About

Gerard C. L. Wong is a Professor in the Department of Bioengineering, Department of Chemistry, and the California NanoSystems Institute at UCLA. He received his BS at Caltech in physics and his PhD at Berkeley in physics. Wong joined the Materials Science & Engineering Department and Physics Department at the University of Illinois at Urbana-Champaign in 2000 and moved to UCLA in 2009. His research focuses on a multidisciplinary approach to solving problems in biology and biomedicine, integrating physics, chemistry, biology, and engineering. His group is highly interdisciplinary, collaborating with physicists, chemists, material scientists, biologists, medical doctors, and bioengineers. Wong's research interests include bacterial biofilm communities, innate immunity, antibiotic design, and various aspects of physical chemistry and soft matter physics. He has been recognized with numerous awards and honors, including fellowships in the American Physical Society, the American Academy of Microbiology, and the American Institute for Medical and Biological Engineering.

Research topics

• Genetics
• Biology
• Chemistry
• Microbiology
• Biochemistry
• Biophysics
• Materials science
• Cognitive science
• Nanotechnology
• Psychology
• Cell biology
• Physics
• Quantum mechanics

Selected publications

• SARS-CoV-2 peptide fragments selectively dysregulate specific immune cell populations via Gaussian curvature targeting

  UNC Libraries · 2026-01-16

  articleOpen access

  Significance Previous work has demonstrated that the proteome of SARS-CoV-2 can potentially be a rich source of AMP-like viral fragments, exemplars of which are associated with severe COVID-like inflammation in vitro and in vivo. Here, we demonstrate that direct proteolytic processing of SARS-CoV-2 proteins can yield xenoAMPs, and that the full heterogeneous ensemble of resultant fragments can collectively exert AMP-like pore-forming activity. We describe an unanticipated general mechanism of host cellular targeting for viral AMP-like pore forming peptides, based on local Gaussian curvatures of the host cell membrane, and show that this mechanism can selectively target and deplete specific immune cell types in a manner consistent with clinical observations for severe COVID-19 patients. Immune cell populations are dysregulated in COVID-19 for currently unknown reasons: Plasmacytoid dendritic cell (pDC) populations are reduced, thus hampering antiviral responses. CD8+ T cell populations are reduced, the level of which has emerged as an index of disease severity. Recent work has shown that the proteome of SARS-CoV-2 is a rich reservoir of antimicrobial peptide-like sequence motifs (xenoAMPs) which can chaperone and organize dsRNA for amplified Toll-Like Receptor 3 (TLR3)-mediated inflammation in vitro and in vivo. Here, we demonstrate that proteolytic digestion of the SARS-CoV-2 spike protein by host trypsin-like serine proteases directly produces xenoAMPs. Synchrotron Small Angle X-ray Scattering, mass spectrometry, and a theoretical analysis based on continuum membrane elasticity show that proteolytically generated xenoAMPs from SARS-CoV-2 proteins in vitro and machine learning-predicted high-scoring xenoAMPs all induce negative Gaussian curvature (NGC) necessary for pore formation in membranes. We find that xenoAMPs alone as well as xenoAMPs synergistically with endogenous AMP LL-37 can induce NGC in membranes. A computational analysis of immune cells with morphologically complex shapes (e.g., pDC, CD8+, and CD4+ T cells) suggests that surfaces with high local NGC can concentrate AMP-like sequences and promote selective membrane disruption. Consistent with this hypothesis, experiments with freshly isolated human peripheral blood mononuclear cells confirm that viable pDCs, DCs, and T cells are significantly depleted after xenoAMP exposure, in contrast to monocytes and neutrophils, the immune cell subsets with spheroidal morphology. Structural data from Omicron variant xenoAMP homologs indicate reduced pore formation, consistent with clinical observations of reduced T cell cytopenia in Omicron variant infections.

  PublisherDOI

• SARS-CoV-2 peptide fragments selectively dysregulate specific immune cell populations via Gaussian curvature targeting

  Proceedings of the National Academy of Sciences · 2026-01-08

  articleOpen accessSenior author

  Immune cell populations are dysregulated in COVID-19 for currently unknown reasons: Plasmacytoid dendritic cell (pDC) populations are reduced, thus hampering antiviral responses. CD8 + T cell populations are reduced, the level of which has emerged as an index of disease severity. Recent work has shown that the proteome of SARS-CoV-2 is a rich reservoir of antimicrobial peptide-like sequence motifs (xenoAMPs) which can chaperone and organize dsRNA for amplified Toll-Like Receptor 3 (TLR3)-mediated inflammation in vitro and in vivo. Here, we demonstrate that proteolytic digestion of the SARS-CoV-2 spike protein by host trypsin-like serine proteases directly produces xenoAMPs. Synchrotron Small Angle X-ray Scattering, mass spectrometry, and a theoretical analysis based on continuum membrane elasticity show that proteolytically generated xenoAMPs from SARS-CoV-2 proteins in vitro and machine learning-predicted high-scoring xenoAMPs all induce negative Gaussian curvature (NGC) necessary for pore formation in membranes. We find that xenoAMPs alone as well as xenoAMPs synergistically with endogenous AMP LL-37 can induce NGC in membranes. A computational analysis of immune cells with morphologically complex shapes (e.g., pDC, CD8 + , and CD4 + T cells) suggests that surfaces with high local NGC can concentrate AMP-like sequences and promote selective membrane disruption. Consistent with this hypothesis, experiments with freshly isolated human peripheral blood mononuclear cells confirm that viable pDCs, DCs, and T cells are significantly depleted after xenoAMP exposure, in contrast to monocytes and neutrophils, the immune cell subsets with spheroidal morphology. Structural data from Omicron variant xenoAMP homologs indicate reduced pore formation, consistent with clinical observations of reduced T cell cytopenia in Omicron variant infections.

  PublisherDOI

• Intercalated bacterial biofilms are intrinsic internal components of calcium-based kidney stones

  Proceedings of the National Academy of Sciences · 2026-01-26 · 1 citations

  articleOpen accessCorresponding

  Calcium oxalate stones comprise greater than 70% of all kidney stones. In the current conceptual framework, the initial stone nidus is thought to include the aggregation of inorganic crystallites, the formation of which is favored by elevated concentrations of dissolved constituents. Here, we show that this highly prevalent stone type comprises a form of organic-inorganic polycrystalline biocomposite with integrated bacterial biofilms. Evidence from electron microscopy and fluorescence microscopy reveal the unanticipated internal structure of kidney stones from human patients, where bacterial biofilms are intercalated between polycrystalline mineral layers, even in stones identified as "noninfectious" clinically, including those in patients without underlying urinary tract infections. We observe similar bacterial biofilm architectures on the surfaces of stone fragments obtained due to lithotripsy, suggesting that bacteria are intrinsic to the process of nephrolithiasis. Crystallites proximal to biofilm layers exhibit significantly smaller grain sizes, which indicate a larger local concentration of nucleation sites. Staining reveals that biofilm areas of these stones are enriched with bacterial DNA. That bacteria are now observed so broadly in kidney stones (including even in less prevalent struvite stones) may be conceptually salient: Based on the evidence adduced here, we propose a model in which the urine-rich environment of the kidney can impinge on bacterial calcium homeostasis and amplify bacterial production of nucleation templates such as extracellular DNA. The resultant counterion condensation intrinsic to polyelectrolytes charged beyond the Manning criterion (such as DNA) drastically enhances the probability of heterogeneous nucleation, thereby amplifying calcium oxalate stone formation.

  PublisherOA PDFDOI

• Dynamin-like Proteins Combine Mechano-constriction and Membrane Remodeling to Enable Two-Step Mitochondrial Fission via a “Snap-through” Instability

  Journal of the American Chemical Society · 2025-07-08 · 3 citations

  articleOpen accessSenior authorCorresponding

  Mitochondrial fission is controlled by dynamin-like proteins, the dysregulation of which is correlated with diverse diseases. Fission dynamin-like proteins are GTP hydrolysis-driven mechanoenzymes that self-oligomerize into helical structures that constrict membranes to achieve fission while also remodeling membranes by inducing negative Gaussian curvature, which is essential for the completion of fission. Despite advances in optical and electron imaging technologies, the underlying mechanics of mitochondrial fission remain unclear due to the multiple times involved in the dynamics of mechanoenzyme activity, oligomer disassembly, and membrane remodeling. Here, we examine how multiscale phenomena in dynamin Drp1 synergistically influence membrane fission using a mechanical model calibrated with small-angle X-ray scattering structural data and informed by a machine learning analysis of the Drp1 sequence, and tested the concept using optogenetic mechanostimulation of mitochondria in live cells. We find that free dynamin-like proteins can trigger a "snap-through instability" that enforces a shape transition from an oligomer-confined cylindrical membrane to a drastically narrower catenoid-shaped neck within the spontaneous hemi-fission regime, in a manner that depends critically on the length of the confined tube. These results indicate how the combination of assembly and paradoxically disassembly of dynamin-like proteins can lead to diverse pathways to scission.

  PublisherDOI

• Kilohertz volumetric imaging of in vivo dynamics using squeezed light field microscopy

  Nature Methods · 2025-09-23 · 7 citations

  articleOpen access
  PublisherOA PDFDOI

• Chemokines kill bacteria without triggering antimicrobial resistance by binding anionic phospholipids

  Science Advances · 2025-06-06 · 5 citations

  articleOpen access

  Classically, chemokines coordinate leukocyte trafficking; however, many chemokines also have direct antibacterial activity. The bacterial killing mechanism of chemokines and the biochemical properties that define which members of the chemokine superfamily are antimicrobial remain poorly understood. We report that the antimicrobial activity of chemokines is defined by their ability to bind phosphatidylglycerol and cardiolipin, two anionic phospholipids commonly found in the bacterial plasma membrane. We show that only chemokines able to bind these two phospholipids kill bacteria and that they exert rapid bacteriostatic and bactericidal effects with a higher potency than the antimicrobial peptide β-defensin 3. Both biochemical and genetic interference with the chemokine-cardiolipin interaction impaired microbial growth arrest, bacterial killing, and membrane disruption by chemokines. Moreover, unlike conventional antibiotics, Escherichia coli failed to develop resistance when placed under increasing antimicrobial chemokine pressure in vitro. Thus, we have identified cardiolipin and phosphatidylglycerol as binding partners for chemokines responsible for chemokine antimicrobial action.

  PublisherDOI

• BPS2025 - Antagonistic curvature mechanisms of BCL-2 family proteins regulate mitochondrial apoptosis

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Inhibition of oligomeric BAX by an anti-apoptotic dimer

  Cell · 2025-11-21 · 4 citations

  article
  PublisherDOI

• MP21-12 BIOFILM-FORMING BACTERIA FOUND WITHIN CALCIUM-BASED KIDNEY STONES

  The Journal of Urology · 2025-04-08

  article
  PublisherDOI

• Dynamics of Th1/Th17 responses and antimicrobial pathways in leprosy skin lesions

  Journal of Clinical Investigation · 2025-06-26 · 3 citations

  articleOpen access

  BACKGROUNDReversal reactions (RRs) in leprosy are acute immune episodes marked by inflammation and bacterial clearance, offering a model to study the dynamics of host responses to Mycobacterium leprae. These episodes are often severe and difficult to treat, frequently progressing to permanent disabilities. We aimed to characterize the immune mechanisms and identify antimicrobial effectors during RRs.METHODSWe performed RNA-Seq on paired skin biopsy specimens collected from 9 patients with leprosy before and at RR diagnosis, followed by differential gene expression and functional analysis. A machine-learning classifier was applied to predict membrane-permeabilizing proteins. Antimicrobial activity was assessed in M. leprae-infected macrophages and axenic cultures.RESULTSIn the paired pre-RR and RR biopsy specimens, a 64-gene antimicrobial response signature was upregulated during RR and correlated with reduced M. leprae burden. Predicted upstream regulators included IL-1β, TNF, IFN-γ, and IL-17, indicating activation of both the Th1 and Th17 pathways. A machine-learning classifier identified 28 genes with predicted membrane-permeabilizing antimicrobial activity, including S100A8. Four proteins (S100A7, S100A8, CCL17, and CCL19) demonstrated antimicrobial activity against M. leprae in vitro. Scanning electron microscopy revealed membrane damage in bacteria exposed to these proteins.CONCLUSIONRR is associated with a robust antimicrobial gene program regulated by Th1 and Th17 cytokines. We identified potentially novel host antimicrobial effectors that showed activity against M. leprae, suggesting potential strategies to bolster Th1 and Th17 responses for combating intracellular mycobacterial infections.FUNDINGNIH grants R01 AI022553, R01 AR040312, R01 AR073252, R01 AI166313, R01 AI169526, P50 AR080594, and 4R37 AI052453-21 and National Science Foundation (NSF) grant DMR2325840.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL087920

  NIH · $554k · 2012

• Molecular-Scale Membrane Curvature Generation in Protein-Lipid Systems: Electrostatics, Hydrophobicity, and Geometry

  NSF · $450k · 2011–2015

• Control of Electrostatic Interactions in Complex Biological Systems

  NSF · $336k · 2009–2012

• Integrated Bioengineering Approach to Recovering Antimicrobial Function in Cystic Fibrosis Mucus

  NSF · $154k · 2009–2012

• RAPID: Biomimicry of SARS-CoV-2 and its consequences for infectivity and inflammation

  NSF · $200k · 2020–2021

Frequent coauthors

• Jaime de Anda

  University of California, Los Angeles

  122 shared

• Nathan W. Schmidt

  Ginkgo BioWorks (United States)

  86 shared

• Calvin K. Lee

  University of California, San Diego

  86 shared

• Ernest Y. Lee

  California NanoSystems Institute

  83 shared

• Michelle W. Lee

  University of California, Los Angeles

  56 shared

• Ghee Hwee Lai

  University of California, Los Angeles

  49 shared

• Abhijit Mishra

  Indian Institute of Technology Gandhinagar

  47 shared

• Fan Jin

  Heidelberg University

  41 shared

Education

• Ph.D., Physics

  University of California Berkeley

  1994

• B.S., Physics

  California Institute of Technology

  1987

Awards & honors

• Beckman Young Investigator Award
• Alfred P Sloan Foundation Fellowship
• Sackler Distinguished Speaker
• Fellow of the American Physical Society (2011)
• Fellow of the American Academy of Microbiology (2016)