The Hofer laboratory applies a wide range of molecular, biophysical and fluorescence imaging techniques for probing interactions between two fundamental second messengers, cyclic AMP (cAMP) and calcium. Her team discovered a new signal transduction pathway that connects calcium levels within the ER lumen to the activation of the enzyme that generates cAMP, adenylyl cyclase. Her group has also devised approaches to monitor and tune cAMP in various subcellular compartments using targeted genetically encoded sensors and tools.
The ciliopathy-tauopathy connection in neurodegenerative disorders
Another dimension to calcium signaling: a look at extracellular calcium. J Cell Sci. 2005 Mar 01; 118(Pt 5):855-62.
Another dimension to calcium signaling: a look at extracellular calcium.
Gerbino A, Hofer AM, McKay B, Lau BW, Soybel DI
Divalent cations regulate acidity within the lumen and tubulovesicle compartment of gastric parietal cells. Gastroenterology. 2004 Jan; 126(1):182-95.
Divalent cations regulate acidity within the lumen and tubulovesicle compartment of gastric parietal cells.
Murakami T, Ockinger J, Yu J, Byles V, McColl A, Hofer AM, Horng T
Proceedings of the National Academy of Sciences of the United States of America
Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci U S A. 2012 Jul 10; 109(28):11282-7.
Critical role for calcium mobilization in activation of the NLRP3 inflammasome.
Gerbino A, Ruder WC, Curci S, Pozzan T, Zaccolo M, Hofer AM
Termination of cAMP signals by Ca2+ and G(alpha)i via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations. J Cell Biol. 2005 Oct 24; 171(2):303-12.
Termination of cAMP signals by Ca2+ and G(alpha)i via extracellular Ca2+ sensors: a link to intracellular Ca2+ oscillations.
Maiellaro I, Lefkimmiatis K, Moyer MP, Curci S, Hofer AM
Journal of cellular and molecular medicine
Termination and activation of store-operated cyclic AMP production. J Cell Mol Med. 2012 Nov; 16(11):2715-25.
Termination and activation of store-operated cyclic AMP production.
The extracellular calcium-sensing receptor and cell-cell signaling in epithelia. Cell Calcium. 2004 Mar; 35(3):297-306.
The extracellular calcium-sensing receptor and cell-cell signaling in epithelia.
Extracellular calcium and cAMP: second messengers as "third messengers"? Physiology (Bethesda). 2007 Oct; 22:320-7.
Extracellular calcium and cAMP: second messengers as "third messengers"?
Cardone A, Lopez F, Affortunato F, Busco G, Hofer AM, Mallamaci R, Martinelli C, Colella M, Farinola GM
An aryleneethynylene fluorophore for cell membrane staining. Biochim Biophys Acta. 2012 Nov; 1818(11):2808-17.
An aryleneethynylene fluorophore for cell membrane staining.
Methods in molecular biology (Clifton, N.J.)
Measurement of free [Ca2+] changes in agonist-sensitive internal stores using compartmentalized fluorescent indicators. Methods Mol Biol. 2006; 312:229-47.
Measurement of free [Ca2+] changes in agonist-sensitive internal stores using compartmentalized fluorescent indicators.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Spatial distribution and quantitation of free luminal [Ca] within the InsP3-sensitive internal store of individual BHK-21 cells: ion dependence of InsP3-induced Ca release and reloading. FASEB J. 1995 Jun; 9(9):788-98.
Spatial distribution and quantitation of free luminal [Ca] within the InsP3-sensitive internal store of individual BHK-21 cells: ion dependence of InsP3-induced Ca release and reloading.
Direct measurement of free Ca in organelles of gastric epithelial cells. Am J Physiol. 1994 Sep; 267(3 Pt 1):G442-51.
Direct measurement of free Ca in organelles of gastric epithelial cells.
Landolfi B, Curci S, Debellis L, Pozzan T, Hofer AM
Ca2+ homeostasis in the agonist-sensitive internal store: functional interactions between mitochondria and the ER measured In situ in intact cells. J Cell Biol. 1998 Sep 07; 142(5):1235-43.
Ca2+ homeostasis in the agonist-sensitive internal store: functional interactions between mitochondria and the ER measured In situ in intact cells.
K-induced alkalinization in all cell types of rabbit gastric glands: a novel K/H exchange mechanism. J Membr Biol. 1992 Mar; 126(3):245-56.
K-induced alkalinization in all cell types of rabbit gastric glands: a novel K/H exchange mechanism.
ATP regulates calcium leak from agonist-sensitive internal calcium stores. FASEB J. 1996 Feb; 10(2):302-8.
ATP regulates calcium leak from agonist-sensitive internal calcium stores.
ShEEP Request for Leica SP8 Confocal Microscope with Light Sheet
Kuo IY, Brill AL, Lemos FO, Jiang JY, Falcone JL, Kimmerling EP, Cai Y, Dong K, Kaplan DL, Wallace DP, Hofer AM, Ehrlich BE
Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2. Sci Signal. 2019 05 07; 12(580).
Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2.
Hayakawa H, Hofer A, Thelander L, Kitajima S, Cai Y, Oshiro S, Yakushiji H, Nakabeppu Y, Kuwano M, Sekiguchi M
Metabolic fate of oxidized guanine ribonucleotides in mammalian cells. Biochemistry. 1999 Mar 23; 38(12):3610-4.
Metabolic fate of oxidized guanine ribonucleotides in mammalian cells.
Veterans Affairs Boston Healthcare System
Direct visualization of cAMP signaling in primary cilia reveals up-regulation of ciliary GPCR activity following Hedgehog activation. Proc Natl Acad Sci U S A. 2019 06 11; 116(24):12066-12071.
Direct visualization of cAMP signaling in primary cilia reveals up-regulation of ciliary GPCR activity following Hedgehog activation.
Associate Professor of Physical Medicine and Rehabilitation
Aldo R. Castaneda Professor of Cardiovascular Research, Emeritus
cAMPing out with the keepers of the gate: Adenylyl cyclases get cozy with Orai. Cell Calcium. 2019 09; 82:102054.
cAMPing out with the keepers of the gate: Adenylyl cyclases get cozy with Orai.
University of California at Berkeley, Physiology
Research Associate in Biological Chemistry and Molecular Pharmacology - CTD
Harnessing the potential of GPCRs localized to the primary cilium for the treatment of renal disease
Kitamura Y, Kanaya N, Moleirinho S, Du W, Reinshagen C, Attia N, Bronisz A, Revai Lechtich E, Sasaki H, Mora JL, Brastianos PK, Falcone JL, Hofer AM, Franco A, Shah K
Anti-EGFR VHH-armed death receptor ligand-engineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers. Sci Adv. 2021 03; 7(10).
Anti-EGFR VHH-armed death receptor ligand-engineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers.
Cyclic AMP does double duty to support parallel signaling in primary cilium and cytosol. Cell Calcium. 2021 07; 97:102436.
Cyclic AMP does double duty to support parallel signaling in primary cilium and cytosol.
Editorial overview: Calcium signaling. Curr Opin Physiol. 2020 Oct; 17:iii-v.
Imaging the cAMP Signaling Microdomain of the Primary Cilium Using Targeted FRET-Based Biosensors. Methods Mol Biol. 2022; 2483:77-92.
Imaging the cAMP Signaling Microdomain of the Primary Cilium Using Targeted FRET-Based Biosensors.
The Love Story between Orai Calcium Entry Channels and Adenylyl Cyclases Gets even more Complicated. Function (Oxf). 2021; 2(5):zqab044.
The Love Story between Orai Calcium Entry Channels and Adenylyl Cyclases Gets even more Complicated.
Defining the Specialized Functions of cAMP Signals in an Organelle Formerly Deemed to Have No Function: The Primary Cilium. Function (Oxf). 2023; 4(2):zqad007.
Defining the Specialized Functions of cAMP Signals in an Organelle Formerly Deemed to Have No Function: The Primary Cilium.
Strobel MR, Zhou Y, Qiu L, Hofer AM, Chen X
bioRxiv : the preprint server for biology
Temporal Ablation of the Ciliary Protein IFT88 Alters Normal Brainwave Patterns. bioRxiv. 2024 Nov 27.
Temporal Ablation of the Ciliary Protein IFT88 Alters Normal Brainwave Patterns.
The inner and outer compartments of mitochondria are sites of distinct cAMP/PKA signaling dynamics. J Cell Biol. 2013 Aug 05; 202(3):453-62.
The inner and outer compartments of mitochondria are sites of distinct cAMP/PKA signaling dynamics.
Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns. Sci Rep. 2025 01 02; 15(1):347.
Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns.
Ca²? signaling at membrane contact sites. Cell Calcium. 2015 Oct; 58(4):331-2.
Ca²? signaling at membrane contact sites.
Nichols JM, Maiellaro I, Abi-Jaoude J, Curci S, Hofer AM
American journal of physiology. Gastrointestinal and liver physiology
"Store-operated" cAMP signaling contributes to Ca2+-activated Cl- secretion in T84 colonic cells. Am J Physiol Gastrointest Liver Physiol. 2015 Oct 15; 309(8):G670-9.
"Store-operated" cAMP signaling contributes to Ca2+-activated Cl- secretion in T84 colonic cells.
Novel STIM1-dependent cyclic AMP signaling pathway in colonic epithelial function
Probing the cAMP signaling microdomain of the primary cilium
Store-operated cAMP signaling in colon pathophysiology
VA Boston Healthcare System, W. Roxbury VA Med Ctr
Recent advances in understanding the extracellular calcium-sensing receptor. F1000Res. 2016; 5.
Recent advances in understanding the extracellular calcium-sensing receptor.
Caroppo R, Gerbino A, Fistetto G, Colella M, Debellis L, Hofer AM, Curci S
Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion. J Cell Biol. 2004 Jul 05; 166(1):111-9.
Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion.
Quantification of intraluminal free [Ca] in the agonist-sensitive internal calcium store using compartmentalized fluorescent indicators: some considerations. Cell Calcium. 1996 Sep; 20(3):235-42.
Quantification of intraluminal free [Ca] in the agonist-sensitive internal calcium store using compartmentalized fluorescent indicators: some considerations.
Interrogating cyclic AMP signaling using optical approaches. Cell Calcium. 2017 06; 64:47-56.
Interrogating cyclic AMP signaling using optical approaches.
Zou J, Hofer AM, Lurtz MM, Gadda G, Ellis AL, Chen N, Huang Y, Holder A, Ye Y, Louis CF, Welshhans K, Rehder V, Yang JJ
Developing sensors for real-time measurement of high Ca2+ concentrations. Biochemistry. 2007 Oct 30; 46(43):12275-88.
Developing sensors for real-time measurement of high Ca2+ concentrations.
Measurement of free [Ca2+] changes in agonist-sensitive internal stores using compartmentalized fluorescent indicators. Methods Mol Biol. 1999; 114:249-65.
Review series on the extracellular Ca(2+)-sensing receptor. J Cell Mol Med. 2007 Sep-Oct; 11(5):906-7.
Review series on the extracellular Ca(2+)-sensing receptor.
Caroppo R, Gerbino A, Debellis L, Kifor O, Soybel DI, Brown EM, Hofer AM, Curci S
Asymmetrical, agonist-induced fluctuations in local extracellular [Ca(2+)] in intact polarized epithelia. EMBO J. 2001 Nov 15; 20(22):6316-26.
Asymmetrical, agonist-induced fluctuations in local extracellular [Ca(2+)] in intact polarized epithelia.
Evidence that Ca(2+) cycling by the plasma membrane Ca(2+)-ATPase increases the 'excitability' of the extracellular Ca(2+)-sensing receptor. J Cell Sci. 2003 Apr 15; 116(Pt 8):1527-38.
Evidence that Ca(2+) cycling by the plasma membrane Ca(2+)-ATPase increases the 'excitability' of the extracellular Ca(2+)-sensing receptor.
Extracellular calcium sensing and signalling. Nat Rev Mol Cell Biol. 2003 Jul; 4(7):530-8.
Extracellular calcium sensing and signalling.
Lefkimmiatis K, Srikanthan M, Maiellaro I, Moyer MP, Curci S, Hofer AM
Store-operated cyclic AMP signalling mediated by STIM1. Nat Cell Biol. 2009 Apr; 11(4):433-42.
Store-operated cyclic AMP signalling mediated by STIM1.
Capacitative Ca2+ entry is closely linked to the filling state of internal Ca2+ stores: a study using simultaneous measurements of ICRAC and intraluminal [Ca2+]. J Cell Biol. 1998 Jan 26; 140(2):325-34.
Capacitative Ca2+ entry is closely linked to the filling state of internal Ca2+ stores: a study using simultaneous measurements of ICRAC and intraluminal [Ca2+].
Lefkimmiatis K, Moyer MP, Curci S, Hofer AM
"cAMP sponge": a buffer for cyclic adenosine 3', 5'-monophosphate. PLoS One. 2009 Nov 03; 4(11):e7649.
"cAMP sponge": a buffer for cyclic adenosine 3', 5'-monophosphate.
Roy J, Lefkimmiatis K, Moyer MP, Curci S, Hofer AM
The {omega}-3 fatty acid eicosapentaenoic acid elicits cAMP generation in colonic epithelial cells via a "store-operated" mechanism. Am J Physiol Gastrointest Liver Physiol. 2010 Sep; 299(3):G715-22.
The {omega}-3 fatty acid eicosapentaenoic acid elicits cAMP generation in colonic epithelial cells via a "store-operated" mechanism.
Hofer AM, Curci S, Doble MA, Brown EM, Soybel DI
Intercellular communication mediated by the extracellular calcium-sensing receptor. Nat Cell Biol. 2000 Jul; 2(7):392-8.
Intercellular communication mediated by the extracellular calcium-sensing receptor.
Measurement of free [Ca²+] changes in agonist-sensitive internal stores using compartmentalized fluorescent indicators. Methods Mol Biol. 2005; 312:229-47.
Measurement of free [Ca²+] changes in agonist-sensitive internal stores using compartmentalized fluorescent indicators.
Lau BW, Colella M, Ruder WC, Ranieri M, Curci S, Hofer AM
Deoxycholic acid activates protein kinase C and phospholipase C via increased Ca2+ entry at plasma membrane. Gastroenterology. 2005 Mar; 128(3):695-707.
Deoxycholic acid activates protein kinase C and phospholipase C via increased Ca2+ entry at plasma membrane.
Technique for in situ measurement of calcium in intracellular inositol 1,4,5-trisphosphate-sensitive stores using the fluorescent indicator mag-fura-2. Proc Natl Acad Sci U S A. 1993 Apr 01; 90(7):2598-602.
Technique for in situ measurement of calcium in intracellular inositol 1,4,5-trisphosphate-sensitive stores using the fluorescent indicator mag-fura-2.
Schwarzer C, Wong S, Shi J, Matthes E, Illek B, Ianowski JP, Arant RJ, Isacoff E, Vais H, Foskett JK, Maiellaro I, Hofer AM, Machen TE
Pseudomonas aeruginosa Homoserine lactone activates store-operated cAMP and cystic fibrosis transmembrane regulator-dependent Cl- secretion by human airway epithelia. J Biol Chem. 2010 Nov 05; 285(45):34850-63.
Pseudomonas aeruginosa Homoserine lactone activates store-operated cAMP and cystic fibrosis transmembrane regulator-dependent Cl- secretion by human airway epithelia.
Interactions between calcium and cAMP signaling. Curr Med Chem. 2012; 19(34):5768-73.
Interactions between calcium and cAMP signaling.
Gerbino A, Fistetto G, Colella M, Hofer AM, Debellis L, Caroppo R, Curci S
Real time measurements of water flow in amphibian gastric glands: modulation via the extracellular Ca2+-sensing receptor. J Biol Chem. 2007 May 04; 282(18):13477-86.
Real time measurements of water flow in amphibian gastric glands: modulation via the extracellular Ca2+-sensing receptor.
Caroppo R, Colella M, Colasuonno A, DeLuisi A, Debellis L, Curci S, Hofer AM
A reassessment of the effects of luminal [Ca2+] on inositol 1,4,5-trisphosphate-induced Ca2+ release from internal stores. J Biol Chem. 2003 Oct 10; 278(41):39503-8.
A reassessment of the effects of luminal [Ca2+] on inositol 1,4,5-trisphosphate-induced Ca2+ release from internal stores.
Hofer AM, Landolfi B, Debellis L, Pozzan T, Curci S
Free [Ca2+] dynamics measured in agonist-sensitive stores of single living intact cells: a new look at the refilling process. EMBO J. 1998 Apr 01; 17(7):1986-95.
Free [Ca2+] dynamics measured in agonist-sensitive stores of single living intact cells: a new look at the refilling process.