Wong Xianrong

Biography

Dr. Xianrong Wong co-leads the Laboratory of Cell and Tissue Mechanosignalling at A*STAR Skin Research Labs. Initially trained in engineering, Dr. Wong transitioned into molecular and cell biology, bringing a multidisciplinary perspective to understanding how cells interpret and respond to mechanical cues in development, homeostasis, and disease. His long-term goal is to bridge physical and molecular principles to uncover how mechanical forces regulate cellular behavior and ultimately translate this knowledge into targeted therapeutic strategies. He is a co-inventor on several patent applications related to mechanobiological approaches for treating disease.

Dr. Wong received his PhD in 2016 from the Johns Hopkins University School of Medicine, where he studied the role of nuclear lamins in regulating genome organization under the mentorship of Dr. Karen Reddy. During his PhD, he led several interdisciplinary collaborations, including with Dr. Denis Wirtz to explore how substrate stiffness influences chromatin structure and gene expression, and with Dr. Susan Michaelis to understand how the mutant lamin A variant, progerin, interferes with genome reorganization through the cell cycle.

As a postdoctoral fellow with Dr. Colin Stewart at the A*STAR Institute of Medical Biology and its successor institutions, Dr. Wong demonstrated that A-type lamins act as molecular nexuses within the nucleus—bringing signalling proteins into close spatial proximity to facilitate regulatory crosstalk. His research showed that this integrative function is disrupted in Familial Partial Lipodystrophy of the Dunnigan type (FPLD2), a disease caused by mutations in the LMNA gene. In this condition, patients experience a selective loss of subcutaneous white adipose tissue in the limbs and trunk, leading to significant metabolic disturbances such as insulin resistance and dyslipidemia. Dr. Wong’s work revealed how impaired lamin-mediated coordination of signaling networks compromises adipocyte identity and maintenance. Additionally, he identified novel pathways that regulate adipogenesis, providing mechanistic insight into how nuclear signaling hubs influence cell fate decisions in metabolic disease contexts.

Research Interests

    
In tissues such as skin, adipose, and striated muscle, mechanical stress is a constant feature of the microenvironment. Cells adapt to these forces through changes in cytoskeletal structure, nuclear organization, and gene expression. A key component of these adaptations is lamin A/C, a nuclear intermediate filament protein that contributes to both mechanical resilience and transcriptional regulation. Although adipose tissue is not typically considered a mechanically stressed organ, emerging evidence suggests that the mechanical microenvironment of adipose tissue undergoes significant alterations in diseased states such as lipodystrophy, metabolic disorders, and aging that impairs adipose function and primes affected individuals for metabolic syndrome.

Dr. Wong’s current work focuses on how mechanical cues regulate adipose tissue dynamics, particularly in the context of metabolic syndrome and aging. His lab investigates how changes in the mechanical microenvironment influence the behaviour of distinct cellular subtypes within adipose tissue, and how this disruption alters the interdependent signalling and interactions between these cell types, ultimately impacting overall tissue function. These insights are critical for understanding how biomechanical dysregulation in adipose tissue contributes to systemic metabolic dysfunction.

With a broader interest in adipose tissue health and its impact on overall metabolic status, Dr. Wong’s research is particularly focused on how different adipose depots—such as dermal, subcutaneous, and visceral depots (including mesenteric/intestinal, epididymal/gonadal, renal, and cardiac)—exhibit distinct properties, varying in their composition and function. While the metabolic effects of adipose tissue through the long-distance circulatory system are well-established, the impact of distinct adipose depots and their varying metabolic states on adjacent organs and tissues remains less understood. Of particular interest is the role of dermal adipose tissue, which not only regulates skin development but is also closely linked to skin health. Understanding these inter-tissue interactions could provide novel insights into how adipose tissue contributes to both normal organ function and the pathogenesis of metabolic diseases, ultimately guiding the identification of new therapeutic targets.

Selected publications

• Kohwi Y, Wong X, …, T. Kohwi. Genome organization by SATB1 binding to base-unpairing regions (BURs) provides scaffold for SATB1-regulated gene expression. eLife. Reviewed Preprint March 13, 2025
• Reddy KL., Wong X. An optimized adaptation of DamID for NGS applications. Methods Mol Biol. 2025:2866:245-262.
• Wong X, Menlendez-Perez A.J., Reddy KL. The Nuclear Lamina. Cold Spring Harbor Perspectives in Biology, 2022.
• Vahabikashi A, … Wong X, … Goldman R. Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics. PNAS, 2022.
• Wong X, Hoskins VE, Harr JC, Gordon M, Reddy KL. Lamin C regulates genome organization after mitosis. Genome Biology, 2021.
• Wong X, Cutler AC, Hoskins VE, Gordon M, Madugundu AK, Pandey A, Reddy KL. Mapping the micro-proteome of the nuclear lamina and lamin associated domains. Life Science Alliance, 2021.
• Wong X, Loo TH, Stewart CL. LINC Complex regulation of Genome Organization and Function. Current Opinions in Genetics and Development, 2021.
• Wong X, Stewart CL. The laminopathies and the insights they provide into the structural and functional organization of the nucleus. Annual Review of Genomics and Human Genetics, 2020, Vol 21.
• Chojnowski A, Sobota RM, Ong PF, Xie W, Wong X, Dreesen O, Burke B, Stewart CL. 2C-BioID: An advanced two component BioID system for precision mapping of protein interactomes. ISCIENCE, 2018.
• Cutler JA, Tahir R, Sreenivasamurthy SK, Mitchell C, Renuse S, Nirujogi RS, Patil AH, Heydarian M, Wong X, Wu X, Huang TC, Kim MS, Reddy KL, Pandey A. Differential signaling through p190 and p210 BCR-ABL fusion proteins revealed by interactome and phosphoproteome analysis. Leukemia, 2017 Jul;31(7):1513-1524.
• Wong X, Reddy K. Finding the Middlemen in Genome Organization. Developmental Cell. Volume 35, Issue 6, p670–671, 21 December 2015.
• Wong X, Luperchio TR, Reddy K. NET losses and gains: The role of the changing nuclear envelope proteome in genome regulation. Current Opinion Cell Biology, 28C:105-120.
• Luperchio TR, Wong X, Reddy K. Genome regulation at the peripheral zone: lamina associated domains in development and disease. Current Opinion Genes and Development, Volume 25, Pages 50–61.
• Harr J, Luperchio TR, Wong X, Cohen E, Wheelan S, Reddy, K. Directed reorganization of chromatin to the nuclear lamina is mediated by YY1 and A-type lamins. Journal of Cell Biology, 208 (1): 33.

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