Browsing by Author "Naren, Anjaparavanda P."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair
    (Elsevier, 2015-09) Balogh, Andrea; Shimizu, Yoshibumi; Lee, Sue Chin; Norman, Derek D.; Gangwar, Ruchika; Bavaria, Mitul; Moon, ChangSuk; Shukla, Pradeep; Rao, Radakrishna; Ray, Ramesh; Naren, Anjaparavanda P.; Banerje, Souvik; Miller, Duane D.; Balazs, Louisa; Pelus, Louis; Tigyi, Gabor; Department of Microbiology and Immunology, IU School of Medicine
    In this study we characterized the effects of radiation injury on the expression and function of the autotaxin (ATX)-LPA2 GPCR axis. In IEC-6 crypt cells and jejunum enteroids quantitative RT-PCR showed a time- and dose-dependent upregulation of lpa2 in response to γ-irradiation that was abolished by mutation of the NF-κB site in the lpa2 promoter or by inhibition of ATM/ATR kinases with CGK-733, suggesting that lpa2 is a DNA damage response gene upregulated by ATM via NF-κB. The resolution kinetics of the DNA damage marker γ-H2AX in LPA-treated IEC-6 cells exposed to γ-irradiation was accelerated compared to vehicle, whereas pharmacological inhibition of LPA2 delayed the resolution of γ-H2AX. In LPA2-reconstituted MEF cells lacking LPA1&3 the levels of γ-H2AX decreased rapidly, whereas in Vector MEF were high and remained sustained. Inhibition of ERK1&2 or PI3K/AKT signaling axis by pertussis toxin or the C311A/C314A/L351A mutation in the C-terminus of LPA2 abrogated the effect of LPA on DNA repair. LPA2 transcripts in Lin(-)Sca-1(+)c-Kit(+) enriched for bone marrow stem cells were 27- and 5-fold higher than in common myeloid or lymphoid progenitors, respectively. Furthermore, after irradiation higher residual γ-H2AX levels were detected in the bone marrow or jejunum of irradiated LPA2-KO mice compared to WT mice. We found that γ-irradiation increases plasma ATX activity and LPA level that is in part due to the previously established radiation-induced upregulation of TNFα. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair.
  • Thumbnail Image
    Item
    Elexacaftor/Tezacaftor/Ivacaftor Improved Clinical Outcomes in a Patient with N1303K-CFTR Based on In Vitro Experimental Evidence
    (American Thoracic Society, 2021) Huang, Yunjie; Paul, Grace; Lee, Jesun; Yarlagadda, Sunitha; McCoy, Karen; Naren, Anjaparavanda P.; Pediatrics, School of Medicine
  • Thumbnail Image
    Item
    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.