Scientific Positions:

1984-1989: Graduate Student, Cold Spring Harbor Laboratory, Laboratory of Dr. Mark J. Zoller

1990-1994: Post-doctoral Fellow, HHMI, Johns Hopkins School of Medicine, Laboratory of Dr. Randall R. Reed

1994-2001: Assistant Professor, Department of Pharmacology, Weill Medical College of Cornell University

2001-2009: Associate Professor, Department of Pharmacology, Weill Medical College of Cornell University

2009-: Professor, Department of Pharmacology, Weill Medical College of Cornell University

Education:

1979-1983: Cornell University, School of Agriculture and Life Sciences, B.S. in Biology

1983-1989: State University of New York at Stony Brook, Ph.D. in Genetics

Scientific Activities:

1998-2002: American Heart Association Affiliate Study Group

2001-2002: National Institutes of Health: Reproductive Biology Study Section

University Activities:

1994-present: Member, Graduate Program in Pharmacology

1995-present: Member, Graduate Program in Neuroscience

1995-1997, 1999-2002: Co-Chair, Pharmacology Graduate Program Retreat Planning Committee

1996-1999: Basic Sciences-At Large Representative, General Faculty Council of the Weill Medical College of Cornell University

1996-1999: Member, Molecular and Cellular Biology Training Grant Advisory Committee

1997-present: Gene Therapy Core Facility Steering Committee

1997-present: Pharmacology Graduate Program Curriculum Committee

1997-present: Pharmacology Graduate Program Network Committee

2001-2004: Pharmacology Department Representative, General Faculty Council of the Weill Medical College of Cornell University

2002-2005: GFC Representative, Biomedical Research Cores Facility Oversight Committee

2006-2007: Weill Cornell Graduate School Program Organization Committee

2007-2008: Core Basic Science Curriculum Committee, Task Force on Teaching Pharmacology

2007: Core Basic Science Curriculum Committee, Task Force on Teaching at Weill Cornell Medical College in Qatar

2008: Weill Cornell Graduate School Code of Legislation Revision Committee

Graduate Teaching :

1992: Instructor, Neurobiology Summer Course, Marine Biological Laboratories, Woods Hole, MA.

1995-present: Lecturer, Introduction to Pharmacological Principles

1995-2000: Lecturer and Discussion Leader, Graduate School Core Course; Cell Structure and Function

1995-1999: Lecturer, Neuropharmacology

1996, 1998-2000: Instructor, Frontiers in Biomedical Sciences

1996-1997: Course Director, Introduction to Neuroscience Research

1997: Structure and Function of the Nervous System

2001-present: Course co-Director and Lecturer, Systems Pharmacology

Medical Teaching :

1995-1997: Lecturer and Discussion Leader, Medical Pharmacology

1996-present: Lecturer and Discussion Leader, Molecules to Cells

1997-2007: Discussion Leader, Host Defenses

2001-present: Lecturer, Basis of Disease

2005-present: Course Design Committee, Molecules, Genes, & Cells

2008-present: Lecturer, Host Defenses

Major Research Interests:

Genetic and biochemical characterization of CO2/HCO3/pH regulated adenylyl cyclases.
• The function of soluble adenylyl cyclase in mammals.
  • Metabolic sensing via cAMP.
  • Compartmentalization of cAMP signaling.
  • The function of CO2/HCO3/pH regulated adenylyl cyclases in pathogenesis.




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Publications:
(Go here for the Lab Page of Links to Journals and PDF files)

Broek, D., Toda, T., Michaeli, T., Levin, L., Birchmeier, C., Zoller, M., Powers, S., and Wigler, M. (1987). The S. cerevisiae CDC25 gene product regulates the RAS/Adenylate cyclase pathway. Cell 48:789-799.

Levin, L.R., Kuret, J., Johnson, K.E., Powers, S., Cameron, S., Michaeli, T., Wigler, M., and Zoller, M.J. (1988). A mutation in the catalytic subunit of cAMP-dependent protein kinase that disrupts regulation. Science 240: 68-70.

Cameron, S., Levin, L., Zoller, M., and Wigler, M. (1988). cAMP-independent control of sporulation, glycogen metabolism, and heat shock resistance in Saccharomyces cerevisiae. Cell 53: 555-566.

Zoller, M.J., Kuret, J., Cameron, S., Levin, L., and Johnson, K.E. (1988). Purification and characterization of C1, the catalytic subunit of Saccharomyces cerevisiae cAMP-dependent protein kinase encoded by TPK1. J. Biol. Chem. 263: 9142-9148.

Levin, L.R., and Zoller, M.J. (1990). Association of catalytic and regulatory subunits of cAMP-dependent protein kinase requires a negatively charged side group at a conserved threonine. Mol. Cell. Biol. 10: 1066-1075.

Zoller, M.J., Johnson, K.E., Yonemoto, W., and Levin, L. (1991). Functional expression of mammalian adenosine cyclic monophosphate-dependent protein kinase in Saccharomyces cerevisiae. Meth. Enzymol. 200: 605-627.

Glass, D.B., Feller, M.J., Levin, L.R., and Walsh, D.A. (1992). Structural basis for the low affinities of yeast cAMP-dependent and mammalian cGMP-dependent protein kinases for protein kinase inhibitor peptides. Biochemistry 31: 1728-1734.

Levin, L.R., Han, P.-L., Hwang, P.M., Feinstein, P.G., Davis, R.L., and Reed, R.R. (1992). The Drosophila learning and memory gene, rutabaga, encodes a Ca2+/Calmodulin-responsive adenylyl cyclase. Cell 68: 479-489.

Han, P.-L., Levin, L.R., Reed, R.R., and Davis, R.L. (1992). Preferential expression of the Drosophila rutabaga gene in mushroom bodies, neural centers for learning in insects. Neuron9: 619-627.

Insall, R., Kuspa, A., Lilly, P.J., Shaulsky, G., Levin, L.R., Loomis, W.F., and Devreotes, P. (1994). CRAC, a cytosolic protein containing a pleckstrin homology domain, is required for receptor and G protein-mediated activation of adenylyl cyclase in Dictyostelium. J. Cell Biol. 126: 1537-1545.

Levin, L.R. and Reed, R.R. (1995). Identification of functional domains of adenylyl cyclase using in vivo chimeras. J. Biol. Chem. 270: 7573-7579.

Iourgenko, V., Kliot, B., Cann, M.J., and Levin, L.R. (1997). Cloning and Characterization of a Drosophila adenylyl cyclase homologous to mammalian Type IX. FEBS Letters413:104-108.

Cann, M.J. and Levin. L.R. (1998). Genetic analysis of adenylyl cyclase function. In Advances in Second Messenger and Phosphoprotein Research: Adenylyl Cyclases, D.M.F. Cooper, ed. (New York: Raven Press), pp 121-135.

Buck, J.*, Sinclair, M.L.*, Schapal, L. Cann, M.J., and Levin, L.R. (1999). Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals. Proc. Natl. Acad. Sci. 96: 79-84.

Cann, M.J. and Levin, L.R. (2000). Restricted expression of a truncated adenylyl cyclase in the cephalic furrow of Drosophila melanogaster. Dev. Genes & Evol.210: 34-40.

Iourgenko, V. and Levin, L.R. (2000). A calcium inhibited Drosophila adenylyl cyclase. Biochem. et Biophysica acta1495:125-139.

Sinclair, M.L., Wang, X.-Y., Mattia, M., Conti, M., Buck, J., Wolgemuth, D.J., and Levin, L.R. (2000). Specific expression of soluble adenylyl cyclase in male germ cells. Mol. Repro. & Dev.56:6-11.

Cann, M.J., Chung, E., and Levin, L.R. (2000). A new family of adenylyl cyclase genes in the male germline of Drosophila melanogaster. Dev. Genes & Evol.210: 200-206.

Chen, Y., Cann, M.J., Litvin, T.N., Iourgenko, V., Sinclair, M.L., Levin, L.R., and Buck, J. (2000). Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 289: 625-628.

Wuttke, M.S., Buck, J., and Levin, L.R., (2001). Bicarbonate-regulated soluble adenylyl cyclase. Journal of the Pancreas 2:154-158.

Zippin, J.H., Levin, L.R., and Buck, J. (2001). Bicarbonate/CO₂ responsive soluble adenylyl cyclase as a putative metabolic sensor. Trends in Endocrinology & Metabolism 12:366-370.

Cann, M.J. and Levin, L.R. (2002). Improved methods for identification of novel transmembrane adenylyl cyclase isoforms. Meth. Enzymol. 345:150-159.

Buck, J., Sinclair, M.L., and Levin, L.R., (2002). Purification of soluble adenylyl cyclase. Meth. Enzymol. 345:95-105.

Zippin, J.H.*, Chen, Y.*, Nahirney, P.*, Kamenetsky, M., Wuttke, M.S., Fischman, D.A., Levin, L.R. and Buck, J. (2003). Compartmentalization of bicarbonate-sensitive adenylyl cyclase in distinct signaling microdomains. FASEB Journal 17: 82-84.

Sun, X.C., Zhai, C.-B., Miao, C., Chen, Y., Levin, L.R., Buck, J., and Bonanno, J.A. (2003). HCO₃-dependent soluble adenylyl cyclase activates the cystic fibrosis transmembrane conductance regulator in corneal endothelium. Amer. J. of Physiol. 284:C1114-1122.

Litvin, T.N., Kamenetsky, M., Zarifyan, A., Buck, J., and Levin, L.R. (2003). Kinetic Properties of 'soluble' adenylyl cyclase: synergism between calcium and bicarbonate. J. Biol. Chem. 278:15922-15926.

Pastor-Soler, N., Beaulieu, V., Litvin, T.N., Da Silva, N., Chen, Y., Brown, D., Buck, J., Levin, L.R., and Breton, S. (2003). Bicarbonate regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling. J. Biol. Chem. 278:49523-49529.

Zippin, J.H., Farrell, J., Huron, D., Kamenetsky, M., Hess, K.C., Fischman, D.A., Levin, L.R., and Buck, J. (2004). Bicarbonate responsive 'soluble' adenylyl cyclase defines a nuclear cAMP microdomain. J. Cell. Biol. 164:527-534.

Kobayashi, M., Buck, J., and Levin, L.R. (2004). Conservation of functional domain structure in bicarbonate-regulated 'soluble' adenylyl cyclases in bacteria and eukaryotes. Dev. Genes & Evol. 214:503-509.

Steegborn, C., Litvin, T.N., Levin, L.R., Buck, J., and Wu, H. (2005). Bicarbonate activation of adenylyl cyclase via promotion of the catalytic cycle: active site closure and metal recruitment. Nature Str. & Mol. Biol. 12:32-37.

Han, H., Stessin, A.M., Roberts, J., Hess, K.C., Gautam, N., Kamenetsky, M., Lou, O., Hyde, E., Nathan, N., Muller, W.A., Buck, J., Levin, L.R., and Nathan, C. (2005). Role of Calcium-Sensing Soluble Adenylyl Cyclase in TNF Signal Transduction in Human Neutrophils. J. Exp. Med. 202: 353-361.

Hess, K.C.*, Jones, B.H.*, Marquez, B., Chen, Y., Ord, T.S., Kamenetsky, M., Myamoto, C., Zippin, J.H., Kopf, G.S., Suarez, S.S., Levin, L.R.*, Williams, C.J.*, Buck, J.*, and Moss, S.B.* (2005). ÔSoluble' Adenylyl Cyclase mediates Multiple Specific Signaling Events in Sperm Required for Fertilization. Dev. Cell 9249-259.

Steegborn, C.*, Litvin, T.N.*, Hess, K.C., Capper, A.B., Taussig, R., Buck, J., Levin, L.R., and Wu, H. (2005). A novel mechanism for adenylyl cyclases inhibition from the crystal structure of its complex with catechol estrogen. J. Biol. Chem. 280:31754-9.

Klengel, T.*, Liang, W-J.*, Chaloupka, J.A.*, Ruoff, C., Schroppel, K., Naglik, J.R., Eckert, S.E., Gewiss, E., Haynes, K., Tuitte, M.F., Levin, L.R., Buck, J., and Muhlschlegel, F.A. (2005). Fungal adenylyl cyclase integrates CO2 sensing with cAMP signalling and virulence. Curr. Biol.15:2021-2026.

Mogensen, E.G., Janbon, G., Chaloupka, J., Steegborn, C., Fu, M.S., Moyrand, F., Klengel, T., Pearson, D.S., Geeves, M.A., Buck, J., Levin, L.R. and Muhlschlegel, F.A. (2006). Cryptococcus senses CO2 through the carbonic anhydrase Can2 and the adenylyl cyclase Cac1. Eukaryotic Cell5:103-111.

Chaloupka, J.A., Bullock, S.A., Iourgenko, V., Levin, L.R., and Buck, J. (2006). Auotinhibitory regulation of soluble adenylyl cyclase. Mol. Repro. & Dev.73:361-368.

Stessin, A.M., Zippin, J.H., Kamenetsky, M., Hess, K.C., Buck, J., and Levin, L.R. (2006). Soluble adenylyl cyclase mediates NGF-induced activation of RAP1. J. Biol. Chem. 281: 17253-17258.

Kamenetsky, M., Middelhaufe, S. Bank, E.M., Levin, L.R., Buck, J., and Steegborn, C. (2006). Molecular details of cAMP generation in mammalian cells: A tale of two systems. J. Mol. Biol. 362: 623-629.

Wu, K.Y., Zippin, J.H., Huron, D.R., Kamenetsky, M., Hengst, U., Buck, J., Levin, L.R., and Jaffrey, S.R. (2006). Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones. Nature Neuroscience. 9: 1257-1264.

Beltran, C., Vacquier, V.D., Moy, G., Chen, Y., Buck, J., Levin, L.R., and Darszon, A. (2007). Particulate and soluble adenylyl cyclases participate in the sperm acrosome reaction. BBRC 358: 1128-1135.

Schmid, A., Sutto, Z., Nlend, M., Horvath, G., Schmid, N., Buck, J., Levin, L.R., Conner, G., Fregien, N., and Salathe, M. (2007). Soluble adenylyl cyclase is localized to cilia and contributes to ciliary beat frequency regulation via production of cAMP. J. Gen. Phys. 130: 99-109.

Young, J.J.*, Mehdi, A.*, Stohl, L., Levin, L.R., Buck, J., Wagner, J.A., and Stessin, A.M. (2007). 'Soluble' adenylyl cyclase-generated cyclic AMP promotes fast migration in PC12 cells. J. Neurosci. Res. 86: 118-124.

Schlicker, C., Rauch, A., Hess, K.C., Kachholz, B., Levin, L.R., Buck, J., and Steegborn, C. (2008). Structure-based development of novel adenylyl cyclase inhibitors. J. Med. Chem. 51: 4456-4464.

Ramos, L.*, Zippin, J.H.*, Kamenetsky, M., Buck, J., and Levin, L.R. (2008). Glucose and GLP-1 stimulate cAMP production via distinct adenylyl cyclases in INS-1E insulinoma cells. J. Gen. Physiol. 132: 329-338.

Farrell, J.*, Ramos, L.*, Tresguerres, M., Kamenetsky, M., Levin, L.R., and Buck, J. (2008). Somatic 'soluble' adenylyl cyclase isoforms are unaffected in Sacy^tm1Lex/Sacy^tm1Lex 'knockout' mice. PLoS ONE 3(9) e3251.

Hallows, K.R., Wang, H., Edinger, R.S., Butterworth, M.B., Oyster, N.M., Li, H., Buck, J., Levin, L.R., Johnsson, J.P., and Pastor-Soler, N.M. (2009). Regulation of epithelial Na⁺ transport by soluble adenylyl cyclase in kidney collecting duct cells. JBC 284: 5774-5783.

Acin-Perez, R., Salazar, E., Kamenetsky, M., Buck, J., Levin, L.R., and Manfredi, G. (2009). Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation. Cell Metabolism 9: 265-276.

Tresguerres, M., Parks, S.K., Salazar, E., Levin, L.R., Goss, G.G, and Buck, J. (2010). Bicarbonate-sensing soluble Adenylyl Cyclase is an essential sensor for acid-base homeostasis.PNAS 107: 442-447.

Zippin, J.H, Chadwick, P., Levin, L.R., Buck, J., and Magro, C. (2010). Soluble adenylyl cyclase defines a nuclear cAMP microdomain in keratinocyte hyperproliferative skin diseases. J. Investigative Dermatology 130 1279-1287.

Tresguerres, M, Levin, L.R., Buck, J., and Grosell, M.. (2010). Modulation of NaCl absorption by [HCO3-] in the marine teleost intestine is mediated by soluble adenylyl cyclase. AJP-Regulatory, Integrative and Comparative Physiology 299:R62-R71.

Tresguerres, M, Buck, J.,and Levin, L.R. (2010). Physiological carbon dioxide, bicarbonate and pH sensing. Pflugers Archiv - European Journal of Physiology 460:953-964.

Hall, R.A., De Sordi, L., MacCallum, D.M., Topal, H., Eaton, R., Bloor, J.W., Robinson, G.K., Levin, L.R., Buck, J., Wang, Y., Gow, N.A.R., Steegborn, C., and Muhlschlegel, F.A. (2010). CO2 acts as a signalling molecule in the fungal pathogen Candida albicans. PLoS Pathogens 6(11): e1001193.

Tresguerres, M, Levin, L.R., and Buck, J. (2011). Signaling by Soluble Adenylyl Cyclase. Kidney International 79:1277-1288.

Buck, J. and Levin, L.R. (2011). Physiological sensing of carbon dioxide/bicarbonate/pH via cyclic nucleotide signaling. Sensors 2011 , 11, 2112-2128.

Ramos-Espiritu, L.S., Hess, K.C., Buck, J. and Levin, L.R. (2011). The soluble guanylyl cyclase activator YC-1 increases intracellular cGMP and cAMP via independent mechanisms. JPET 338: 925-931.

Acin-Perez, R., Russwurm, M., Gunnewig, K., Gertz, M., Zoidl,G., Ramos, L., Buck, J., Levin, L.R., Rassow, J., Manfredi, G., and Steegborn, C. (2011). A phosphodiesterase 2A isoform localized to mitochondria regulates respiration. JBC 286: 30423-30432.

Hall, R.A., Turner, K.J., Chaloupka, J., Cottier, F, De Sordi, L., Sanglard, D., Levin, L.R., Buck, J, and Muhlschlegel, F. (2011). The quorum sensing molecules Farnesol/Homoserine lactone and Dodecanol operate via distinct modes of action in Candida albicans. Euk Cell 10: 1034-1042.

Lee, Y-S., Tresguerres, M., Hess, K., Marmorstein, L.Y., Levin, L.R., Buck, J., and Marmorstein, A.D. (2011). Regulation of anterior chamber drainage by bicarbonate sensitive adenylyl cyclase in the ciliary body. J. Biol. Chem. 286:41353-8.

Mohammad, S., Ramos, L.S., Buck, J., Levin, L.R., Rubino, F., and McGraw, T.E. (2011). Gastric inhibitory peptide controls adipose insulin sensitivity via activation of CREB and p110beta isoform of PI3 kinase. J. Biol. Chem. 286: 43062-70.

Chen, J., Levin, L.R., and Buck, J. (2011). Role of soluble adenylyl cyclase in the heart. AJP - Heart. : doi:10.1152/ajpheart00701.2011.

Topal, H., Fulcher, N.B., Bitterman, J., Salazar, E., Buck, J., Levin, L.R., Cann, M.J., Wolfgang, M.C., and Steegborn, C. (2012). Crystal Structure and Regulation Mechanisms of the CyaB Adenylyl Cyclase from the Human Pathogen Pseudomonas aeruginosa. J. Mol. Biol. : doi:10.1016/j.jmb.2011.12.045.



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Updated 1/4/12


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Levin/Buck Lab Home Page
Questions, please contact llevin@med.cornell.edu