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Feilim Mac Gabhann
Assistant Professor, Department of Biomedical Engineering
Institute for Computational Medicine
Address:
3400 N. Charles Street
Computational Science & Engineering Building, Room 316a
Baltimore, MD 21218
Phone: (410) 516-4723
Fax: (410) 516-5294
E-mail: feilim@jhu.edu
Research Interest Statement
Our laboratory takes a combined experimental-computational approach to generating novel therapeutic approaches to major human diseases, including cancer, peripheral artery disease, and HIV.
Computational modeling of growth factor-receptor networks – the building of multiscale models integrating highly local molecular-level detail, tissue-level microvascular responses, and whole-body pharmacokinetics and pharmacodynamics. These models are directly druggable, allowing testing of many therapeutic strategies, including different drugs, modes of administration, dosing and timing.
Personalized Medicine – the identification of patient subgroups (e.g. in cancer) that respond differently to therapeutic strategies using genomics, proteomics and morphology, and the design of subgroup-specific therapies.
Therapeutic Cardiovascular Remodeling – preventive or preëmptive remodeling of the microvasculature (in mice and people) vulnerable to ischemic diseases (e.g. peripheral arterial disease, stroke and coronary artery disease) following identification of vulnerable population.
Novel methods for data visualization and automated image analysis – Just as the large volumes of data generated by genomic studies require skilled interpretation, the creation of larger and more detailed computational models and the acquisition of larger and more detailed microscopic image sets requires data presentation tools that can reduce complexity to improve clarity and aid hypothesis generation, without obscuring important effects or events.
Current Projects
Inhibiting vascular endothelial growth factor signaling in cancer. Using druggable multiscale computational models of the transport and signaling of Vascular Endothelial Growth Factor (VEGF), we test therapies to block the signaling pathways that lead to vascularization of tumors and metastasis.
Promoting vascular endothelial growth factor signaling in ischemic disease. Using druggable multiscale computational models of the transport and signaling of Vascular Endothelial Growth Factor (VEGF), we test therapies to increase nonpathological pro-angiogenic signaling that lead to increased perfusion of muscle and other tissues vulnerable to ischemia.
Microvascular network organization. We study the variability in microvascular network structure in mice from different strains, both before and after intervention. Induced ischemic or other injury results in different remodeling responses that may hold the key to therapy development.
Impact of extracellular matrix on VEGF signaling. Using a combination of in vitro, in vivo and in silico approaches, we study the ability of extracellular matrix sequestration of VEGF to impact the extracellular VEGF signal as perceived by cell-surface receptors.
Molecular mechanisms of small-genome diseases: host-virus interactions of HIV. We have created molecular-level simulations of HIV, that complement existing models of viral development and cellular infection. By including the effects of the genes that HIV expresses, particularly those that have evolved to combat our host defenses, we can test new therapies that boost host antiviral responses.
Publications
Qutub A.A., F. Mac Gabhann, P. Karagiannis, P. Vempati, A.S. Popel (2009). "Multiscale models of angiogenesis." IEEE Eng Med Biol Mag., 28(2): 14-31.
Wu F.T., M.O. Stefanini, F. Mac Gabhann, A.S. Popel (2009). "A compartment model of VEGF distribution in humans in the presence of soluble VEGF receptor-1 acting as a ligand trap." PLoS One, 4(4): e5108.
Demetriades A.M., T. Deering, H. Liu, L. Lu, P. Gehlbach, J.D. Packer, F. Mac Gabhann, A.S. Popel, L.L. Wei, P.A. Campochiaro (2008). "Trans-scleral delivery of antiangiogenic proteins." J Ocul Pharmacol Ther., 21(1): 70-9.
Mac Gabhann F., A.S. Popel (2008). "Systems biology of vascular endothelial growth factors." Microcirculation, 15(8): 715-38.
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