My lab studies the role of endothelial cells and pericytes in various settings of vascular disease and in the normal repair of the vasculature. Here I describe the four areas we are pursuing.
Infantile hemangioma is a vascular tumor that can grow rapidly, causing organ damage, disfigurement and morbidity. We’ve focused on identifying cellular mechanisms that drive this uncontrolled vascular growth. We identified a multi-potent stem cell that can recapitulate hemangioma in immune-deficient mice. We are also studying pericytes from hemangioma and the glucose transporter-1 positive endothelial cells, which are a hallmark of hemangioma. Our goal is to use cellular and animal models to identify new drugs that will work safely and quickly to prevent hemangiomas from growing to an endangering size.
Vascular malformations are distinct from ascular tumors such as hemangioma but are also little understood and medical therapies are needed. We have recently begun new projects on the cellular and molecular basis of capillary malformations, lymphatic malformation and venous malformations.
Endothelial progenitor cells (EPCs), also called endothelial colony forming cells (ECFCs) are rare cells found in the blood. They can be isolated based on their high proliferative capacity in vitro. We demonstrated the usefulness of EPC/ECFC for endothelializing small diameter vascular grafts in a sheep model and for building networks of human blood vessels rapidly in vivo using athymic nude mice. We also showed that ECFC were able to assemble into perfused vessels when injected into ischemic rat myocardium, and that the presence of these cells was beneficial to recovery of heart function over time.
Heart valve endothelial cells - The endothelial cells lining heart valves exhibit unique plasticity compared endothelial cells of large vessels (veins and arteries) or microvessels (capillaries). The valve endothelial cells can undergo endothelial to mesenchymal transition (EndMT) in response to TGFβ, and this process is highly regulated. We study the mitral valve endothelium as part of a multi-disciplinary team focused on how the mitral valve adapts after myocardial infarction.
About Joyce Bischoff
Joyce Bischoff received an A.B. in chemistry from Duke University and a Ph.D. in biochemistry from the Washington University School of Medicine. She was a post-doctoral fellow at the Whitehead Institute for Biomedical Research. She joined the Surgical Research Laboratories, now called the Vascular Biology Program, at Children's Hospital in 1990. She was elected to serve as President of the North American Vascular Biology Organization (NAVBO) from July 2015-June 2016.
- Kaushal S, Amiel GE, Guleserian KJ, Shapira OM, Perry T, Sutherland FW, Rabkin E, Moran AM, Schoen FJ, Atala A, Soker S, Bischoff J, Mayer JE Jr. Functional small diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med. 2001 Sep; 7(9): 1035-40.
- Boye E, Yu Y, Paranya G, Mulliken JB, Olsen BR, and Bischoff J. Clonality and altered behavior of endothelial cells from infantile hemangioma. J. Clinical Invest. 2001 107(6): 745-52.
- Paruchuri S, Yang J-H, Aikawa E, Melero-Martin JM, Khan ZA, Loukogeorgakis S, Schoen FJ, Bischoff J. Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity in response to VEGF-A and TGFβ2. Circulation Research. 2006 Oct 13; 99(8): 861-9.
- Melero-Martin JM, Khan ZA, Picard A, Wu X, Paruchuri S, Bischoff J. In vivo vasculogenic potential of human blood-derived endothelial progenitor cells. Blood. 2007 Jun 1; 109(11): 4761-8.
- Khan ZA, Boscolo E, Picard A, Psutka S, Melero-Martin JM, Bartch TC, Mulliken JB, Bischoff J. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. J. Clin Invest. 2008 Jul; 118(7): 2592-9.
- Melero-Martin JM, De Obaldia ME, Kang SY, Khan ZA, Yuan L, Oettgen P, Bischoff J. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circulation Research. 2008 Jul 18; 103(2): 194-202.
- Greenberger S, Boscolo E, Adini I, Mulliken JB, Bischoff J. Corticosteroid suppression of VEGF-A in infantile hemangioma-derived stem cells. N Engl J Med 2010 363 (11):1005-1013
- Wylie-Sears J, Aikawa E, Levine RA, Yang J-H, Bischoff J. Mitral valve endothelial cells with osteogenic differentiation potential. Arterioscler Thromb Vasc Biol. 2011; 31(3):598-607.
- Human vasculogenic cells form functional blood vessels and mitigate adverse remodeling after ischemia reperfusion injury in rats. Kang KT, Coggins M, Xiao C, Rosenzweig A, Bischoff J.
Angiogenesis. 2013 Oct;16(4):773-84.
- Pericytes from infantile hemangioma display proangiogenic properties and dysregulated angiopoietin-1. Boscolo E, Mulliken JB, Bischoff J. Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):501-9.
- Huang L, Nakayama H, Klagsbrun M, Mulliken JB, Bischoff J. Glucose transporter 1-positive endothelial cells in infantile hemangioma exhibit features of facultative stem cells. Stem Cells 2015; 33(1): 133-45.
- Shapero K, Wylie-Sears H, Levine RA, Meyer JE Jr., Bischoff J. Reciprocal interactions between mitral valve endothelial and interstitial cells reduce endothelial to mesenchymal transition and myofibroblastic activation. J Mol Cell Cardiol. 2015; 80:175-85
- Boscolo E, Limaye N, Huang L, Kang KT, Soblet J, Uebelhoer M, Mendola A, Natynki M, Seront E, Dupont S, Hammer J, Legrand C, Brugnara C, Eklund L, Vikkula M*, Bischoff J*, Boon LM.* (*indicates co-senior authors) Rapamyicn improves TIE2-mediated venous malformation in animal models and human subjects. J Clin Invest 2015; Aug 10. (Epub ahead of print)