Zhihui (Sherry) Xie, Ph.D.

Zhihui (Sherry) Xie, Ph.D.

Credit: NIAID
Staff Scientist, Lung and Vascular Inflammation Section

Major Areas of Research

  • Pathogenesis of a Rare Vascular Disorder of Systemic Capillary Leak Syndrome (SCLS)
  • Molecular mechanisms of vascular hyper-permeability in patients with SCLS

Program Description

The primary research focus of our laboratory is to understand: 1) The pathogenesis of Systemic Capillary Leak Syndrome (SCLS); 2) How a specific group of signaling molecule, regulator of G-protein signal (RGS), are involved in allergic diseases such as asthma by modulating airway hyper-responsiveness and airway inflammation.

SCLS is an extreme rare disease of vascular disorder of sudden collapse of vasculature due to the massive leakage of plasma volume into the tissues. There is no specific treatment or diagnosis available for this disease so far. Our lab has accumulated world largest SCLS cohort since 2009, and we have identified disease-associated genomic locus (3p25.3) and established a mouse model of SCLS (SJL), which would allow us to perform more depth in mechanistic studies. We discovered that pro-inflammatory cytokines and permeability mediators are dramatically increased when patients experienced the acute disease attack, which disrupted endothelial integrity by internalization of junctional molecule VE-Cad and actin fiber stress formation. Endothelial cells from patients with SCLS appear to be “hard-wired”, hyper-responsiveness to permeability mediators including VEGF and histamine. We and a European registry of SCLS have proved that high dose of monthly intravenous injection of immunoglobulin (IVIg) could be used as prophylaxis therapy for this disease.

Biography

Dr. Xie received her Ph.D. in basic medical science from The Chinese University of Hong Kong, School of Medicine in 1996. She obtained postdoctoral training in the areas of IgE receptor FcεRI-mediated mast cell signal transduction and functions at the National Institute of Dental and Craniofacial Research from 1997 to 2001. Prior to joining the Laboratory of Allergic Diseases in 2004, Dr. Xie conducted cancer research at the Lombardi Cancer Center, Georgetown University.

Memberships

  • North American Vascular Biology Organization
  • American Society for Biochemistry and Molecular Biology

Selected Publications

Raza A, Xie Z, Chan EC, Chen WS, Scott LM, Robin Eisch A, Krementsov DN, Rosenberg HF, Parikh SM, Blankenhorn EP, Teuscher C, Druey KM. A natural mouse model reveals genetic determinants of systemic capillary leak syndrome (Clarkson disease). Commun Biol. 2019 Oct 31;2:398. PMID: 31701027

Xie Z, Chen WS, Yin Y, Chan EC, Terai K, Long LM, Myers TG, Dudek AZ, Druey KM. Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease). J Leukoc Biol. 2018 Apr;103(4):749-759. PMID: 29360169

Xie Z, Chan EC, Long LM, Nelson C, Druey KM. High-dose intravenous immunoglobulin therapy for systemic capillary leak syndrome (Clarkson disease). Am J Med. 2015 Jan;128(1):91-5. PMID: 25193271 

Xie Z, Nagarajan V, Sturdevant DE, Iwaki S, Chan E, Wisch L, Young M, Nelson CM, Porcella SF, Druey KM. Genome-wide SNP analysis of the Systemic Capillary Leak Syndrome (Clarkson disease). Rare Dis. 2013 Dec 12;1(1):e27445. PMID: 24808988

Xie Z, Ghosh CC, Patel R, Iwaki S, Gaskins D, Nelson C, Jones N, Greipp PR, Parikh SM, Druey KM.  Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson disease (the systemic capillary leak syndrome). Blood. 2012 May 3;119(18):4321-32. PMID: 22411873

Xie Z, Geiger TR, Johnson EN, Nyborg JK, Druey KM. RGS13 acts as a nuclear repressor of CREB. Mol Cell. 2008 Sep 5;31(5):660-70. PMID: 18775326

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