David R. Giovannucci, Ph.D.
Director, Raymond & Beverly Sackler Laboratory for Neuroendocrine Tumor Research
Office: 105 Block Health Sciences Building
1993: Ph.D., Wayne State University, Detroit, MI.
1998: Postdoctoral Fellow, University of Michigan Medical School, Ann Arbor, MI
2002: Research Assistant Professor, University of Rochester Medical Center, Rochester, NY.
Cellular and molecular basis of peptide and protein secretion; Ca 2+ signaling mechanisms; Neuroendocrine cancer; Mitochondrial function in health and disease.
Electrophysiology; Confocal and multiphoton microscopy; Molecular biology and protein biochemistry.
The exocytotic secretion of peptide neurotransmitters and hormones has wide-ranging consequences for neuronal function, cardiovascular homeostasis and GI tract regulation. Work in our lab is focused on how intracellular levels of Ca 2+, ATP and cyclic AMP control the release of vasoactive molecules. This is achieved using a combination of electrophysiological and optical methods to follow in real-time the secretory activity and Ca 2+ dynamics of single isolated nerve endings and a variety of acutely isolated or cultured cell types.
References (Partial List):
Giovannucci DR & Stuenkel EL. (1995) Glutamate receptor agonists modulate [Ca2+]i in isolated rat melanotropes. Neuroendocrinology 62, 111-122.1.
Giovannucci DR & Stuenkel EL. (1995) An NMDA receptor on isolated secretory nerve endings. Brain Research 702, 246-250.
Giovannucci DR & Stuenkel EL. (1997) Regulation of secretory granule recruitment and exocytosis at rat neurohypophysial nerve endings. Journal of Physiology 498.3, 735-751.
Rusin KI, Giovannucci DR , Stuenkel EL & Moises HC. (1997) k-Opioid receptor activation modulates Ca2+ currents and secretion in isolated neuroendocrine nerve terminals. Journal of Neuroscience 17(17): 6565-74.
Giovannucci DR, Yule, D.I. & Stuenkel EL (1998) Optical measurement of stimulus-evoked membrane turnover in single pancreatic acinar cells. American Journal of Physiology. (3 Pt 1):C732-9.
Giovannucci DR & Stephenson RS. (1999) Identification and distribution of dietary precursors of the Drosophila visual pigment chromophore: analysis of carotenoids in wild type and ninaD mutants by HPLC. Vision Research 39(2):219-29.
Fletcher AI, Shuang R, Giovannucci DR, Zhang L, Bittner M, & Stuenkel EL (1999) Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18. Journal of Biological Chemistry 274(7):4027-35.
Giovannucci DR, Hlubek MD, & Stuenkel EL. (1999) Mitochondria Regulate the Ca2+-exocytosis Relationship of Bovine Adrenal Chromaffin Cells. Journal of Neuroscience 19(21): 9261-9270.
Giovannucci DR , Sneyd J, Groblewski GE & Yule DI. (2000) Modulation of InsP3 receptor properties by phosphorylation. J Korean Med. Sci. S55-6.
Giovannucci DR , Sneyd J, Groblewski GE & Yule DI. (2000) Targeted phosphorylation of the inositol trisphosphate receptor selectively inhibits localized Ca2+ release and shapes oscillatory Ca2+ signals. Journal of Biological Chemistry 275: 33704–33711.
Giovannucci DR , Straub & Yule, DI. (2000) Calcium wave propagation in pancreatic acinar cells: functional interaction of inositol trisphosphate receptors, ryanodine receptors, and mitochondria. Journal of General Physiology 116 :547–559.
Beutner G, Sharma VK, Giovannucci DR, Yule DI, & Sheu S-S. (2001) Identification of a ryanodine receptor in rat heart mitochondria. Journal of Biological Chemistry 276(24): 21482-8.
Bruce JIE, Shuttleworth TJ, Giovannucci DR & Yule DI. (2002) Phosphorylation of inositol 1,4,5-trisphosphate receptors: a mechanism for the synergistic effects of cAMP on Ca2+ signaling. Journal of Biological Chemistry 277(2), 1340-1348.
Giovannucci DR, Bruce JIE, Straub SV, Arreola J, Shuttleworth TJ & Yule DI. Cytosolic Ca2+ and Ca2+-activated Cl- current dynamics: insights from two functionally distinct exocrine cells. Journal of Physiology (2002) 540.2: 469-484.
Straub SV, Giovannucci DR*, Bruce JI & Yule DI. A role for phosphorylation of inositol 1,4,5-trisphosphate receptors in defining calcium signals induced by Peptide agonists in pancreatic acinar cells. (2002) Journal of Biological Chemistry, 277(35): 31949-56.
Sneyd J, Tsaneva-Atanasova K, Bruce JI, Straub SV, Giovannucci DR, Yule DI. (2003) A model of calcium waves in pancreatic and parotid acinar cells. Biophys J. 85(3):1392-405.
Soldo BL, Giovannucci DR*, Stuenkel EL, Moises HC. (2004) Ca2+ and frequency dependence of exocytosis in isolated somata of magnocellular supraoptic neurones of the rat hypothalamus. J Physiol. 16;555(Pt 3):699-711.
Bruce JI, Giovannucci DR, Blinder G, Shuttleworth TJ, Yule DI. (2004) Modulation of [Ca2+]i signaling dynamics and metabolism by perinuclear mitochondria in mouse parotid acinar cells. J Biol Chem. 279(13):12909-17.
Chen Y, Warner JD, Yule DI, Giovannucci DR. (2005) Spatiotemporal Analysis of Exocytosis in Mouse Parotid Acinar Cells. American Journal of Physiology (Cell), published on-line ahead of print.
Yuan Z, Cai T, Tian J, Ivanov AV, Giovannucci DR, Xie Z. (2005) Na/K-ATPase Tethers Phospholipase C and IP3 Receptor into a Calcium-regulatory Complex. Mol Biol Cell. 2005 16(9): 4034-45.
Mignen O, Brink C, Enfissi A, Nadkarni A, Shuttleworth TJ, Giovannucci DR, Capiod, T. (2005) Carboxyamidotriazole-induced inhibition of mitochondrial calcium import blocks capacitative calcium entry and cell proliferation in HEK 293 cells. J Cell Sci. 2005 118(Pt 23): 5615-23.
Peters CG, Miller DF, Giovannucci DR. (2006) Identification, localization and interaction of SNARE proteins in atrial cardiac
myocytes, Journal of Molecular and Cellular Cardiology 40(3): 361-374.