Research Interests:
Functional genomics. Advances in high-throughput genotyping technologies and large collaborative efforts which combine genetic datasets have brought to light several novel candidate genes involved in a variety of diseases. In particular, studies of complex trait diseases such as diabetes and cardiovascular disease have been great beneficiaries of these efforts and a number of highly replicated loci have been identified. The bottleneck in translating these findings towards clinical intervention is determining the causative mechanisms of the allelic variants within these loci. To this end, one of the primary goals of my laboratory is to leverage clinically relevant genetic data with functional data at the cellular level.
Functional mapping. One of our current initiatives is "functional mapping of diabetes-susceptibility loci" to identify novel genes involved in diabetes. In brief, we systematically dissect clinically relevant chromosome regions with molecular biology strategies that alter the expression of candidate genes. Expression of specific allelic variants and/or gene knockdown (via RNA interference methods) are functionally assessed by a panel of cell-based functional assays.
 High-throughput, high-content screening. A second area of research in my laboratory is the development of cell-based assays for our functional mapping projects. The goal of this research area is to increase the throughput of the functional screening by assay miniturization and multiplexing readouts. Our current strategies include a combination of assays that are image-based (via automated fluorescence microscopy) and plate reader-based (fluorescence, luminescence, absorbance).
Other reseach interests include metabolism-secretion coupling, beta-cell transcription factors, and the mechanisms of antigen presentation in regards to type I diabetes.
Publications:
Peter A. Antinozzi, Alejandro Garcia-Diaz, Chuan Hu, and James E. Rothman. 2006. Functional mapping of disease-susceptibility loci using cell biology. Proc. Nat. Acad. Sci. 103:3698-3703.
Wang H, Iezzi M, Theander S, Peter A. Antinozzi, Gauthier BR, Halban PA, Wollheim CB. 2005. Suppression of Pdx-1 perturbs proinsulin processing, insulin secretion and GLP-1 signalling in INS-1 cells. Diabetologia 8(4):720-31.
Wang, H., Maechler, P., Peter A. Antinozzi, Herrero, L., Hagenfeldt-Johansson, K. and Wollheim, C.B. 2003. The transcription factor SREBP-1c is instrumental in the development of pancreatic b-cell lipotoxicity. J. Biol.Chem. 278:16622-16629.
Peter A. Antinozzi, Hisamitsu Ishihara, Christopher B. Newgard, Claes, B. Wollheim. 2002 Mitochondrial metabolism sets the maximal limit of fuel-stimulated insulin secretion in a model pancreatic beta-cell: A survey of four fuel-secretagogues. J. Biol. Chem. 277:11746-11755.
Blanca Rubí, Peter A. Antinozzi, Pierre Maechler, Laura Herrero, Hisamitsu Ishihara, Guillermina Asins, Dolors Serra, Claes B. Wollheim, Fausto G. Hegardt. 2002. Adenovirus-mediated overexpression of liver carnitine palmitoyl transferase I in INS1E cells. Effects on cell metabolism and insulin secretion. Biochem. J. 364:219-226.
Robert H. Skelly, Barton L. Wicksteed, Peter A. Antinozzi, Christopher J. Rhodes. 2001. Glycerol stimulated proinsulin biosynthesis in isolated pancreatic rat islets via recombinant adenovirus induced expression of glycerol kinase is mediated via mitochondrial metabolism. Diabetes 50:1791-1798.
Hindrik Mulder, Danhong Lu, John Finley IV, Jie An, Jonathan Cohen, Peter A. Antinozzi, J. Denis McGarry, Christopher B. Newgard. 2001. Overexpression of a modified human malonyl-CoA decarboxylase blocks the glucose-induced increase in malonyl CoA level but has no impact on insulin secretion in INS-1-derived (832/13) b-cells. J. Biol. Chem. 276:6479-6484.
Haiyan Wang, Pierre Maechler, Peter A. Antinozzi, Kerstin A. Hagenfeldt, Claes B. Wollheim. 2000. HNF4a regulates the expression of pancreatic b-cell genes implicated in glucose metabolism and nutrient-induced insulin secretion. J. Biol. Chem. 275:35953-35959.
Pierre Maechler, Peter A. Antinozzi, Claes B. Wollheim. 2000. Modulation of glutamate levels in the mitochondria affects hormone secretion in INS1-E b-cells. IUBMB Life 50:27-31.
Haiyan Wang, Peter A. Antinozzi, Kerstin A. Hagenfeldt, Pierre Maechler, Claes B. Wollheim 2000. Molecular targets of a human HNF1a mutation responsible for pancreatic b-cell dysfunction. EMBO J. 19(16):4257-4264.
Hal K. Berman, Khiet Trinh, Robert M. O'Doherty, Peter A. Antinozzi, Rosa Gasa, Christopher B. Newgard. 2000. Metabolic mechanisms and diabetes candidate genes: insights gained from genetic engineering with recombinant adenoviruses. Molecular Pathogenesis of MODY's. vol 15. pp 61-84.
Peter A. Antinozzi, Hal K. Berman, Robert M O'Doherty, Christopher B. Newgard. 1999. Metabolic engineering with recombinant adenoviruses. Annu. Rev. Nutr. 19:511-544.
Peter A. Antinozzi, Laura Segall, Marc Prentki, J. Denis McGarry, Christopher B. Newgard. 1998. Molecular or pharmacologic perturbation of the link between glucose and lipid metabolism is without effect on glucose-stimulated insulin secretion: a re-evaluation of the long-chain acyl CoA hypothesis. J. Biol. Chem 273:16146-16154.
Richard J. Noel, Peter A. Antinozzi , J. Denis McGarry, Christopher B. Newgard. 1997. Engineering of glycerol-stimulated insulin secretion in islet b-cells. J. Biol. Chem. 272:18621-18627.
Peter A. Antinozzi, Charles M. Brown, Daniel L. Purich. 1992. Calcium oxalate monohydrate crystallization: citrate inhibition of nucleation and growth steps. Journal of Crystal Growth 125:215-222.
For a listing of additional publications, refer to PubMed, a service provided by the National Library of Medicine
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