About

Dr. Mei-Ling Ting Lee is a Professor in the Department of Epidemiology & Biostatistics at the University of Maryland, College Park. Her research focuses on models for time-to-event data, analysis of genomic data, statistical distributional theory and applications, nonparametric methods, and statistical applications in epidemiology and medical research. She developed the first hitting-time based threshold regression (TR) model for analyzing survival data, which has been extended to machine learning neural networks for AI applications. Dr. Lee has extensive experience analyzing large-scale high-dimensional genomic data and authored a widely used monograph titled "Analysis of Microarray Gene Expression Data" in 2004, which includes sample size and power calculations for microarray studies and chapters on machine learning bioinformatics methods. She is the founding editor and Editor-in-Chief of the international journal "Lifetime Data Analysis," which emphasizes methods for analyzing time-to-event data. Dr. Lee has published over 150 articles, contributed to multiple edited books, and has received numerous awards and honors, including fellowships in major statistical societies and service awards.

Research topics

• Biology
• Biochemistry
• Chemistry
• Microbiology
• Cell biology

Selected publications

• Identification of <i>Pseudomonas aeruginosa</i> genetic determinants that connect redox metabolism to alginate biosynthesis

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-06

  articleOpen accessSenior authorCorresponding

  ABSTRACT Pseudomonas aeruginosa is a well-known human pathogen that contributes significantly to chronic infections, particularly in cystic fibrosis (CF) patients. During this chronic infection, P. aeruginosa undergoes a phenotype change, the inactivation of mucA , which leads to the production of exopolysaccharide alginate, known as mucoid, a key virulence factor associated with biofilm formation. This mucoid phenotype allows the bacterium to persist in the lungs of CF patients for the duration of their lives. Previously, we identified ebselen oxide (EbO) as an inhibitor that suppresses alginate production in P. aeruginosa . In the current study, we synthesized a series of structural analogs based on EbO and ebselen (Eb) and evaluated their ability to inhibit alginate production. These analogs did have similar or lower inhibitory activity than EbO. The mechanism by which EbO inhibits alginate production remains unclear. We employed RNA sequencing analysis of P. aeruginosa treated with inhibitors and identified several candidate genes potentially involved in this inhibitory pathway. Interestingly, we observed that a transposon and in-frame deletion mutants of the candidate genes were defective for alginate production. These findings suggest there are additional requirements for optimal alginate production in conditions that mimic the CF lung beyond the algD-A operon. IMPORTANCE When bacteria encounter the correct conditions, they can dedicate their energy toward a specific function to maximize the function. One example is the low calcium response in Yersinia pestis in which the bacteria arrest growth when grown at 37 °C in the absence of calcium because it uses all its energy for type III secretion. Another example is production of alginate by P. aeruginosa in the lungs of CF patients that can lead to occlusion of the airways. In both cases, the dedicated use of energy toward type III secretion for Y. pestis and alginate biosynthesis for P. aeruginosa reduces the ability of the bacteria to multiply. In the lab, suppressors can be easily identified that restore bacteria growth. The suppressor mutations are often located in the operons that are up-regulated and thereby prevent the execution of the energetically costly process. While these results indicate these processes are energetically costly, we still do not understand how the bacteria dedicate their energy toward these processes over other cellular processes such as growth. Previously, we identified ebselen oxide (EbO) as an inhibitor that suppresses alginate production in P. aeruginosa , but chemical analogues fail to improve the inhibitory activity. We used RNA sequencing analysis of P. aeruginosa treated with inhibitors and identified several candidate genes potentially involved in this inhibitory pathway. Interestingly, we observed that a transposon and in-frame deletion mutants of these genes involved in redox reactions were defective for alginate production. These findings suggest there proteins may shunt energy for optimal alginate production in conditions that mimic the CF lung beyond the algD-A operon. Results from P. aeruginosa alginate production may inform how other bacteria can similarly focus energy toward specific cellular processes.

  PublisherOA PDFDOI

• Structural and bioinformatics analyses identify deoxydinucleotide-specific nucleases and their association with genomic islands in gram-positive bacteria

  Nucleic Acids Research · 2025-01-07 · 2 citations

  articleOpen access

  Dinucleases of the DEDD superfamily, such as oligoribonuclease, Rexo2 and nanoRNase C, catalyze the essential final step of RNA degradation, the conversion of di- to mononucleotides. The active sites of these enzymes are optimized for substrates that are two nucleotides long, and do not discriminate between RNA and DNA. Here, we identified a novel DEDD subfamily, members of which function as dedicated deoxydinucleases (diDNases) that specifically hydrolyze single-stranded DNA dinucleotides in a sequence-independent manner. Crystal structures of enzyme-substrate complexes reveal that specificity for DNA stems from a combination of conserved structural elements that exclude diribonucleotides as substrates. Consistently, diDNases fail to complement the loss of enzymes that act on diribonucleotides, indicating that these two groups of enzymes support distinct cellular functions. The genes encoding diDNases are found predominantly in genomic islands of Actinomycetes and Clostridia, which, together with their association with phage-defense systems, suggest potential roles in bacterial immunity.

  PublisherOA PDFDOI

• Functional analyses of bacterial NanoRNase B proteins reveals defining features of this enzyme family

  DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron) · 2025-01-01

  articleOpen access

  A combination of exoribonucleases and endoribonucleases degrades RNA polymers to recycle nucleoside monophosphates. A byproduct of these reactions is the accumulation of short RNAs, 2–5 nucleotides in length. Characteristic enzymes, generally referred to as nanoRNases, specifically process short RNAs. Genes encoding nanoRNases are essential in some bacteria; therefore, it is assumed that the accumulation of short RNAs is detrimental to cells. However, the substrate preferences and enzymatic mechanisms of the known categories of nanoRNase enzymes have not been equally investigated. The NrnB category of nanoRNases has been particularly understudied. In this study, we identified bacterial NrnB homologs and discovered they can be grouped into three classes of proteins, which can be identified by their characteristic sequence features. Purified representatives of these classes of proteins revealed that they all process RNA substrates from the 3′-terminus. The presence of sequence features at the C-terminus was shown to be diagnostic for general exoribonuclease activity against long RNA substrates, whereas the absence of these C-terminal elements was correlated with proteins that preferentially acted against shorter RNA substrates. Together, these data define members of the overall NrnB family of nanoRNase proteins and identify some of their key features.

  PublisherDOI

• Functional analyses of bacterial NanoRNase B proteins reveals defining features of this enzyme family

  Nucleic Acids Research · 2025-11-22

  articleOpen access

  A combination of exoribonucleases and endoribonucleases degrades RNA polymers to recycle nucleoside monophosphates. A byproduct of these reactions is the accumulation of short RNAs, 2-5 nucleotides in length. Characteristic enzymes, generally referred to as nanoRNases, specifically process short RNAs. Genes encoding nanoRNases are essential in some bacteria; therefore, it is assumed that the accumulation of short RNAs is detrimental to cells. However, the substrate preferences and enzymatic mechanisms of the known categories of nanoRNase enzymes have not been equally investigated. The NrnB category of nanoRNases has been particularly understudied. In this study, we identified bacterial NrnB homologs and discovered they can be grouped into three classes of proteins, which can be identified by their characteristic sequence features. Purified representatives of these classes of proteins revealed that they all process RNA substrates from the 3'-terminus. The presence of sequence features at the C-terminus was shown to be diagnostic for general exoribonuclease activity against long RNA substrates, whereas the absence of these C-terminal elements was correlated with proteins that preferentially acted against shorter RNA substrates. Together, these data define members of the overall NrnB family of nanoRNase proteins and identify some of their key features.

  PublisherDOI

• Leveraging a Multi-Disciplinary Approach to Appraise the Permian’s Southern Delaware Basin

  2025-01-01

  article
  PublisherDOI

• A CHALLENGING CASE OF RECURRENT PERICARDITIS AND POSSIBLE NOVEL ASSOCIATION WITH MUTATION IN INTERFERONOPATHY-CAUSING GENE

  Annals of Allergy Asthma & Immunology · 2024-10-25 · 1 citations

  article1st authorCorresponding
  PublisherDOI

• Abstract 2306 Signaling by cyclic and linear dinucleotides

  Journal of Biological Chemistry · 2024-03-01

  articleOpen access1st authorCorresponding

  Microbes respond to environmental changes by generating a signal transduction cascade including the synthesis and degradation of signaling nucleotides such as cyclic-di-GMP and cyclic-di-AMP. Recent studies revealed that these cyclic dinucleotides are often recycled by a two-step process in which the molecules are linearized into linear dinucleotide that is subsequent cleaved into mononucleotides to complete the recycling process. This was discovered for Pseudomonas aeruginosa in which oligoribonuclease (Orn) cleaves the linear dinucleotides into mononucleotides. Mutants lacking orn accumulate linear dinucleotides and, through feedback inhibition, leads to the accumulation of cyclic dinucleotides and signaling. The observation that orn is not essential in P. aeruginosa is not conserved in other gamma proteobacteria. In Escherichia coli, Vibrio cholerae, and Yersinia pestis, orn is an essential gene. Here I will discuss the molecular basis for the biochemical function of Orn (not an oligoribonuclease), why orn is not essential P. aeruginosa, and how these results suggest linear dinucleotides act as a set of critical signaling molecules in gamma proteobacteria.

  PublisherOA PDFDOI

• IMG-19. CLINICAL UTILITY OF NON-FDG PET-MRI IN CHILDREN WITH CNS NEOPLASMS: A TERRITORY-WIDE STUDY FROM HONG KONG

  Neuro-Oncology · 2024-06-18

  articleOpen access

  Abstract INTRODUCTION Magnetic resonance imaging (MRI) is the gold-standard for neuroimaging, yet details from anatomical scans might be inconclusive in certain scenarios. This study aimed to investigate the utility of amino-acid tracer positron emission tomography-magnetic resonance imaging (PET-MRI) based on a territory-wide Pediatric Neuro-Oncology cohort from Hong Kong. METHODS We reviewed the PET-MRI scans of pediatric patients with suspected/confirmed CNS neoplasms co-managed by Hong Kong Children’s Hospital and St. Teresa’s Hospital, Hong Kong from 5/2022-1/2024. Tracers used included C11-MET (n=10, before 5/2023) and F18-FET (n=15, in/after 5/2023). Lesion-to-normal SUVmax ratios (LNRmax) were measured with reference to adjacent or contralateral normal brain structures. RESULTS Twenty-five patients were included (M:F=13:12) with a median age of 10 years (range: 1-17). Anatomical sites of interest were the pituitary (n=13), basal ganglia (n=3), cerebellum (n=3), brainstem (n=2), frontal lobe (n=2), cerebellopontine angle (n=1), and spine (n=1). PET-MRI was performed as part of initial diagnostics in 21, to assess post-operative residual in 2, and for possible relapse in 2. Among those evaluated upfront (n=21), median SUVmax and LNRmax were 1.53 (range: 0.87-2.6) and 0.87 (range: 0.45-1.92) respectively in patients with presumed/confirmed low-grade glioneuronal (n=5) or non-oncologic lesions (n=8), versus 4.75 (range: 2.58-9.6) and 3.26 (range: 1.78-4.9) in patients with histologically/biochemically confirmed high-grade lesions (germinoma=6, high-grade glioma=2). Availability of functional PET imaging was deemed useful for scan interpretation in all 25 patients. Specifically, the use of PET-MRI facilitated decision for radiographic surveillance without biopsy/resection in 12 patients, refined tumor grading in 2 patients with discrepant clinical-histologic features, and allowed response-adapted therapy after serial scans in 5 patients. CONCLUSIONS Our study demonstrates the potential benefits of PET-MRI in the management of children with CNS pathologies. PET-MRI contributes to the diagnosis, monitoring, and treatment guidance of these patients, providing crucial information for clinical decision-making.

  PublisherOA PDFDOI

• Urinary tract infections and catheter-associated urinary tract infections caused by <i>Pseudomonas aeruginosa</i>

  Microbiology and Molecular Biology Reviews · 2024-10-21 · 19 citations

  reviewOpen accessSenior authorCorresponding

  SUMMARY Urinary tract infection (UTI) is one of the most common infections in otherwise healthy individuals. UTI is also common in healthcare settings where patients often require urinary catheters to alleviate urinary retention. The placement of a urinary catheter often leads to catheter-associated urinary tract infection (CAUTI) caused by a broad range of opportunistic pathogens, commonly referred to as ESKAPE ( Enterococcus , Staphylococcus , Klebsiella , Acinetobacter , Pseudomonas , and Enterobacter ) pathogens. Our understanding of CAUTI is complicated by the differences in pathogens, in initial microbial load, changes that occur due to the duration of catheterization, and the relationship between infection (colonization) and disease symptoms. To advance our understanding of CAUTI, we reviewed UTI and CAUTI caused by Pseudomonas aeruginosa which is unique in that it is not commonly found associated with human microbiomes. For this reason, the ability of P. aeruginosa to cause UTI and CAUTI requires the introduction of the bacteria to the bladder from catheterization. Once in the host, the virulence factors used by P. aeruginosa in these infections remain an area of ongoing research. In this review, we will discuss studies that focus on P. aeruginosa UTI and CAUTI to better understand the infection dynamics and outcome in clinical settings, virulence factors associated with P. aeruginosa isolated from the urinary tract, and animal studies to test which bacterial factors are required for this infection. Understanding how P. aeruginosa can cause UTI and CAUTI can provide an understanding of how these infections initiate and progress and may provide possible strategies to limit these infections.

  PublisherOA PDFDOI

• Diribonuclease activity eliminates toxic diribonucleotide accumulation

  Cell Reports · 2024-09-01 · 3 citations

  articleOpen accessSenior author

  <h2>Summary</h2> RNA degradation is a central process required for transcriptional regulation. Eventually, this process degrades diribonucleotides into mononucleotides by specific diribonucleases. In <i>Escherichia coli</i>, oligoribonuclease (Orn) serves this function and is unique as the only essential exoribonuclease. Yet, related organisms, such as <i>Pseudomonas aeruginosa</i>, display a growth defect but are viable without Orn, contesting its essentiality. Here, we take advantage of <i>P</i>. <i>aeruginosa orn</i> mutants to screen for suppressors that restore colony morphology and identified <i>yciV</i>. Purified YciV (RNase AM) exhibits diribonuclease activity. While RNase AM is present in all γ-proteobacteria, phylogenetic analysis reveals differences that map to the active site. RNase AM_Pa expression in <i>E. coli</i> eliminates the necessity of <i>orn</i>. Together, these results show that diribonuclease activity prevents toxic diribonucleotide accumulation in γ-proteobacteria, suggesting that diribonucleotides may be utilized to monitor RNA degradation efficacy. Because higher eukaryotes encode Orn, these observations indicate a conserved mechanism for monitoring RNA degradation.

  PublisherDOI

Recent grants

• NIH Grant K22AI065828

  NIH · $268k · 2009

• NIH Grant R21AI096083

  NIH · $398k · 2014

• NIH Grant F32AI052694

  NIH · $134k · 2005

• Oligoribonuclease regulation of cyclic-di-GMP signaling and chronic biofilm infections

  NIH · $2.9M · 2019–2025

• Training in Host-Pathogen Interactions

  NIH · $1.9M · 2010–2026

Frequent coauthors

• Mona W. Orr

  University of Maryland, College Park

  17 shared

• Asan Turdiev

  University of Maryland, College Park

  14 shared

• Holger Sondermann

  Deutsches Elektronen-Synchrotron DESY

  14 shared

• Soo-Kyoung Kim

  University of Maryland, College Park

  13 shared

• Geoffrey I. McFadden

  University of Melbourne

  12 shared

• Stuart A. Ralph

  University of Melbourne

  12 shared

• Lee M. Yeoh

  University of Melbourne

  12 shared

• Vanessa Mollard

  University of Melbourne

  12 shared

Education

• Ph.D, Microbiology and Immunology

  UCLA

  2001

Awards & honors

• Elected Member, International Statistical Institute, the Net…
• Elected Fellow, Royal Statistical Society, United Kingdom (1…
• Elected Fellow, American Statistical Association, USA (1999)
• Elected Fellow, Institute of Mathematical Statistics, USA (2…
• Mosteller Statistician of the Year, American Statistical Ass…