Signal Transduction

Signal transduction is the study of how cells control their own and each other's behaviors through physical (light, sound) or chemical (hormone, neutrotransmitter) signals.  Signal transduction research is an intensely active field of research, and UNH faculty are engaged in a variety of research programs that employ biochemical, molecular, cellular, and genetic/genomic approaches to understand cellular communication.

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Foci Chu chromatinFeixia Chu -- Epigenetics of histone post-translational modifications
 

Chromatin, the complex of genomic DNA and its associated proteins, constitutes the converging focus of various signaling pathways, and its structure defines the inheritable identity and fate of the cell. Histones are major chromatin proteins that are responsible for packaging genomic DNA into higher-order structures. Modifications of histone proteins can regulate effector protein binding or directly modulate chromatin structure, hence playing an important role in mediating various cellular responses to environmental influences. Using quantitative mass spectrometry, the Chu lab is capturing a panoramic view of the histone epigenetic “landscape,” and how it changes dynamically in response to cellular signaling processes such as differentiation and the DNA damage response. The functional significance of histone modifications during specific cellular processes are also being independently approached from both biochemical and cell biological perspectives.

Feixia Chu - Rudman Hall, Room 306
Phone: (603) 862-2436
Email: Feixia.Chu@unh.edu  

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Foci Cote rod and coneRick Cote -- Visual transduction pathway in retinal rod and cone photoreceptors
 

Rick Cote’s lab studies the visual signaling pathway in retinal rod and cone photoreceptors, focusing on the regulation of photoreceptor phosphodiesterase (PDE6) during light activation of the phototransduction cascade. The experimental tools we rely on include a variety of molecular, enzymological, and cell biological approaches, along with collaborations with the Thomas laboratory (structural genomics of PDEs), with the Chu laboratory (proteomic discovery of the PDE6 protein “interactome”), and with the Laue laboratory (biophysical approaches to PDE6 structure/regulation). Ultimately, our biomedical research will contribute to the development of therapeutic approaches to intervene in retinal diseases.

Rick Cote – Rudman Hall, Room 379
Phone: (603) 862-2458
Email: Rick.Cote@unh.edu
Lab web site: www.cotelab.org

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Foci Culigan resonse to DNAKevin Culligan -- Molecular and cellular responses to DNA damage
 

Kevin Culligan's research is focused on the molecular and cellular response to DNA damage in the model plant Arabidopsis thaliana.  DNA damage occurs from both exogenous (environmental) sources such as UV light, and endogenous sources such as reactive oxygenproduced during metabolism. Detected cellular DNA damage initiates a cascade of signaling events within the cell to determine the most appropriate response.  For example, is it better for the cell to induce repair of the DNA damage and risk mutation, or simply induce programmed cell death if damage is too great.  Kevin’s research group studies the molecular pathways of these cellular life-and-death decisions, including the protein kinases ATR and ATM, which are master regulators of the DNA damage response in eukaryotic cells.  Both genetic and genomic approaches are currently being used in the lab to study these pathways.

Kevin Culligan - Rudman Hall, Room 302
Phone: (603) 862-2430
Email: K.Culligan@unh.edu

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Foci Denis complexesClyde Denis -- Protein translation complexes
 

The research in Clyde Denis' lab concerns deciphering the mechanisms by which environmental stresses control mRNA translation and stability.  Stress conditions, such as starvation, high temperatures, and excessive UV radiation, commonly lead to cessation of protein synthesis, an adaptation critical to eukaryotic cell survival.  In studying the yeast, Saccharomyces cerevisiae, we are examining how particular stresses affect protein translation complexes by different mechanisms and lead to the formation of stress granules, the site where quiescent mRNA complexes are often held until conditions improve.  Using the novel technique of analytical ultracentrifugation with fluorescent detection system (AU-FDS) (research conducted in collaboration with the Laue laboratory), we have been able to detect specific translational complexes present in complex mixtures.  AU-FDS allows us to discriminate between stress conditions that alter protein phosphorylation patterns and those that involve stress granule formation.  Moreover, by conducting mass spectrometeric studies on these protein complexes (in collaboration with the Chu laboratory (UNH)), we intend to identify how enviornmental effects alter protein interactions in order to control protein synthesis.  

Clyde L. Denis – Rudman Hall, Room 387
Phone: (603) 862-2427
Email: Clyde.Denis@unh.edu  

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Foci Estelle signal transductionEstelle Hrabak -- Signal transduction in Arabidopsis: regulation by post-translational modifications
 

Estelle Hrabak's lab uses genetic and biochemical approaches to study enzymes involved in signal transduction in plants.  Our primary study organism is Arabidopsis thaliana.  The two major projects in the Hrabak lab focus on protein phosphatases and palmitoyltransferases; both enzymes are encoded by large gene families in Arabidopsis.  Protein phosphatase 2A (PP2A) is known to regulate many hormone response pathways in plants and likely has other functions as well.  For example, using a reverse genetic approach, we found that some pp2a mutants have altered responses to sodium stress.  Currently, we are dissecting the cellular and subcellular basis of this mutant phenotype.  Palmitoyltransferases (PAT) are integral membrane proteins that acylate their substrates by covalent attachment of the fatty acid palmitate.  Acylation can have major effects on the subcellular localization, half-life, or activity of the substrate proteins.  We are interested in identifying the substrates of PATs, determining in which cellular membrane(s) each PAT resides, and characterizing the phenotypes of pat mutants.  The long-term goal of our research is to thoroughly understand basic biology of plants for application to biotechnology or agriculture.

Estelle Hrabak - Rudman Hall, Room 105
Phone: (603) 862-0716
Email: Estelle.Hrabak@unh.edu

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Foci Sower g-proteinStacia A. Sower -- Molecular mechanisms of neurohormone interactions with G-protein-coupled receptors 
 

Using molecular, anatomical, cellular, and systems biological approaches, the Sower laboratory seeks to understand how modifications in cellular signaling networks — represented by genes, hormones, receptors, and other signaling molecules — act on biological and reproductive functions. Reproduction in all vertebrates is regulated by gonadotropin-releasing hormone (GnRH). In the anterior pituitary, GnRH’s action is mediated via the GnRH receptor, a class A (or rhodopsin-like) seven transmembrane segment G-protein-coupled receptor (GPCR). The presence or absence of the C-terminal tail in the type-II or type-I GnRH receptors, respectively, results in differences in receptor functional organization and in the mechanism of signal termination (mediated by agonist-induced phosphorylation, desensitization and internalization). The Sower group is examining the molecular mechanisms of GnRH receptor binding and signaling using site-directed mutagenesis, pharmacological profiling, identification of binding and activating sites, and characterization of downstream signaling pathways.

Stacia Sower – Rudman Hall, Room 316
Phone: (603) 862-2013
Email: Stacia.Sower@unh.edu 

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Foci Tisa host-mictrobe interactionsLouis Tisa -- Genome-wide approaches toward host-microbe interactions
 

The Tisa lab is interested in genome-wide approaches toward studying host-microbe interactions in symbiosis and pathogenesis. These relationships have common mechanisms for establishment of the association including the ability to overcome the host defenses.  The roles of microbial behavior, signal molecules, natural products, and signal transduction in host-microbe interactions are areas of focus. Current work centers on two major model systems: plant-microbe and microbe-nematode interactions. The plant-microbe system is centered on the Frankia-actinorhizal plants, which has an infection process to develop a root nodule structure. This actinobacteria shows many similarities to another actinobacteria, Mycobacteria, intercellular pathogen. Because of the global nature of the research, the Tisa has established several International collaborations including laboratories in France, India, Tunisia, Egypt, Japan, and Argentina.  The Tisa lab has also explored microbe-nematode interactions, initially concentrating on Photorhabdus-entomopathogenic nematodes (Heterorhabditis) association, which is useful biological control agent for several insect pest. Nematode development and reproduction has an obligate requirement for their bacterial symbiont. The bacterium Photorhabdus maintains two distinct life styles as a nematode symbiont and as an insect pathogen. Thus, it provides a unique and beneficial model system for host-microbe interactions and for studying the genes controlling pathogenesis, symbiosis, and the switch between these two states. We are interested in understanding the roles that bacterial motility, biofilm formation and signal transduction play in in insect pathogenesis and nematode symbiosis. In collaboration with Thomas and Cooper labs (UNH), the Tisa has begun to study a newly identified microbe-nematode interaction (Serratia-C. briggsae) that forms an entomopathogenic complex.

Louis S. Tisa - Rudman Hall, Room 289
Phone: (603)-862-2442
Email: Louis.Tisa@unh.edu  

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Foci Tsang femal reproductivePaul Tsang -- Female reproductive physiology

 

Paul Tsang's lab studies female reproductive physiology using the sheep, cow and fish animal models.  The varieties of experimental tools we use include whole animal, cellular, molecular and cell culture approaches.  In sheep, we study the molecular mediators of corpus luteum regression initiated by prostaglandin F2 alpha (see accompanying cell model).  In the cow, we are profiling the molecular medators associated with the angiogenic switch that occurs in the ovarian follicle and the corpus luteum.  In sharks and skates, we study the life history of these elasmobranchs, including reproduction, age and growth and poupulation structure.  Our collaborators include John McCracken (sheep; University of Connecticut), Marsha Moses (cows; Children's Hospital Boston) and James Sulikowski (sharks and skates; University of New England).  Ultimately, our research has applications in biomedicine (infertility and cancer) and in fishery management. 

Paul Tsang – Rudman Hall, Room 187
Phone: (603) 862-3479
Email: Paul.Tsang@unh.edu 

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Foci Whistler planktonicCheryl Whistler -- Transition of bacteria from the planktonic to the host lifestyle
 

The Whistler lab is investigating hierarchical signal transduction systems that trigger the transition of certain bacteria from the planktonic to the host lifestyle.  During host colonization, bacteria must coordinate a number of traits in order to overcome host defenses and establish an infection.  To do this, they sense signals from their environment and then appropriately regulate gene expression.  A number of bacterial species utilize a classical two-component signal transduction system comprised of the GacS sensory kinase and the GacA response regulator. Interestingly, this signaling system can result in either disease or establishment of a beneficial symbiotic association.  We are characterizing the transcriptional and translational regulatory mechanisms by which GacS/GacA governs the ability of bacteria to activate genes by cell density in response to chemical pheromones (quorum sensing).  In addition, research is directed at understanding how changes in temperature of the host induces a transition to the pathogenic state. Our lab is also focusing effort on how symbiosis and virulence are regulated by complex gene networks through use of whole genome transcriptomics and proteomics approaches.  Our goal is to understand how bacteria integrate horizontally acquired colonization genes within these ancient regulatory networks in order to adapt to new environments.

Cheryl Whistler - Rudman Hall, Room 208
Phone: (603) 862-2359
Email: Cheryl.Whistler@unh.edu