Browsing by Author "Campbell-Thompson, Martha"

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    A genomic data archive from the Network for Pancreatic Organ donors with Diabetes
    (Springer Nature, 2023-05-26) Perry, Daniel J.; Shapiro, Melanie R.; Chamberlain, Sonya W.; Kusmartseva, Irina; Chamala, Srikar; Balzano-Nogueira, Leandro; Yang, Mingder; Brant, Jason O.; Brusko, Maigan; Williams, MacKenzie D.; McGrail, Kieran M.; McNichols, James; Peters, Leeana D.; Posgai, Amanda L.; Kaddis, John S.; Mathews, Clayton E.; Wasserfall, Clive H.; Webb-Robertson, Bobbie-Jo M.; Campbell-Thompson, Martha; Schatz, Desmond; Evans-Molina, Carmella; Pugliese, Alberto; Concannon, Patrick; Anderson, Mark S.; German, Michael S.; Chamberlain, Chester E.; Atkinson, Mark A.; Brusko, Todd M.; Pediatrics, School of Medicine
    The Network for Pancreatic Organ donors with Diabetes (nPOD) is the largest biorepository of human pancreata and associated immune organs from donors with type 1 diabetes (T1D), maturity-onset diabetes of the young (MODY), cystic fibrosis-related diabetes (CFRD), type 2 diabetes (T2D), gestational diabetes, islet autoantibody positivity (AAb+), and without diabetes. nPOD recovers, processes, analyzes, and distributes high-quality biospecimens, collected using optimized standard operating procedures, and associated de-identified data/metadata to researchers around the world. Herein describes the release of high-parameter genotyping data from this collection. 372 donors were genotyped using a custom precision medicine single nucleotide polymorphism (SNP) microarray. Data were technically validated using published algorithms to evaluate donor relatedness, ancestry, imputed HLA, and T1D genetic risk score. Additionally, 207 donors were assessed for rare known and novel coding region variants via whole exome sequencing (WES). These data are publicly-available to enable genotype-specific sample requests and the study of novel genotype:phenotype associations, aiding in the mission of nPOD to enhance understanding of diabetes pathogenesis to promote the development of novel therapies.
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    Design and Rationale for the Use of Magnetic Resonance Imaging Biomarkers to Predict Diabetes After Acute Pancreatitis in the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: From the Type 1 Diabetes in Acute Pancreatitis Consortium
    (Wolters Kluwer, 2022) Tirkes, Temel; Chinchilli, Vernon M.; Bagci, Ulas; Parker, Jason G.; Zhao, Xuandong; Dasyam, Anil K.; Feranec, Nicholas; Grajo, Joseph R.; Shah, Zarine K.; Poullos, Peter D.; Spilseth, Benjamin; Zaheer, Atif; Xie, Karen L.; Wachsman, Ashley M.; Campbell-Thompson, Martha; Conwell, Darwin L.; Fogel, Evan L.; Forsmark, Christopher E.; Hart, Phil A.; Pandol, Stephen J.; Park, Walter G.; Pratley, Richard E.; Yazici, Cemal; Laughlin, Maren R.; Andersen, Dana K.; Serrano, Jose; Bellin, Melena D.; Yadav, Dhiraj; Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC); Radiology and Imaging Sciences, School of Medicine
    This core component of the Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM) study will examine the hypothesis that advanced magnetic resonance imaging (MRI) techniques can reflect underlying pathophysiologic changes and provide imaging biomarkers that predict diabetes mellitus (DM) following acute pancreatitis (AP). A subset of participants in the DREAM study will enroll and undergo serial MRI examinations using a specific research protocol. We aim to differentiate at-risk individuals from those who remain euglycemic by identifying parenchymal features following AP. Performing longitudinal MRI will enable us to observe and understand the natural history of post-AP DM. We will compare MRI parameters obtained by interrogating tissue properties in euglycemic, prediabetic and incident diabetes subjects and correlate them with metabolic, genetic, and immunological phenotypes. Differentiating imaging parameters will be combined to develop a quantitative composite risk score. This composite risk score will potentially have the ability to monitor the risk of DM in clinical practice or trials. We will use artificial intelligence, specifically deep learning, algorithms to optimize the predictive ability of MRI. In addition to the research MRI, the DREAM study will also correlate clinical computerized tomography and MRI scans with DM development.
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    Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19
    (Elsevier, 2020-11-13) Kusmartseva, Irina; Wu, Wenting; Syed, Farooq; Van Der Heide, Verena; Jorgensen, Marda; Joseph, Paul; Tang, Xiaohan; Candelario-Jalil, Eduardo; Yang, Changjun; Nick, Harry; Harbert, Jack L.; Posgai, Amanda L.; Paulsen, John David; Lloyd, Richard; Cechin, Sirlene; Pugliese, Alberto; Campbell-Thompson, Martha; Vander Heide, Richard S.; Evans-Molina, Carmella; Homann, Dirk; Atkinson, Mark A.; Medical and Molecular Genetics, School of Medicine
    Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.
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    Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases: Workshop Proceedings
    (Wolters Kluwer, 2022) Mastracci, Teresa L.; Apte, Minoti; Amundadottir, Laufey T.; Alvarsson, Alexandra; Artandi, Steven; Bellin, Melena D.; Bernal-Mizrachi, Ernesto; Caicedo, Alejandro; Campbell-Thompson, Martha; Cruz-Monserrate, Zobeida; El Ouaamari, Abdelfattah; Gaulton, Kyle J.; Geisz, Andrea; Goodarzi, Mark O.; Hara, Manami; Hull-Meichle, Rebecca L.; Kleger, Alexander; Klein, Alison P.; Kopp, Janel L.; Kulkarni, Rohit N.; Muzumdar, Mandar D.; Naren, Anjaparavanda P.; Oakes, Scott A.; Olesen, Søren S.; Phelps, Edward A.; Powers, Alvin C.; Stabler, Cherie L.; Tirkes, Temel; Whitcomb, David C.; Yadav, Dhiraj; Yong, Jing; Zaghloul, Norann A.; Sander, Maike; Pandol, Stephen J.; Biology, School of Science
    The Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases Workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report summarizes the workshop proceedings. The goal of the workshop was to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into six major themes, including: (a) Pancreas Anatomy and Physiology; (b) Diabetes in the Setting of Exocrine Disease; (c) Metabolic Influences on the Exocrine Pancreas; (d) Genetic Drivers of Pancreatic Diseases; (e) Tools for Integrated Pancreatic Analysis; and (f) Implications of Exocrine-Endocrine Crosstalk. For each theme, there were multiple presentations followed by panel discussions on specific topics relevant to each area of research; these are summarized herein. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of the normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.
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    Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Type 1 Diabetes in Acute Pancreatitis Consortium
    (Wolters Kluwer, 2022) Wasserfall, Clive; Dyer, Anne-Marie; Speake, Cate; Andersen, Dana K.; Baab, Kendall Thomas; Bellin, Melena D.; Broach, James R.; Campbell-Thompson, Martha; Chinchilli, Vernon M.; Lee, Peter J.; Park, Walter G.; Pratley, Richard E.; Saloman, Jami L.; Sims, Emily K.; Tang, Gong; Yadav, Dhiraj; Yazici, Cemal; Conwell, Darwin L.; Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC); Pediatrics, School of Medicine
    Differences in methods for biospecimen collection, processing, and storage can yield considerable variability and error. Therefore, best practices for standard operating procedures are critical for successful discovery, development, and validation of disease biomarkers. Here, we describe standard operating procedures developed for biospecimen collection during the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) Study within the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC). Notably these protocols were developed using an integrative process based on prior consortium experience and with input from working groups with expertise in immunology, pancreatitis and diabetes. Publication and adoption consistent biospecimen protocols will inform future studies and allow for better comparisons across different metabolic research efforts.