Specific aims of this study are (i) To determine whether liver DC convert from inert inducers of tolerance to potent immune-stimulators and mediators of inflammation in liver fibrosis, (ii) To determine the contributory role of DC in the pathogenesis of fibrosis and their direct role in HSC activation, (iii) To determine whether blockade of the immunogenic function of liver DC can mitigate the fibrogenic response to liver injury. In vitro and in vivo experiments in Aims 2 and 3 were affected by our loss of cell cultures, mice, and our lab shutdown and then relocation. An extension will help us complete the Aims of the grant which has been very fruitful till this point.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
3K08DK085278-05S1
Application #
8673488
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
2014-01-21
Project End
2016-01-20
Budget Start
2014-01-21
Budget End
2016-01-20
Support Year
5
Fiscal Year
2014
Total Cost
$148,595
Indirect Cost
$11,007
Name
New York University
Department
Surgery
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Daley, Donnele; Mani, Vishnu R; Mohan, Navyatha et al. (2017) Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance. Nat Med 23:556-567
Greco, Stephanie H; Torres-Hernandez, Alejandro; Kalabin, Aleksandr et al. (2016) Mincle Signaling Promotes Con A Hepatitis. J Immunol 197:2816-27
Deutsch, M; Graffeo, C S; Rokosh, R et al. (2015) Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury. Cell Death Dis 6:e1759
Seifert, Lena; Deutsch, Michael; Alothman, Sara et al. (2015) Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways. Cell Rep 13:1909-1921
Rao, Raghavendra; Graffeo, Christopher S; Gulati, Rishabh et al. (2014) Interleukin 17-producing ??T cells promote hepatic regeneration in mice. Gastroenterology 147:473-84.e2
Zambirinis, Constantinos P; Ochi, Atsuo; Barilla, Rocky et al. (2013) Induction of TRIF- or MYD88-dependent pathways perturbs cell cycle regulation in pancreatic cancer. Cell Cycle 12:1153-4
Henning, Justin R; Graffeo, Christopher S; Rehman, Adeel et al. (2013) Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice. Hepatology 58:589-602
Rehman, Adeel; Hemmert, Keith C; Ochi, Atsuo et al. (2013) Role of fatty-acid synthesis in dendritic cell generation and function. J Immunol 190:4640-9
Court, Helen; Amoyel, Marc; Hackman, Michael et al. (2013) Isoprenylcysteine carboxylmethyltransferase deficiency exacerbates KRAS-driven pancreatic neoplasia via Notch suppression. J Clin Invest 123:4681-94
Ochi, Atsuo; Graffeo, Christopher S; Zambirinis, Constantinos P et al. (2012) Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans. J Clin Invest 122:4118-29

Showing the most recent 10 out of 18 publications