Medical Pathology Commons^™

Assessing Hpv And Hpv Vaccine Awareness And Perception Amongst Undergraduate Students, Maura Hawkins

Honors Theses

Human Papillomavirus (HPV) is one of the most common sexually transmitted infections in the United States. Vaccination rates remain low among college-aged students despite an effective vaccine being available. This study investigates HPV and HPV vaccination-related knowledge, beliefs, and perceptions among undergraduate students to inform targeted intervention strategies. Participants included undergraduate students (n = 19) who attended one of three focus groups conducted in April 2025 at the University of South Alabama. Structured interview guides explored HPV knowledge, perceived risk and severity, attitudes towards vaccination, autonomy in health decision-making, trust in health information sources, and preferred educational strategies. Discussions were …

Impact Of Senescence On Breast Cancer Outcomes, Gracie Sous

Honors Undergraduate Theses

Cellular senescence is a biological process in which damaged cells exit the cell cycle while remaining metabolically active and accumulating within tissues. Senescence plays a complex role in breast cancer progression, largely through the secretion of senescence-associated secretory phenotype (SASP) factors. These factors include a broad range of inflammatory cytokines, chemokines, and signaling molecules that can influence the tumor microenvironment.

Studies suggest that senescence may significantly promote cancer metastasis. Therefore, this study aims to investigate the genes involved in cancer progression and to improve understanding of how SASP is regulated, which is critical for improving breast cancer outcomes. The central …

Human Endogenous Retroviruses (Hervs) Associated With Glioblastoma Risk And Prognosis, Harun Mazumder, Hui Yi Lin, Melody Baddoo, Wojciech Gałan, Diana Polania-Villanueva, Chindo Hicks, David Otohinoyi, Francesca Peruzzi, Zbigniew Madeja, Victoria P. Belancio, Erik K. Flemington, Krzysztof Reiss, Monika Rak

School of Medicine Faculty Publications

Emerging evidence suggests expression from human endogenous retrovirus (HERV) loci likely contributes to, or is a biomarker of, glioblastoma multiforme (GBM) disease progression. However, the relationship between HERV expression and GBM malignant phenotype is unclear. Applying several in silico analyses based on data from The Cancer Genome Atlas (TCGA), we derived a locus-specific HERV transcriptome for glioma that revealed 211 HERVs significantly dysregulated in the comparisons of GBM vs. normal brain (NB), GBM vs. low-grade glioma (LGG), and LGG vs. NB. Our analysis supported development of a unique HERV scoring algorithm that segregated GBM, LGG, and NB. Interestingly, lower HERV …

Pembrolizumab-Associated Acute Esophageal Necrosis: A Case Report And Literature Review, Mark Tawfik, Elie Bou Sanayeh, Stephanie Chain, Ahmed Elfiky, Stephen Mulrooney

HCA Healthcare Journal of Medicine

Background

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. They pose challenges, particularly in the form of immune-related adverse events (irAEs). Although cases of gastrointestinal irAEs have been well-documented, acute esophageal necrosis (AEN) characterized by a circumferential blackening and fragility of the esophagus, weeks after immunotherapy discontinuation, has not been reported.

Case Presentation

A 75-year-old diabetic male who was recently diagnosed with high-grade papillary urothelial cancer with liver and retroperitoneal metastases and had undergone radical cystectomy with ileal conduit urinary diversion, presented to the hospital for sepsis secondary to a urinary tract infection. While in the hospital, he experienced hematemesis, …

Long-Term Neurocognitive And Behavioral Outcomes In Survivors Of Pediatric Brain Tumors: A Systematic Review, Tori Sayers, Megan W. Szobody, Nina Mourao, Blake C. Martin, Sriya Gullapalli, Kory Punch, Tirath Patel, Murali Yallapu, Bharathi Shrikanth Gadad

Research Symposium

Background: Pediatric populations have an increased susceptibility for brain tumors and suffer from neurocognitive impairment due to the neoplasm itself, and side effect of subsequent treatments. This causes many patients to experience a subpar quality of life (QoL), affecting academic endeavors, social interaction and mental well-being. Increasing our understanding of the long-term effects associated with brain tumors and the side effects from our current treatment methodology will help us formulate better treatment protocols and improve survivors’ QoL. This review aims to investigate different long-term neurocognitive and behavioral outcomes in pediatric brain tumor survivors, as well as evaluate how various treatment …

Coronavirus Disease 2019 (Covid-19) Real World Data Infrastructure: A Big-Data Resource For Study Of The Impact Of Covid-19 In Patient Populations With Immunocompromising Conditions, James M. Crawford, Lynne Penberthy, Ligia A. Pinto, Keri N. Althoff, Magdalene M. Assimon, Oren Cohen, Laura Gillim, Tracy L. Hammonds, Shilpa Kapur, Harvey W. Kaufman, David Kwasny, Jean W. Liew, William A. Meyer 3rd, Shannon L. Reynolds, Cheryl B. Schleicher, Suki Subbiah, Catherine Theruviparampil, Zachary S. Wallace, Jeremy L. Warner, Suhyeon Yoon, Yonah C. Ziemba

School of Medicine Faculty Publications

Background. We developed a United States–based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials. Methods. The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and …

Microrna 133a Regulates Squalene Epoxidase Expression In Colorectal Cancer Cells To Control Cell Proliferation And Cholesterol Production, Ji Su Mo, Santosh Lamichhane, Grinsun Sharma, Soo Cheon Chae

School of Medicine Faculty Publications

Background/Objectives: Colorectal cancer (CRC) is one of the most common cancers worldwide, with high incidence and mortality rates. MicroRNAs are endogenous and non-coding RNAs that play a pivotal role in the development and progression of various cancers by targeting specific genes. Previously, we identified MIR133A to be significantly decreased in human CRC tissues. This study aims to identify the relationship with SQLE, one of the candidate target genes of MIR133A, and study their interaction in CRC cells. Methods: Through the luciferase reporter assay, quantitative RT-PCR (qRT-PCR), and Western blot analysis. Results: We identified SQLE as a direct target gene of …

An In Vivo Study Of Lns8801, A Gper Agonist, In A Spontaneous Melanoma-Prone Mouse Model, Tgs., Christina Marinaro, John Sauer, Christopher A Natale, Todd Ridky, Suzie Chen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Melanoma is the most aggressive and deadly form of skin cancer that arises from the transformation of melanocytes, the pigment producing cells of the skin. In the year 2024 there will be approximately 10,000 new cases of melanoma diagnosed and approximately 8,000 deaths attributed to melanoma in the United States. In this study we treated a group of male and female transgenic mice that spontaneously develop metastatic melanoma, TGS, with a G-protein-coupled estrogen receptor agonist LNS8801 to assess the efficacy on disease progression. A second group of male and female TGS mice was also exposed to UVB irradiation to mimic …

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …

Characterization Of Pancreatic Collagen-Expressing Fibroblasts In Mouse Acute Pancreatitis, Amy Qin, Kevin Shi, Rachel R. Tindall, Jiajing Li, Binglu Cheng, Jing Li, Baibing Yang, Qiang Yu, Yinjie Zhang, Bangxing Hong, Balveen Kaur, Mamoun Younes, Qiang Shen, Jennifer M. Bailey-Lundberg, Yanna Cao, Tien C. Ko

School of Medicine Faculty Publications

Background and Aims: Pancreatic stellate cells (PSCs) are critical mediators in chronic pancreatitis with an undefined role in acute pancreatitis (AP). PSCs consist of a heterogenous group of cells and are considered interchangeable with pancreatic fibroblasts. This study explored the heterogeneous nature of PSCs by characterizing pancreatic collagen-expressing fibroblasts (PCFs) via lineage tracing in mouse normal and AP pancreas and determining the effect of PCF depletion in AP. Methods: Tandem dimer Tomato (tdTom+) PCFs in collagen type 1 (Col1)a2CreERtdTomato (Tom) mice receiving tamoxifen were characterized via fluorescence, Oil Red staining, and flow cytometry. AP was induced by cerulein, AP injury …

Dual Inhibition Of The Trka And Jak2 Pathways Using Entrectinib And Pacritinib Suppresses The Growth And Metastasis Of Her2-Positive And Triple-Negative Breast Cancers, Angelina T Regua, Shivani Bindal, Mariana K Najjar, Chuling Zhuang, Munazza Khan, Austin B J Arrigo, Anneliese O Gonzalez, Xinhai R Zhang, Jay-Jiguang Zhu, Kounosuke Watabe, Hui-Wen Lo

Faculty, Staff and Student Publications

HER2-positive and triple-negative breast cancers (TNBC) are difficult to treat and associated with poor prognosis. Despite showing initial response, HER2-positive breast cancers often acquire resistance to HER2-targeted therapies, and TNBC lack effective therapies. To overcome these clinical challenges, we evaluated the therapeutic utility of co-targeting TrkA and JAK2/STAT3 pathways in these breast cancer subtypes. Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells. The Entrectinib-Pacritinib combination inhibited the breast cancer stem cell subpopulation, reduced expression of stemness …

Enolase Inhibitors As Therapeutic Leads For Naegleria Fowleri Infection, Jillian E Milanes, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian N Dominy, Daniel C Whitehead, Steven W Millward, Madison Bolejack, Roger Shek, Logan Tillery, Isabelle Q Phan, Bart Staker, E Ashley Moseman, Xiang Zhang, Xipeng Ma, Audriy Jebet, Xinmin Yin, James C Morris

Faculty, Staff and Student Publications

Infections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used …

Aging- And Alcohol-Associated Spatial Transcriptomic Signature In Mouse Acute Pancreatitis Reveals Heterogeneity Of Inflammation And Potential Pathogenic Factors, Rachel R. Tindall, Yuntao Yang, Isabella Hernandez, Amy Qin, Jiajing Li, Yinjie Zhang, Thomas H. Gomez, Mamoun Younes, Qiang Shen, Jennifer M. Bailey-Lundberg, Zhongming Zhao, Daniel Kraushaar, Patricia Castro, Yanna Cao, W. Jim Zheng, Tien C. Ko

School of Medicine Faculty Publications

Abstract: The rapidly aging population is consuming more alcohol, leading to increased alcohol-associated acute pancreatitis (AAP) with high mortality. However, the mechanisms remain undefined, and currently there are no effective therapies available. This study aims to elucidate aging- and alcohol-associated spatial transcriptomic signature by establishing an aging AAP mouse model and applying Visium spatial transcriptomics for understanding of the mechanisms in the context of the pancreatic tissue. Upon alcohol diet feeding and caerulein treatment, aging mice (18 months) developed significantly more severe AAP with 5.0-fold increase of injury score and 2.4-fold increase of amylase compared to young mice (3 months). …

Viral Reprogramming Of Host Transcription Initiation, Nathan A. Ungerleider, Claire Roberts, Tina M. O’Grady, Trang T. Nguyen, Melody Baddoo, Jia Wang, Eman Ishaq, Monica Concha, Meggie Lam, Jordan Bass, Truong D. Nguyen, Nick Van Otterloo, Nadeeshika Wickramarachchige-Dona, Dorota Wyczechowska, Maria Morales, Tianfang Ma, Yan Dong, Erik K. Flemington

School of Medicine Faculty Publications

Viruses are master remodelers of the host cell environment in support of infection and virus production. For example, viruses typically regulate cell gene expression through modulating canonical cell promoter activity. Here, we show that Epstein Barr virus (EBV) replication causes ‘de novo’ transcription initiation at 29674 new transcription start sites throughout the cell genome. De novo transcription initiation is facilitated in part by the unique properties of the viral pre-initiation complex (vPIC) that binds a TATT[T/A]AA, TATA box-like sequence and activates transcription with minimal support by additional transcription factors. Other de novo promoters are driven by the viral transcription factors, …

Intrabiliary Metastasis Of Colorectal Mucinous Adenocarcinoma Mimicking Choledocholithiasis 18 Years After The Primary Tumor, Sumaya Abdul Ghaffar, David Pfau, Nikhil Madhuripan, Robert Christopher Harmon, Antonio Galvao Neto, Ana Luiza Gleisner

Faculty, Staff and Student Publications

This case report presents a 62-year-old male who had previously undergone curative colectomy and neoadjuvant chemotherapy in 2005 for colorectal cancer. He presented with jaundice, which was initially attributed to choledocholithiasis. After cholecystectomy and repeat ERCPs, hyperbilirubinemia persisted. There was persistent dilation of the right posterior duct on imaging, concerning for biliary stricture, possibly due to cholangiocarcinoma or intraductal papillary neoplasm. During a right posterior hepatectomy, a peripheral liver lesion was found in association with the dilated bile duct. On frozen evaluation, the lesion was found to be invasive adenocarcinoma. The final pathology was compatible with a metastatic mucinous adenocarcinoma …

Typhlitis In A Neutropenic Patient, Alice He Bs, Wern Lynn Ng Md, Lay She Ng Md, Si Yuan Khor Md, Chandi Garg Md

Tower Health Research Day

No abstract provided.

Li-Fraumeni Syndrome And The Benefits Of Annual Comprehensive Screening: A Pancreatic Adenocarcinoma Case, Alice He Bs, Wern Lynn Ng Md, Faith Seltun Do, Lay She Ng Md, Si Yuan Khor Md, Elham Nasrollahi Md, Chandi Garg Md, Rong Rong Ge Md

Tower Health Research Day

No abstract provided.

Spontaneous Tumor Lysis Syndrome In A Patient With Recent Diagnosis Of Multiple Myeloma — An Unusual Presentation, Taha Al Hassan, Olga G. Cantu-Rodriguez, Eunbee Cho, Edgar G. Dorsey Trevino

Research Symposium

Background: Tumor lysis syndrome (TLS) is an oncologic emergency that surfaces as a constellation of metabolic imbalances due to the rapid destruction of cancer cells and subsequent dissemination of their contents. However, a markedly rare subtype of TLS, known as spontaneous TLS (STLS), occurs without an evident trigger, such as cytotoxic therapy, and carries a similar mortality risk. It is paramount to recognize high-risk cases early and implement therapeutic measures to prevent complications of STLS.

Case Presentation: We present the case of a 74-year-old gentleman with a recent diagnosis of Kappa-restricted multiple myeloma who presented with worsening weakness, tremors, ataxia, …

Trps1 Expression In Non-Melanocytic Cutaneous Neoplasms: An Immunohistochemical Analysis Of 200 Cases, Yi A Liu, Phyu P Aung, Yunyi Wang, Jing Ning, Priyadharsini Nagarajan, Jonathan L Curry, Carlos A Torres-Cabala, Doina Ivan, Victor G Prieto, Qingqing Ding, Woo Cheal Cho

Faculty, Staff and Student Publications

BACKGROUND: Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ.

METHODS: Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit …

Chronic Wasting Disease: State Of The Science, Jason C Bartz, Rebeca Benavente, Byron Caughey, Sonja Christensen, Allen Herbst, Edward A Hoover, Candace K Mathiason, Debbie Mckenzie, Rodrigo Morales, Marc D Schwabenlander, Daniel P Walsh, The Nc North American Interdisciplinary Chronic Wasting Disease Research Consortium Members

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting cervid species, both free-ranging and captive populations. As the geographic range continues to expand and disease prevalence continues to increase, CWD will have an impact on cervid populations, local economies, and ecosystem health. Mitigation of this "wicked" disease will require input from many different stakeholders including hunters, landowners, research biologists, wildlife managers, and others, working together. The NC1209 (North American interdisciplinary chronic wasting disease research consortium) is composed of scientists from different disciplines involved with investigating and managing CWD. Leveraging this broad breadth of expertise, the Consortium has created a state-of-the-science …

Cd133-Dependent Activation Of Phosphoinositide 3-Kinase /Akt/Mammalian Target Of Rapamycin Signaling In Melanoma Progression And Drug Resistance, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Youssef Al Hmada, Sofie Yasmin Hassan, Hosam Shalaby, Simeon Santourlidis, Sarah Lilly Hassan, Youssef Haikel, Mossad Megahed, Robert T. Brodell, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent …

Mechanisms Of Melanoma Progression And Treatment Resistance: Role Of Cancer Stem-Like Cells, Youssef Al Hmada, Robert T. Brodell, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Sofie Yasmin Hassan, Hosam Shalaby, Sarah Lilly Hassan, Youssef Haikel, Mosaad Megahed, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% …

Preclinical Repurposing Of Sitagliptin As A Drug Candidate For Colorectal Cancer By Targeting Cd24/Ctnnb1/Sox4-Centered Signaling Hub, Jing-Wen Shih, Alexander T H Wu, Ntlotlang Mokgautsi, Po-Li Wei, Yan-Jiun Huang

Faculty, Staff and Student Publications

Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased CD24/SOX4 expression in CRC samples associated with poor prognosis. We also …

Insights Into The Assembly And Regulation Of The Bacterial Divisome, Todd A Cameron, William Margolin

Faculty, Staff and Student Publications

The ability to split one cell into two is fundamental to all life, and many bacteria can accomplish this feat several times per hour with high accuracy. Most bacteria call on an ancient homologue of tubulin, called FtsZ, to localize and organize the cell division machinery, the divisome, into a ring-like structure at the cell midpoint. The divisome includes numerous other proteins, often including an actin homologue (FtsA), that interact with each other at the cytoplasmic membrane. Once assembled, the protein complexes that comprise the dynamic divisome coordinate membrane constriction with synthesis of a division septum, but only after overcoming …

Exosome Shedding Is Concordant With Objective Treatment Response Rate And Stratifies Time To Progression In Treatment Naïve, Non-Resectable Hepatocellular Carcinoma, Kelley G. Núñez, Dorota Wyczechowska, Mina Hibino, Tyler Sandow, Juan Gimenez, Ali R. Koksal, Yucel Aydin, Srikanta Dash, Ari J. Cohen, Paul T. Thevenot

School of Medicine Faculty Publications

Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for time to progression (TTP) following first-cycle liver-directed therapy (LDT). Plasma EXs were isolated from HCC patients undergoing LDT using ultracentrifugation. Purified EXs were stained using markers CD9 and CD63 and quantified using an ImageStreamX flow cytometer. Circulating EXs expressing CD9 were isolated at 10-fold higher levels compared to CD63. The intensity of CD9+ EX shedding following LDT …

Ezh2 Cooperates With Brd4-Nut To Drive Nut Carcinoma Growth By Silencing Key Tumor Suppressor Genes, Yeying Huang, R Taylor Durall, Nhi M Luong, Hans J Hertzler, Julianna Huang, Prafulla C Gokhale, Brittaney A Leeper, Nicole S Persky, David E Root, Praju V Anekal, Paula D L M Montero Llopis, Clement N David, Jeffery L Kutok, Alejandra Raimondi, Karan Saluja, Jia Luo, Cynthia A Zahnow, Biniam Adane, Kimberly Stegmaier, Catherine E Hawkins, Christopher Ponne, Quan Le, Geoffrey I Shapiro, Madeleine E Lemieux, Kyle P Eagen, Christopher A French

Faculty, Staff and Student Publications

NUT carcinoma (NC) is an aggressive carcinoma driven by the BRD4-NUT fusion oncoprotein, which activates chromatin to promote expression of pro-growth genes. BET bromodomain inhibitors (BETi) are a promising treatment for NC that can impede BRD4-NUT’s ability to activate genes, but the efficacy of BETi as monotherapy are limited. Here, we demonstrated that EZH2, which silences genes through establishment of repressive chromatin, is a dependency in NC. Inhibition of EZH2 with the clinical compound tazemetostat (taz) potently blocked growth of NC cells. Epigenetic and transcriptomic analysis revealed that taz reversed the EZH2-specific H3K27me3 silencing mark and restored expression of multiple …

Atm Deficiency Confers Specific Therapeutic Vulnerabilities In Bladder Cancer, Yuzhen Zhou, Judit Börcsök, Elio Adib, Sophia C. Kamran, Alexander J. Neil, Konrad Stawiski, Dory Freeman, Dag Rune Stormoen, Zsofia Sztupinszki, Amruta Samant, Amin Nassar, Raie T. Bekele, Timothy Hanlon, Henkel Valentine, Ilana Epstein, Bijaya Sharma, Kristen Felt, Philip Abbosh, Chin-Lee Wu, Jason A. Efstathiou, David T. Miyamoto, William Anderson, Zoltan Szallasi, Kent W. Mouw

Einstein Health Papers

Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair-targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss …

Inflammation In The Tumor-Adjacent Lung As A Predictor Of Clinical Outcome In Lung Adenocarcinoma, Igor Dolgalev, Hua Zhou, Nina Murrell, Hortense Le, Theodore Sakellaropoulos, Nicolas Coudray, Kelsey Zhu, Varshini Vasudevaraja, Anna Yeaton, Chandra Goparaju, Yonghua Li, Imran Sulaiman, Jun-Chieh J Tsay, Peter Meyn, Hussein Mohamed, Iris Sydney, Tomoe Shiomi, Sitharam Ramaswami, Navneet Narula, Ruth Kulicke, Fred P Davis, Nicolas Stransky, Gromoslaw A Smolen, Wei-Yi Cheng, James Cai, Salman Punekar, Vamsidhar Velcheti, Daniel H Sterman, J T Poirier, Ben Neel, Kwok-Kin Wong, Luis Chiriboga, Adriana Heguy, Thales Papagiannakopoulos, Bettina Nadorp, Matija Snuderl, Leopoldo N Segal, Andre L Moreira, Harvey I Pass, Aristotelis Tsirigos

Faculty, Staff and Student Publications

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell …

Enolase Inhibitors As Early Lead Therapeutics Against Trypanosoma Brucei, Colm P Roster, Danielle Lavigne, Jillian E Milanes, Emily Knight, Heidi D Anderson, Sabrina Pizarro, Elijah M Harding, Meredith T Morris, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian Dominy, Daniel C Whitehead, Md Nasir Uddin, Steven W Millward, James C Morris

Faculty, Staff and Student Publications

Glucose metabolism is critical for the African trypanosome, Trypanosoma brucei, serving as the lone source of ATP production for the bloodstream form (BSF) parasite in the glucose-rich environment of the host blood. Recently, phosphonate inhibitors of human enolase (ENO), the enzyme responsible for the interconversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP) in glycolysis or PEP to 2-PG in gluconeogenesis, have been developed for the treatment of glioblastoma multiforme (GBM). Here, we have tested these agents against T. brucei ENO (TbENO) and found the compounds to be potent enzyme inhibitors and trypanocides. For example, (1-hydroxy-2-oxopyrrolidin-3-yl) phosphonic acid (deoxy-SF2312) …

Identification Of Immune Biomarkers In Thyroid Cancer, Anupam Kotwal

Theses & Dissertations

Thyroid cancer is the most common endocrine malignancy, estimated to be the second most common cancer in women by 2030. The frequency of differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, is higher in patients with autoimmune thyroid disease but the influence of the immune milieu on thyroid carcinogenesis remains unclear. To address this gap in knowledge, we performed clinical and translational experiments to identify immune biomarkers for the occurrence and prognosis of DTC. Multiparameter flow cytometry of peripheral blood from 32 adults found advanced thyroid cancer either at presentation or during the disease-course to be associated …