About

Yueming Li, PhD, is a researcher at the Sloan Kettering Institute with a focus on the disease mechanisms of Cancer and Alzheimer’s disease, aiming to develop novel therapeutics for clinical use. His research encompasses basic and translational studies, including target identification and drug discovery, chemical biology, medicinal chemistry, biochemistry, enzymology, biophysics, structural biology, neurobiology, neuroinflammation, autophagy, protein aggregation, and clearance. Dr. Li's work involves developing agents that inhibit intramembrane proteases associated with cancer and exploring the links between inflammation and Alzheimer’s disease development. His contributions include advancing understanding of enzyme functions in disease contexts and utilizing nanotechnology for diagnosis. Dr. Li holds a PhD from the University of California Berkeley and is actively involved in leading a research lab dedicated to elucidating disease mechanisms and therapeutic development.

Research topics

• Internal medicine
• Biology
• Chemistry
• Medicine
• Immunology
• Food science
• Biochemistry
• Intensive care medicine
• Cell biology
• Chromatography
• Organic chemistry

Selected publications

• Miniaturized optically generated Bessel beam ultrasound for volumetric transcranial brain stimulation

  Science Advances · 2026-04-10

  preprintOpen access1st author

  Non-invasive stimulation of small, variably shaped brain sub-regions is crucial for advancing our understanding of brain functions. Current ultrasound neuromodulation faces two significant trade-offs when targeting brain sub-regions: miniaturization versus volumetric control and spatial resolution versus transcranial capability. Here, we present an optically-generated Bessel beam ultrasound (OBUS) device designed to overcome these limitations. This 2.33 mm-diameter miniaturized device delivers a column-shaped field achieving a lateral resolution of 152 um and an axial resolution of 1.93 mm, targeting brain sub-regions with an elongated volume of tissue activation. Immunofluorescence imaging of mouse brain slices confirms its ability to stimulate cells at a depth of 2.2 mm. Additionally, OBUS outperforms conventional Gaussian ultrasound in transcranial transmission efficiency and beam shape preservation. Electrophysiological recordings and functional MRI captured rodent brain responses evoked by OBUS, demonstrating OBUS's ability to non-invasively activate neural circuits in intact brains. This technology offers new possibilities for studying brain functions with precision and volumetric control.

  PublisherDOI

• Recent Advances in the Development of γ-Secretase Modulators to Treat Alzheimer’s Disease

  Topics in medicinal chemistry · 2026-01-01

  book-chapterSenior author
  PublisherDOI

• Improving wort filtration using extruded cassava flour: insights from macromolecular analysis

  Journal of the Institute of Brewing · 2025-07-18

  articleOpen access

  Why was the work done: The high starch content of cassava flour makes it a potential adjunct for beer production, but its poor filtration performance limits its utilisation. How was the work done: This study investigated how the inclusion of extruded cassava flour (30%) affected the filtration of malt wort by analysis of the content and molecular weight distribution of macromolecules - starch, β-glucan, arabinoxylans, and protein - in both wort and fine particles from spent grain. What are the main findings: Extrusion enhanced the hydrolysis of starch, β-glucan, and protein, leading to a lower soluble starch and β-glucan content, higher total nitrogen levels, and reduced high molecular weight fractions in extruded cassava flour (ECF) wort. These changes also reduced the viscosity of the ECF wort compared to native cassava flour (NCF) wort. Additionally, more low and medium molecular weight polysaccharides were found in fine particles from wort from the ECF mash separated from spent grain. Accordingly, these polysaccharides were less likely to aggregate with gel-protein, thereby improving filtration speed. Scanning electron microscopy and particle size analysis supported these findings, showing that fine particles in wort from the ECF wort had a looser, more porous structure and a smaller particle size. Why is the work important: This study provides practical insight into how extrusion can improve the filtration efficiency of cassava flour used as an adjunct, broadening its potential use in the production of beer.

  PublisherOA PDFDOI

• Research on DOA Estimation Method of Vector Hydrophone Array in Low SNR Based on CNN

  2025-04-08

  article

  This paper presents a direction of arrival (DOA) estimation method for vector sensor arrays based on convolutional neural networks (CNN) to improve the estimation accuracy. The model consists of four convolutional layers and three fully connected layers. The network input is a three-channel data consisting of real part, imaginary part, and phase from the signal covariance matrix received by the array. Each node of the output stands for a presented directional grid, and the output value on that node indicates the probability of a signal locating in the neighborhood of the grid. The experimental results show that the neural network model can achieve 360-degree unambiguous estimation and is capable of acquiring precise and accurate estimation of DOA, especially in the cases of low signal-to-noise ratio (SNR).

  PublisherDOI

• Arbuscular mycorrhizal fungi confer aluminum toxicity tolerance in Ricinus communis via modulating root metabolic mechanisms and the composition and quantity of root exudates

  Plant Physiology and Biochemistry · 2025-06-09 · 1 citations

  article
  PublisherDOI

• Less training, better improvement: effects of velocity-based complex training on lower-limb maximal strength and explosive performance in highly-trained volleyball athletes

  BMC Sports Science Medicine and Rehabilitation · 2025-10-28

  articleOpen access

  OBJECTIVES: This randomized controlled trial compared the effects of velocity-based complex training (VBCT) and traditional complex training (TCT) on lower-limb maximal strength and explosive performance in male volleyball athletes during the competitive season. METHODS: Thirty athletes were randomly assigned to VBCT (n = 10), TCT (n = 10), or a control group (CON, n = 10). The VBCT and TCT groups trained twice weekly for eight weeks. Pre- and post-intervention assessments included 1RM squat, countermovement jump (CMJ), squat jump (SJ), eccentric utilization rate (EUR), and standing long jump (SLJ). RESULTS: Both VBCT and TCT improved 1RM squat, CMJ, SJ, and SLJ, whereas only VBCT improved EUR (p < 0.01). Post-intervention, VBCT demonstrated significantly greater improvements than TCT in CMJ (VBCT: η² = 0.65; TCT: η² = 0.41) and EUR (VBCT: η² = 0.45; TCT: η² = 0.07) (p < 0.05). Training intensity did not differ between groups (p > 0.05), but VBCT showed lower training volume, fewer repetitions, and lower rating of perceived exertion, while exhibiting higher mean concentric velocity for each repetition within squat sets compared with TCT (p < 0.01). CONCLUSIONS: VBCT resulted in greater improvements in CMJ and EUR, while its effects on 1RM, SJ, and SLJ were similar to TCT. With lower volume and fatigue, VBCT may be a more efficient strategy for enhancing lower-limb strength and explosiveness during the competitive season. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ) with the following details: Registration Number: ChiCTR2400093910. Registration Date: 13/12/2024.

  PublisherOA PDFDOI

• Dynamic deadband intermittent event-triggered strategy for formation control of multiple unmanned surface vehicles

  Journal of Vibration and Control · 2025-01-03 · 15 citations

  article

  This paper focuses on the leaderless formation control of multiple unmanned surface vehicles (MUSVs) with external disturbances, communication interruptions, and model parametric uncertainties. Firstly, the auxiliary variables are introduced to transform MUSVs’ formation control into consensus achievement of these auxiliary variables. Then, to realize consensus of these auxiliary variables, the reference variables which can achieve the average consensus are defined based on the proposed dynamic deadband intermittent event-triggered mechanism (ETM). Superior to general dynamic ETMs, the proposed dynamic deadband ETM applies nonlinear coupled communication protocols and ensures the existence of positive minimum inter-event times (PMIET). Further, by guaranteeing the auxiliary variables superior tracking capability for the reference variables, the consensus of the auxiliary variables can be achieved. Thus, the desired formation is realized. Besides, the adaptive strategy and the radial basis function neural network (RBFNN) are utilized against external disturbances and dynamic uncertainties. Finally, through rigorous theoretical analysis and numerical simulations, the effectiveness and superiority of the proposed method are effectively demonstrated.

  PublisherDOI

• Advances in photoacoustic retina stimulation: from in vivo studies to injectable approach

  2025-03-19

  article

  Retina prosthesis are implantable devices stimulating diseased retina of individuals to restore vision. New technologies are needed for precise and non-genetic retinal stimulation. Here we report new development in photoacoustic retina stimulation. First, we confirmed successful blind retina stimulation through a PDMS-based photoacoustic film safely ex vivo and in vivo in the rat model. Second, we explored new materials for injectable photoacoustic film and evaluated its potential in retinal stimulation through multi-electrode recording of RGC responses ex vivo. These results show the potential of using optoacoustic signal to drive activity in photoreceptor-damaged retinas.

  PublisherDOI

• ZDHHC5 deficiency impairs spermatogenesis and causes male infertility in mice

  Reproduction · 2025-10-14 · 1 citations

  article

  In brief: S-palmitoylation is a key protein modification, but the role of ZDHHC5 in male fertility was unknown. This study shows ZDHHC5 loss impairs spermatogenesis, causing male infertility, and identifies ZDHHC5 as a key regulator, offering new insights into infertility mechanisms. Abstract: S-palmitoylation is a reversible post-translational modification critical for protein localization and function. ZDHHC5, a member of the ZDHHC family of palmitoyltransferases, has well-established roles in cardiovascular, neural, and metabolic systems, but its function in male reproduction remains unclear. To investigate this, we generated Zdhhc5-knockout (KO) mice using CRISPR/Cas9 and found that male KO mice exhibited complete infertility. Phenotypic analysis revealed significantly reduced testis-to-body weight ratios, decreased sperm count and motility, and increased sperm malformations, including abnormal heads and folded tails. Histological and ultrastructural analyses demonstrated defective spermatogenesis, with aberrant retention of sperm during seminiferous tubule maturation and abnormal membranous structures in sperm. Immunofluorescence showed that ZDHHC5 predominantly localizes to the Golgi apparatus of round spermatids (steps 2-8) without affecting Golgi morphology or acrosome biogenesis. While in vitro fertilization with Zdhhc5 -/- sperm failed, intracytoplasmic sperm injection (ICSI) successfully rescued male infertility, suggesting functional disruption at the protein modification level rather than genetic material impairment. We also found that ZDHHC5 mediates IFT81 palmitoylation, regulates IFT81 in round spermatids, and links to sperm tail malformations. These findings establish ZDHHC5, a palmitoyltransferase, as a pivotal regulator of spermatogenesis, thereby yielding new insights into the molecular mechanisms underlying male infertility.

  PublisherDOI

• <i>In Situ</i> Labeling of Pathogenic Tau Using Photo-Affinity Chemical Probes

  ACS Chemical Biology · 2025-03-13 · 1 citations

  articleSenior authorCorresponding

  Tau aggregation plays a crucial role in the development of Alzheimer’s disease (AD). Developing specific techniques that can isolate pathogenic tau from brain tissue is important for understanding tauopathies and advancing targeted therapies. Here, we develop photoaffinity small molecular probes and a novel method for in situ tissue labeling and investigate their activity in interacting with tau in cells and AD patient brains. Based on the reported chemical structures of tau PET tracers, we designed and synthesized two tau-specific probes, namely, Tau-2 and Tau-4. After validation in cell, mouse model, and patient brain samples, our photolabeling results suggested that Tau-2 effectively labels soluble tau in cell and mouse models, while Tau-4 selectively binds high-molecular-weight tau aggregates in late-stage AD patient brain tissues. Proteomic analysis verified the specific isolation of pathogenic tau from AD brain samples. Collectively, these findings underscore the potential of our photoaffinity probes as powerful tools for investigating tau proteins and neurofibrillary tangles in neurodegenerative diseases.

  PublisherDOI

Recent grants

• NIH Grant R01AG026660

  NIH · $3.5M · 2017

• Substrate Feedback Mechanism of gamma-Secretase

  NIH · $2.1M · 2018–2023

• NIH Grant R01NS076117

  NIH · $2.8M · 2017

• Regulation of y-secretase activity by modulatory proteins

  NIH · $4.3M · 2019–2024

• Molecular mechanisms of gamma-secretase modulation central to Alzheimer’s disease

  NIH · $3.2M · 2022–2027

Frequent coauthors

• Eitan Wong

  Memorial Sloan Kettering Cancer Center

  55 shared

• Georgia Frost

  36 shared

• Shane A. Liddelow

  Neurosciences Institute

  34 shared

• Paul M. Mathews

  34 shared

• Robert J. Schneider

  University of Iowa Hospitals and Clinics

  33 shared

• Youssef Zaim Wadghiri

  33 shared

• Nicole M. Eskow

  New York University

  33 shared

• Ronald B. DeMattos

  Eli Lilly (United States)

  33 shared

Labs

• Yueming Li LabPI

Awards & honors

• BrightFocus Foundation Professional Services and Activities
• Cure Alzheimer's Fund Professional Services and Activities