Kenneth Lay

Biography

Kenneth is a Principal Investigator of the Laboratory of Skin Stem Cell Dynamics and National Research Foundation (NRF) Fellow. He obtained his PhD from Rockefeller University under the A*STAR National Science Scholarship, where he investigated the tissue-regenerative properties of hair follicle stem cells in homeostasis and aging. As a postdoctoral fellow in Genome Institute of Singapore and recipient of National Medical Research Council’s Young Individual Research Grant, he studied human genetic skin disorders so as to uncover novel biological mechanisms underpinning skin health and disease. Further, as co-investigator of a Singapore Therapeutics Development Review grant, he spearheaded efforts to develop drugs for treatment of auto-inflammatory skin and airway diseases.

Research interests

Please visit our lab website https://www.laylab.org/ for more details of our research, publications and team, as well as our latest news and openings.

The Lay Lab investigates how stem cells of the skin govern tissue homeostasis and contribute to disease pathogenesis so as to reveal novel pharmacological intervention points. We focus on two stem cell populations that maintain distinct compartments of the skin throughout our lifetime: epidermal stem cells and hair follicle stem cells.

Epidermal stem cells are responsible for replacing the millions of cells that our skin sheds daily. They integrate signals from their niche, and either self-renew to maintain their numbers, or differentiate into the protective barrier cells of our skin. However, how they change their behaviours in diseased states remains unknown. Further, how they sense dangers that have breached the skin, and in turn communicate with our immune system to maintain a healthy skin barrier, remain poorly understood. We strive to unravel these mysteries and establish epidermal stem cells as a tractable target for disease therapeutics.

In contrast, hair follicle stem cells fuel cyclical hair regeneration, in between periods of rest and regression. Their activity must be tightly regulated so as to preserve their lifelong capacity to self-renew and differentiate into the various intricate cell layers of our hair follicles. We aim to identify physiological signals of hair cycling and in turn mechanisms that safeguard hair follicle stem cells throughout these cycles. We envision our findings to unlock avenues for tackling hair loss caused by dysregulated hair cycling.

Selected publications

Harapas CR*, Robinson KS*, Lay K*, Wong J, Moreno Traspas R, Nabavizadeh N, Rass-Rothschild A, Boisson B, Drutman SB, Laohamonthonkul P, Bonner D, Xiong JR, Gorrell MD, Davidson S, Yu CH, Fleming MD, Gudera J, Stein J, Ben-Harosh M, Groopman E, Shimamura A, Tamary H, Kayserili H, Hatipoğlu N, Casanova J-L, Bernstein JA, Zhong FL, Masters SL & Reversade B (2022). DPP9 deficiency: An inflammasomopathy that can be rescued by lowering NLRP1/IL-1 signaling. Science Immunology 7, eabi4611 (*co-first authors)

Planès R, Pinilla M, Santoni K, Hessel A, Passemar C, Lay K, Paillette P, Valadão A-LC, Robinson KS, Bastard P, Lam N, Fadrique R, Rossi I, Pericat D, Bagayoko S, Leon-Icaza SA, Rombouts Y, Perouzel E, Tiraby M, COVID Human Genetic Effort, Zhang Q, Cicuta P, Jouanguy E, Neyrolles O, Bryant CE, Floto AR, Goujon C, Lei FZ, Martin-Blondel G, Silva S, Casanova J-L, Cougoule C, Reversade B, Marcoux J, Ravet E & Meunier E (2022). Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells. Molecular Cell 82, 2385–2400.e9

Gonzales KAU, Polak L, Matos I, Tierney MT, Gola A, Wong E, Infarinato NR, Nikolova M, Luo S, Liu S, Novak JSS, Lay K, Pasolli HA & Fuchs E (2021). Stem cells expand potency and alter tissue fitness by accumulating diverse epigenetic memories. Science 374, eabh2444

Gong Q, Robinson K, Xu C, Huynh PT, Chong KHC, Tan EYJ, Zhang J, Boo ZZ, Teo DET, Lay K, Zhang Y, Lim JSY, Goh WI, Wright G, Zhong FL, Reversade B and Wu B (2021). Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8. Nature Communications 12(1): 188

Robinson KS, Teo DET, Tan KS, Toh GA, Ong HH, Lim CK, Lay K, Au BV, Lew TS, Chu JJH, Chow VTK, Wang Y, Zhong FL, and Reversade B (2020). Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia. Science 370(6521)

Lay K, Yuan S, Gur-Cohen S, Miao Y, Han T, Naik S, Pasolli HA, Larsen SB and Fuchs E (2018). Stem cells repurpose proliferation to contain a breach in their niche barrier. eLife 7:e41661

Lay K, Kume T and Fuchs E (2016). FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential. Proceedings of the National Academy of Sciences of the United States of America 113(11), E1506-1515

Lien WH, Polak L, Lin M, Lay K, Zheng D and Fuchs E (2014). In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators. Nature Cell Biology 16(2), 179-190

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