For an organism to survive, the genome, the complete set of DNA in a cell, must be stably maintained and correctly regulated. Given the central importance of the genome, it is surprising that some organisms simply eliminate significant portions of it from some or all cells. Genome changes are also linked to cancer, a fundamentally genomic disease. My lab works on interesting questions surrounding genome dynamics: how does the organism maintain—and sometimes purposefully alter—its genome architecture, and how can it go awry in disease? Genomic methods used in this work include next-generation sequencing of DNA and RNA, cell culture, and computational methods. A particular focus of my laboratory is the role of epigenetics—a genetic code-on-a-code—in controlling genome structure and function.
The Bracht lab investigates the process of genome rearrangement in the ciliate Oxytricha trifallax. During genome rearrangement, this remarkable organism pieces together its genome from pieces much as one might assemble a jigsaw puzzle.
I am interested in molecular evolution and empirical population genetics. Current projects in my lab include: 1) transcriptome profiling of cave and surface populations of freshwater crustaceans, with an aim toward identifying and characterizing patterns of variation in differentially regulated genes, 2) experimental alteration of synonymous codons in bacterial antibiotic resistance genes, and 3) characterization of oncogenic mutations in squamous cell carcinomas of Tpl2-knockout mice.
Dr. Connaughton's research interests encompass the disciplines of developmental biology (nervous system development) and neurobiology. Specifically, she is interested in examining the relation between visually-guided behaviors in larval teleosts and maturation of retinal neurons, circuits, and receptor mechanisms. She is also interested in examining how the development of neural connections could be altered due to mutations or drugs. She has performed experiments that address behavioral/ecological questions, as well as those that employ cell biology techniques to examine retinal circuitry in both developing and adult retinal tissue.
Broadly speaking our laboratory studies molecular changes that contribute to cancer development as well as the role of the tumor microenvironment in the initiation and progression of cancer. We have two active areas of research in our laboratory. (1) The first area of research investigates one specific signaling pathway defect and how it predisposes to squamous cell carcinoma, a form of skin cancer. The tumor progression locus 2 (Tpl2) gene is involved in a variety of cellular functions including inflammatory processes and immune function. We have recently identified a novel tumor suppressor role of Tpl2 in chemically-induced skin cancer. Tpl2-/-mice have higher incidences of cutaneous papillomas than wildtype mice and these papillomas convert to cutaneous squamous cell carcinoma more readily than in wildtype mice. Currently, we are working to understand the stromal-epithelial interactions that drive skin cancer development and progression in Tpl2-/- mice. (2) Multiple myeloma is the second most common blood cancer in the United States. Epidemiological studies have identified obesity as a risk factor for multiple myeloma. Obesity increases both the risk of developing multiple myeloma and decreases overall patient survival. However, the molecular underpinnings by which adipocytes (fat cells) contribute to multiple myeloma growth and progression is relatively unknown. Our laboratory is working to understand the hormonal, lipid, and signaling factor dysregulation in obese adipocytes that contribute to MM growth and progression.
My research is focused on the evolution, ecology, and conservation of subterranean organisms, especially groundwater-dwelling amphipod and isopod crustaceans. The amphipod Gammarus minus is an especially useful model organism because subterranean and surface populations with different morphologies exist, allowing for comparative studies. Current ongoing projects include:
- Long-term monitoring of population dynamics of the amphipod Stygobromus tenuis potamacus and the isopod Caecidotea kenki from seepage springs using mark-recapture methods
- Interactions of size-selective predation by fish and sexual selection on the body size of the amphipod Gammarus minus, and the cascading effect of body size variation among populations on macroinvertebrate community structure in karst springs
- Molecular phylogeography and genetic adaptations to the subterranean environment, in collaboration with David Carlini
- Mechanisms of evolutionary loss of body pigmentation in subterranean organisms.
Biofilms are densely-packed communities of bacteria, encased in a self-synthesized polymeric matrix, growing attached to a tissue or surface. Biofilm is the predominant mode of growth for bacteria in most natural, industrial and clinical environments. Biofilm formation causes major problems ranging from industrial corrosion and biofouling to chronic or nosocomial infections. Kaplan's lab is studying the detachment and dispersal of cells from bacterial biofilms. The emphasis of his research is the use of biofilm matrix-degrading enzymes as potential antibiofilm therapies for the treatment and prevention of various human, animal and plant infections. Kaplan's lab has received funding from the National Institute of Allergy and Infectious Diseases and from private industry.
Stem cells are crucial for the growth and development of multicellular organisms. We are interested in how stem cell activity is regulated by gene expression. Our work focuses on transcription factors that dictate the proper spatial and temporal expression of genes in stem cell microenvironments. Without this regulation, stem cell activity is dysfunctional and organisms develop abnormally. Our investigations utilize the plant model Arabidopsis thaliana since stem cells are essential for the generation of new organs throughout its lifecycle. We primarily study reproductive development, and employ molecular, genetic and genomic approaches to interrogate the role of stem cell populations during this agronomically important stage. With this work, we aim to better understand how transcriptional regulation maintains stem cell integrity and to offer strategies for improving crop productivity.
Dr. Laubach is a neurobiologist interested in how groups of neurons work together to process information. His research has focused on the frontal cortex and basal ganglia and their roles in executive control and decision making. His laboratory uses a systems and computational approach and core methods include multi-electrode recordings, optogenetics, anatomical tract-tracing, multivariate statistics, and computational models of neural circuits. His is currently funded by the National Science Foundation to understand neural circuits that allow for "performance monitoring" (updating plans for action based on past behavioral outcomes) and the Klarman Family Foundation to understand neuronal circuits that control food-seeking behavior.
Hormones are profound modulators of brain structure and function; with influences that span the lifetime of an organism. The muti-faceted and pluripotent neural effects of steroids require that a specific hormone be delivered to the right target at precisely the right time. Members of my laboratory and I are curious as to how this process occurs. We have discovered that estrogen is synthesized in synaptic boutons and in astroglia (a type of non-neuronal cell in the brain). This compartment- and cell-specific hormone provision may be responsible for the effects of estrogen on learning, memory, neural degeneration and perhaps neuroprotection and repair.
Dr. Schaeff's training is in behavior and evolutionary biology. Her research interests include social behavior, conservation biology, molecular ecology and most recently, human sexual identity - examining the biological foundations of human gender and sexual orientation.
There is data that suggests that individuals with gender dysphoria (i.e., transgendered individuals) who receive sex hormones as part of their transition may experience a shift in their sexual orientation and/or gender identities. To social scientists, gender is primarily a social construct, connected to an individual's sex or sexual orientation mostly through socially constructed links. To natural scientists, it is a flexible behavioral aspect that evolved because it facilitated obtaining high quality mates and maximizing one's reproductive success. Investigating whether, and if so how, sex hormones affect sexual identity (gender and sexual orientation) is important both for enhancing our understanding of sexual identity and because it will provide information and insights for transitioning individuals and the practitioners who support them. This work incorporates biological, psychological, and sociological theories and methodologies.
Dr. Tudge is primarily a reproductive biologist with particular interests in the reproductive biology of invertebrates. His research focuses on the reproductive cells and associated structures, evolutionary mechanisms, and reproductive behaviors of marine decapod crustaceans. He also has experience dealing with other invertebrate and vertebrate groups and his knowledge of reproduction in crustaceans can be directly applied to other taxa. He uses this interest in crustacean reproduction to investigate the evolutionary history (phylogeny) of particular crabs in marine and freshwater environments. Tudge also has an interest in bird biology, ecology and systematics.
- Carlini, D. B., Manning, J., Sullivan, P. G., Fong, D. W., 2009. Molecular genetic variation and population structure in morphologically differentiated cave and surface populations of the freshwater amphipod Gammarus minus. Molecular Ecology. 18, 1932-1945.
- Cederlund, ML, ME Morrissey, T Baden, D Scholz, V Vendrell, L Lagnado, VP Connaughton, and BN Kennedy. 2010. Zebrafish Tg(7.2mab2112:EGFP)ucd2 transgenics reveal a unique population of retinal amacrine cells. Investigative Ophthalmology and Visual Science. In press.
- Chapman, GB, R Tarboush, DA Eagles, and VP Connaughton. 2009. A light and transmission electron microscope study of the distribution and ultrastructural features of the peripheral nerve processes in the non-retinal layers of the zebrafish eye. Tissue Cell. 41: 286-298.
- Connaughton, VP. 2010. Bipolar cells in the zebrafish retina. Visual Neuroscience. 16:1-17.
- Connaughton, VP, A Bender, and R Nelson. 2008. Electrophysiological evidence of GABAA and GABAC receptors on zebrafish bipolar cells. Visual Neuroscience. 25(2): 139-154.
- Connaughton, VP and R Nelson. 2010. Spectral responses in zebrafish horizontal cells include a tetraphasic response and a novel UV-dominated triphasic response. Journal of Neurophysiology. 104: 2407-2422.
- D'Antonio JM, et.al., (2010) Loss of Androgen Receptor-Dependent Growth Suppression by Prostate Cancer Cells Can Occur Independently from Acquiring Oncogenic Addiction to Androgen Receptor Signaling. PLoS ONE 5, e11475.
- DeCicco-Skinner, KL, Trovato, EL, Simmons, JK, Lepage, PK, Wiest, J. (2010) Loss of Tumor Progression Locus 2 (TPL2) enhances tumorigenesis and inflammation in two-stage skin carcinoigenesis. Oncogene. 2010 Oct 11. [Epub ahead of print].
- Fortunato CS, Carlini DB, Ewers E, Bushaw-Newton KL, 2009. Nitrifier and denitrifier molecular operational taxonomic unit compositions from sites of a freshwater estuary of Chesapeake Bay. Canadian Journal of Microbiology. 55, 333-346.
- Hanson, N., M. Fogel, D.W. Fong, and S.E. MacAvoy. 2010. Marine nutrient transport: anadromous fish migration linked to the freshwater amphipod Gammarus fasciatus. Canadian Journal of Zoology 88: in press. DOI:10.1139/Z10-030
- Hense, W., Anderson, N., Hutter, S., Stephan, W., Parsch, J., Carlini, D. B., 2010. Experimentally Increased Codon Bias in the Drosophila Adh Gene Leads to an Increase in Larval, But Not Adult, Alcohol Dehydrogenase Activity. Genetics. 184, 547-555.
- Hutchins, B., D.W. Fong, and D.B. Carlini. 2010. Genetic population structure of the Madison Cave Isopod, Antrolana lira (Cymothoida: Cirolanidae) in the Shenandoah Valley of the eastern United States. Journal of Crustacean Biology 30(2): 312-322. DOI: 10.1651/09-3151.1
- Lemaitre, R. Tudge, C.C. and McLaughlin, P.A. 2010. Preliminary study of the preungual process in the Paguroidea, with emphasis on the Paguridae (Crustacea: Decapoda: Anomura). Nauplius 18, 13-23.
- Robles, R., Tudge, C.C., Dworschak, P.C., Poore, G.C.B., and Felder, D.L.. Molecular Phylogeny of the Thalassinidea Based on Nuclear and Mitochondrial Genes. In (J.W. Martin, K.A. Crandall, D.L. Felder, Eds.): Decapod Crustacean Phylogenetics. CRC Press, Boca Raton, 2009, pp. 309-326.
- Tirelli, T., Silvestro, D., Pessani, D., and Tudge, C.C. 2010. Description of the male reproductive system of Paguristes eremita (Anomura, Diogenidae) and its placement in a phylogeny of diogenid species based on spermatozoal and spermatophore ultrastructure. Zoologischer Anzeiger 248, 299-312.
- Tudge, C.C. Spermatozoal Morphology and Its Bearing on Decapod Phylogeny. In (J.W. Martin, K.A. Crandall, D.L. Felder, Eds.): Decapod Crustacean Phylogenetics. CRC Press, Boca Raton, 2009, pp. 101-119.
- Zacharda, M., D.W. Fong, H.H. Hobbs, III, E. Piva, M.E. Slay, and S.J. Taylor. 2010. A review of the genus Traegaardhia (Acari, Prostigmata, Rhagidiidae) with descriptions of new species and a key to species. Zootaxa 2474:1-64.
- Zagmajster, M, M.L. Porter, and D.W. Fong. 2010. Hydrozoans in subterranean freshwater habitats with new findings from North America. Speleobiology Notes: in press.