Medical Specialties Commons^™

Gene Expression And Apoptotic Responses To Panobinostat Treatment And Yap Knockdown In Ewing Sarcoma Cells, Luna Collazo-Garcia, Alejandra Favela Santos, Madeline Torres-Salazar, Isabella Toscano

Posters - 2026

Ewing sarcoma is an aggressive pediatric cancer driven by abnormal gene expression caused by the EWS-FLI1 fusion protein

Usually treated with intensive treatments such as chemotherapy and radiation

Outcomes remain poor for metastatic disease, highlighting the need for new therapeutic strategies

The Hippo signaling pathway regulates cell proliferation and survival through the transcriptional co-activator YAP1

Differential Effects Of Veratridine And 5-Fluorouracil On Ubxn2a-Targeted Mortalin And Rictor Proteins In Patient-Derived Colorectal Cancer Cells, Kate S. Schraufnagel

Honors Thesis

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, particularly in patients with metastatic CRC and/or those who have developed resistance to conventional chemotherapy. There has been a significant rise in early-onset CRC (EOCRC) incidences in patients under age 50. Due to lack of screening, these patients are commonly diagnosed in the later stages where there is a lack of effective therapies. This highlights the need for targeted therapies that address the molecular drivers of tumor progression and treatment resistance. UBXN2A is a tumor suppressor protein that regulates key oncogenic pathways in CRC, including Mortalin-2 (mot-2)-mediated p53 suppression and …

Detection And Quantification Of Allergen Cross-Contact In Shared Frying Oil Using Targeted Mass Spectrometry, Francisca Asigri

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Cow’s milk and egg allergies are prevalent IgE-mediated food allergies that pose significant public health concerns worldwide. Although strict avoidance remains the primary management strategy, unintended exposure can still occur through allergen cross-contact, particularly in commercial and industrial food operations that utilize shared frying oils. The objective of this study was to identify and quantify allergen transfer in shared frying oil and assess the robustness of existing targeted mass spectrometry methods (LC-MS/MS) for detecting milk and egg proteins in heated oil matrices.

Heated oil spikes were developed by incorporating non-fat dry milk (NFDM) and whole egg powder (WEP) into oil …

All-Cause And Cause-Specific Mortality In Patients With Bipolar Ii Disorder, Chih-Wei Hsu, Yang-Chieh Brian Chen, Edward Chia-Cheng Lai, Andrew A Nierenberg, Michael Berk, Sheng-Yu Lee, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Andre F Carvalho

Children’s Nutrition Research Center Staff Publications

Importance: Whether bipolar II disorder (BD-II) is associated with increased long-term mortality remains uncertain because most studies have not distinguished BD-II from bipolar I disorder (BD-I).

Objective: To examine whether BD-II is associated with elevated all-cause and cause-specific mortality compared with population controls, unaffected siblings, and those with BD-I.

Design, setting, and participants: This population-based, retrospective cohort study used data from Taiwan's National Health Insurance Database from January 1, 2000, to December 31, 2022. Individuals 12 years or older with 2 or more psychiatrist-assigned BD-II diagnoses were individually matched to 4 controls without BD-II by sex and birthdate. Additional comparisons …

Weaning Drives Microbiome-Mediated Epigenetic Regulation To Shape Immune Memory In Mice, Li Yang, Robert C Peery, Shirui Zhou, Xiaomin Chen, Leah M Farmer, Fabiola Gutierrez, Stephanie Fowler, Lanjing Zhang, Julia M Salamat, Karen Riggins, Jiejun Shi, Lanlan Shen

Children’s Nutrition Research Center Staff Publications

During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning-driven microbiome changes shape the DNA methylome and transcriptome of murine ISCs in an IFNγ-dependent manner. Specifically, we observe demethylation of enhancer elements essential for MHC class II genes, which results in a transcriptional memory that persists through differentiation into adulthood. IFNγ blockade, or low-dose penicillin to target Gram-positive bacteria, …

Multiparametric Mri To Predict Response To Irreversible Electroporation Plus Anti-Pd-1 Immunotherapy In Pancreatic Ductal Adenocarcinoma, Qizhen Cao, Mark D Pagel, Charles V Kingsley, Jingfei Ma, James P Long, Xiaoxia Wen, Seth T Gammon, Jorge Delacerda, Sanaz Javadi, Chun Li

Faculty, Staff and Student Publications

Purpose: To investigate contrast-enhanced T1-weighted MRI and diffusion-weighted magnetic resonance imaging (DWI) for early prediction of tumor response to combined irreversible electroporation (IRE) and anti-PD-1 immunotherapy.

Methods: Murine pancreatic ductal adenocarcinoma (PDAC) cells KRAS* were inoculated into the pancreas of C57BL/6 mice. IRE was performed when tumors became palpable. After IRE, mice received six intraperitoneal injections of anti-PD-1 over 2 weeks. T2-weighted MRI, T1-weighted MRI with macromolecular contrast agent poly(L-glutamic acid)-conjugated gadolinium (PG-Gd), and DWI were performed before and after IRE. Survival was analyzed using Kaplan-Meier curves. Mice surviving at least 100 days without recurrence after IRE were considered complete …

Neutrophil-Microglia Interaction Drives Motor Dysfunction In A Neuromyelitis Optica Model Induced By Subarachnoid Aqp4-Igg, Fangfang Qi, Vanda A Lennon, Shunyi Zhao, Yong Guo, Husheng Ding, Caiyun Liu, Whitney M Bartley, Tingjun Chen, Claudia F Lucchinetti, Long-Jun Wu

Faculty, Staff and Student Publications

Neutrophils and neutrophil extracellular traps (NETs) contribute to early neuromyelitis optica (NMO) histopathology initiated by IgG targeting astrocytic aquaporin-4 (AQP4) water channels. Yet, the mechanisms underlying neutrophil recruitment and their pathogenic roles in disease progression remain unclear. To investigate molecular-cellular events preceding classical complement cascade activation in a mouse NMO model, we continuously infused, via spinal subarachnoid route, a non-complement-activating mouse monoclonal AQP4-IgG. Parenchymal infiltration of netting neutrophils containing C5a ensued with microglial activation and motor impairment but no blood-brain barrier leakage. Motor impairment and neuronal dysfunction both reversed when AQP4-IgG infusion stopped. Two-photon microscopy and electron microscopy-based reconstructions revealed …

Gompertz Growth With A Shared Carrying Capacity Optimally Simulates Primary And Metastatic Tumor Growth Dynamics, Pirmin Schlicke, Preethi Korangath, Xiaoxi Pan, Caner Ercan, Kathleen Gabrielson, Lyndsey Werhane, Yinyin Yuan, Sébastien Benzekry, Robert Ivkov, Heiko Enderling

Faculty, Staff and Student Publications

Background: Cancer is a systemic disease with most deaths attributed to metastatic burden. Primary and metastatic tumors, albeit at different anatomic locations, are interconnected through multiple biological processes. Pre-clinical and clinical observations of growth acceleration of metastases after surgery, or abscopal effects outside the radiation field are widely reported, yet reliably triggering favorable and avoiding unfavorable systemic responses remains an unmet clinical need. Understanding local and systemic tumor interaction dynamics will help guide future treatments.

Methods: We analyze the data of multiple in vivo tumor models. We formalize the systemic interplay of tumors as mathematical differential equation and calibrate parameters …

Structural-Functional Analyses Of The Huntingtin/Hap40 Complex In Drosophila And Humans, Stephen M Farmer, Amanda Solbach, Shiyu Xu, Beatriz Rios, Xin Ye, Amy Gao, Daniela Covarrubias, Yue Yu, Lili Ye, Vicky Chuong, Erin Furr Stimming, Haiqing Zhao, Sheng Zhang

Faculty, Staff and Student Publications

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal CAG expansion in the Huntingtin (HTT) gene. Given its simple genetic cause but complex pathogenic mechanisms, interest in targeting HTT for HD treatment is growing, necessitating a clear understanding of HTT regulation. HTT protein primarily exists in a core complex with HAP40, forming a highly ordered structure with two large globular domains connected by a bridge. We previously demonstrated that HAP40 is conserved in

Unraveling The Nexus: Tumor Mutational Burden, Pd-L1 Expression, And Oncogenic Alterations In Non-Small Cell Lung Cancer Cytology Specimens, Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P Patel, Asif Rashid, Shun Rao, Mark J Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Methods: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Results: …

Baseline Parp-1 Pet Imaging In Patients With Advanced Solid Tumors With Dna Damage Response Mutations, Tarek Daoud, Jiansong Chen, Peng Wei, Franklin Wong, Timothy A Yap, Lilie L Lin

Faculty, Staff and Student Publications

Purpose: Inhibitors of poly(ADP-ribose) polymerase (PARP), an enzyme with numerous roles in DNA damage response signaling, represent a class of anti-cancer drugs approved for treating solid tumors with defects in the DNA damage response. However, additional methods for identifying patients who would benefit from the use of PARP inhibitors are urgently needed. We evaluated a novel radiotracer, 18F-FluorThanatrace ([18F]-FTT), to noninvasively assess PARP activity with PET/CT before treatment and determine associations between uptake, tumor mutation status, and prior receipt of therapy including PARP inhibitors.

Methods: Fifty-two patients with solid tumors underwent whole-body (skull base to thigh) [18F]-FTT PET/CT scans before …

Tumor Flare Reaction With Brentuximab-Vedotin In Mycosis Fungoides, Rishabh Lohray, Seda Purnak, Samruddhi Arkatkar, Madeleine Duvic, Victor Prieto, Carlos Torres-Cabala, Auris Huen

Faculty, Staff and Student Publications

No abstract provided.

Identifying Sorafenib Benefit Among Patients With Hepatocellular Carcinoma: A Transcriptomic And Genomic Approach, Sun Young Yim, Hayeon Kim, Tae Hyung Kim, Sang-Hee Kang, Youngwoo Lee, Eunho Choi, Yang Jae Yoo, Seong Hee Kang, Young-Sun Lee, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon, Kyung Suk Yang, Yitao Tang, Bowha Sohn, Yun Seong Jeong, Hyewon Park, Han Liang, Ju-Seog Lee, Ji Hoon Kim

Faculty, Staff and Student Publications

Background & aims: Sorafenib has been a cornerstone of hepatocellular carcinoma (HCC) therapy; however, its efficacy is limited, and identifying patients who will benefit from sorafenib is challenging. We aimed to identify predictive biomarkers of sorafenib benefit in patients with HCC.

Methods: Gene expression data from 33 HCC tumors treated with sorafenib were analyzed to construct a prediction model aimed at identifying patients with greater benefit from sorafenib treatment. The robustness of the predictor was validated using gene expression data from two phase III clinical trials, IMbrave150 and STORM.

Results: The analysis of transcriptome data revealed a 50-gene signature, the …

Eating For Healthy Eyes: The Role Of Nutrition In Ocular Health, Brianna Stroh

Honors Program: Senior Projects (Public)

The central research question of this thesis asks: How does nutrition influence ocular health overall and the impact of nutrition on the development or progression of common eye diseases? Building upon existing research in optometry/ophthalmology, nutrition science, and public health, this project examines the physiological mechanisms linking diet to eye health and evaluates how specific nutrients and dietary patterns contribute to disease prevention and visual function. This thesis employs a comprehensive review of peer-reviewed literature to evaluate the relationship between nutrition and ocular disease. Key areas of focus include the role of oxidative stress in eye disease development, the protective …

Axillary Management After Neoadjuvant Endocrine Therapy (Net), Laura Leonard, Min Yi, Emma Wingate, Puneet Singh, Abigail Caudle, Rosa F Hwang, Isabelle Bedrosian, Vicente Valero, Jennifer Litton, Nuhad Ibrahim, Kelly K Hunt

Faculty, Staff and Student Publications

BACKGROUND: In patients with hormone receptor-positive (HR

PATIENTS AND METHODS: We performed a retrospective review of patients with clinical stage I-III, HR

RESULTS: A total of 230 patients were included; 120 (52.2%) were clinically node-negative (cN0), while 110 (47.8%) were clinically node-positive (cN+). In the cN+ group, 7.3% (8/110) had a nodal pathologic complete response (pCR). In total, 76.4% (84/110) in the cN+ group underwent axillary lymph node dissection (ALND) as the initial axillary procedure, and 90.9% (100/110) underwent ALND overall. In total, 98.3% (118/120) with cN0 disease underwent sentinel lymph node dissection (SLND), and 28 (23.7%) had positive nodes. …

Mechanisms Of Synergy Between Nanosecond Pulsed Electric Field (Nspef) And Cold Atmospheric Pressure Plasma Discharge (Cap) In Pancreatic Cancer: The Role Of Ros-Mediated Oxidative Stress And Apoptosis, Zobia Minhas

Theses and Dissertations in Biomedical Sciences

Pancreatic ductal adenocarcinoma is a highly lethal malignancy characterized by poor prognosis and resistance to conventional therapies. Novel treatment strategies are needed to overcome this resistance. Non-thermal physical modalities, including nanosecond pulsed electric field (nsPEF) and cold atmospheric pressure plasma discharge (CAP), have emerged as potential anticancer approaches; however, the mechanisms underlying their combined effects remain unclear.

This study evaluated whether nsPEF enhances CAP-induced cytotoxicity and investigated the associated molecular mechanisms using the murine Pan02 pancreatic cancer cell line. Cell viability was assessed by WST-1 metabolic activity assays and electric cell–substrate impedance sensing (ECIS). Intracellular reactive oxygen species (ROS) were …

(Giga)Time For The Era Of Ai: Virtual Multiplex Immunofluorescence From Routine H&E For Large Populations, Shao-Ping Yang, Dihua Yu

Faculty, Staff and Student Publications

No abstract provided.

Phenol–Chloroform Dna Extraction For Dna Amplification From Personal Items, Aditya Rahman Ernanto, Dinda Amaliyatul Khasanah, Yunita Aldirahayu, Rizki Setiyaningrum, Arya Iswara

Makara Journal of Science

This study examined the feasibility of extracting DNA from various personal items using the phenol–chloroform–isoamyl alcohol (PCIA) method. A towel, collared shirt, toothbrush, shower puff, comb, hair tie, and buccal swabs were analyzed. The quality of the DNA extraction, along with DNA concentration, purity, and suitability for multiplex PCR amplification, were evaluated. The shower puff exhibited the highest DNA concentration (68.35 ng/µL), whereas the collared shirt yielded the lowest (26.43 ng/µL). All samples exhibited good DNA purity (A260 nm/A280 nm ranging from 1.827 to 1.985), emphasizing the potential of this method for forensic analysis. Factors influencing DNA concentration included material …

The Effects Of Ultra-Processed Food Consumption On Cancer Development, Bailey G. Ottmann

Emerging Writers

The dramatic rise in ultra-processed food (UPF) consumption worldwide has sparked growing concerns about its impact on cancer development and human health. UPFs contain high levels of added sugars, unhealthy fats, chemical additives, dyes, and toxic compounds formed during cooking and processing. This study investigates the relationship between UPF consumption and cancer through a review of primary and secondary sources, alongside an observational survey conducted among 15 healthcare professionals, including physicians, nurses, and nursing educators. Survey findings indicate that 53% of participants observed higher cancer prevalence in patients consuming large amounts of UPFs, with colorectal cancer most frequently reported. The …

An Atlas Of Genetic Effects On The Monocyte Methylome Across European And African Populations, Wanheng Zhang, Chuan Qiu, Xiao Zhang, Zichen Zhang, Kuan-Jui Su, Zhe Luo, Minghui Liu, Bingxin Zhao, Lang Wu, Qing Tian, Hui Shen, Chong Wu, Hong-Wen Deng

Faculty, Staff and Student Publications

No abstract provided.

3'Utr Mapping Reveals Alternative Polyadenylation In Right Ventricular Failure, Rahul Neupane, Kartiga Natarajan, Erik E Suarez, Henry J Pownall, Kai-Lieh Huang, Eric J Wagner, Ajay Kumar Verma, Rambabu Majji, Hari Krishna Yalamanchili, Ashrith Guha, Rajarajan A Thandavarayan

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Monitoring Relapse In Post-Transplant Acute Myeloid Leukemia Requires Integrated Assessment, With Flow Cytometry Showing The Highest Efficacy, Wei J Wang, Sa A Wang, Hong Fang, Qing Wei, Shimin Hu, Sanam Loghavi, Gheath Al-Atrash, Chenxuan Zang, Peng Wei, Jeffrey L Medeiros, Wei Wang

Faculty, Staff and Student Publications

No abstract provided.

Fecal Carbohydrate-Degrading Bacteria Are Associated With Reduced Incidence Of Lower Gastrointestinal Gvhd, Christopher Fan, Tomo Hayase, Chia-Chi Chang, Israel K Glover, Ivonne I Flores, Lauren K Mcdaniel, Miriam R Ortega, Christopher A Sanchez, Rawan K El-Himri, Alexandria N Brown, Jennifer L Karmouch, Mohamed A Jamal, Saira S Ahmed, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Ashish Damania, Nadim J Ajami, Jennifer A Wargo, Christine B Peterson, Gabriela Rondon, Taha Al-Juhaishi, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Eric Martens, Cesar A Arias, Robert R Jenq, Eiko Hayase

Faculty, Staff and Student Publications

Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of stool from patients with allo-HSCT (N = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate-degrading functionality of these bacteria, we investigated gene abundances for carbohydrate-active enzymes (CAZymes) and found that Parabacteroides merdae, P distasonis, and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop …

Genome-Wide Crispr Screen Identifies A Cytokine-Enhancer Circuit Driving Hif-2Α Activation In Renal Cancer, Jun Fang, Jeremy M Simon, Tao Wang, Yunpeng Gao, Xianju Bi, Lianxin Hu, Chengheng Liao, Cheng Zhang, Yayoi Adachi, Jin Zhou, Hongyi Liu, Qian Liang, James A Nathan, Ram Mani, James Brugarolas, Qing Zhang

Faculty, Staff and Student Publications

Resistance to HIF-2α inhibitors such as Belzutifan underscores the need to better understand how HIF-2α is transcriptionally regulated in clear cell renal cell carcinoma (ccRCC). Here, we uncover a cytokine-driven enhancer mechanism that sustains HIF-2α expression through the JAK1-STAT3 signaling pathway. Using a genome-wide CRISPR screen in VHL-deficient ccRCC cells, we identified SOCS3 as a key negative regulator of HIF-2α. Mechanistically, loss of SOCS3 activates JAK1-STAT3 signaling, leading to the recruitment of STAT3 to distal enhancers upstream of EPAS1 that physically loop to its promoter to drive HIF-2α transcription. This cytokine-enhancer circuit was recapitulated in ccRCC patient samples and functionally …

A Retrospective Analysis Of Taxane-Based Chemotherapy In Small Bowel Adenocarcinoma, Mir Lim, Nikhil Grandhi, Preksha Shah, Kanwal Raghav, Victoria Serpas, Maria Pia Morelli, Katrina Pedersen, Aparna Kalyan, Mohamed Salem, Ryan Huey, John Paul Shen, Huamin Wang, Hua Wang, Anjali Vinocha, Jane Thomas, Robert Wolff, Michael J Overman

Faculty, Staff and Student Publications

Background: Small bowel adenocarcinoma (SBA) is molecularly distinct from colorectal and gastric cancers, yet treatment typically parallels colorectal cancer. We evaluated the activity of taxane-based therapy in the largest SBA cohort to date.

Methods: We retrospectively reviewed SBA patients treated with taxane-based chemotherapy at MD Anderson Cancer Center from 1994-2024. Eligible patients had pathologic confirmation, received >1 treatment cycle, and had tumor response evaluation. Survival analyses were analyzed using Kaplan-Meier and Cox proportional hazard models.

Results: Seventy patients were identified. Median age was 57, and 59% were male. Primary sites were duodenum (44%), jejunum (34%), and Ileum (16%). Metastatic sites …

Evaluating Eight Smoking Metrics For Modelling Survival In Non-Small Cell Lung Cancer, Andrew Cl Lam, Yao Li, M Catherine Brown, Yangqing Deng, Katrina Hueniken, Natasha B Leighl, Frances A Shepherd, Kiera Murison, Zhichao Wang, Jui Kothari, Angela S Wenzlaff, Haoran Liu, Takashi Kohno, Angela Cecilia Pesatori, Curtis Harris, Hongxia Ma, Juncheng Dai, Matthew J Barnett, Ryan Diver, Leticia Ferro Leal, Guillermo Fernandez-Tardon, Mónica Pérez-Ríos, Michael Pa Davies, Bernd Holleczek, Paul Brennan, David Zaridze, Ivana Holcatova, Jolanta Lissowska, Beata Świątkowska, Dana Mates, Milan Savic, Hermann Brenner, Angeline S Andrew, Fiona Taylor, John K Field, Alberto Ruano-Ravina, Sanjay S Shete, Adonina Tardon, Ying Wang, Loic Le Marchand, Rui Manuel Reis, Matthew B Schabath, Marian L Neuhouser, Hongbing Shen, Maria Teresa Landi, Kouya Shiraishi, Jie Zhang, Ann G Schwartz, Ming S Tsao, David C Christiani, Ping Yang, Rayjean J Hung, Wei Xu, Geoffrey Liu

Faculty, Staff and Student Publications

Introduction: Smoking is a strong modifiable prognostic factor for lung cancer survival. We compared eight smoking metrics to determine which metric best models the relationship between smoking exposure with overall survival (OS) and lung cancer-specific survival (LCSS). These metrics included cigarettes-per-day, smoking duration, pack-years, square-root pack-years, logcig-years, the comprehensive smoking index, age-of-initiation, and years-since-quit.

Materials/methods: This retrospective, pooled analysis included 25 International Lung Cancer Consortium studies between June 1, 1983-December 31, 2019. The performance of smoking metrics for modelling OS was compared based on 1) strength and significance in adjusted Cox-proportional hazard models and 2) linearity based on the goodness-of-fit …

Polθ Activity Modulates Sensitivity To Standard Therapies In Dnmt3a-Deficient Leukemia, Bac Viet Le, Umeshkumar Vekariya, Monika M. Toma, Margaret Nieborowska-Skorska, Marie-Christine Caron, Malgorzata Gozdecka, Zayd Haydar, Martin Walsh, Jayashri Ghosh, Elaine Vaughan-Williams, Paulina Podszywalow-Bartnicka, Anna-Mariya Kukuyan, Sylwia Ziolkowska, Jessica Atkins, Emir Hadzijusufovic, Gurushankar Chandramouly, Reza Nejati, Katarzyna Piwocka, Richard T. Pomerantz, George S. Vassiliou, Brian J.P. Huntly, Peter Valent, Mariusz Wasik, Alfonso Bellacosa, Jean-Yves Masson, Gaorav P. Gupta, Grant A. Challen, Tomasz Skorski

Department of Biochemistry and Molecular Biology Faculty Papers

Myeloid malignancies carrying somatic DNMT3A mutations (DNMT3Amut) are refractory to standard therapy. DNMT3Amut leukemia cells accumulate toxic DNA double-strand breaks (DSBs) and stalled replication forks, rendering them dependent on DNA damage response (DDR). We report here that DNA polymerase theta (Polθ), a key element in DSB repair by end-joining (Polθ-mediated end-joining [TMEJ]) and in fork restarting, promotes survival and proliferation of DNMT3Amut leukemia cells. Polθ is overexpressed in DNMT3Amut leukemia cells due to abrogation of PARP1 PARylation-dependent UBE2O E3 ligase-mediated ubiquitination and proteasomal degradation of Polθ. In addition, PARP1-mediated recruitment of the SMARCAD1-MSH2/MSH3 repressive complex to DSBs is diminished in …

Visdb 20: A Manually Curated Resource Of Viral Integration Sites And Their Regulatory Maps In Human Diseases, Citu Citu, Ajeet Singh, Xinyi Liu, Mounika Ashannagari, Rinki Ratnapriya, Zhongming Zhao

Faculty, Staff and Student Publications

The integration of viral sequence into the human genome plays critical role in the onset of various diseases, especially cancers. To facilitate systematic analysis of these events, we present VISDB 2.0, an expanded and updated database of human viral integration sites (VISs). The current release contains more than 270,000 manually curated VISs derived from 209 peer-reviewed publications, covering 11 viruses, including four retroviruses and seven DNA viruses. This represents a 3.5-fold increase in VIS entries compared with the previous version. Each VIS record includes standardized genomic coordinates and annotations describing local genomic context, CpG islands, repetitive elements, chromosomal fragile sites, …

Misregulated Alternative Splicing In Endometriosis: A Role For Aberrant Mrna Variants In Endometriotic Cell Growth, Venkata Naga Goutham Davuluri, Michelle Dias, Roxanna Llinas, Kamath Neha, Pooja Popli, Shannon M Hawkins, Chandrakant Tayade, Elise T Courtois, Hari Krishna Yalamanchili, Ramakrishna Kommagani

Children’s Nutrition Research Center Staff Publications

Endometriosis is a chronic gynecological disorder marked by the growth of endometrial-like tissue outside the uterus, often leading to pelvic pain, inflammation, and infertility. Despite its global prevalence, diagnosis remains delayed, and effective non-surgical treatments are lacking. While recent transcriptomic studies have identified mRNA transcript changes in ectopic lesions, the contribution of alternative pre-mRNA splicing, a key posttranscriptional regulatory layer, remains largely unknown. In this study, we performed a comprehensive analysis of alternative splicing (AS) events in endometriotic lesions using transcriptomic data. We uncovered distinct alterations in alternative splicing events are associated with endometriosis, highlighting a previously underappreciated layer of …

Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.

Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …