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Interests and Research Activities
Dr. Sabbadini was a Professor of Biology for 32 years at San Diego State University and is currently Emeritus Professor of Biology. He founded three biotechnology companies, including Lpath, Vaxiion and Mpex, incubated out of SDSU. Dr. Sabbadini has been interested in the role of bioactive lipids in disease, including cancer, ocular disorders, neurotrauma, neuropathic pain, inflammation and heart disease. Dr. Sabbadini’s research focused on developing novel antibody-based therapeutics against bioactive lipids such as the sphingolipid, S1P and LPA. The anti-S1P antibodies are in clinical trials for AMD and cancer. Sphingolipids multifunctional lipid mediators largely involved in signaling activities required for normal cellular function. However, bioactive lipids can become dysfunctional and directly contribute to the pathophysiology of diseases.
Selected Peer-Reviewed Publications
Sabbadini RA, Betto R, Teresi A, Fachechi-Cassano G & Salviati G (1992). The effects of sphingosine on sarcoplasmic reticulum membrane calcium release. J Biol Chem 267(22), 15475-15485.
Krown, K., K. Yasui, M. Brooker, A. Dubin, C. Nguyen,
G. Harris, P. McDonough, C. Glembotski, P. Palade
and R. Sabbadini. TNFa receptor expression in rat
cardiac myocytes: TNFa inhibition of L-type Ca2+
current and Ca2+ transients. FEBS Letters 376:24-30.
1995.
Krown, K., M. T. Page, C. Nguyen, V. Gutierrez,
K. L. Comstock, P. J. E. Quintana, C. C. Glembotski
& R. A. Sabbadini. TNFa-induced apoptosis in
cardiac myocytes: Involvement of the sphingolipid
signalling cascade in cardiac cell death. J. Clin.
Invest. 98:2854-2865. 1996.
Betto, R., A. Teresi, F. Turcato, G. Salviati, R.
Sabbadini, K. Krown, C. Glembotski, C. Dettbarn,
K. Yasui, P. Palade. Sphingosylphosphorylcholine
modulates the ryanodine receptor calcium release
channel of cardiac sarcoplasmic reticulum membranes.
Biochem. J. 322:327-333. 1997.
Comstock KL, Krown KA, Page MT, Martin D, Ho P, Pedraza M, Castro EN, Nakajima N, Glembotski CC, Quintana PJ & Sabbadini R (1998). LPS-induced TNF-a release from and apoptosis in rat cardiomyocytes: Obligatory role of CD14 in mediating the LPS response. J Mol Cell Cardiol 30:2761-2775.
Zechner, D., R. Craig, D. Hanford, P.M. McDonough,
R. A. Sabbadini and C.C. Glembotski. MKK6 inhibits
myocardial cell apoptosis via a p38 MAP kinase-dependent
mechanism. J. Biol. Chem. 272:8232-8239. 1998.
Kevyn L. Comstock, Kevin A. Krown, M. Trevor Page,
Don Martin, Peter Ho, Melinda Pedraza, Ernesto N.
Castro, Nobuko Nakajima, Christopher C. Glembotski,
P.J. Quintana and Roger Sabbadini. LPS-induced TNFa
release from and apoptosis in rat cardiomyocytes:
Obligatory role of CD14 in mediating the LPS response.
J. Mol. Cell. Cardiol. 30:2761-2775. 1998.
Ghosh, N. R. Sabbadini and S. Chatterjee. Identification,
partial purification and localization of a neutral
sphingomyelinase in rabbit skeletal muscle: neutral
sphingomyelinase in skeletal muscle. Mol. Cell.
Biochem. 189: 161-168. 1998.
Krown, K. and R. A. Sabbadini. Preparation and Use
of Myocardial Cells in Culture to Study Effects
of Cytokines in Methods in Molecular Medicine: Septic
Shock Methods and Protocols.Humana Press. Ed. T.
Evans. 36:181-188. 1999.
Sabbadini, R.A., D. Danielli-Betto and R. Betto.
Role of sphingolipids in muscle function. Ital.
Journal of Neurological Sciences. 20:423-430. 1999.
Page, M.T., P.J.E. Quintana, J. A. Ligutti and R.
A. Sabbadini. Cell death in cultured adult rat cardiomyocytes:
use of the COMET assay to distinguish apoptosis
from necrosis. Basic and Appl. Myology 10: 159-170.
2000.
Nakajima, N.J. A. Ligutti, A. L. Cavalli, D. Biral,
C.C. Glembotski, P. M. McDonough, P. D. Ho, R. Betto,
D. Sandona, P. T. Palade, C. A. Dettbarn, R. E.
Klepper and R. A. Sabbadini. Expression and characterization
of Edg-1 receptors in rat cardiomyocytes: Calcium
deregulation in response to sphingosine-1-phosphate.
Eur. J. Biochem. 267: 5679-5686. 2000.
Ligutti, J., Nakajima, N., Cavalli, A.L, Betto,
R., Biral, D., Sabbadini, R. G protein-coupled receptors,
calcium deregulation and apoptosis in the heart.
Basic Appl. Myol. 10: 75-76. 2000..
Dalla Libera, L., R. Sabbadini, B. Ravara, M. Sandri,
R. Betto and G. Vescovo. Apoptosis in the skeletal
muscle of rats with heart failure is associated
with increase serum levels of TNFa and sphingosine.
J. Mol. Cell. Cardiol. 31: 1871-1878. 2001.
Betto, R. A. Teresi, F. Turcato, M. Duca, D. Danieli-Betto
and R. Sabbadini. Inability of sphingosine and calmodulin
to control ryanodine receptor in malignant hyperthermia.
Basic and Appl. Myology 12: 167-176. 2002.
Cavalli, A.L. J. A. Ligutti, N.M. Gellings, E. Castro,
M. T. Page, R. E. Klepper, and R. A. Sabbadini.
The role of TNFa and sphingolipid signaling in cardiac
hypoxia: Evidence that cardiomyocytes release TNFa
and sphingosine. Basic and Appl. Myology 12: 159-167.
2002.
Cavalli, A., N. O’Brien, S. Barlow, R. Betto,
C. Glembotski, P. Palade and R. Sabbadini. Expression
and functional characterization of SCaMPER: A calcium
channel of cardiomyocytes. Am. J. Physiol. 284:
C780-C790. 2003.
O’Brien, N, N. Gellings, M. Guo, C. C. Glembotski,
and R. A. Sabbadini. Molecular Identification of
Rat FAN and its Role in hypoxia reoxygenation induced
cell death in cardiomyocytes. Circ. Res., 92: 589-91.
2003.
Deutschman, D., Carstens, J.S., R. L. Klepper, W.
S. Smith, M. T. Page, T. R. Young, L. Gleason, N.
Nakajima and R. A. Sabbadini. Predicting coronary
artery disease using serum sphingosine-1-phosphate.
Am. Heart J. 146: 62-68. 2003.
Danieli-Betto, D., E. Germinario, A. Esposito, A.
Megeghian, M. Midrio, B. Ravara, E. Damiani, L.
Dalla Libera, R. A. Sabbadini and R. Betto. Sphingosine-1-phosphate
protects mouse EDL skeletal muscle during fatigue.
Am. J. Physiol. 288:C1367-73. 2005.
Visentin, B., J. Vekich, J., B. Sibbald, A. Cavalli, R. Matteo, K. Moreno, Wm. Garland, Y. Lu, F. Xing, V. Kumar, G. Mills and R. Sabbadini. Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages Cancer Cell 9:225-238. 2006
Giacalone, M. A, R. A. Sabbadini, A. L. Chambers, S. Pillai and K. McGuire Immune responses elicited by bacterial minicells capable of simultaneous DNA and protein antigen delivery. Vaccine 24:6009-17. 2006.
Giacalone, M. A. M. Gentile, B. T. Lovitt, M. W. Surber and R. Sabbadini. Bacterial minicells can target and transfer plasmid DNA to eukaryotic cells. Cellular Microbiology 8:1624-1633. 2006.
Giacalone, M. A, , J. A. Zapata, N. L. Berkley, R. A. Sabbadini, Y. L. Chu, , M. Salvato and K. L McGuire. Immunization with non-replicating bacterial minicells delivering both protein antigen and DNA antigens protects mice from lethal challenge with Lymphocytic Choriomeningitis Virus. Vaccine 25: 2279-2287. 2007.
Swaney, J., K. M. Moreno, A. M. Gentile, R. A. Sabbadini and G. L. Stoller. Sphingosine-1-phosphate (S1P) is a novel fibrotic mediator in the eye. Experimental Eye Research 87:367-75. 2008.
Caballero, S., K. Moreno, G. Stoller, A. Cavalli, Wm, Garland, G. Hansen, R. Sabbadini and M. Grant. Anti-sphingosine-1-phosphate monoclonal antibody inhibits angiogenesis and sub-retinal fibrosis in a murine model of laser induced choroidal neovascularization. Experimental Eye Research 88:367-377. 2009.
Gellings Lowe., N., James S. Swaney, Kelli M. Moreno, and Roger A. Sabbadini. Sphingosine-1-phosphate and sphingosine kinase are critical for TGFb-stimulated collagen production by cardiac fibroblasts. Cardiovascular Research;82:303-12. 2009
O'Brien N, Jones ST, Williams DG, Cunningham HB, Moreno K, Visentin B, Gentile A, Vekich J, Shestowsky W, Hiraiwa M, Matteo R, Cavalli A, Grotjahn D, Grant M, Hansen G, Campbell MA, Sabbadini R. Production and characterization of monoclonal anti-sphingosine-1-phosphate antibodies. J Lipid Res. 2009 50, 2245-2257, Epub Jun 9 2009.
Wojciak, J., N. Zhu, K. Schuerenberg, K. Moreno, W. Shestowksy, M . Hiraiwa, R. Sabbadini and T. Huxford .The crystal structure of sphingosine-1-phosphate in complex with a Fab fragment reveals metal bridging of an antibody and its antigen. Proc. Nat. Acad. Sci. 2009 Oct 20;106(42):17717-22. Epub Oct 7 2009.
Sabbadini, R. A. Sphingosine-1-Phosphate Antibodies as Potential Agents in the Treatment of Cancer and Age-related Macular Degeneration. British J. Pharmacology 2011 Mar;162(6):1225-38 . Epub 2010 Nov 22
Berdyshev EV, Gorshkova I, Usatyuk P, Kalari S, Zhao Y, Pyne NJ, Pyne S, Sabbadini RA, Garcia JG, Natarajan V. Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase. PLoS One. Jan 31;6(1):e16571. Epub Jan 31;6(1):e1657. 2011
Gu Y, Forostyan T, Sabbadini R, Rosenblatt J. Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway. J Cell Biol. May 16;193(4):667-76. Epub 2011 May 9. 2011
Visentin B, Reynolds G, Sabbadini, R. Immunohistochemical detection of sphingosine-1-phosphate and sphingosine kinase-1 in human tissue samples. Methods Mol Biol. 2012;874:55-67.2012
Frisca, F., Sabbadini, R.A., Goldshmit, Y. & Pebay, A. Biological Effects of Lysophosphatidic Acid in the Nervous System. International Review of Cellular and Molecular Biology 296:273-322. 2012
Ponnusamy, S, S.P. Selvam, S. Mehrotra,T. Kawamori, A. J. Snider, L. M. Obeid, Y. Shao, R. Sabbadini, B. Ogretmen. Communication between host organism and cancer cells is transduced by systemic sphingosine kinase 1/sphingosine 1-phosphate signalling to regulate tumour metastasis. EMBO Mol Med. 2012 Aug;4(8):761-75. doi: 10.1002/emmm.201200244. Epub 2012 Jun 18, 2012
Goldshmit Y, Matteo R, Sztal T, Ellett F, Frisca F, Moreno K, Crombie D, Lieschke GJ, Currie PD, Sabbadini RA and Pébay A. Blockage of lysophosphatidic acid signalling improves spinal cord injury outcomes. Am J Pathol. 2012 Sep;181(3):978-92. Epub 2012 Jul 20, 2012
Finley A, Chen Z, Esposito E, Cuzzocrea S, Sabbadini R, Salvemini D. Sphingosine 1-Phosphate Mediates Hyperalgesia via a Neutrophil-Dependent Mechanism. PLoS One. 2013;8(1):e55255. doi: 10.1371/journal.pone.0055255. Epub 2013 Jan 25
Sabbadini, R., J. M. Wojciak, K, Moreno, and B. Visentin. Antibodies to bioactive lysophospholipids in Lysophospholipid Receptors: Signaling and Biochemistry ed. J. Chun, et al. John Wiley, 2012 (in press).
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