Bio

Bio


Sacha Khong received her Bachelor of Biomedical Sciences (first class honors) and her PhD from Monash University in Australia. She completed a year of Postdoctoral training at the laboratory of renowned Australian Immunologist, Professor Richard Boyd, before accepting a position as a Postdoctoral Scholar at Stanford University. Her research at Stanford focuses on developing better therapeutic strategies for non-healing chronic wounds as well as for cancer, “the wound that never heals”.

Professional Education


  • Doctor of Philosophy, Monash University (2013)
  • Bachelor of BiomedSci (Hons), Monash University (2007)
  • Bachelor of Science, Monash University (2006)

Stanford Advisors


Publications

Journal Articles


  • Alveolar Macrophages Are Critical for the Inhibition of Allergic Asthma by Mesenchymal Stromal Cells JOURNAL OF IMMUNOLOGY Mathias, L. J., Khong, S. M., Spyroglou, L., Payne, N. L., Siatskas, C., Thorburn, A. N., Boyd, R. L., Heng, T. S. 2013; 191 (12): 5914-5924

    Abstract

    Multipotent mesenchymal stromal cells (MSCs) possess reparative and immunoregulatory properties, making them attractive candidates for cellular therapy. However, the majority of MSCs administered i.v. encounter a pulmonary impasse and soon disappear from the lungs, raising the question of how they induce such durable immunosuppressive effects. Using a mouse model of allergic asthma, we show that administration of MSCs isolated from human bone marrow, umbilical cord, or adipose tissue provoked a pronounced increase in alveolar macrophages and inhibited hallmark features of asthma, including airway hyperresponsiveness, eosinophilic accumulation, and Th2 cytokine production. Importantly, selective depletion of this macrophage compartment reversed the therapeutic benefit of MSC treatment on airway hyperresponsiveness. Our data demonstrate that human MSCs exert cross-species immunosuppressive activity, which is mediated by alveolar macrophages in allergic asthma. As alveolar macrophages are the predominant immune effector cells at the air-tissue interface in the lungs, this study provides a compelling mechanism for durable MSC effects in the absence of sustained engraftment.

    View details for DOI 10.4049/jimmunol.1300667

    View details for Web of Science ID 000328483900018

    View details for PubMedID 24249728

  • Arginase II inhibition prevents nitrate tolerance BRITISH JOURNAL OF PHARMACOLOGY Khong, S. M., Andrews, K. L., Huynh, N. N., Venardos, K., Aprico, A., Michell, D. L., Zarei, M., Moe, K. T., Dusting, G. J., Kaye, D. M., Chin-Dusting, J. P. 2012; 166 (7): 2015-2023

    Abstract

    Nitrate tolerance, the loss of vascular responsiveness with continued use of nitrates, remains incompletely understood and is a limitation of these therapeutic agents. Vascular superoxide, generated by uncoupled endothelial NOS (eNOS), may play a role. As arginase competes with eNOS for L-arginine and may exacerbate the production of reactive oxygen species (ROS), we hypothesized that arginase inhibition might reduce nitrate tolerance.Vasodilator responses were measured in aorta from C57Bl/6 and arginase II knockout (argII -/-) mice using myography. Uncoupling of eNOS, determined as eNOS monomer : dimer ratio, was assessed using low-temperature SDS-PAGE and ROS levels were measured using L-012 and lucigenin-enhanced chemiluminescence.Repeated application of glyceryl trinitrate (GTN) on aorta isolated from C57Bl/6 mice produced a 32-fold rightward shift of the concentration-response curve. However this rightward shift (or resultant tolerance) was not observed in the presence of the arginase inhibitor (s)-(2-boronethyl)-L-cysteine HCl (BEC; 100 µM) nor in aorta isolated from argII -/- mice. Similar findings were obtained after inducing nitrate tolerance in vivo. Repeated administration of GTN in human umbilical vein endothelial cells induced uncoupling of eNOS from its dimeric state and increased ROS levels, which were reduced with arginase inhibition and exogenous L-arginine. Aortae from GTN tolerant C57Bl/6 mice exhibited increased arginase activity and ROS production, whereas vessels from argII -/- mice did not.Arginase II removal prevents nitrate tolerance. This may be due to decreased uncoupling of eNOS and consequent ROS production.

    View details for DOI 10.1111/j.1476-5381.2012.01876.x

    View details for Web of Science ID 000306186700004

    View details for PubMedID 22288373

  • Selective Endothelial Overexpression of Arginase II Induces Endothelial Dysfunction and Hypertension and Enhances Atherosclerosis in Mice PLOS ONE Vaisman, B. L., Andrews, K. L., Khong, S. M., Wood, K. C., Moore, X. L., Fu, Y., Kepka-Lenhart, D. M., Morris, S. M., Remaley, A. T., Chin-Dusting, J. P. 2012; 7 (7)

    Abstract

    Cardiovascular disorders associated with endothelial dysfunction, such as atherosclerosis, have decreased nitric oxide (NO) bioavailability. Arginase in the vasculature can compete with eNOS for L-arginine and has been implicated in atherosclerosis. The aim of this study was to evaluate the effect of endothelial-specific elevation of arginase II expression on endothelial function and the development of atherosclerosis.Transgenic mice on a C57BL/6 background with endothelial-specific overexpression of human arginase II (hArgII) gene under the control of the Tie2 promoter were produced. The hArgII mice had elevated tissue arginase activity except in liver and in resident peritoneal macrophages, confirming endothelial specificity of the transgene. Using small-vessel myography, aorta from these mice exhibited endothelial dysfunction when compared to their non-transgenic littermate controls. The blood pressure of the hArgII mice was 17% higher than their littermate controls and, when crossed with apoE -/- mice, hArgII mice had increased aortic atherosclerotic lesions.We conclude that overexpression of arginase II in the endothelium is detrimental to the cardiovascular system.

    View details for DOI 10.1371/journal.pone.0039487

    View details for Web of Science ID 000306956300007

    View details for PubMedID 22829869

  • ENDOTHELIAL OVEREXPRESSION OF ARGINASE II INDUCES ENDOTHELIAL DYSFUNCTION AND PROMOTES ATHEROSCLEROSIS HYPERTENSION Khong, S. M., Andrews, K. L., Vaisman, B. L., Remaley, A. T., Chin-Dusting, J. 2011; 58 (1): 115-116
  • Overexpression of arginase II worsens endothelial dysfunction and atherosclerosis while arginase I overexpression may have cardioprotective effects CARDIOVASCULAR RESEARCH Chin-Dusting, J. P., Vaisman, B. L., Khong, S. M., Remaley, A. T., Andrews, K. L. 2010; 87: S130-S131
  • Arginase II Knockout Mouse Displays a Hypertensive Phenotype Despite a Decreased Vasoconstrictory Profile HYPERTENSION Huynh, N. N., Andrews, K. L., Head, G. A., Khong, S. M., Mayorov, D. N., Murphy, A. J., Lambert, G., Kiriazis, H., Xu, Q., Du, X., Chin-Dusting, J. P. 2009; 54 (2): 294-U188

    Abstract

    Arginase upregulation is associated with aging and cardiovascular diseases. In this study we report on the cardiovascular phenotype of the arginase II knockout (KO) mouse. We demonstrate that vascular sensitivity and reactivity altered over time in these animals such that no influence on responses to vasoconstrictor activity was observed in 7-week-old KO mice, but dampened responses to norepinephrine and phenylephrine were observed by 10 and 15 weeks with Rho kinase influencing these effects in the 15-week-old animals. Despite these dampened vasoconstrictory responses, KO mice demonstrated increased mean arterial pressure from 8 weeks old. This hypertensive phenotype was associated with an increase in left ventricular weight, left ventricular systolic pressure, and diminished diastolic function. KO mice also show enhanced plasma norepinephrine turnover, suggesting an increased sympathetic outflow. In conclusion, our data suggest that global loss of arginase II activity results in hypertension. We suggest that this strain of mouse warrants further investigation as a potentially novel model of hypertension.

    View details for DOI 10.1161/HYPERTENSIONAHA.108.121731

    View details for Web of Science ID 000268250300022

    View details for PubMedID 19546381

Presentations


  • A Role For Arginase in the Regulation of Nitric Oxide

    Presented To

    BakerIDI Heart and Diabetes Institute

    Location

    Melbourne, Australia

  • Arginase in the Vasculature: Regulator of Nitric Oxide?

    Presented To

    Columbia University

    Location

    New York City, USA

  • Targeting Arginase in the Vasculature

    Time Period

    2010 - 2010

    Presented To

    Johns Hopkins University

    Location

    Baltimore, Maryland

  • The Role of Arginase in Peripheral Arterial Occlusive Disease

    Time Period

    2010 - 2010

    Presented To

    National Institutes of Health

    Location

    Bethesda, Maryland, USA

  • Targeting Arginase in Atherosclerosis and Peripheral Arterial Occlusive Disease

    Presented To

    Center for Vascular Health, Monash University

    Location

    Melbourne, Australia

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