Satpal Singh, Ph.D.

Associate Professor

Pharmacology & Toxicology

singhs@acsu.buffalo.edu

(716) 645-3870

 


 

1989-present,  Assistant Professor/Associate professor,  SUNY-Buffalo.

1985 - 1989, Postdoctoral Associate,  University of Iowa, IA.

1982-1985, Assistant Professor,  G.N.D. University, India. 

1981, Postdoctoral Associate, Frankfurt university, Germany.

1980, Ph.D. (Molecular Biology).  Tata Institute of Fundamental Research, Bombay, India.

1973,  M.Sc. Honors (Physics). Punjab University, Chandigarh, India

 


RESEARCH INTERESTS

        Complete sequencing of human and other genomes has pointed to an extremely important role played by genes in many diseases. In particular, mutations in various ion channels and related genes have been linked to a large number of neurological and cardiovascular disorders. Genomic information also highlights the strong evolutionary conservation of molecular mechanisms. This makes the use of genetic model systems, such as Drosophila, very powerful for understanding molecular mechanisms underlying most biological phenomena, including neuromuscular disorders.

        Using genetic protocols developed in our laboratory, we have identified more than 15 novel mutations that produce striking alterations in calcium and potassium currents in Drosophila. These mutations also affect other functions in flies, such as locomotor ability, heart rate, and/or sensitivity to the toxic effects of drugs that act on ion channels. Cloning and molecular analysis of nine genes, and the gene products disrupted by these  mutations, is underway in the laboratory. Some of these genes are completely novel, with nothing known about them in any organism. This analysis is yielding important information on modulation and regulation of ion channels, and their essential role in maintaining cellular physiology.

        In addition to identifying and studying the above mutations, we are using existing mutations to analyze modulation of calcium channels via signal transduction pathways. Combining mutations with pharmacological agents that disrupt specific signal transduction components, we have shown that the L-type calcium channels in Drosophila are modulated via the PLC - DAG - PKC pathway and a pathway involving PACAP, PAC1 receptors, adenylyl cyclase, cAMP, and PKA.


PUBLICATIONS

Articles in Refereed Journals:

Peri, R., Triggle, D. J. and Singh, S.  (2001)  Regulation of L-type of calcium channels in pituitary GH4C1 cells by depolarization.  J. Biol. Chem., (accepted for publication).  

Chopra, M., Gu, G.-G. and Singh, S. (2000)  Mutations Affecting the Delayed Rectifier Potassium Current in Drosophila. J. Neurogenetics  14:107-123.

Peri, R., Padmanabhan, S., Rutledge, A, Singh S. and Triggle, D. J.(2000) Permanently charged chiral 1,4-dihydropyridines: molecular probes of L-type calcium channels. Synthesis and Pharmacological characterization of methyl (w-trimethylalkylammonium)1,4-dihydro-2,6-dimethyl-4-(3nitrophenyl)-3,5-pyridinedicarboxylateiodide, calcium channel antagonists. J. Med. Chem. 43:2906-2914.

Hegde, P., Gu, G-G., Chen, D., Free, S. J. and Singh, S. (1999)Mutational Analysis of the Shab-encoded Delayed Rectifier K+ channels in Drosophila. J. Biol. Chem. 274,22109-22113.

Singh, A., and Singh, S. (1999) Unmasking of a Novel Potassium Current in Drosophila by a Mutation and Drugs. J. Neurosci. 19, 6838-6843.

Bhattacharya, A., Gu., G.-G. and Singh S. (1999)  Modulation of the Dihydropyridine-Sensitive Calcium Channels in Drosophila by a cAMP-Mediated Pathway. J. Neurobiol. 39, 491-500.

Kraliz, D., Bhattacharya, A. and Singh, S. (1998)  Blockade of the Delayed Rectifier Potassium Current in Drosophila by Quinidine and Related Compounds. J. Neurogenet. 12: 25-39

Gu G.-G. and Singh, S. (1997) Modulation of the dihydropyridine-sensitive Ca2+ channels in Drosophila by a phospholipase C-mediated pathway. J. Neurobiology. 33:265-275

Kraliz, D. and Singh, S. (1997) Selective blockade of the delayed rectifier potassium current by tacrine in Drosophila. J. Neurobiology 32: 1-10

Gielow, M. L., Gu, G.-G. and Singh, S. S. (1995) Resolution and pharmacological analysis of the voltage-dependent calcium channels of Drosophila larval muscles. J. Neuroscience 15:6085-6093

Gu, G.-G. and Singh, S. (1995)  Pharmacological analysis of heart beat in Drosophila.  J. Neurobiology 28: 269-280

Chopra, M. and Singh, S. (1994).  Developmental temperature selectively regulates a voltage-activated potassium current in Drosophila. J. Neurobiol. 25, 119-126

Singh S. (1993).  Quantification of countercurrent distribution: from molecular partition to animal behavior. Biochem. Biophys. Res. Comm.196: 430 - 434

Komatsu, A. K., Singh, S., Rathe, P. and Wu, C.-F. (1990).Mutational and gene-dosage analysis of calcium-activated potassium channels in Drosophila : Correlation of micro- and macroscopic currents. Neuron 4: 313-321

Singh, S. and Wu, C.-F. (1990).  Properties of potassium currents and their role in membrane excitability in Drosophila larval muscle fibers. J. Exp. Biol. 152: 59-76

Singh, S. and Wu, C.-F. (1989).  Complete separation of four potassium currents in Drosophila.  Neuron 2: 1325-1329.

Wu, C.-F., Tsai, M.-C., Chen, M.-L., Zhong, Y., Singh, S. and Lee, C.Y. (1989).  Actions of dendrotoxin on K+ channels and neuromuscular transmission in Drosophila melanogaster and its effects in synergy with K+  channel-specific drugs and mutations. J. Exp. Biol. 147: 21-41.

Schlegel, P., Jen, P. H.-S. and Singh, S. (1988).  Auditory spatial sensitivity of inferior collicular neurons of echo locating bats. Brain Res. 456: 127-138.

Singh, S., Bhandari, P., Chopra, M. J. S. and Guha, D. (1987).Isolation of autosomal mutations in Drosophila melanogaster without setting up lines. Molec. Gen. Genet. 208: 226-229.

Neuweiler, G., Singh, S. and Sripathi, K. (1984).  Audiograms of a South Indian bat community. J. Comp. Physiol. 154: 133-142.

Schlegel, P. and Singh, S. (1983).  Unmasking in neurons of the inferior colliculus of Eptesicus fuscus with binaural stimulation. Hearing Res. 10: 331-343.

Singh, S. (1983).  A mutagenesis scheme for obtaining autosomal mutations in Drosophila . Ind. J. Exp. Biol. 21:635-636.

Singh, S. and Siddiqi, O. (1981).  torpid , a new sex linked temperature paralytic mutation in Drosophila melanogaster.  Molec. Gen. Genet. 181: 400-402.

Submitted:

Bhattacharya, A., Lakhman, S. S. and Singh, S.  Modulation of L-type Calcium Channels in Drosophila by Pituitary Adenylyl Cyclase Activating Polypeptide

Under preparation:

Peri, R., Aletta, Singh, S. and Triggle, D. J.  Comparative evaluation of potencies of clinical second generation 1,4-dihydropyridines.

Gu, G.-G., Getman, P and Singh, S.   Properties of L-type Ca2+ currents in Drosophila larval muscle fibers.

Review articles/Book Chapters:

Singh, S. and Wu, C.-F. (1999).  Ionic currents in the larval muscles of Drosophila.  In: International Review of Neurobiology (Vol. 43 -Neuromuscular Junctions in Drosophila).  V. Budnik and S. Gramates, eds. Academic Press. pp. 191-220.

Singh, S., Chopra, M. J. S., Bhandari, P. and Guha, D. (1989).   Isolation of autosomal behavioral mutations in Drosophila  In 'Neurobiology of Sensory Systems', (R. N. Singh and N. J. Strausfeld,  eds) Plenum Press, NY, pp 419-426.