Our lab is studying the mechanistic basis for renal ischemia/reperfusion injury-induced tubular fluid backleak through the renal epithelial cell tight junction. These studies use both cell culture and animal model systems. Paracellular flux (through the tight junction) across renal epithelial cell monolayers is monitored without or with treatment with hydrogen peroxide, a compound released during ischemia/reperfusion injury. Studies are aimed at identifying which tight junction protein(s) is (are) involved in mediating the hydrogen peroxide effect, what signaling pathway(s) are initiated by hydrogen peroxide treatment that produce the changes in paracellular permeability, and ameliorating the effect of renal ischemia/reperfusion injury in vivo by interfering with the activated signaling pathway.
Student Project: Role of occludin protein domains in interaction with other tight junction proteins and hydrogen peroxide-induced regulation of paracellular permeability. Students involved in these studies will learn cell culture, transport measurements, molecular biology, protein analysis, and how to design experiments and a research study.
Publications: Caswell, D., S. Jaggi, J. Axis, and K. Amsler. (2013) Src Family Kinases Regulate Renal Epithelial Cell Paracellular Permeability Independent of Occludin Protein. J. Cell. Physiol. 228:1210-1220. (doi: 10.1002/jcp.24274. Epub 2012 Nov 6) PMID:23129414
Our lab is studying the evolution of aquatic mammals from terrestrial species. Dental microwear analysis provides information about the feeding ecology of an organism. Comparison of microwear patterns can provide insight into changes in feeding ecology between related species and can help to trace the transition from a terrestrial to an aquatic environment. The goal of this project is to examine the dental microwear of modern species of otters to better understand the connection between wear patterns and the differences in their feeding ecology so that similar patterns could be applied in the future to fossil organisms, such as early whales.
Evolutionary Origins of Archosaurian Neuroanatomy: The clade Archosauria includes the living crocodylians and birds as well as all extinct dinosaurs, making it one of the behaviorally and ecologically most diverse vertebrate groups known. At the core of this diversity is a complex history of neuroanatomical evolution that we are only beginning to understand. The archosaurs thus provide an opportunity to study neuroanatomical expansion in a group that diverged from humans more than 300 million years ago but whose brain size in many cases rivals that of mammals.
Approach—We will use digital technology to reconstruct the neuroanatomy of certain fossil reptiles that are informative for the early history of the archosaur radiation. The resultant digital endocasts of the cranial and inner ear cavities will be qualitatively and quantitatively compared to existing datasets to test current hypotheses regarding the tempo and mode of neuroanatomical evolution in this important group.
Student Project: Students will be trained in the interpretation and manipulation of neuroanatomical data derived from high-resolution computed tomography scans (I already have the scan data). This training includes the use of such computer programs as Amira, which are standards in the biomedical and engineering fields, as well as basic theory and techniques of comparative evolutionary anatomy.
Our lab is studying the repair of myocardial infarction scar formation and repair. We are studying the effect of gender on scar formation and composition. In addition, we are examining the effect of the heart rate lowering drug, Ivabradine, on scar composition and repair.
Publications: Christensen LP, Zhang RL, Zheng W, Campanelli JJ, Dedkov EI, Weiss RM, Tomanek RJ. Post myocardial infarction remodeling and coronary reserve: effects of ivabradine and beta blockade therapy. American Journal of Physiology – Heart Circulatory Physiology 2009; 297: H322-H330.
Regulation of mitochondrial degradation in cardiac myocytes by AMP-activated protein kinase (AMPK): AMPK is a cellular energy sensor essential for cardiac function under normal and disease conditions. However, the mechanisms that mediate myocardial protection by AMPK remain poorly understood. This project will investigate if AMPK protects cardiac myocytes through enhancing mitophagy, a degradation pathway that selectively eliminates injured or aged mitochondria that would otherwise produce excessive free radicals damaging the heart cell. This project will be performed in cultured cardiac myocytes. AMPK activity will be manipulated by adenovirus-mediated overexpression and siRNA-mediated knockdown or chemical inhibitors. Mitophagic process will be monitored and quantified with a novel mitophagy reporter.
Student Project: The student will have opportunities to learn various techniques including heart cell culture, cell death analysis, protein analysis by Western blotting, confocal microscopy and adenoviral infection.
Testing climate change and overkill extinction hypotheses of Pleistocene equids with dental mesowear: Understanding the diets of extinct species is important for understanding the ecology of extinct species and how climate change influenced their evolution. It has long been recognized that the microscopic scratches and other wear marks found on the surfaces of teeth can be used to test hypotheses about the diets of long extinct species. However, the relationship of dental microwear and diet in modern species is still poorly understood, rendering it difficult to understand dental microwear in fossil species.
Publications: Mihlbachler, Matthew C., Beatty, Brian L., Caldera-Siu, Angela, Chan, Doris, and Lee, Richard, 2012. Error rates and observer bias in dental microwear analysis using light microscopy. Palaeontologia Electronica Vol. 15, Issue 1;12A,22p;
Anatomical changes in brain during development and in Parkinson’s Disease: NYIT undergraduates will be involved in one of several projects that are ongoing in the lab that relate to anatomical (cellular and synaptic) changes that take place in the brain during development as well as Parkinson's disease. These studies employ anatomical methods such as immunohistochemistry in order to visualize unique neuronal types and their synaptic connections. Transgenic mice with fluorescent neurons are used as an additional tool to visualize cells and circuits. Finally, mice with brain malformations or genetic mutation are used as models of neurodevelopmental and neurodegenerative disorders.
Student Project: NYIT students working in the lab will learn general and more specialized histological techniques including tissue sectioning, staining, photomicroscopy, and data analysis. Students who work for several semesters/years may have an opportunity to learn additional techniques such as animal perfusion, brain harvesting, surgery, etc. In addition to learning lab techniques, students will learn the basics of experimental design, hypothesis testing, neuronal development, nervous system disorders, and will get an introduction to reading journal articles. Finally students will learn how to work independently as well as part of a larger team.
Publications: Lipoff DM, Bhambri A, Fokas GJ, Sharma S, Gabel LA, Brumberg JC, Richfield EK, Ramos RL. Neocortical molecular layer heterotopia in substrains of C57BL/6 and C57BL/10 mice. Brain Res. 2011 May 19;1391:36-43.
Research in the Tegay laboratory is focused on discovering genetic and environmental factors that contribute to the development or variability in severity of a number of heritable medical conditions including Parkinson's disease (PD), Essential Tremor (ET) and Fascioscapulohumeral Muscular Dystrophy (FSHD).
Publications: Levy B, Tegay D, Papenhausen P, Tepperberg J, Nahum O, Tsuchida T, Pletcher BA, Ala-Kokko L, Baker S, Frederick B, Hirschhorn K, Warburton P, Shanske A. Tetrasomy 15q26: a distinct syndrome or Shprintzen-Goldberg syndrome phenocopy? Genet Med. 2012 May 31. doi: 10.1038/gim.2012.54. [Epub ahead of print]
We are interested in mapping the regional (i.e., local circuit organization) and cellular distribution of D-Dopachrome tautomerase (D-DT) in the human and mouse brain. We are also interested in studying the functional connectivity of D-DT in an animal model of Parkinson's disease.
Student Project: We will be looking at the effects of the novel antidepressant, ketamine, on bacteria biofilm formation. We will also look for specific bacterial genes responsible for cell growth and cell death. Student responsibilities will include PCR analysis of bacterial genes, In vitro analysis of bacterial cells, microscopy of bacterial cells.
Our current research program aims to investigate the role of a novel form of collective cell migration in kidney development and repair. We use transgenic zebrafish to visualize and explore cellular and molecular mechanisms underlying kidney morphogenesis and regeneration. In our studies, we utilize a variety of techniques including live confocal imaging, surgical, chemical and genetic manipulation, as well as computational modeling. Ultimately, our goal is to identify a set of physical factors that determine functional morphology of the kidney and to develop novel bioengineering approaches to kidney regeneration and organogenesis.
Student Project: We have one potential position in the lab for a new project aimed to investigate the phylogeny and the evolution of kidney regeneration. We want to understand why reptilian kidney is fully capable of adding new nephrons (functional units of the kidney) throughout their life, while mammals completely lack this ability. The project will involve histological and immunohistochemical examination of kidneys from different vertebrate species and experiments using zebrafish as a model organism.
Student Project: We also have an opening for a mechanically skilled person, who is also fluent in Matlab and Arduino/Processing programming, to work on a project involving kidney cell and organ culture.
Thyroid hormone replacement therapy on heart failure and atrial fibrillation: One of my research interests is to study atrioventricular (AV) node electrophysiology, in particular dual pathway AV node electrophysiology. The AV node is the only normal pathway conducting electrical signal from the atria to the ventricles. Although this tiny structure has been discovered for more than 100 years, its electrophysiology remains largely a mystery. By using microelectrode-recording technique, we will record action potentials from different regions of the AV node in vitro. The specific regions to be explored will be guided by a novel dual AV node electrophysiology index discovered by the P.I.
Publications: Zhang, Youhua, Mazgalev Todor. AV nodal dual pathway electrophysiology and wenckebach periodicity. J Cardiovasc Electrophysiol. 2011 Nov;22(11):1256-62. doi: 10.1111/j.1540-8167.2011.02068.x. Epub 2011 Apr 13.
Regulation of movement in Parkinson’s Disease: We compare kinematic measurements of movements of people with Parkinson’s disease to healthy control subjects to learn how Parkinson’s disease affects walking and hand-eye coordination during handwriting. Recordings of movement are with a VICON kinematic camera system and an ISCAN eye-tracker. Data is processed with these systems dedicated software and analyzed with MATLAB.
Student Project: The students will gain experience of computer programming and kinematics data processing and analysis in the context of human-subjects biomedical research.
Publications: Joanne DiFrancisco-Donoghue, Lamberg EM, Rabin E, Elokda A,Fazzini E, Werner W. Effects of exercise and B vitamins on homocysteine and glutathione in Parkinson's disease. Neurodegenerative Diseases 10:127-134
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