Publications

IMPORTANCE: The lack of multidisciplinary workflow guidelines and clear definitions and classifications for neoplasms in and around the ampulla of Vater results in inconsistencies affecting patient care and research.

OBJECTIVE: The PERIPAN international multidisciplinary consensus group aimed to standardize the multidisciplinary diagnostic workflow and achieve consensus on definitions and classifications in order to ensure proper classification and optimal diagnostic assessment and consequently to improve patient care and future research.

DESIGN: An international team of 43 experts (pathologists, surgeons, radiologists, gastroenterologists, oncologists) from 12 countries identified knowledge gaps, reviewed 37061 articles, and proposed recommendations using the Scottish Intercollegiate Guidelines Network methodology …

Risk Of Second Primary Lung Cancer Among Cancer Survivors Stratified By The Site Of First Primary Cancer And The Lung Cancer Screening Eligibility Status, Sara Nofal, Edwin J Ostrin, Jianjun Zhang, Jia Wu, Paul Scheet, Mara B Antonoff, John V Heymach, Iakovos Toumazis

Faculty, Staff and Student Publications

Personal history of cancer is an independent risk factor for developing lung cancer. However, it is not considered in the current US lung cancer screening (LCS) guidelines. In this study, we assessed the risk of developing lung cancer among cancer survivors across 24 different sites of first primary cancer stratified by their LCS eligibility status. Using data from the Patient History Database at the University of Texas MD Anderson Cancer Center, we calculated and compared the cumulative incidence of second primary lung cancer, the overall and the LCS eligibility status-specific, stratified by the site of first primary cancer among cancer …

Whole-Genome Sequence-Based Association Analysis Of African American Individuals With Bipolar Disorder And Schizophrenia, Runjia Li, Sarah A Gagliano Taliun, Kevin Liao, Matthew Flickinger, Janet L Sobell, Giulio Genovese, Adam E Locke, Rebeca Rothwell Chiu, Jonathon Lefaive, Jiongming Wang, Taylor Martins, Sinéad Chapman, Anna Neumann, Robert E Handsaker, Donna K Arnett, Kathleen C Barnes, Eric Boerwinkle, David Braff, Brian E Cade, Myriam Fornage, Richard A Gibbs, Karin F Hoth, Lifang Hou, Charles Kooperberg, Ruth J F Loos, Ginger A Metcalf, Courtney G Montgomery, Alanna C Morrison, Zhaohui S Qin, Susan Redline, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Karine A Viaud-Martinez, Tim B Bigdeli, Stacey Gabriel, Sebastian Zollner, Albert V Smith, Goncalo Abecasis, Steve A Mccarroll, Michele T Pato, Carlos N Pato, Michael Boehnke, James Knowles, Hyun Min Kang, Roel A Ophoff, Jason Ernst, Laura J Scott

Faculty, Staff and Student Publications

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole-genome sequencing (∼27X) of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of …

The Immunophenotypic And Genetic Characterization Of Pediatric T -L Ymphoblastic Leukemia With A Mature Immunophenotype, Mahsa Khanlari, Wei Wang, Parastou Tizro, Mohammad K Eldomery

Faculty, Staff and Student Publications

Not available.

Human Interpretable Grammar Encodes Multicellular Systems Biology Models To Democratize Virtual Cell Laboratories, Jeanette A I Johnson, Daniel R Bergman, Heber L Rocha, David L Zhou, Eric Cramer, Ian C Mclean, Yoseph W Dance, Max Booth, Zachary Nicholas, Tamara Lopez-Vidal, Atul Deshpande, Randy Heiland, Elmar Bucher, Fatemeh Shojaeian, Matthew Dunworth, André Forjaz, Michael Getz, Inês Godet, Furkan Kurtoglu, Melissa Lyman, John Metzcar, Jacob T Mitchell, Andrew Raddatz, Jacobo Solorzano, Aneequa Sundus, Yafei Wang, David G Denardo, Andrew J Ewald, Daniele M Gilkes, Luciane T Kagohara, Ashley L Kiemen, Elizabeth D Thompson, Denis Wirtz, Laura D Wood, Pei-Hsun Wu, Neeha Zaidi, Lei Zheng, Jacquelyn W Zimmerman, Jude M Phillip, Elizabeth M Jaffee, Joe W Gray, Lisa M Coussens, Young Hwan Chang, Laura M Heiser, Genevieve L Stein-O'Brien, Elana J Fertig, Paul Macklin

Faculty, Staff and Student Publications

Cells interact as dynamically evolving ecosystems. While recent single-cell and spatial multi-omics technologies quantify individual cell characteristics, predicting their evolution requires mathematical modeling. We propose a conceptual framework-a cell behavior hypothesis grammar-that uses natural language statements (cell rules) to create mathematical models. This enables systematic integration of biological knowledge and multi-omics data to generate in silico models, enabling virtual "thought experiments" that test and expand our understanding of multicellular systems and generate new testable hypotheses. This paper motivates and describes the grammar, offers a reference implementation, and demonstrates its use in developing both de novo mechanistic models and those informed …