Dr. Annex's laboratory is a true bench to bedside translational research laboratory that focuses on angiogenesis (the growth and proliferation of blood vessels from existing vascular structures) in the context of peripheral arterial disease (PAD). With this as a focus, we have launched a research program that focuses on specific microRNAs that may serve as unique therapeutic approaches for the treatment of PAD in mouse, cell culture, and selected human studies. In addition, we have a continuing NIH funded program using adeno-associated virus-based gene therapy which has mouse, large animal, and human components. We also have two active projects in the area of computational modeling for angiogenesis in PAD. Finally, we have pure human based mechanism testing human studies.
For the most current list of Annex Lab publications, please click here.
Johns Hopkins University
Dr. Brian Annex has held a long standing collaboration with Johns Hopkins and together they have developed several projects that have had very promising results.
A current project is to analyze existing multiple large-scale high-throughput datasets from PAD patients using bioinformatics approaches with the goal of identifying and systematizing important proteins and signaling pathways, discover connections between the proteins in the form of a PAD interactome, perform in silico drug repositioning studies to predict potential therapeutic targets, and validate them using previously accumulated human biopsy samples and a well-established animal model of PAD. A systematic analysis of molecules, pathways, protein-protein interactions, and drug targets will provide much needed guidance for the prevention and treatment of PAD.
Another project is to measure the dynamics of the VEGF receptor and ligand family in skeletal muscle in healthy non-ischemic mice and following hind limb ischemia (HLI), an established preclinical model of PAD. We hypothesize that these diseases quantitatively alter receptor-ligand interactions in the hind limb muscles in a manner that makes the VEGF signaling less efficient and/or less able to be modulated following injury. We plan to experimentally characterize non-ischemic hind limb muscles in healthy mice and the same muscles at selected time points following hind limb ischemia produced by femoral artery ligation and excision. We will then obtain values for the parameters at multiple scales involved in the computational models.
Dr. Brian Annex is currently collaborating with Duke University on a project to determine differences in gastrocnemius muscle via biopsy between patients with PAD, and those without the disease. From this tissue, we will measure capillary density with surrounding pericytes, proliferating cell nuclear antigen, and apoptosis for measures of angiogenesis and arteriogenesis and vascular density, fiber type composition, and an estimation of mitochondria volume with citrate synthase activity. These are measurements for potential mediation analyses. We will gain insight into the relative effect sizes, which will be used to inform mechanistic aims in possible future trial(s).
Dr. Brian Annex has established a collaborative partnership with Yale University where he will provide a subcontract from his recent RO1 titled, “A Bioengineering Approach to Gene Therapy for Peripheral Arterial Disease". The purpose of this subcontract is to provide collaborative support in two areas. The first involves creation of a large animal model of hind limb ischemia for evaluation of gene therapy via AAV9 vectors. These pigs will be evaluated with serial imaging over a 4 week time using novel imaging systems only available at Yale University. The second component of this project is to provide support for development of a novel SPECT reporter system for evaluation of gene expression in murine models of hind limb ischemia and then in pigs with chronic hind limb ischemia. Upon euthanasia, tissue will be collected and sent to UVA for further analysis.
Imoukhuede PI, Dokun AO, Annex BH, Popel AS. Endothelial cell-by-cell profiling reveals temporal dynamics of VEGFR1 and VEGFR2 membrane-localization following murine hindlimb ischemia. Am J Physiol Heart Circ Physiol. 2013 Feb 1. [Epub ahead of print]
Ellati RT, Dokun AO, Kavoussi PK, Steers WD, Annex BH, Lysiak JJ. Increased phosphodiesterase type 5 levels in a mouse model of type 2 diabetes mellitus. J Sex Med. 2013 Feb;10(2):362-9. doi: 10.1111/j.1743-6109.2012.02854.x.
Konkalmatt PR, Wang F, Piras BA, Xu Y, O'Connor DM, Beyers RJ, Epstein FH, Annex BH, Hossack JA, French BA. Adeno-associated virus serotype 9 administered systemically after reperfusion preferentially targets cardiomyocytes in the infarct border zone with pharmacodynamics suitable for the attenuation of left ventricular remodeling. J Gene Med. 2012 Sep-Oct;14(9-10):609-20. doi: 10.1002/jgm.2673. PubMed PMID: 23065925.
McClung JM, McCord TJ, Keum S, Johnson S, Annex BH, Marchuk DA, Kontos CD. Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice. Am J Pathol. 2012 May;180(5):2156-69. doi: 10.1016/j.ajpath.2012.01.032.
Jones WS, Duscha BD, Robbins JL, Duggan NN, Regensteiner JG, Kraus WE, Hiatt WR, Dokun AO, Annex BH. Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training. Vasc Med. 2012 Apr;17(2):94-100. doi: 10.1177/1358863X11436334.
Duscha BD, Annex BH, Johnson JL, Huffman K, Houmard J, Kraus WE. Exercise dose response in muscle. Int J Sports Med. 2012 Mar;33(3):218-23. doi: 10.1055/s-0031-1291323.
West AM, Anderson JD, Epstein FH, Meyer CH, Hagspiel KD, Berr SS, Harthun NL, Weltman AL, Annex BH, Kramer CM. Percutaneous intervention in peripheral artery disease improves calf muscle phosphocreatine recovery kinetics: a pilot study. Vasc Med. 2012 Feb;17(1):3-9. doi: 10.1177/1358863X11431837.
Perin EC, Silva G, Gahremanpour A, Canales J, Zheng Y, Cabreira-Hansen MG, Mendelsohn F, Chronos N, Haley R, Willerson JT, Annex BH. A randomized, controlled study of autologous therapy with bone marrow-derived aldehyde dehydrogenase bright cells in patients with critical limb ischemia. Catheter Cardiovasc Interv. 2011 Dec 1;78(7):1060-7. doi: 10.1002/ccd.23066.