Wen (Amy) Tian

Proficient in conducting laboratory and field experiments while informing new hires on research methods and data collection procedures. Hardworking and driven with superior organizational and analytical skills combined with unparalleled dedication to research excellence. Skilled in conceptualization, design and implementation of [Type] projects.

• Critical Role of LTB4 in Pulmonary Arterial Hypertension, With the knowledge in eicosanoid and protein signaling, I joined the Nicolls’ lab after finishing graduate school. Dr. Nicolls was one of the first Investigators that identified the importance of inflammation in pulmonary arterial hypertension (PAH). It was found that the expression of leukotriene B4 (LTB4) and the upstream enzyme 5-lipogenase was elevated in clinical PAH around the 1970s. But the exact role of these inflammatory mediators was not known. Combining my knowledge in leukotriene biology and Dr. Nicolls’ expertise in PAH, we discovered that macrophage secreted LTB4 induces pulmonary arterial endothelial cell apoptosis (the most early event in disease development) and causes pulmonary arterial smooth muscle cell proliferation and hypertrophy; pulmonary arterial adventitia fibroblast activation (key components of pulmonary vascular remodeling). Blocking LTB4 biosynthesis reverses PAH in three different animal models of PAH. These efforts led to a couple of high impact publications and the currently enrolling LIBERTY trial (using LTB4 antagonism treating PAH)., Bone morphogenetic protein receptor 2 (Bmpr2) predisposes rats to inflammation induced pulmonary arterial hypertension, Circulation, In revision, Tian W, Jiang X, Sung YK, Shuffle E, et al., Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension, Sci Transl Med, 08/28/2013, 5, 200, 200ra117, PMC4016764, LTB4 activates pulmonary artery adventitial fibroblast in pulmonary arterial hypertension, Hypertension, 12/2015, 66, 6, 1227-39, PMC4646718, Leukotrienes in pulmonary arterial hypertension, Immunol Res, 05/2014, 58, 2-3, 387-93, PMC4031261
• Critical Role of LTB4 in Lymphedema, From 2014, I started to collaborate with Dr. Stanley Rockson, who is a world-renowned lymphatic physician scientist, with expertise in translational research in lymphedema, including identifying its genetics and relevant potential biomarkers. I led a collective team of 6 people from both the Nicolls’ lab and the Rockson group, and started a new adventure to investigate lymphatics circulation and related disease, lymphedema, which is poorly understood and has no medical treatment. We discovered that LTB4 causes lymphatic injury and is contributing to lymphedema pathogenesis by inhibiting two pathways essential for the lymphatic repair, the VEGFR3 signaling and the Notch signaling. Antagonizing LTB4 reverses pre-clinical lymphedema. This is the first study ever addressing the role of a specific inflammatory response (LTB4-mediated inflammation) in lymphatic endothelium; the importance of Notch signaling to post-natal lymphatic repair; and a possible non-growth factor treatment approach to lymphedema. These efforts led to 3 phase II clinical trials and development the first possible treatment for lymphedema., Pilot studies demonstrate the potential benefits of anti-inflammatory therapy in human lymphedema, JCI Insight, 10/18/2018, 3, 20, 123775, 10.1172/jci.insight.123775, 30333315, Leukotriene B4 antagonism ameliorates experimental lymphedema, Sci Transl Med, 05/10/2017, 9, 389, eaal3920, 10.1126/scitranslmed.aal3920, 28490670, in process, Leukotriene and lymphedema, Annual Review of Physiology, 10/13/2017, 10.1146/annurev-physiol-022516-034008
• Leading PAH research in the Nicolls’ group and coordinate with collaborators, I am leading both PAH and lymphedema research in the group, that I help my team members to design projects, trouble shoot, help Dr. Nicolls with grant writing, and communicate and work with our collaborators at Stanford and other institutes., Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension, Circ Res, 09/30/2011, 109, 8, 867-79, PMC3204361, Macrophages in solid organ transplantation, Vasc Cell, 03/11/2014, 6, 1, 5, 10.1186/2045-824X-6-5, PMC3975229, Activation of the Wnt/Planar Cell Polarity Pathway Is Required for Pericyte Recruitment during Pulmonary Angiogenesis, Am J Pathol, 11/06/2014, 25447046, PMC4278244
• Study other signaling in transplant biology, With my expertise in cell signaling, inflammation and vascular biology, I helped with multiple projects identifying the protection of transplant micro-vessels as the key for preventing the development of chronic rejection. These studies involved the development of transgenic mice with tissue specific up- and down-regulation of gene products; the performance of sophisticated lineage fate mapping studies; carrying out various cell biology and biochemical studies around hypoxia-inducible factors signaling network. These investigations provide a novel therapeutic target to prolong transplant survival., Endothelial HIF-2α is required for the maintenance of airway microvasculature, Circulation, 01/22/2019, 139, 4, 502-517, Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation, Sci Transl Med, 02/21/2018, 10, 429, eaag2616, Adenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection, J Clin Invest, 06/2011, 121, 6, 2336-49, PMC3104770, Cyclosporine Does Not Prevent Microvascular Loss in Transplantation but Can Synergize with a Neutrophil Elastase Inhibitor, Elafin, to Maintain Graft Perfusion During Acute Rejection, Am J Transplant, 02/27/2015, PMC4474772
• Regulation of Eicosanoid Signaling, I earned my PhD. degree in biochemistry and was trained to study eicosanoid signaling and lipid signaling in Dr. Wonhwa Cho’s lab, which is one of the best eicosanoid labs and the best lipid-signaling lab in the world. I have studied various signaling proteins, including proteins that belong to the eicosanoid signaling (secreted phospholipase A2 (IIA, V, XII), cyclic phospholipase A2, cyclogenase 2, 5-lipogenase and 5-lipogenase activating protein), and proteins that belong to the protein kinase C family (PKC α, β, γ, δ, ε and θ). I was trained to use basic biochemistry and cell biology techniques. In additional, I have learned various cutting-edge technologies to study protein-protein interaction, protein-lipid interaction, and protein signaling, including single-cell microscopy, two photon microscopy, protein crystallization, and surface plasma resonance. All this research experience has provided me tools to further my knowledge in leukotriene biology (one family of eicosanoid lipids) to inflammatory conditions, such as pulmonary hypertension and lymphedema., Mechanism of regulation of group IVA phospholipase A2 activity by Ser727 phosphorylation, J Biol Chem, 02/15/2008, 283, 7, 3960-71, PMC3761091, Synthesis and evaluation of 5-lipoxygenase translocation inhibitors from acylnitroso hetero-Diels-Alder cycloadducts, Org Biomol Chem, 04/21/2011, 9, 8, 2999-3010, 10.1039/c0ob00714e, PMC3297083, Cholesterol Selectively Activates Canonical Wnt Signaling Over Non-Canonical Wnt Signaling, Nature Communications, 2014, 5, 4393, 10.1038/ncomms5393, PMC4100210, Protein kinase Cθ C2 domain is a phosphotyrosine binding module that plays a key role in its activation, J Biol Chem, 08/31/2012, 287, 36, 30518-28, 10.1074/jbc.M112.391557, PMC3436300