Medical Genetics Commons^™

Facilitating Federated Genomic Data Analysis By Identifying Record Correlations While Ensuring Privacy, Leonard Dervishi, Xinyue Wang, Wentao Li, Anisa Halimi, Jaideep Vaidya, Xiaoqian Jiang, Erman Ayday

Faculty, Staff and Student Publications

With the reduction of sequencing costs and the pervasiveness of computing devices, genomic data collection is continually growing. However, data collection is highly fragmented and the data is still siloed across different repositories. Analyzing all of this data would be transformative for genomics research. However, the data is sensitive, and therefore cannot be easily centralized. Furthermore, there may be correlations in the data, which if not detected, can impact the analysis. In this paper, we take the first step towards identifying correlated records across multiple data repositories in a privacy-preserving manner. The proposed framework, based on random shuffling, synthetic record …

A Transgenic Bacterial Artificial Chromosome Approach To Identify Regulatory Regions That Direct Amhr2 And Osterix Expression In Müllerian Duct Mesenchyme, Malcolm M Moses, Rachel D Mullen, Daniel I Idowu, Peter Maye, Soazik P Jamin, Richard R Behringer

Faculty, Staff and Student Publications

A transgenic mouse approach using bacterial artificial chromosomes (BAC) was used to identify regulatory regions that direct Müllerian duct expression for Amhr2 and Osterix (Osx, also known as Sp7). Amhr2 encodes the receptor that mediates anti-Müllerian hormone (AMH) signaling for Müllerian duct regression in male embryos. Amhr2 is expressed in the Müllerian duct mesenchyme of both male and female embryos. A ∼147-kb BAC clone containing the Amhr2 locus was used to generate transgenic mice. The transgene was able to rescue the block in Müllerian duct regression of Amhr2-null males, suggesting that the BAC clone contains regulatory …

Genetic Variants Associated With Circulating Liver Injury Markers In Mexican Americans, A Population At Risk For Non-Alcoholic Fatty Liver Disease, Caroline M Sabotta, Suet-Ying Kwan, Lauren E Petty, Jennifer E Below, Aron Joon, Peng Wei, Susan P Fisher-Hoch, Joseph B Mccormick, Laura Beretta

Faculty, Staff and Student Publications

Objective: Mexican Americans are disproportionally affected by non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma. Noninvasive means to identify those in this population at high risk for these diseases are urgently needed. Approach: The Cameron County Hispanic Cohort (CCHC) is a population-based cohort with high rates of obesity (51%), type 2 diabetes (28%) and NAFLD (49%). In a subgroup of 564 CCHC subjects, we evaluated 339 genetic variants previously reported to be associated with liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in United Kingdom and Japanese cohorts. Results: Association was confirmed for 86 variants. Among …

Guideline For Feedback Of Individual Genetic Research Findings For Genomics Research In Africa, Alice Matimba, Stuart Ali, Katherine Littler, Ebony Madden, Patricia Marshall, Sheryl Mccurdy, Victoria Nembaware, Laura Rodriguez, Janet Seeley, Paulina Tindana, Aminu Yakubu, Jantina De Vries, H3africa Ethics And Community Engagement Working Group

Faculty, Staff and Student Publications

As human genomics research in Africa continues to generate large amounts of data, ethical issues arise regarding how actionable genetic information is shared with research participants. The Human Heredity and Health in Africa Consortium (H3Africa) Ethics and Community Engagement Working group acknowledged the need for such guidance, identified key issues and principles relevant to genomics research in Africa and developed a practical guideline for consideration of feeding back individual genetic results of health importance in African research projects. This included a decision flowchart, providing a logical framework to assist in decision-making and planning for human genomics research projects. Although presented …

Multi-Omics Insights Into The Biological Mechanisms Underlying Statistical Gene-By-Lifestyle Interactions With Smoking And Alcohol Consumption, Timothy D Majarian, Amy R Bentley, Vincent Laville, Michael R Brown, Daniel I Chasman, Paul S De Vries, Mary F Feitosa, Nora Franceschini, W James Gauderman, Casey Marchek, Daniel Levy, Alanna C Morrison, Michael Province, Dabeeru C Rao, Karen Schwander, Yun Ju Sung, Charles N Rotimi, Hugues Aschard, C Charles Gu, Alisa K Manning, Charge Gene-Lifestyle Interactions Working Group

Faculty, Staff and Student Publications

Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium's Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment …

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng

Faculty, Staff and Student Publications

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, several crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

Inhibition Of The Cd47-Sirpα Axis For Cancer Therapy: A Systematic Review And Meta-Analysis Of Emerging Clinical Data, Ji Son, Rodney Cheng-En Hsieh, Heather Y Lin, Kate J Krause, Ying Yuan, Amadeo B Biter, James Welsh, Michael A Curran, David S Hong

Faculty, Staff and Student Publications

CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). …

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and

Comparison Of Psma-Based 18f-Dcfpyl Pet/Ct And Pelvic Multiparametric Mri For Lesion Detection In The Pelvis In Patients With Prostate Cancer, Trinh T Nguyen, Priya R Bhosale, Guofan Xu, Tinsu Pan, Peng Wei, Yang Lu

Faculty, Staff and Student Publications

Purpose: To directly compare the performance of pelvic mpMRI versus recently approved and increasingly used PSMA-based 18F-DCFPyL PET/CT in intermediate-high risk and biochemical recurrent prostate cancer patient cohort while exploring their potential differing applications in specific clinical scenarios.

Methods: A retrospective analysis was performed on patients who had 18F-DCFPyL PET/CT and pelvic mpMRI done from September 2021 to January 2022 at a single institution. The inclusion criteria were paired exams within a 3-month interval. Exclusion criteria were intervening treatment between exams, a change in PSA by more than 50% and absolute difference more than 1 ng/mL, or concurrent history of …

Checkpoint Inhibitors As Immunotherapy For Fungal Infections: Promises, Challenges, And Unanswered Questions, Sebastian Wurster, Stephanie S Watowich, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic …

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang

Faculty, Staff and Student Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …

Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller, Ganesh Rao

Faculty, Staff and Student Publications

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.

Case description: Here, we present the case of …

Highlights From The 7th Oncological Pathology Conference 'Pathological Anatomy In The Context Of The National Cancer Law: An Overview Of The Latin American Experience', 15, 22 And 23 July 2022, Trujillo, Peru, Caddie Laberiano-Fernández, Joan Moreno Luján, Bruno De Carvalho Dornelas, Magali Franco Benites, Patricia Gutiérrez Quispe, Valeria Aguilar Vásquez, Andric Guerrero Espinoza, Elsa Guerra Guerra, Gabriela Gil-Arroyo Álvarez, Juan Astigueta-Pérez, Maria Teresa Garcia De Dávila, Sandro Casavilca Zambrano, Tatiana Vidaurre Rojas, Alejandro Mariños, Emmanuel S González, Rossana Lazcano, Ricardo R Lastra, Isabel Alvarado-Cabrero, Henry Guerra Miller, Ricardo H Bardales, Milagros Abad-Licham

Faculty, Staff and Student Publications

The seventh session of the Oncological Pathology Conference (JoPaO) entitled 'Pathological Anatomy in the context of the National Cancer Law: An overview of the Latin American experience', was held virtually on July 15, 22 and 23. Peru was the headquarters for this event, where 17 national and international professors of high academic standing participated. They interacted in a multidisciplinary context through talks with national panellists and the general public. The recent promulgation of the 'National Cancer Law' fosters the development of discussion forums to analyse the national realities and uphold continuous learning about experiences in other Latin American countries with …

Serglycin Is Involved In Tgf-Β Induced Epithelial-Mesenchymal Transition And Is Highly Expressed By Immune Cells In Breast Cancer Tissue, Marta Tellez-Gabriel, Xavier Tekpli, Trine M Reine, Beate Hegge, Stephanie R Nielsen, Meng Chen, Line Moi, Lisa Svartdal Normann, Lill-Tove R Busund, George A Calin, Gunhild M Mælandsmo, Maria Perander, Achilleas D Theocharis, Svein O Kolset, Erik Knutsen

Faculty, Staff and Student Publications

Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of cancer cells. Here, we show that serglycin expression is upregulated in transforming growth factor beta (TGF-β) induced epithelial-mesenchymal transition (EMT). Functional studies provide evidence that serglycin plays an important role in the regulation of the transition between the epithelial and mesenchymal phenotypes, …

Pathogenic Tau Accelerates Aging-Associated Activation Of Transposable Elements In The Mouse Central Nervous System, Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L Devos, Bradley Hyman, Gabriel Chiu, Ethan R Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J Ray, Bess Frost

Faculty, Staff and Student Publications

Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer's disease and related "tauopathies," and transposable element-induced neurotoxicity. Starting with transcriptomic analyses, we find that age- and tau-induced transposable element activation occurs in the mouse brain. Among transposable elements that are activated at the RNA level in the context of brain aging and tauopathy, we find that the endogenous retrovirus (ERV) class …

Research Career Intentions Among Non-Native English-Speaking Graduate And Postdoctoral Trainees In Stem-Results From Cross-Sectional And Longitudinal Studies, Hwa Young Lee, Shine Chang, Cheryl B Anderson, Erin K Dahlstrom, Carrie Cameron

Faculty, Staff and Student Publications

International graduate trainees, many of whom are non-native English-speaking (L2) trainees, comprise more than half of graduate-level trainees in STEM, but little is known regarding factors that influence their career intentions, especially those that foster their growth as scientists to achieve their full potential in research. Thus, the purpose of our studies was to examine the relationship between L2 status and contextual factors that help shape the learning experiences and plans for research-focused careers. Study 1 collected cross-sectional survey data from doctoral and postdoctoral trainees (N=510) from research institutes in the Texas Medical Center in Houston. We examined which factors …

Transcriptomic-Assisted Immune And Neoantigen Profiling In Premalignancy, Kyle Chang, Florencia Mcallister, Eduardo Vilar

Faculty, Staff and Student Publications

Immune-based cancer therapies such as checkpoint inhibitors (CPI) and vaccines have been increasingly studied across different cancer types. Response to such therapies depends on a number of factors such as mutational burden, neoantigen load, presence of tumor infiltrating lymphocytes, among others. Next-generation sequencing (NGS) technologies are particularly attractive to interrogate the immune response compared to traditional assays such as qRT-PCR and immunohistochemistry (IHC) because they enable the discovery of neoantigens and simultaneous profiling of immune infiltration using gene expression on a large scale. Current approaches in immune profiling utilizes whole-exome sequencing (WES) for human leukocyte allele (HLA) typing and neoantigen …

Cancer Prevention Behaviors In Workers Of A Referral Cancer Center In Mexico City: A Pilot Study On Early Detection Awareness For Cancer, Nancy Reynoso-Noverón, Shine Chang, Luis Alonso Herrera-Montalvo, Abelardo Meneses-García

Faculty, Staff and Student Publications

Background: Prevention strategies for cancer are necessary. Health workers who often serve as role models bear responsibility for prevention counseling and programs. However, whether their habits and behaviors reflect prevention goals are unknown. We describe the prevalence of cancer risk factors and prevention behaviors in health workers of a referral cancer center in Mexico City.

Methods: Cross-sectional study in which workers of the National Cancer Institute were invited to participate in a prevention program, risk factor survey, and nutrition, psychological, and genetic counseling were included. The likelihood of cancer was calculated based on the presence of risk factors. Factors associated …

Electroacupuncture Ameliorates Inflammatory Response Induced By Retinal Ischemia-Reperfusion Injury And Protects The Retina Through The Dor-Bdnf/Trkb Pathway, Runjie Guo, Yongjie Zhang, Yue Geng, Ping Chen, Tiantian Fu, Yong Xia, Ren Zhang, Yuan Zhu, Jingling Jin, Nange Jin, Hong Xu, Xuesong Tian

Faculty, Staff and Student Publications

Objectives: Retinal ischemia-reperfusion injury (RIRI) is the common pathological basis of many ophthalmic diseases in the later stages, and inflammation is the primary damage mechanism of RIRI. Our study aimed to assess whether electroacupuncture (EA) has a protective effect against RIRI and to elucidate its related mechanisms.

Methods: A high-intraocular pressure (HIOP) model was used to simulate RIRI in Wistar rats. EA was applied to the EA1 group [Jingming (BL1) + Shuigou (GV26)] and the EA2 group [Jingming (BL1) + Hegu (LI4)] respectively for 30 min starting immediately after the onset of reperfusion and repeated (30 min/time) at 12 h …

A Multicenter Study Of Icu Resource Utilization In Pediatric, Adolescent And Young Adult Patients Post Car-T Therapy, Dristhi Ragoonanan, Saleh Bhar, Gopi Mohan, Fernando Beltramo, Sajad J Khazal, Caitlin Hurley, Clark Andersen, Steven Margossian, Sattva S Neelapu, Elizabeth Shpall, Cristina Gutierrez, Priti Tewari, Basirat Shoberu, Aimee Talleur, David Mccall, Cesar Nunez, Branko Cuglievan, Francesco Paolo Tambaro, Demetrios Petropoulos, Hisham Abdel-Azim, Kris M Mahadeo

Faculty, Staff and Student Publications

Tisagenlecleucel is associated with remarkable outcomes in treating patients up to the age of 25 years with refractory B-cell acute lymphoblastic leukemia (ALL). Yet, due to unique and potentially life-threatening complications, access remains limited to higher-resource and certified centers. Reports of inequity and related disparities in care are emerging. In this multicenter study of ALL patients admitted for anti-leukemia therapy, who required pediatric intensive care (ICU) support (n = 205), patients receiving tisagenlecleucel (n = 39) were compared to those receiving conventional chemotherapy (n = 166). The median time to ICU transfer was 6 (0-43) versus 1 (0-116) days, respectively …

Immune Checkpoint Inhibitor-Related Gastrointestinal Toxicity In Patients With Malignancy Involving The Luminal Gastrointestinal Tract And Its Impact On Cancer Outcomes, Kevin Yu, Antony Mathew, Fiyinfoluwa Abraham, Rajan Amin, Miho Kono, Michael Overman, Dan Zhao, Anam Khan, Muhammad A Khan, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICI) are known to cause immune-related adverse events (irAE) with the gastrointestinal (GI) tract among the most affected. Our knowledge of GI irAE in patients with luminal GI malignancies is poor. We aimed to characterize the incidence, clinical features, treatment, and outcomes of these GI irAEs.

Methods: This was a retrospective study of patients with malignancies involving the luminal GI tract and GI irAEs at MD Anderson Cancer Center from January 2010 to June 2020. Clinical data were collected and analyzed.

Results: Eighteen patients with luminal GI tract malignancies treated with ICIs had evidence of GI …

Exploiting Induced Vulnerability To Overcome Parpi Resistance And Clonal Heterogeneity In Brca Mutant Triple-Negative Inflammatory Breast Cancer, David J H Shih, Mei-Kuang Chen, Jun Yin, Daniel J Mcgrail, Hui Dai, Rongbin Wei, Jing Zhang, Wenjin Jim Zheng, Kim-Anh Do, Liuqing Yang, Mien-Chie Hung, Shiaw-Yih Lin

Faculty, Staff and Student Publications

Acquired resistance and clonal heterogeneity are critical challenges in cancer treatment, and the lack of effective computational tools hampers the discovery of new treatments to overcome resistance. Using high-throughput transcriptomic databases of compound perturbation profiles, we have developed a bioinformatic strategy for identifying candidate drugs to overcome resistance with combinatorial therapy. We devised this strategy during an investigation into the acquired resistance against PARP inhibitors (PARPi) in a triple-negative inflammatory breast cancer cell line. In this study, we derived multiple PARPi-resistant clones and characterized their transcriptomic adaptations compared to the parental clone. The transcriptomes of the resistant clones showed substantial …

Pld1 Promotes Reactive Oxygen Species Production In Vascular Smooth Muscle Cells And Injury-Induced Neointima Formation, Ming Cai, Ziqing Wang, Thi Thu Trang Luu, Dakai Zhang, Brian Finke, Jingquan He, Li Wei Rachel Tay, Gilbert Di Paolo, Guangwei Du

Faculty, Staff and Student Publications

Phospholipase D (PLD) generates the signaling lipid phosphatidic acid (PA) and has been known to mediate proliferation signal in vascular smooth muscle cells (VSMCs). However, it remains unclear how PLD contributes to vascular diseases. VSMC proliferation directly contributes to the development and progression of cardiovascular disease, such as atherosclerosis and restenosis after angioplasty. Using the mouse carotid artery ligation model, we find that deletion of Pld1 gene inhibits neointima formation of the injuried blood vessels. PLD1 deficiency reduces the proliferation of VSMCs in both injured artery and primary cultures through the inhibition of ERK1/2 and AKT signals. Immunohistochemical staining of …

Granuloma Annulare: An Updated Review Of Epidemiology, Pathogenesis, And Treatment Options, Tejas P Joshi, Madeleine Duvic

Faculty, Staff and Student Publications

Granuloma annulare (GA) is an inflammatory granulomatous skin disease that can be localized (localized GA) or disseminated (generalized GA), with patch, perforating, and subcutaneous subtypes being less common variants of this benign condition. Recently, new research has emerged that further elucidates GA epidemiology and etiopathogenesis; importantly, new therapeutic options for GA have also been described, although there remains a paucity of randomized controlled studies. In this review, we summarize recent updates on GA epidemiology and etiopathogenesis and offer an updated review of the therapeutic options for GA currently reported in the literature. We hope that the current review galvanizes randomized …

The Current Status And Shortcomings Of Stereotactic Radiosurgery, Hunter Mehrens, Trang Nguyen, Sharbacha Edward, Shannon Hartzell, Mallory Glenn, Daniela Branco, Nadia Hernandez, Paola Alvarez, Andrea Molineu, Paige Taylor, Stephen Kry

Faculty, Staff and Student Publications

Background: Stereotactic radiosurgery (SRS) is a common treatment for intracranial lesions. This work explores the state of SRS treatment delivery to characterize current treatment accuracy based on treatment parameters.

Methods: NCI clinical trials involving SRS rely on an end-to-end treatment delivery on a patient surrogate (credentialing phantom) from the Imaging and Radiation Oncology Core (IROC) to test their treatment accuracy. The results of 1072 SRS phantom irradiations between 2012 and 2020 were retrospectively analyzed. Univariate analysis and random forest models were used to associate irradiation conditions with phantom performance. The following categories were evaluated in terms of how they predicted …

High-Resolution Metabolomics Of Exposure To Tobacco Smoke During Pregnancy And Adverse Birth Outcomes In The Atlanta African American Maternal-Child Cohort, Youran Tan, Dana Boyd Barr, P Barry Ryan, Veronika Fedirko, Jeremy A Sarnat, Audrey J Gaskins, Che-Jung Chang, Ziyin Tang, Carmen J Marsit, Elizabeth J Corwin, Dean P Jones, Anne L Dunlop, Donghai Liang

Faculty, Staff and Student Publications

Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014-2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed …

Progression Free Survival Prediction For Head And Neck Cancer Using Deep Learning Based On Clinical And Pet/Ct Imaging Data, Mohamed A Naser, Kareem A Wahid, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Renjie He, Cem Dede, Lisanne V Van Dijk, Clifton D Fuller

Faculty, Staff and Student Publications

Determining progression-free survival (PFS) for head and neck squamous cell carcinoma (HNSCC) patients is a challenging but pertinent task that could help stratify patients for improved overall outcomes. PET/CT images provide a rich source of anatomical and metabolic data for potential clinical biomarkers that would inform treatment decisions and could help improve PFS. In this study, we participate in the 2021 HECKTOR Challenge to predict PFS in a large dataset of HNSCC PET/CT images using deep learning approaches. We develop a series of deep learning models based on the DenseNet architecture using a negative log-likelihood loss function that utilizes PET/CT …

Combining Tumor Segmentation Masks With Pet/Ct Images And Clinical Data In A Deep Learning Framework For Improved Prognostic Prediction In Head And Neck Squamous Cell Carcinoma, Kareem A Wahid, Renjie He, Cem Dede, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Lisanne V Van Dijk, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

PET/CT images provide a rich data source for clinical prediction models in head and neck squamous cell carcinoma (HNSCC). Deep learning models often use images in an end-to-end fashion with clinical data or no additional input for predictions. However, in the context of HNSCC, the tumor region of interest may be an informative prior in the generation of improved prediction performance. In this study, we utilize a deep learning framework based on a DenseNet architecture to combine PET images, CT images, primary tumor segmentation masks, and clinical data as separate channels to predict progression-free survival (PFS) in days for HNSCC …