Dr. Michael Simons laboratory focuses on the study of extra cellular matrix and growth factor interactions with endothelial cells in the control of angiogenesis. A number of projects in the laboratory focus on syndecan-4 signaling, that plays a key role in regulation of endothelial cell adhesion and migration. In particular, efforts are aimed at understanding the control of FGF2 signaling by syndecan-4 endocytosis and the involvement of various small GTPases and PDZ proteins in this signaling cascade.
Other studies are focused on the function of a novel family of angiogenic peptides, PR39. Recent discoveries in the laboratory of novel mechanisms of proteasome-dependent protein degradation have opened a new area of investigations that is focused on studies of small molecule-dependent selective regulation of proteasome function.
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Under construction Under construction.
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Dr. Ebo de Muinck's research is focused on assessing the effects of regenerative therapy on the heart and vascular system. To this end the lab. has developed a targeted molecular imaging approach based on the use of a synthetic peptide sequence NGR (asparagine-glycine-arginine) that can be linked to imaging molecules and selectively targets an endothelial cell surface molecule (CD13/Aminopeptidase N) that is preferentially upregulated on angiogenic endothelial cells. Other imaging modalities that have been developed are a 3 dimensional reconstruction technique for computer tomographic angiography in rodents, 3D echo guidance for intra-myocardial injections of therapeutics, cell tracking techniques and perfusion sensitive magnetic resonance imaging of the heart. The MRI techniques are developed in collaboration with Professor J.D. Pearlman of the Advanced Cardiac Imaging Center at Dartmouth Hitchcock Memorial Hospital and nanoparticles fro targeted imaging of neo-vessels are generated in collaboration with Drs. Y. Durant and J. Claverie from the Nanostructured Polymer Research Center at the University of New Hampshire. Live cell imaging techniques are used to assess binding and internalization of NGR decorated nanoparticles, and at the molecular level the lab. Investigates the role of CD13/Aminopeptidase N in neo-vascularization.
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Dr. Arie Horowitz focuses on molecular mechanisms of endothelial cell migration. The two main objectives of the lab are: (1) to elucidate how the spatiotemporal distribution of Rho GTPases is regulated in response to chemotactic factors; (2) to determine the intracellular signaling pathways downstream of the guidance cue receptors neuropilin, plexin, and the vascular endothelial growth factor receptor.
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Dr. Karen Moodie is investigating potential roles of cell / gene therapy in myocardial functional improvement. In addition to working on large and small animal preclinical studies, Karen is involved in characterizing transgenic mouse models on a physiological basis.
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Dr. Mary Jo Mulligan-Kehoe's research focuses on anti-angiogenesis. She truncated PAI-1 cDNA to produce recombinant PAI-1 proteins to study the role of PAI-1 in angiogenesis. The structural changes in the rPAI-1 proteins determine their pro- or anti-angiogenic activity. Dr. Mulligan-Kehoe studies the mechanisms and signaling pathways that contribute to the anti-angiogenic functions of one specific truncated PAI-1 protein, rPAI-123. The in vivo anti-angiogenic activity of rPAI-123 reduces tumor growth and metastases in a breast tumor xenograft model and reduces atherosclerotic plaque growth in an atherogenic mouse model. The rPAI-123 protein is being developed for gene therapy using a system that will provide specificity in its delivery to sites of neo-angiogenesis.
Dr. Mulligan-Kehoe’s laboratory also examines anti-angiogenesis in translational studies of the vascular abnormalities in patients with systemic sclerosis (scleroderma).
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Dr. Justin D. Pearlman has pioneered a number of novel MR-based imaging approaches to identification, mapping, and functional characterization of collateral beds in the ischemic myocardium. Current investigations are extending these techniques to mice models of angiogenesis. In addition to animal studies, Dr. Pearlman's laboratory is serving as a Core MR laboratory for several multicenter trials of therapeutic angiogenesis.
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Dr. Mark Post is investigating the role of HGF and PDGF role in coronary and peripheral angiogenesis. Other studies are investigating the role of Notch/Jagged system in restenosis. Dr. Post brings to the Center his internationally- recognized expertise in animal studies of vascular remodeling, and extensive hands-on experience with a variety of small and large animal atherosclerotic models.
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Dr. Nicholas Shworak's laboratory is focused on elucidation of the role of heparan sulfates in blood coagulation and atherosclerosis. Recent studies included the generation of a knockout mouse strain deficient for a gene responsible for the synthesis of antithrombin-III binding heparan sulfate sequences and cloning of the enzymes involved in various aspects of heparan sulfate biosynthesis. The laboratory has recently discovered an association between deletion of the ATIII heparan sulfate binding site on cell surface heparan sulfates and the development of degenerative cardiac valve disease.
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Dr. Radu Stan's laboratory is focused on elucidating the molecular mechanisms of transendothelial exchanges between the blood plasma and the interstitial fluid (vascular permeability) in health and disease states such as cancer and inflammation. Within this, of particular interest are the regulation, function and components of endothelial microdomains such as lipid rafts, caveolae, transendothelial channels, fenestrae and vesiculo-vacuolar organelles. Recent studies done in this laboratory have led to the discovery of PV-1 the first marker for the endothelial stomatal as well as fenestral diaphragms. The laboratory uses a variety of approaches including biochemical and molecular biology techniques as well as transgenic and KO mice, electron microscopy, and real time fluorescence live microscopy.
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Dr. Zhenwu Zhuang is investigating the molecular mechanism of post-angioplasty restenosis at the genetic level both in rats and transgenic/knock-out mice, which includes Notch/Jagged system, ApoE/LDLR double KO, and synectin/syndecan. Dr. Zhuang is developing and using advanced image techniques (implantable coil combined with powerful 7.0 Tesla MR) to quantify restenosis and remodeling in vivo. He is also interesting in image reconstruction both in micro-CT and CT images and development of micro-interventional procedures for angiogenesis and Molecular Imaging research. For more details, please visit his personal homepage.
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Dr. Craig Thompson
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Dr. Armin Helisch is interested in the mechanisms involved in the compensatory growth of collateral arteries. Dr. Helisch has extensive experience with the femoral artery ligation model in mice, which he helped to establish as a postdoc in the laboratory of Wolfgang Schaper, one of the pioneers of research on collateral growth. Since that time, Dr. Helisch has been involved in developing and optimizing methods to image and quantify collateral arteries in mice, which has led to a realization of the importance of preexisting collateral vessels in this model, and also resulted in the first in vivo magnetic resonance images of growing collateral vessels in mice. Dr. Helisch’s research is related to the role of circulating and tissue resident cells, strain background, tissue environment, growth factors, chemokines and mechanical forces in collateral artery growth. Furthermore, Dr. Helisch is a faculty advisor of the Dartmouth Argentine Tango Society.
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Armstrong, David, MA - Research Assistant
Chittenden, Thomas, MSc, PhD - Visiting Research Collaborator
Elfenbein, Arye - Graduate Student
Follensbee, Joanie - Administrative Assistant
Fu, Qiangwei, MD - Research Associate
Haj Mohammadi, Sassan, MSc., PhD - Research Associate
Hall, Amy - Laboratory Manager
Hamilton, Joanna, PhD - Research Associate
Kobayashi, Takashi, PhD - Research Associate
Lanahan, Ty, PhD - Research Associate
Lee, Chunsik, PhD - Research Associate
Li, Hui, MD, M.Sc - Research Associate
Liu, Michael, MD, M.Sc - Research Associate
Murakami, Masahiro, MD, PhD - Research Associate
Partovian, Chohreh, MD, PhD - Research Associate
Paye, Julie, PhD - Research Associate
Ren, Bin, PhD - Research Associate
Rhodes, John, PhD - Research Associate
Shipman, Samantha - Research Technician
Smits, Nicole, PhD - Research Associate
Tirziu, Daniela, PhD - Research Associate
