A5045840183- Planarian Biology and Electrostimulation
- Marine Ecology and Invasive Species
- Plant and Biological Electrophysiology Studies
- Neuroendocrine regulation and behavior
- Neuroscience of respiration and sleep
- DNA and Nucleic Acid Chemistry
- Marine Invertebrate Physiology and Ecology
- Pluripotent Stem Cells Research
- Ocular Surface and Contact Lens
- Marine Biology and Environmental Chemistry
- Aquaculture Nutrition and Growth
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Animal Genetics and Reproduction
- Neuropeptides and Animal Physiology
- Protist diversity and phylogeny
- Reproductive biology and impacts on aquatic species
- Effects and risks of endocrine disrupting chemicals
- Developmental Biology and Gene Regulation
- Ocean Acidification Effects and Responses
- Genetics, Aging, and Longevity in Model Organisms
- Salivary Gland Disorders and Functions
- Cellular Mechanics and Interactions
- Pharmaceutical and Antibiotic Environmental Impacts
Tufts University
2012-2025
Harvard University
2008
National Institutes of Natural Sciences
2007
National Institute for Basic Biology
2004-2007
Harvard University Press
2007
Tokyo Institute of Technology
1999-2002
Hiroshima University
1994-1997
A main goal of regenerative medicine is to replace lost or damaged tissues and organs with functional parts the correct size shape. But proliferation new cells not sufficient; we will also need understand how scale ultimate form newly produced are determined. Using planarian model system, report that membrane voltage-dependent bioelectric signaling determines both head organ scaling during regeneration. RNA interference H(+),K(+)-ATPase ion pump results in hyperpolarization, which has no...
We show that regenerating planarians' normal anterior-posterior pattern can be permanently rewritten by a brief perturbation of endogenous bioelectrical networks. Temporary modulation regenerative bioelectric dynamics in amputated trunk fragments planaria stochastically results constant ratio regenerates with two heads to morphology. Remarkably, this is shown due not partial penetrance treatment, but profound yet hidden alteration the animals' patterning circuitry. Subsequent amputations...
The shape of an animal body plan is constructed from protein components encoded by the genome. However, bioelectric networks composed many cell types have their own intrinsic dynamics, and can drive distinct morphological outcomes during embryogenesis regeneration. Planarian flatworms are a popular system for exploring patterning due to regenerative capacity, but despite considerable molecular information regarding stem differentiation basic axial patterning, very little known about how head...
The molecular mechanisms governing the cell behaviors underlying morphogenesis remain a major focus of research in both developmental biology and cancer biology. TGF-β ligands control fate specification via Smad-mediated signaling. However, their ability to guide cellular variety biological contexts is poorly understood. We report on discovery novel signaling-mediated occurring during vertebrate gastrulation. Activin/nodal members superfamily induce expression two genes regulating adhesion...
Ion transporters, and the resulting voltage gradients electric fields, have been implicated in embryonic development regeneration. These biophysical signals are key physiological aspects of microenvironment that epigenetically regulate stem tumor cell behavior. Here, we identify a previously unrecognized function for KCNQ1, potassium channel known to be involved human Romano-Ward Jervell-Lange-Nielsen syndromes when mutated. Misexpression its modulatory wild-type beta-subunit XKCNE1 Xenopus...
Control of axial polarity during regeneration is a crucial open question. We developed quantitative model regenerating planaria, which elucidates self-assembly mechanisms morphogen gradients required for robust body-plan control. The computational has been to predict the fraction heteromorphoses expected in population planaria fragments subjected different treatments, and originating from regions along anterior-posterior medio-lateral axis. This allows direct comparison between experimental...
Several ion transporters have been implicated in left-right (LR) patterning. Here, we characterize a new component of the early bioelectrical circuit: potassium channel KCNQ1 and its accessory subunit KCNE1. Having cloned native Xenopus versions both genes, show that are asymmetrically localized as maternal proteins during first few cleavages frog embryo development process dependent on microtubule actin organization. Molecular loss-of-function using dominant negative constructs demonstrates...
Anatomical homeostasis results from dynamic interactions between gene expression, physiology, and the external environment. Owing to its complexity, this cellular organism-level phenotypic plasticity is still poorly understood. We establish planarian regeneration as a model for acquired tolerance environments that alter endogenous physiology. Exposure barium chloride (BaCl2) in rapid degeneration of anterior tissue Dugesia japonica. Remarkably, continued exposure fresh solution BaCl2 heads...
The lacrimal gland (LG) is the major source of aqueous tears, and insufficient LG secretion leads to aqueous-deficient dry eye (ADDE) disease. To provide a foundational description LG's protein expression patterns, we prepared extracts LGs from wild-type an ADDE mouse model analyzed proteome by quantitative mass spectrometry. were isolated model, male non-obese diabetic (NOD) mice control BALB/c (n = 6 each). Protein samples in urea-based lysis buffer concentrations determined BCA method....
The ability to stop producing or replacing cells at the appropriate time is essential, as uncontrolled growth can lead loss of function and even cancer. Tightly regulated mechanisms coordinate stem cell progeny with patterning needs host organism. Despite importance proper termination during regeneration, turnover, embryonic development, very little known about how tissues determine when complete these processes. Using planarian flatworms, we show that planar polarity (PCP) pathway required...
Regeneration is regulated not only by chemical signals but also physical processes, such as bioelectric gradients. How these may change in the absence of normal gravitational and geomagnetic fields largely unknown. Planarian flatworms were moved to International Space Station for 5 weeks, immediately after removing their heads tails. A control group spring water remained on Earth. No manipulation planaria occurred while they orbit, space-exposed worms returned our laboratory analysis. One...
Automated computational methods can infer dynamic regulatory network models directly from temporal and spatial experimental data, such as genetic perturbations their resultant morphologies. Recently, a method was able to reverse-engineer the first mechanistic model of planarian regeneration that recapitulate main anterior-posterior patterning experiments published in literature. Validating this comprehensive via novel had not yet been performed would add our understanding remarkable capacity...
We reported that oxytocin (OXT), added to freshly prepared lacrimal gland lobules, induced myoepithelial cell (MEC) contraction. In other systems, OXT activates phospholipase C (PLC) generating Inositol 1,4,5-trisphosphate (IP3) which increases intracellular calcium concentration ([Ca2+]i) causing The aim of the current study was investigate role this pathway in OXT-induced contraction MEC.Tear volume measured using cotton thread method. Lacrimal MEC were isolated and propagated from...
In the lacrimal gland, myoepithelial cells (MEC) express muscle contractile proteins such as alpha smooth actin (SMA) and calponin therefore can contract to help expel fluid. a previous study, we demonstrated that gland MEC oxytocin receptor (OXTR) they under (OXT) stimulation. Using NOD MRL/lpr mice (animal models of Sjogren’s syndrome), reported decrease in SMA protein levels plus decline acini contraction after stimulation with OXT. It is known proinflammatory cytokines, interleukin-1β...
The aim of the present study is to investigate role c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-2 (MMP-2) in mediating effects interleukin-1β (IL-1β) on function lacrimal gland myoepithelial cells (MECs). MECs isolated from an α-smooth muscle actin–green fluorescent protein (SMA-GFP) transgenic mouse were treated with IL-1β alone or presence SP600125, a JNK inhibitor, ARP100, MMP-2 inhibitor. GFP intensity cell size/area measured, day 7, SMA, calponin, pro-MMP-2 levels MEC...
The 5′ flanking region of the sea urchin Hemicentrotus pulcherrimus arylsulfatase ( Ars ) gene was scanned to define cis ‐regulatory elements required for proper expression congruent that endogenous gene. between −100bp and +38 bp from transcription start site contains minimum information temporal initiation Progressive deletion analysis ‐luciferase reporter constructs containing sequence −3484 +38bp suggests existence several within this region. Results luciferase assays internal mutants...