Leah Vardy

Biography
Leah Vardy is a Senior Principal Investigator at the Skin Research Institute of Singapore in A*STAR and an Adjunct Assistant Professor at the Nanyang Technological University. Leah received her Ph.D at the Imperial Cancer Research Fund in London and did post-doctoral work at the Whitehead Institute in Cambridge at the MIT in the US. In 2007, she was appointed to A*STAR’s Institute of Medical Biology before joining SRIS in 2018. Leah has worked in a diverse array of systems including yeast, fruit flies, embryonic stem cells and epidermal cells. Her current research focuses on understanding how cellular behavior within the epidermis is controlled. Projects in the lab address this in the context of pigmentation, tissue repair and skin aging.
Vardy lab is interested in understanding how gene expression changes contribute to different skin pathologies. We use a combination of human ex-vivo tissue along with 2D and 3D skin culture models to study how gene expression changes drive cellular behaviors. Research in the Vardy lab focuses on a group of metabolites called polyamines. The polyamines putrescine, spermidine, and spermine drive gene expression changes in part, through control of RNA. Additional projects in the lab look at the role of post-transcriptional control in the regulation of skin homeostasis. Projects in the lab focus on wound healing, epidermal pigmentation and skin barrier function.

Wound Healing
Non-healing or slow-healing wounds represent a significant healthcare burden. An increased understanding of the pathways driving normal wound healing will help in understanding the biology behind a non-healing wound. We use human ex-vivo tissue along with 2D skin cultures to model re-epithelialization during wound healing. We have identified polyamine regulator AMD1 as being essential in the early wound response. AMD1 controls the ratios and levels the polyamines and its increased levels on wounding are required to drive cell migration. We are currently exploring how AMD1 and the polyamines promote cell migration and how they are mis-regulated in clinically slow-to-heal wounds.

Pigmentation
Epidermal pigmentation is a tightly controlled and regulated process. Melanocytes in human skin generate melanin which is then transferred to the keratinocytes where it forms a protective cap above the nuclei. The melanin in the skin is what gives skin its color. We have identified the polyamine putrescine as being an important regulator of the melanogenesis process. Our data suggests that local changes in polyamine levels can drive increased Tyrosinase levels in the melanocytes which promotes pigmentation. We are looking at this in clinical samples of hyperpigmentation and identifying the molecular targets of the polyamines in a combination of Ex-vivo human tissue and cell culture studies.

Aging
We have shown that tight control of the ratios and levels of the three polyamines is essential for the formation of a healthy skin barrier. We are currently addressing this in the context of skin aging to determine how altered polyamine levels may contribute to the aging skin phenotype.
Sridharan A, John Lim SY, Wright GD, Vardy LA. Quantification of Melanosome Transfer Using Immunofluorescence Microscopy and Automated Image Analysis. Methods Mol Biol. 2020;2109:55-65. doi: 10.1007/7651_2019_241. PMID: 31161578.

Lim HK, Rahim AB, Leo VI, Das S, Lim TC, Uemura T, Igarashi K, Common J, Vardy LA. Polyamine Regulator AMD1 Promotes Cell Migration in Epidermal Wound Healing. J Invest Dermatol. 2018 Dec;138(12):2653-2665. doi: 10.1016/j.jid.2018.05.029. Epub 2018 Jun 12. PMID: 29906410.

James C, Zhao TY, Rahim A, Saxena P, Muthalif NA, Uemura T, Tsuneyoshi N, Ong S, Igarashi K, Lim CY, Dunn NR, Vardy LA. MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal. Stem Cells. 2018 Aug;36(8):1170-1178. doi: 10.1002/stem.2830. Epub 2018 Apr 22. PMID: 29644784.

Carlevaro-Fita J, Rahim A, Guigó R, Vardy LA, Johnson R. Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells. RNA. 2016 Jun;22(6):867-82. doi: 10.1261/rna.053561.115. Epub 2016 Apr 18. PMID: 27090285; PMCID: PMC4878613.

Zhang D, Zhao T, Ang HS, Chong P, Saiki R, Igarashi K, Yang H, Vardy LA. AMD1 is essential for ESC self-renewal and is translationally down-regulated on differentiation to neural precursor cells. Genes Dev. 2012 Mar 1;26(5):461-73. doi: 10.1101/gad.182998.111. PMID: 22391449; PMCID: PMC3305984.

ORCID