Mailing Address:
Department of Pharmacology
Wayne State University School of Medicine
540 East Canfield Avenue
Detroit, Michigan   48201  
Telephone: 313-577-0793 
email: rsilver@med.wayne.edu 

Summer contact information: 
Marine Biology Laboratory 
7 M.B.L. Street 
Woods Hole, MA02543 
Telephone: 508 548 3705 
email: rsilver@mbl.edu
 

RESEARCH INTERESTS 

Cells make decisions.  We study how living cells make decisions.  The focus of our research is on two main areas: 

1. The role of calcium, eicosanoids and networked metabolic enzyme pathways in regulation of calcium signals and mitotic cell division (sea urchins, sand dollars, et cetera) 

2. Synaptic transmission and secretion (squid, skate). 

Our efforts also include elucidation of matrix melattoprotease activties in breast tumors, structure/function relationships of hair cell stereociliary movements in vestibular physiology (oyster toadfish).  Other related areas of study are also pursued through collaborative efforts. 

We make extensive use of quantitative video light microscopy, multispectral and very high-speed video imagery of living cells and tissues, biochemistry and enzymology, quantitative direct pressure microinjection, and modeling and simulation. 

A cornerstone of our efforts is high performance computational processing and analysis of video microscopy images that range from signal detection and analysis single photon sources to mapping of patterns of intracellular chemical reactions and calcium signaling in living cells.  We also use a variety of biochemical, biophysical and immunological methods, and modeling and simulation in our studies. 

In addition to our fundamental biological studies, we design and fabricate optical hardware, and the design of software for processing and analysis of large video image data sets. 

 The organisms we study include: 

•   Sea urchins (e.g., Strongylocentrotus purpuratus, Strongylocentrotus droebachiensis, Lytechinus pictus, Arbacia punctulata). 
•   Sand dollars  (e.g., Echinaracnius parma) 
•   Skate (e.g., Raja raja) 
•   Squid (e.g., Loligo peali) 

These marine organisms provide outstanding model systems for study of fundamental biological processes, with application of that new information to understanding of human conditions (e.g., cancer, regeneration of cells and tissues, neurological disorders, et cetera). 

Professor Silver is also the founding director of two courses taught at the Marine Biologiocal Laboratory in Woods Hole, Massachusetts: 

•   Microinjection Techniques in Cell Biology 
•   Modeling of Biological Systems 

UPCOMING EVENTS 

SELECTED REFERENCES 

• Moore, H.-P. H., Silver, R.B., Bernlohr, D.A., and Granneman, J.G. (2005) Perilipin Targets a Novel Pool of Lipid Droplets for Lipolytic Attack by Hormone-Sensitive Lipase. J. Biol. Chem. 280:43109-43120, and 2005 Oct 21
• Silver, R.B. and Pappas, G.D. (2005) Secretion without Membrane Fusion:  Porocytosis. Anat. Rec. 282B:18–37.
• Kriebel, M.E., Keller, B., Silver, R.B., and Pappas, G.D. (2005) Porocytosis: A Transient Pore array secretes the Neuro-transmitter packet. Anat. Res. 282B:38–41.
• Silver, R.B. (2005) Secretion – Essential Transport at the Plasma Membrane.  Anat. Res. 282B:1–2.
• Kriebel, M.E., Keller, B., Silver, R.B., and Pappas, G.D.  (2004) The synaptic bouton acts like a salt shaker.  Cell Biochem. Biophys. 41:259-264
• Sbrissa, D., Strakova, J., Ikonomov, O.C., Dondapati, R., Mlak, K., Deeb, R., Silver, R.B., and Shisheva, A. (2004) ArPIKfyve:  a mammalian ortholog of yeast Vac14 that associates with and up-regulates PIKfyve phosphoinositide 5-kinase activity.   Molec. Cell Biol. 24:10437-10447.
• Silver, R.B., Kriebel, M., Keller, B. and Pappas, G.D. (2003) Porocytosis: Secretion from small and medium diameter vesicles and vesicle arrays without membrane fusion. J. Neurocytology. 32:277-291.
• Amin, R.H. Chen, H.-Q., Veluthakal, R., Silver, R.B., Li, J., Li, GD. and Kowluru, A. (2003) Mastoparan-Induced Insulin Secretion from Insulin-Secreting βTC3 and INS-1 cells: Evidence for its Regulation by Rho Subfamily of G-Proteins.  Endocrinology, 144:4508-4518.
• Tisdale, E.J., Wang, J., Silver, R.B., Artalejo, C.R. (2003) Atypical Protein Kinase C Plays a Critical Role in Protein Transport From Pre-Golgi Intermediates.  J. Biol. Chem. 278:38015-38021.
• Silver, R.B. and Bartman, M. (2002) A Metronome Like Control of the Calcium Signal Leading to Nuclear Envelope Breakdown and Mitosis in Sand Dollar (Echinaracnius parma) Cells.  Biol. Bulletin 203:213-215.
• Hummel, J.R. and Silver, R.B. (2002) IQARIS: A Tool for the Intelligent Querying, Analysis, and Retrieval from Information Systems.  The 2002 International Conference on Information and Knowledge Engineering (IKE'02: Las Vegas, USA, June 24-27, 2002).
• Silver, R.B. and Hummel, J.R. (2002) Trained Cell: A multi-modal biosensor and decision system.  Proceedings 70th Military Operations Research Society Symposium.
• Silver, R.B., Kriebel, M., Keller, B. and Pappas, G.D. (2001) Porocytosis:  Quantal Synaptic Secretion at the Neuromuscular Junction.  Biol. Bulletin  201:263-264.
• Mensinger, A.F., Anderson, D., Martin, D., Tresco, P., Silver, R.B., and Highstein, S.M. (2000) Chronic recording of VIIIth nerve axons with a sieve electrode. J. Neurophysiol. 83:611-615. 
• Kriebel, M., Keller, B. Silver, R.B., Fox, G.Q. and Pappas, G.D. (2001) Porocytosis: Quantal synaptic secretion by an array of pores. Brain Research. 38:20-32.
• Silver, R.B., Kriebel, M., Keller, B. and Pappas, G.D. (2001) Porocytosis:  Quantal Synaptic Secretion at the Neuromuscular Junction.  Biol. Bulletin  201:263-264.
• Silver, R.B. (2001) LtB4 Evokes the Calcium Signal That Initiates Nuclear Envelope Breakdown through a Multi-enzyme Network in Sand Dollar (Echinaracnius parma) Cells.  Biol Bulletin. 201:248-250
• Silver, R.B., Hummel, J.R., Christiansen, J.H., Filer, S.R., and Stevens, F.  (2001) A Multi-modal Biosensor and Decision System.  Proceedings of the Fifth Joint Conference on Standoff Detection for Chemical and Biological Defense.
• Silver, R.B., Kriebel, M., Keller, B. and Pappas, G.D. (2001) Porocytosis:  Quantal Synaptic Secretion at the Neuromuscular Junction.  Biol. Bulletin  201:263-264.
• Silver, R.B. (2001) LtB4 Evokes the Calcium Signal That Initiates Nuclear Envelope Breakdown through a Multi-enzyme Network in Sand Dollar (Echinaracnius parma) Cells.  Biol Bulletin. 201:248-250.
• Hummel, J.R., Silver, R.B. and Christianson, J.H. (2001) Modeling of Biological Processes in an Object-Oriented Environment. High Performance Computing 2001 – Grand Challenges in Computer Simulation. Editor – Adrian Tentner.  ISBN 1-56555-237-7, pp 58-63. 
• Silver, R.B. (1999) Structured space-time patterns of Ca2+ signals:  Essential information for decisions in cell division.  FASEB Journal. 13:S209-S215. 
• Silver, R.B. and Deming, N.M. (1999) Leukotriene B4 as calcium agonist for nuclear envelope breakdown.  An enzymological survey of endomembranes of mitotic cells.  Biol. Bulletin 197:268-270.
• Silver, R.B., King, L.A. and Wise, A.F. (1998)  Calcium Regulatory Endomembranes of Prophase Mitotic Apparatus of Sand Dollar Cells Contain Enzyme Activities that produce Leukotriene B4 but lack Phospholipase C Activity.  Biol. Bulletin 195:209-210. 
• Silver, R.B., Reeves, A.P., Steinacker, A., and Highstein, S.M. (1998)  Examination of the Cupula and   Stereocilia of the Horizontal Semicircular Canal in the Toadfish Opsanus tau.  J. Compar. Neurol. 402:48-61. 
• Silver, R.B. and Reeves, A.P.  (1997)  Statistical Image Analysis of Spatial and Temporal Patterns in the Pre-Nuclear Envelope Breakdown Calcium Signal.  Biol. Bulletin.  193:238-239. 
• Silver, R.B., Strongin, D.E., Hurwitz, L.R. and Reeves, A.P.  (1997)  Identification of Phospholipase A2 and Phospholipase C Activities in Calcium Regulatory Endomembranes of Sand Dollar Cells.  Biol. Bulletin.   193:236-237. 
• Silver, R.B. (1996)  Calcium, BOBs, QEDs, Microdomains and a Cellular Decision:  Control of Mitotic Cell Division in Sand Dollar Blastomeres.  Cell Calcium. 20:161-179. 
• Silver, R.B. (1995)  Leukotriene B4 induces release of calcium from endomembrane stores in eggs and mitotic cells of the sand dollar Echinaracnius parma. Biol. Bulletin. 189:203-204. 
• Silver, R.B. (1994) Video light microscopic imaging of the calcium signal that initiates nuclear envelope breakdown in sand dollar (Echinaracnius parma) cells.  Biol. Bulletin.  187:235-237.
• Silver, R.B., Reeves, A.P., Whitman, M. and Kelley, B. (1994) Analysis of spatial and temporal patterns in the Ca2+ signal that signals nuclear envelope breakdown in sand dollar (Echinaracnius parma) cells.  Biol. Bulletin.  187:237-238. 
• Silver, R.B., Oblak, J.B., Jeun, G.S., Sung, J., Dutta, T. (1994) Leukotriene B4, an arachidonic acid metabolite, regulates intracellular free calcium release in eggs and mitotic cells of the sand dollar Echinaracnius parma.  Biol. Bulletin.  187:242-244. 
• Johnston, J.A., Sloboda, R.D. and Silver, R.B. (1994)  Phosphoprotein phosphatase 1 (PP1) is a component of the isolated sea urchin mitotic apparatus. Cell Motil. And Cytoskel. 29:280-290. 
• Synaptic Transmission, Secretion and Neurophysiology 
• Kriebel, M., Keller, B. Silver, R.B., Fox, G.Q. and Pappas, G.D. (2001) Porocytosis: Quantal synaptic secretion by an array of pores. Brain Research. 38:20-32.
• Silver, R.B., Kriebel, M., Keller, B. and Pappas, G.D. (2001) Porocytosis:  Quantal Synaptic Secretion at the Neuromuscular Junction.  Biol. Bulletin  201:263-264.
• Llinás, R., Sugimori, M. and Silver, R.B. (1995) The concept of calcium concentration microdomains in   synaptic transmission.  Neuropharm. 36:1443-1451. 
• Llinás, R., Sugimori, M. and Silver, R.B. (1995) Time resolved calcium microdomains and synaptic transmission.  J. Physiol. (Paris) 89:77-81. 
• Sugimori, M., Lang, E.J., Silver, R.B. and Llinás, R. (1994)  High resolution measurement of the time course of calcium-concentration microdomains at squid presynaptic terminals.  Biol. Bulletin.  187:300-303.
• Silver, R.B., Sugimori, M., Lang, E.J. and Llinás, R. (1994)  Time resolved imaging of Ca2+-dependent aequorin luminescence of microdomains and QEDs in synaptic preterminals.  Biol. Bulletin.  187:293-299. 
• Llinás, R., Sugimori, M. and Silver, R.B. (1992) Microdomains of high calcium concentration in a presynaptic terminal.  Science.  256:677-679. 

• Silver, R.B. (1997)  Imaging and measurement of intracellular free calcium in living cells.  In Cells:  A Laboratory Manual.  D.L. Spector, R.D. Goldman and L. Leinwand, editors.  Cold Spring Harbor Laboratory Press. Pp 80.1 – 13. 
• Silver, R.B. (1997)  Quantitative microinjection of living cells.  In Cells:  A Laboratory Manual.  D.L. Spector, R.D. Goldman and L. Leinwand, editors.  Cold Spring Harbor Laboratory Press. Pp 83.1 – 20.