About

The Language Understanding and Knowledge Acquisition (LUKA) Lab is directed by Dr. Muhao Chen. Our research focuses on robust and accountable machine learning methods for natural language processing and multi-modal data processing. Most recently, we have been focusing on robustness and safety problems with large (multi-modal) language models and foundation model agents. Our long-term goal is to develop robust, generalizable and trustworthy learning systems that help machines understand nature.

Research topics

• Biology
• Genetics
• Computational biology
• Cell biology
• Cancer research

Selected publications

• First Report of <i>Penicillium citreonigrum</i> Causing Root Rot Disease in Blueberries in China

  Plant Disease · 2025-08-04

  article

  Blueberry (Vaccinium corymbosum) plants are small, berry-producing shrubs belonging to the family Ericaceae. On July 24, 2024, root rot symptoms were observed in Huaining, Anhui Province, China (30°44′12.8″N, 116°49′28.4″E). Similar symptoms were observed in approximately 5% of 420 blueberry seedlings cultivated in substrate containers under greenhouse conditions. Affected plants exhibited leaf yellowing, curling, wilting, and eventually defoliation. Symptomatic roots were harvested and washed with sterile water, surface-sterilized twice using 75% ethanol for 30 s, and rinsed 3–4 times with sterile water. The roots were placed on potato dextrose agar (PDA) medium and incubated at 25°C for 7 days. Three isolates (HN-Pc1, HN-Pc2, and HN-Pc3) exhibiting similar morphology were obtained using single-spore isolation. The isolates produced aerial mycelium that appeared white to pale gray on the front view and light yellow on the reverse view. After 7 days of incubation, colonies reached a diameter of 29 mm. The conidia were single-spored, spherical or ellipsoid grayish green (2.56 ± 0.36 μm in diameter, n = 50). Conidiophores produced broom-like conidiosphores with multiple branches bearing phialides. These morphological characteristics were similar to those described for P. citreonigrum, P. citreosulfuratum, and P. fundyense (Hu et al. 2021; Visagie et al. 2016). To further confirm species identity, the conserved regions of RNA polymerase II second-largest subunit (RPB2), β-tubulin (TUB2), and calmodulin (CaM) genes were amplified using primer pairs RPB1-5f/RPB2-7cR, Bt2a/Bt2b, and CMD5/CMD6, respectively (Visagie et al. 2014). The resulting RPB2, TUB2, and CaM sequences were deposited in GenBank under accession Nos. PV593986, PQ887759, and PQ887758, respectively. In a BLASTn search, the CaM, TUB2, and RPB2 sequences showed 96.11%, 98.25%, and 98.27% similarity to P. citreonigrum strains in the NCBI database (accession numbers EF198581, OU641462, EF198500). Multiple-locus (RPB2–TUB2–CaM) alignment confirmed the highest similarity to P. citreonigrum NRRL 761 and NRRL 1187. To fulfill Koch’s postulates, inoculation trials were conducted using healthy ‘O’ Neal’ blueberry plants (Vaccinium corymbosum). Each plant received a P. citreonigrum HN-Pc1 spore suspension (25 mL, 1 × 10⁶ conidia/mL) through root irrigation. In parallel, control ‘O’ Neal’ plants were treated with an equivalent volume of sterile water. All treated plants were maintained at 25°C for 7 days. The inoculated plants developed symptoms identical to field observations and root discoloration (brown to dark brown). In contrast, no symptoms were observed in the control plants. The fungus was re-isolated and identified as P. citreonigrum based on morphological characteristics and conserved multiple sequence alignment analysis (RPB2–TUB2–CaM) (Visagie et al. 2016). To the best of our knowledge, this is the first report of root rot disease caused by P. citreonigrum in blueberry plants in China. These findings provide a basis for the early detection of P. citreonigrum, and lay a crucial foundation for developing effective management strategies.

  PublisherDOI

• LB1248 Improving the therapeutic potential of intravenous recombinant collagen VII as a protein replacement therapy for recessive dystrophic epidermolysis bullosa

  Journal of Investigative Dermatology · 2025-07-21

  articleOpen access
  PublisherOA PDFDOI

• Consensus statement on the multidisciplinary treatment of nasopharyngeal carcinoma with immune checkpoint inhibitors in China

  ESMO Open · 2025-09-01 · 4 citations

  reviewOpen access

  INTRODUCTION: This study aims to establish a multidisciplinary consensus on the treatment of nasopharyngeal carcinoma (NPC) in China, with a particular focus on the guidelines for the use of immune checkpoint inhibitors (ICIs) to ensure scientific and rational treatment protocols. METHODS: The consensus was formulated based on the 'guidelines for the diagnosis and treatment of NPC (2024 edition)' issued by the Chinese Society of Clinical Oncology. The Delphi method was used to collect and consolidate expert opinions. Through repeated solicitation and integration of expert opinions, an expert consensus on combined ICI therapy for NPC was ultimately reached. Additionally, a literature review approach was used to facilitate consensus building. RESULTS: The consensus encompasses the current status of NPC diagnosis and treatment, synthesizing existing clinical evidence to deeply discuss major clinical issues. The primary focus of the consensus is on the clinical practice principles and methods of combinatory ICI therapy. It provides guidelines for patient selection, treatment protocols, and management of adverse events in clinical practice. The consensus emphasizes that multidisciplinary collaboration can further enhance the treatment outcomes and quality of life for NPC patients. Future research needs to continue exploring optimized treatment protocols and predictive biomarkers to achieve more precise personalized therapy. CONCLUSION: The consensus underscores the role of ICIs in NPC treatment and provides understanding and reference for clinical application. Given the differences in drug approval and availability across countries and the high incidence of NPC in southern China, this consensus particularly focuses on the treatment of Chinese patients.

  PublisherDOI

• A Study on the Extraction, Fermentation Condition Optimization, and Antioxidant Activity Assessment of Polysaccharides Derived from Kluyveromyces marxianus

  Foods · 2025-08-12 · 1 citations

  articleOpen access

  Kluyveromyces marxianus exhibits advantages such as strong thermotolerance, rapid growth rate, and high safety, making it an excellent host cell for the production of bio-based products. In this study, two exopolysaccharides, KE1 and KE2, were isolated from the fermentation broth of the strain K. marxianus KM-502, and their hydroxyl radical scavenging, DPPH scavenging, and Fe2+-reducing activities were evaluated. In vitro antioxidant assays demonstrated that exopolysaccharide KE2 exhibited superior antioxidant activity compared to KE1. The fermentation conditions were optimized using single-factor experiments followed by response surface methodology (RSM). The optimized fermentation process revealed that the most suitable fermentation medium consisted of 8% sucrose, 1.99% peptone, and 0.13% CaCl2, while the optimal fermentation conditions were a medium volume of 74 mL in a 300 mL flask, pH 6.7, an inoculum size of 1.99%, a temperature of 30 °C, a shaking speed of 160 r/min, and a cultivation time of 96 h. After optimizing the fermentation conditions of K. marxianus KM-502, the exopolysaccharide (EPS) yield reached 5842.42 mg/L, representing a 22.77-fold increase compared to the yield before optimization. In summary, this study isolated exopolysaccharides KE1 and KE2 from K. marxianus KM-502. These exopolysaccharides demonstrated significant antioxidant activities, and the fermentation conditions for exopolysaccharide production were optimized. The findings of this study will facilitate the further development and utilization of exopolysaccharides from K. marxianus.

  PublisherDOI

• Silencing of SPI1/OLAH Axis Inhibits Pancreatic Acinar Cell Oxidative Stress, Inflammation and Apoptosis to Alleviate Hyperlipidemic Acute Pancreatitis

  Pancreas · 2025-07-28

  articleSenior authorCorresponding

  BACKGROUND: Oleoyl-ACP hydrolase (OLAH), a fatty acid metabolism-related gene, is abnormally expressed in many diseases. Using the GEO database, we found that OLAH was highly expressed in acute pancreatitis (AP) patients. However, whether it mediates hyperlipidemic AP (HAP) progression remains unclear. MATERIALS AND METHODS: Mouse pancreatic acinar cells (MPC-83) were treated with palmitic acid (PA) and cerulein (CER) to mimic HAP cell models, and HAP mice models were constructed by injecting with P-407 and CER. The mRNA and protein levels of OLAH and Salmonella pathogenicity island 1 (SPI1) were determined by qRT-PCR and western blot. The oxidative stress and inflammation in MPC-83 cells and the pancreatic tissues of HAP mice models were assessed by measuring the levels of MDA, SOD, ROS, IL-1β, TNF-α and IL-6. Cell apoptosis was examined using flow cytometry. The interaction between SPI1 and OLAH promoter was evaluated using ChIP assay and dual-luciferase reporter assay. RESULTS: OLAH was upregulated in PA+CER-induced MPC-83 cells, and its silencing suppressed pancreatic acinar cell oxidative stress, inflammation and apoptosis. Transcription factor SPI1 bound to OLAH promoter region to enhance its expression. SPI1 knockdown inhibited PA+CER-induced MPC-83 cell oxidative stress, inflammation and apoptosis, as well as alleviated HAP process in mice models, while these effects were reversed by OLAH overexpression. CONCLUSION: SPI1-mediated transcriptional activation of OLAH promoted pancreatic acinar cell oxidative stress, inflammation and apoptosis to accelerate HAP progression.

  PublisherDOI

• Targeting Hsp90 in Cancer for 25 Years: Failure of Previous Clinical Trials and New Hope for Future Therapeutics

  Cells · 2025-12-15

  articleOpen access1st authorCorresponding

  All previous IND (investigational new drug) applications to US FDA for launching clinical trials with Hsp90 ATP-binding inhibitors only provided a partial, if not misleading, account of the inhibitors' actual MOA (mechanism of action). Since 2004, studies have repeatedly shown a previously unanticipated "extra effect" of these inhibitors, but it has been incomprehensively ignored by the Hsp90 community. Membrane-impermeable, otherwise structurally identical, ATP-binding Hsp90 inhibitors show robust inhibition of tumor cell invasion in vitro and metastasis in vivo. Based on this new finding, the reported outcomes of around 90 monotherapy clinical trials with Hsp90 ATP-binding inhibitors since 1999 were actually a combined effect of targeting both intracellular Hsp90 chaperone and extracellular Hsp90 (eHsp90) non-chaperone functions by the inhibitors. A critical unanswered question remains: which form of the dual inhibitions caused the observed toxicity in humans that led to the spectacular failure of the trials and which underlies the limited efficacy that might be the real reason for the only approval of the orally administered ATP-binding inhibitor, Pimitespib (TAS-116), in 2022 by Japan? We suggest that addressing this question could prompt a paradigm shift in the design of next-generation anti-Hsp90 cancer therapeutics.

  PublisherOA PDFDOI

• A comprehensive study of carboxylesterases involved in the degradation of volatile esters in horticultural crops

  Industrial Crops and Products · 2025-10-13

  articleOpen access1st author

  Volatile esters play a crucial role in shaping the aroma profiles and sensory attributes of horticultural crops. In this study, we comprehensively investigated the volatile esters, alcohols, and acids profiles of different tea plant varieties and tissues to identify the key metabolites responsible for tea flavors. Subsequently, two homologous genes, CXE2 and CXE3 , which encode a carboxylesterase and are involved in the hydrolysis of esters, were screened from Camellia sinensis , Vaccinium darrowii , Myrica rubra , and Actinidia chinensis via multiomics analysis. In vitro , the purified recombinant enzyme CXE2 and CXE3 catalyze the hydrolysis of acetate esters into alcohols and acids. Molecular docking, site-directed mutagenesis, and enzyme activity analysis revealed that Tyr-15 and Gly-81 were the key amino acids that imparted hydrolytic activity to CsCXE2 , whereas Gly-81 and Gly-82 were the key amino acids that imparted hydrolytic activity to CsCXE3 . In vivo , the low expression of CsCXE2 and CsCXE3 led to decreased normal pollen and an increased presence of triangular pollen. In tender tea shoots, the results of gene silencing and withering treatments revealed that CsCXE2 and CsCXE3 disrupted acetate metabolism and altered the dynamic balance between green grassy and fruity aroma-related compounds by hydrolyzing acetate esters. Overall, this study highlights the significant potential of targeting CXE2 and CXE3 for precise flavor modulation in horticultural crop cultivation and processing, offering novel strategies to optimize the aroma profiles of horticultural crops in industrial applications. • A method for excavating functional genes via multi-omics association analysis has been provided. • The functions of CXE2 and CXE3 were conserved in horticultural crops and catalyzed the hydrolysis of hexyl acetate. • Elucidated catalytic mechanisms of CXE2 and CXE3 via molecular docking, site-directed mutagenesis, and biochemical assays. • CXE2 and CXE3 alter the dynamic balance between green and fruity aroma by catalyzing the hydrolysis of hexyl acetate.

  PublisherDOI

• The value of urinary gonadotropin after triptorelin stimulation tests for diagnosing central precocious puberty in girls with overweight or obesity: a single-center study

  BMC Pediatrics · 2025-10-21 · 1 citations

  articleOpen access

  BACKGROUND: There are different opinions about the effect of body mass index on gonadotropin-releasing hormone stimulation tests in the laboratory diagnosis of precocious puberty in girls. The blood collection of precocious puberty girls with overweight or obesity is more difficult than those with normal body mass index. It is urgent to find non-invasive diagnostic methods for these girls. The purpose of the study was to evaluate the value of urinary gonadotropin after triptorelin stimulation tests for diagnosing central precocious puberty (CPP) in girls with overweight or obesity. METHODS: This was a hospital data-based retrospective study. Overweight or obese girls with precocious puberty who presented to our pediatric endocrine clinic were involved. Triptorelin (Decapeptyl, 0.1 mg) stimulation tests were performed at 8:30 am. On the triptorelin test day, urine sample collected from 08:30 am to 8:30 pm was defined as the first stimulated urine. Serum and urinary luteinizing hormone (LH) were measured by immunochemiluminometric assay. Urinary creatinine (Cr) was also measured. RESULTS: There were 52 girls with overweight or obesity. They were divided into CPP (n = 36) and peripheral precocious puberty (PPP) (n = 16) groups. The stimulated urinary LH (ULH) concentration corrected by Cr (ULH/Cr), ULH concentration, and ULH content in the CPP group were significantly higher than those in the PPP group. When the first stimulated ULH/Cr, ULH concentration and ULH content were ≥ 239.142 IU/mol, 1.690 IU/L and 619.750 IU, and sensitivity for diagnosing CPP in girls with overweight or obesity were 90.9%, 78.8% and 81.8%, respectively, and specificity were all 100%, and the area under the curve were 0.939, 0.932 and 0.909, respectively. CONCLUSIONS: For overweight or obese girls with precocious puberty, the first stimulated ULH/Cr (cut-off value 240 IU/mol) may be used as a possible alternative to the invasive blood detection of triptorelin stimulation tests for diagnosing CPP. TRIAL REGISTRATION: Not applicable.

  PublisherOA PDFDOI

• Prolactin links psychological stress to psoriasis via a fibroblast-chemokine pathway

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-13

  preprintOpen access

  Abstract Psoriasis is a chronic inflammatory skin disease that forms a vicious cycle with psychological stress. Whether and how the hypothalamic-pituitary (HP) axis-mediated neuroendocrine system regulates psoriasis remains obscure. Here, we report elevated levels of the pituitary hormone prolactin (PRL) in both psoriasis patients and imiquimod (IMQ)-induced psoriasis mice. Mechanistically, PRL acts on dermal PRLR-expressing fibroblasts to promote the production of the chemokines CCL2 and CCL7, which then recruit monocytes/macrophages into psoriatic lesional skin, thereby activating local IL-17A-producing T cells. Accordingly, pharmacological targeting of PRL signaling inhibits the recruitment of monocytes/macrophages, decreases the frequency of IL-17A-producing T cells, and alleviates IMQ-induced psoriasis in mice. In summary, our results delineate a mechanism by which the neuroendocrine hormone PRL aggravates psoriasis and highlight a potential therapeutic strategy of inhibiting PRL-PRLR signaling, particularly in psoriasis patients experiencing psychological stress.

  PublisherOA PDFDOI

• LB1196 Evaluating the diagnostic accuracy of AI models in dermatology: Addressing skin tone bias to improve outcomes for ethnic skin types

  Journal of Investigative Dermatology · 2025-07-21

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• NIH Grant R01AR033625

  NIH · $6.9M · 2015

• NIH Grant RC4AR060535

  NIH · $3.1M · 2013

• NIH Grant R01AR047981

  NIH · $2.9M · 2012

Frequent coauthors

• David T. Woodley

  USC Norris Comprehensive Cancer Center

  140 shared

• Edel A. O’Toole

  Queen Mary University of London

  123 shared

• John A. McGrath

  King's College London

  112 shared

• Dédée F. Murrell

  UNSW Sydney

  99 shared

• Andrew P. South

  Thomas Jefferson University

  70 shared

• J. Kelly

  64 shared

• C O'farrely

  St. James's Hospital

  64 shared

• Emiko Mizoguchi

  Brown University

  64 shared

Education

• PhD, Cell Biology, Virology and Molecular Biology

  Albert Einstein College of Medicine

Awards & honors

• NSF Proto-OKN
• Amazon Research Award on Generative AI
• NSF CRII Award
• Cisco Faculty Award