London Metropolitan University Research Institutes
 
 

Dr Christopher P Palmer

Research description

 

My interests are in membrane receptors/ion channels and membrane signalling in general.

Current projects-

 

 

(1) Ion channels and their involvement in cancer

Breast and prostate cancers are a leading cause of cancer-associated death in women and men respectively. It most commonly metastasizes to the bone, with 70% of patients who develop bone metastases dying. Finding early markers of metastasis and developing effective therapies against their development is a priority. Investigation of functional expression of membrane ion channels is an exciting development in cancer research. Increased expression of voltage-sensitive ion channels is directly associated with malignancy, as evidenced by their role in cell proliferation, migration and survival. As such, my research laboratory has begun to develop these channels as targets for cancer drug design using phage display technology and high throughput screening.

 

(2) Polycystic kidney disease ion channels

In humans, autosomal dominant polycystic kidney disease is one of the most commonly inherited disorders, with an incidence of approx. 1 in 1000. The disease is characterized by the formation of large fluid-filled cysts in kidneys caused by abnormal differentiation and proliferation of kidney tubular epithelial cells, which result in chronic renal failure in 50% of patients by the age of 60. Cystic epithelial cells display changes in proliferation, apoptosis, differentiation, polarity, extracellular matrix synthesis and fluid transport. In 15% of patients, the causative mutation is located in the PKD2 gene, which belongs to the family of TRP (transient receptor potential) ion channel genes which are thought to be involved in cellular sensing of temperature, touch, pain, osmolarity, pheromones, taste and other stimuli. Evidence suggests that the polycystin complex (which includes PKD2) may act as a mechanosensor, receiving signals from the extracellular matrix, adjacent cells and tubule lumen (through cilia) and transducing them into cellular responses that regulate proliferation, adhesion, migration, differentiation and maturation essential to the control of the diameter of renal tubules and kidney morphogenesis. Our aims are to use a combination of advanced electrophysiological techniques and yeast expression of PKD2 to characterize the structure/function relationship of this mechanosensitive ion channel.

 

(3) Ca2+ ion channels and pain

Voltage-dependent calcium channels (VDCC) are a group of voltage-gated ion channels found in excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the ion Ca2+. At physiologic or resting membrane potential, VDCCs are normally closed. They are activated (i.e., opened) at depolarized membrane potentials and this is the source of the "voltage-dependent" epithet. Activation of particular VDCCs allows Ca2+ entry into the cell, which depending on the cell type, results in muscular contraction, excitation of neurons, up-regulation of gene expression, or release of hormones or neurotransmitters. Over the past 25 years of low voltage-activated (LVA), T-type calcium channels research, and especially within the last 10 years since their cloning, enormous progress has been achieved in the understanding of these channels', biophysical function, and their physiological and pathological roles in mammalian tissues. Recent discoveries confirm that T-channels contribute to the generation of electrical pacemaker currents in neurons and non-neuronal cells. T-channels-mediated oscillations in neuronal networks underlie thalamocortical rhythms in sleep, and epilepsy, cognitive processes in the hippocampus, and peripheral and central pain processing. We are interested in developing pharmacological agents which block T-type channels using phage display and high throughput screening.

 

 

(4) Modulation of ion channels by Sigma receptors

The so-called sigma receptor has been something of a mystery molecule for some time. First described as an opioid receptor, it was later found to interact with many types of drug and to affect the nervous, endocrine and immune systems. One example of sigma receptor function is its ability to mediate the modulatory effects of psychotropic compounds on some ion channels. As sigma receptors bind antipsychotic drugs, understanding their mechanism of action might have practical implications. At the same time, channel regulation by protein-protein interactions deserves further attention, as it adds degrees of freedom to the way in which ion channels govern neuronal function.

 

(5) Systems biology of cation transport in yeast

Cationic toxicity is involved in a substantial number of biological phenomena, such as salt stress in crops and many human diseases. The yeast Saccharomyces cerevisiae is a versatile model system with a myriad of biotechnological applications.  In yeast, maintenance of cation homeostasis is an essential process that affects parameters such as membrane potential, intracellular pH, cell volume and that directly influences nutrient uptake and growth.

 

Previous posts

2003-2008 Senior Researcher at Imperial College, London, UK.

1996-2002 Research Scientist at University of Wisconsin-Madison, USA.

1993-1996 Postdoctoral Researcher at Reading University, UK.

 

Publications

  • Mazurek MP, Prasad PD, Gopal E, Fraser SP, Bolt L, Rizaner N, Palmer CP, Foster CS, Palmieri F, Ganapathy V, Stühmer W, Djamgoz MB, Mycielska ME (2010) Molecular origin of plasma membrane citrate transporter in human prostate epithelial cells. EMBO Rep.  11:431-7.

  • Aydar E, Yeo S, Djamgoz M, Palmer C (2009) Abnormal expression, localization and interaction of canonical transient receptor potential ion channels in human breast cancer cell lines and tissues: a potential target for breast cancer diagnosis and therapy. Cancer Cell Int.  9: 23.

  • Aydar E and Palmer CP (2009) Polycystic Kidney Disease and Synaptotagmin homologues Play Roles in Schizosaccharomyces pombe Cell Wall Synthesis/Repair and Membrane Protein Trafficking. J. Membrane Biology 229:141-152.

  • Palmer C., Mycielska M., Burcu H., Osman K., Collins T., Perrett R., Aydar E., and Djamgoz M.B.A. (2008) A micro-pressure system for measuring single cell adhesion: application to cancer cell lines of different metastatic potential and voltage-gated Na+ channel expression. Eur Biophys J. 37, 359-68.

  • Palmer C.P., Mahen R., Edwards C., & Aydar E. (2007) Sigma (σ) 1 receptors bind cholesterol and remodel lipid rafts in breast cancer cell lines- effects on β1 integrin mediated adhesion. Cancer Res . 2007 67, 11166-75.

  • Palmer C.P., Aydar E. and Jackson M.B. (2007) Sigma receptor modulation of ion channels. In: Sigma Receptors: Chemistry, Cell Biology, and Clinical Implications . Ed. R. Matsumoto, Kluwer Academic Publishers. Pg127-149.
  • Mycielska, M.E., Broke-Smith, T., Palmer, C.P., Nastos, T., Backerman, R., Egruler, K. and Djamgoz, M.B.A. (2006). Citrate uptake enhances in vitro metastatic behaviours of PC3M human prostate cancer cells: aconitase and fatty acid synthase. International Journal of Chemistry and Cell Biology. Int. J. Biochem. Cell Biol. 38, 1766-77.
  • Aydar, E. and Palmer, C.P. (2006). A cardiac HERG channel splice variant. J. Membr. Biol. 211, 115-26.
  • Aydar E, Onganer P, Perrett R, Djamgoz MB and Palmer C.P. (2006). The expression and functional characterization of sigma (σ) 1 receptors in breast cancer cell lines. Cancer Lett. 242, 245-57
  • Mycielska, M., Palmer, C., Brackenbury, W. and Djamgoz M.B.A. (2005) Expression of Na+-dependent citrate transport in strongly metastatic human prostate cancer PC-3M cell line: regulation by voltage-gated Na+ channel activity. J. Physiology 563, 393-408.
  • Palmer, C., Aydar E. and Djamgoz M.B.A. (2005). A microbial TRP-like polycystic kidney disease related ion channel gene. Biochemical Journal 387, 211-9.
  • Palmer, C.P., Batiza, A., Zhou, X.-L., Loukin, S.H., Saimi, Y. and Kung, C. (2004) Ion channels of microbes. in Cell Signalling in Prokaryotes and Lower Metazoa. ed. I. Fairweather. Kluwer Academic Publishers. pp. 325-345 (Chapter 10).
  • Aydar E., Palmer C.P. and Djamgoz M.B. (2004). Sigma receptors and cancer: possible involvement of ion channels. Cancer Res. 64, 5029-35.
  • Zhou X.L., Batiza A.F., Loukin S.H., Palmer C.P., Kung C., and Saimi Y. (2003). The transient receptor potential channel on the yeast vacuole is mechanosensitive. Proc Natl Acad Sci U S A. 100, 7105-10.
  • Aydar E., Palmer C., Klachko V. and Jackson M. (2002) The Sigma receptor as a ligand modulated auxiliary potassium channel subunit. Neuron 34, 339-410.
  • Loukin S., Lin J., Athar U., Palmer C. and Saimi Y (2002) The carboxyl tail forms a discrete functional domain that blocks closure of the yeast K+ channel. Proceedings of the National Academy of Science, USA 99, 1926-30.
  • Aydar E. and Palmer C. (2001) Functional characterization of the C-terminus of the human ether-a-go-go-related gene K+ channel (HERG). Journal of Physiology 534, 1-14.
  • Palmer C., Zhou X-L., Lin J., Loukin S., Kung C. & Saimi Y. (2001) A TRP homolog in Saccharomyces cerevisiae forms an intracellular Ca2+ permeable channel in the yeast vacuolar membrane. Proceedings of the National Academy of Science 98, 7801-7805.
  • Lupardus P., Wilke R., Aydar E., Palmer C., Chen Y., Ruoho A. and Jackson M. (2000) Membrane-delimited coupling between sigma receptors and K+ channels in rat neurohypophysial terminals requires neither G-protein nor ATP. Journal of Physiology 526, 527-39.
  • Israel Z., Gorny M., Palmer C., McKeating J. and Zolla-Pazner S. (1997) Prevalence of a V2 epitope in clade B primary isolates and its recognition by sera from HIV-1-infected individuals. AIDS 11, 128-30.
  • Fox D., Balfe P., Palmer C., May J., Arnold C. and McKeating J. (1997) Length polymorphism within the second variable region of the human immunodeficiency virus type 1 envelope glycoprotein affects accessibility of the receptor binding site. Journal of Virology 71, 759-65.
  • McKeating J., Shotton C., Jeffs S., Palmer C., Hammond A., Lewis J., Oliver K., May J. and Balfe P. (1996) Immunogenicity of full length and truncated forms of the human immunodeficiency virus type I envelope glycoprotein. Immunology Letters 51, 101-5.
  • Palmer C., Balfe P., Fox D., May J., Frederiksson R., Fenyo E. and McKeating J. (1996) Functional characterization of the V1V2 region of human immunodeficiency virus type 1. Virology 220, 436-49.
  • Palmer C., Miller D., Marlow S., Wilson L., Lawrie A. and King L. (1995) Genetic modification of an entomopoxvirus: deletion of the spheroidin gene does not affect virus replication in vitro. Journal of General Virology 76, 15-23.
  • King L.A., Possee R.D., Hughes D.S., Atkinson A.E., Palmer C.P., Marlow S.A.,Pickering J.M., Joyce K.A., Lawrie A.M., Miller D.P. and Beadle D.J. (1994). Advances in Insect Virology. In Advances in Insect Physiology. Ed P. Evans, Academic Press
  • Marlow S., Billam L., Palmer C. and King L. (1993) Replication and morphogenesis of Amsacta moorei entomopoxvirus in cultured cells of Estigmene acrea (salt marsh caterpillar). Journal of General Virology 74, 1457-61.
  • Marlow S., Palmer C. and King L. (1992) Cytoplasmic effects of Amsacta moorei Entomopoxvirus infection on cytoskeleton of Estigmene acrea cells. Virus Research 26, 41-55.

 

Grants awarded

SysMol-2 project grant (BBSRC) "Systems biology of cation transport in yeast". 2010-2013. Total £300,000.

Emerald project grant. "Novel peptide inhibitors of Cav3.2 T-type channels".  2010-11. Total budget £10,000.

Principal Investigator and principal grant holder on Wellcome Trust project grant at Imperial College London. "Investigation of the molecular nature and physiology of mechanosensitive ion channels in the yeast Schizosaccahromyces pombe and their role in cell cycle control and dynamic determination of cell shape." 2003-2006. Total budget £254,199.

Principal Grant Holder on Polycystic Kidney Foundation project grant (USA). "A microbial model for polycystic disease related ion channels" 2005-2007. Total budget £68,000.

 

Collaborations

Systems biology of cation transport in yeast in collaboration with TRANSLUCENT-2. TRANSLUCENT-2 is composed of six partners plus an associate partner, assembling a powerful team of 9 independent laboratories.

Joaquin Ariño, Autonomous University of Barcelona

Edda Klipp, Humboldt-Universität zu Berlin

Jost Ludwig, University of Bonn

Maik Kschischo, University of Koblenz

José Ramos, University of Cordoba

Paul van Heusden, University of Leiden,

Christopher Palmer, London Metropolitan University

 






 

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