Amber Stratman, Ph.D.

Assistant Professor
Cell Biology and Physiology

Developmental, Regenerative and Stem Cell Biology Program
Molecular Cell Biology Program
Molecular Genetics and Genomics Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314 273-7928

  • McDonnell Sciences, Room 416

  • a.stratman@wustl.edu

  • Understanding the normal developmental processes regulating mural cell stabilization of the vasculature as a platform to assess alterations in signaling pathways during disease

Research Abstract:

To build a functionally stable blood vessel that is able to withstand changes in shear stress and modulate vascular tone requires cooperation between two cell types: the endothelial cell (EC) and the mural cell (MC). MCs, a perivascular cell population that provides structural support to EC tube networks, can be split into subclasses, including smooth muscle cells and pericytes, based on the anatomical location of the MC population within the vascular network. EC-MC interactions are known to be critical in stabilizing the vasculature by helping to withstand forces such as high shear stress/pulsatile pressure exerted on the vessels from blood flow coming out of the heart. MCs also promote barrier function at the blood brain barrier (BBB). Despite the critical nature of these cell-to-cell interactions, much more is known about genes regulating EC versus MC function.

Many diseases such as atherosclerosis/restenosis, cancer, stroke and diabetic retinopathies have known connections to vascular dysfunction exemplified by targeted disruptions in MC support of the vasculature. In diabetic retinopathy for instance, there is thought to be a drop-out of MCs surrounding blood vessels, making the remaining vasculature much more susceptible to micro-hemorrhages that are ultimately responsible for the blindness associated with the disorder. In atherosclerotic plaques, MCs are known to dedifferentiate to adopt a synthetic matrix producing phenotype that has been intimately connected to the progression of the disease. Despite the fact that there is a known phenotypic relationship between multiple diseases and MCs, there is an associated lack of mechanistic understanding of normal MC function to effectively develop specific therapeutics targeted at prevention and treatment of disorders. Therefore, my labs long-term research interests focus on understanding MC biology during development and disease.

My lab uses zebrafish to study MC development and behavior. Zebrafish as a vertebrate model organism offer a number of advantages that make it an ideal system to study development of the vascular wall- including external fertilization, proper embryonic growth in the absence of functional vasculature or blood flow, optical clarity for longitudinal imaging, and genetic/experimental accessibility. The field remains largely uncharted giving us the unique opportunity to exploit newly developed tools to broaden the understanding of MC biology and the mechanisms regulating their behavior. Research in my laboratory will aid in the understanding of developmental processes regulating MC function and will in turn 1) provide a broader understanding of how the blood vessel wall is assembled, 2) define genetic pathways critical for MC function and 3) provide a platform to assess dysfunction in EC-MC interactions during disease.

Selected Publications:

Stratman AN, Farrelly OM, Miller MF, Mikelis CM, Wang Z, Burns MC, Pezoa SA, Pham VN, Castranova D, Davis AE, Kilts TM, Davis GE, Gutkind JS, Pan W and Weinstein BM (2018). Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling. bioRxiv: doi: https://doi.org/10.1101/402362

Krispin S*, Stratman AN*, Melick CH, Stan RV, Malinverno M, Gleklen J, Castranova D, Dejana E and Weinstein BM (2018). Growth Differentiation Factor 6 (GDF6) promotes vascular stability by restraining VEGF signaling. ATVB. PMCID: 29284606 *equal contributors

Stratman AN, Pezoa SA, Farrelly OM, Castranova D, Dye LE, Butler MG, Sidik H, Talbot WS and Weinstein BM (2017). Interactions between mural cells and endothelial cells stabilize the developing zebrafish dorsal aorta. Development, 144(1): 115-127. PMCID: 27913637

Venero Galanternik M, Castranova D, Gore AV, Blewett NH, Jung HM, Stratman AN, Kirby MR, Iben J, Miller MF, Kawakami K, Maraia RJ and Weinstein BM (2017). A novel perivascular cell population in the zebrafish brain. Elife, 11;6. PMCID: 28395729

Nohata N, Uchida Y, Stratman AN, Adams RH, Zheng Y, Weinstein BM, Mukouyama YS, Gutkind JS (2016). Temporal-specific roles of Rac1 during vascular development and retinal angiogenesis. Developmental Biology, 411(2): 183-94. PMCID: 26872874

Pan W*, Pham VN*, Stratman AN, Castranova D, Kamei M, Kidd KR, Lo BD, Shaw KM, Torres-Vasquez J, Mikelis CM, Gutkind JS, Davis GE and Weinstein BM (2012). CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits VEGFA signaling and vascular morphogenesis. Blood, 120(2): 489-98. PMCID: 22649102 *equal contributors

Stratman AN and Davis GE (2012). Endothelial cell-pericyte interactions stimulate basement membrane matrix assembly: Influence on vascular tube remodeling, maturation and stabilization. Microscopy and Microanalysis, 18: 1-13 PMCID: 22166617

Stratman AN, Davis MJ and Davis GE (2011). VEGF and FGF prime vascular tube morphogenesis and sprouting directed by hematopoietic stem cell cytokines. Blood, 117(14): 3790-19. PMCID: 21239704

Stratman AN, Schwindt AE, Malotte KM and Davis GE (2010). Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization. Blood, 116: 4720-30. PMCID: 20739660

Stratman AN, Malotte KM, Mahan RD, Davis MJ and Davis GE (2009). Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood, 114(24): 5091-101. PMCID: 19822899

Last Updated: 12/12/2018 2:01:00 PM

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