Darren F. Boehning, Ph.D.
Associate Professor

Darren Boehning, Ph.D.

Education

Bachelor of Science, Syracuse University, 1994
Doctor of Philosophy, Thomas Jefferson University, 2001
Post-Doctoral Training, Johns Hopkins University, 2001-2004

About the Lab

Our laboratory has two main foci, but the overall theme is elucidating the mechanisms of cell death or apoptosis. One project focuses on apoptosis caused by calcium release from the inositol 1,4,5-trisphosphate receptor (IP3R), which is the primary calcium release channel in the endoplasmic reticulum. Our laboratory has exerted significant efforts to determine the contribution of this channel to programmed (apoptotic) cell death. Our current thrust is to understand the mechanisms regulating calcium-dependent apoptosis after death receptor stimulation, in particular the Fas/Fas ligand system. We have found that one of the IP3 producing enzymes, phospholipase C-gamma, is activated after Fas stimulation, leading to IP3 production and IP3R-dependent calcium release. Our current research is directed at further elucidating the signaling pathways mediating calcium release after death receptor ligation, and application of these findings to in vivo models of diseases associated with altered Fas signaling.

Our second project investigates the molecular mechanisms of neurodegeneration in late-onset Alzheimer's disease (AD), the most common neurodegenerative disorder associated with aging. Although much is known about the pathogenesis of familial or early-onset AD, the underlying causes of late-onset AD are poorly understood. We are studying the role of the protein ubiquilin-1 in the pathogenesis of late-onset AD.  We have found that ubiquilin may be a key quality control molecule regulating APP folding and maturation along the secretory pathway. Our current efforts are directed towards elucidating the mechanisms by which ubiquilin regulates APP biosynthesis and toxicity.

Selected Publications

M.G. Jeschke, G. Gauglitz, J. Song, G.A. Kulp, C.C. Finnerty, R.A. Cox, J.M. Barral, D.N. Herdon, and D. Boehning; Calcium and ER stress mediate hepatic apoptosis after burn injury.  Journal of Cellular and Molecular Medicine Epub Jan 14 (2009).

C. Steinmann, M.L. Landsverk, J.M. Barral, D. Boehning; Requirement of IP3R for Tumor-Mediated Lymphocyte Apoptosis.  J. Biol. Chem.,  May 16;283(20):13506-9. Epub Mar 25 (2008). 

A.L. Wozniak, X. Wang, E.S. Stieren, S.G. Scarbrough, C.J. Elferink, D. Boehning;  Requirement Of Biphasic Calcium Release From The Endoplasmic Reticulum For Fas-Mediated Apoptosis.  J. Cell Biol. Dec 4; 175(5): 709-14 (2006).

D. Boehning, D.B. van Rossum, R.L. Patterson, S.H. Snyder; A Peptide Inhibitor of Cytochrome c/Inositol 1,4,5-Trisphosphate Receptor Binding Blocks Intrinsic and Extrinsic Cell Death Pathways. PNAS 102(5): 1466-1471 (2005).

R.L. Patterson, D. Boehning, S.H. Snyder; Inositol 1,4,5-Trisphosphate Receptors as Signal Integrators.  Annual Review of Biochemistry 73, 437-65 (2004).

D. Boehning, R.L. Patterson, L. Sedaghat, N.O. Glebova, T. Kurosaki and S.H. Snyder; Cytochrome C Binds To Inositol (1,4,5) Trisphosphate Receptors, Amplifying Calcium-dependent Apoptosis. Nat. Cell Biology, 5(12):1051-1061 (2003).

D. Boehning, C. Moon, S. Sharma, K. J. Hurt, L.D. Hester, G.V. Ronnett, D. Shugar and S.H. Snyder; Carbon Monoxide Neurotransmission Activated by CK2 Phosphorylation of Heme Oxygenase-2. Neuron, 40, 129-137 (2003).

D. Boehning and S.H. Snyder; Novel Neural Modulators. Annu. Rev. Neurosci. 26, 105-131 (2003).

D. Boehning, D.-O.D. Mak, J.K. Foskett and S.K. Joseph; Molecular Determinants of Ion Permeation and Selectivity in Inositol 1,4,5-trisphosphate Receptor Ca2+ Channels.  J. Biol. Chem. 276, 13509-13512 (2001). 

D. Boehning and S.K. Joseph; Direct association of ligand-binding and pore domains in homo- and heterotetrameric inositol 1,4,5-trisphosphate receptors. EMBO J. 19 (20), 5450-5459 (2000).

Full publication list on Pubmed