About

Dr. Danith H. Ly is a Professor in the Department of Chemistry at Carnegie Mellon University. Born and raised in Cambodia, he completed his Bachelor Degree in Chemical Engineering with a Minor in Philosophy at the Georgia Institute of Technology in 1994. He continued his education at the same institution, earning a Ph.D. in Organic Chemistry in 1998 under the supervision of Professor Gary B. Schuster. Following his doctoral studies, Dr. Ly conducted postdoctoral research at UC Berkeley and the Scripps Research Institute from 1998 to 2001 under the guidance of Professor Peter G. Schultz. In 2001, he joined Carnegie Mellon University as an Assistant Professor in the Department of Chemistry. His academic and professional journey reflects a strong foundation in chemical engineering and organic chemistry, with extensive postdoctoral experience at leading research institutions.

Research topics

• Biology
• Computational biology
• Biochemistry
• Computer Science
• Chemistry
• Nanotechnology
• Combinatorial chemistry
• Materials science
• Data science
• Cell biology
• Biophysics
• Genetics

Selected publications

• A pothole-filling strategy for selective targeting of rCUG-repeats associated with myotonic dystrophy type 1

  Proceedings of the National Academy of Sciences · 2026-01-09

  articleOpen accessSenior author

  We present an alternative approach to conventional small-molecule and antisense strategies for selectively targeting expanded CUG-RNA repeats associated with Myotonic Dystrophy type 1. Our alternatively designed nucleic acid ligands uniquely integrate advantageous features from both existing methods: They are compact (only three units in length), structurally resembling small molecules, yet recognize RNA targets through directional hydrogen-bonding similar to antisense oligonucleotides. Notably, these ligands exhibit greater specificity and selectivity than either approach alone. This enhanced specificity results from their bifacial recognition mechanism, wherein mismatches on one binding interface are reciprocally mirrored on the complementary face. Additionally, their short length significantly amplifies specificity, as even a single mismatch substantially reduces the overall binding free energy, effectively minimizing off-target interactions. Unlike conventional oligonucleotides, these ligands avoid binding single-stranded RNA and only recognize defined hairpin motifs via a "pothole-filling" mechanism. This method amplifies recognition specificity and selectivity, circumventing the thermodynamic penalties associated with RNA unfolding. This proof-of-concept study thus lays a foundation for developing versatile nucleic acid ligands capable of selectively targeting not only pathogenic CUG-RNA repeats in Myotonic Dystrophy type 1 but also other disease-associated triplet-repeat expansions prevalent in various neuromuscular disorders.

  PublisherDOI

• Self-Avoiding Gamma Peptide Nucleic Acids for Selective Targeting of RNA Secondary Structures

  ACS Chemical Biology · 2026-03-17

  articleOpen accessSenior authorCorresponding

  RNA molecules play essential roles in all aspects of cellular function, but their complex secondary and tertiary structures pose significant challenges for selective targeting. Traditional antisense strategies often avoid these structured regions, focused instead on unstructured sequences. In this study, we present an enhanced Self-Avoiding Molecular Recognition System designed to selectively recognize and bind structured RNA elements, offering an alternative approach for targeting biologically relevant RNA conformations with improved specificity and selectivity. This is achieved by incorporating established self-avoidance nucleobases (t and c) along with a deazapurine series (a and g)─designed to provide greater flexibility in fine-tuning binding affinity─into a conformationally preorganized gamma peptide nucleic acid backbone. Despite possessing self-complementary arms (b and b’), the system resists self-hybridization and selectively binds to the intended stem-loop RNA target (bcb’). Thermal stability measurements, electrophoretic mobility assays, and mismatch specificity analyses confirm the effectiveness of this approach, offering a general strategy for targeting structured RNA with precision.

  PublisherDOI

• The CRP-to-Uric Acid Index (CURI): A Novel Inflammatory–Metabolic Index to Enhance Noninvasive Screening for MASLD and Liver Fibrosis

  medRxiv · 2025-09-02

  preprintOpen access

  Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) and significant liver fibrosis (SLF) require noninvasive screening. This study evaluates the C-reactive protein-to-uric acid index (CURI), combining inflammation and metabolic dysfunction, as a biomarker for early detection of MASLD and SLF. Methods Using NHANES 2017–2020 data (n=6,687), participants were divided into training and validation cohorts. CURI was calculated as high-sensitivity C-reactive protein (hs-CRP; mg/L) × [uric acid (mg/dL)] 3 . Associations with MASLD and SLF were analyzed via logistic regression, restricted cubic splines, and mediation analysis considering insulin resistance and adipose indices. Diagnostic performance was evaluated using the area under the curve (AUC), decision curve analysis (DCA), comparing CURI with established indices: fatty liver index (FLI), hepatic steatosis index (HSI), and fibrosis-4 (FIB-4). Results MASLD and SLF prevalence were 49.6% and 10.7%, respectively. CURI was independently associated with MASLD and SLF. Nonlinear relationships were observed. Combining CURI with FLI, HSI, or FIB-4 improved diagnostic performance compared to using them alone (AUC for MASLD: 0.852 with FLI, 0.819 with HSI, 0.690 with FIB-4; AUC for SLF: 0.811 with FLI, 0.750 with HSI, 0.699 with FIB-4, p<0.001). DCA showed net benefit for MASLD. Mediation analysis show 98.1% (MASLD) and 84.8% (SLF) of effects. Conclusion CURI is a promising, cost-effective biomarker for MASLD/SLF risk stratification. Highlights WHAT IS KNOWN MASLD and SLF require noninvasive screening. Existing methods like liver biopsy are invasive. Indices like FLI, HSI, and FIB-4 are commonly used for screening. WHAT IS NEW HERE CURI is a novel biomarker combining inflammation and metabolic dysfunction for screening. CURI is independently associated with MASLD and SLF. CURI enhances prediction when combined with FLI or HSI. Insulin resistance mediates most of CURI effect on MASLD and SLF. CURI is a cost-effective tool for risk stratification in resource-limited settings.

  PublisherOA PDFDOI

• Synthesis of Janus Bases for Targeting C-G and U–U Pairs of CUG-RNA Repeats Associated with Myotonic Dystrophy Type 1

  ACS Omega · 2025-10-06 · 1 citations

  articleOpen accessSenior authorCorresponding

  We report the synthesis of bifacial Janus bases E and K, along with their corresponding γ peptide nucleic acid monomers, designed to recognize C-G and U-U pairs within CUG-RNA repeats implicated in Myotonic Dystrophy Type 1. This study establishes the foundation for a fully programmable system of 16 Janus bases capable of recognizing all possible RNA base-pairsboth canonical and noncanonicalallowing precise manipulation of RNA structure and function. Importantly, beyond targeting CUG-repeats, this system holds a potential promise for addressing other triplet repeat expansions linked to over 35 neuromuscular and neurodegenerative disorders, thereby opening up new avenues for therapeutic intervention.

  PublisherDOI

• Feasibility analysis of geriatric assessment and remote symptom monitoring in older men with advanced prostate cancer on androgen receptor pathway inhibitor

  Journal of Geriatric Oncology · 2025-11-01

  article
  PublisherDOI

• Supplementary Figure 1 from First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy

  2023-04-03

  preprintOpen access

  <p>PDF file - 70K, Lack of anti-tumor effects of systemically administered parental STAT3 decoy</p>

  PublisherOA PDFDOI

• Supplementary Table 2 from First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy

  2023-04-03

  supplementary-materialsOpen access

  <p>PDF file - 165K, EC50 values of STAT3 decoy in cancer cell lines</p>

  PublisherOA PDFDOI

• Supplementary Table 1 from First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy

  2023-04-03

  supplementary-materialsOpen access

  <p>PDF file - 23K, Quantitative determination of the binding affinities of the parent and modified STAT3 decoys</p>

  PublisherOA PDFDOI

• Data from First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy

  2023-04-03

  preprintOpen access

  <div>Abstract<p>Despite evidence implicating transcription factors, including STAT3, in oncogenesis, these proteins have been regarded as “undruggable.” We developed a decoy targeting STAT3 and conducted a phase 0 trial. Expression levels of STAT3 target genes were decreased in head and neck cancers following injection with the STAT3 decoy compared with tumors receiving saline control. Decoys have not been amenable to systemic administration due to instability. To overcome this barrier, we linked the oligonucleotide strands using hexaethylene glycol spacers. This cyclic STAT3 decoy bound with high affinity to STAT3 protein, reduced cellular viability, and suppressed STAT3 target gene expression in cancer cells. Intravenous injection of the cyclic STAT3 decoy inhibited xenograft growth and downregulated STAT3 target genes in the tumors. These results provide the first demonstration of a successful strategy to inhibit tumor STAT3 signaling via systemic administration of a selective STAT3 inhibitor, thereby paving the way for broad clinical development.</p><p><b>Significance:</b> This is the first study of a STAT3-selective inhibitor in humans and the first evidence that a transcription factor decoy can be modified to enable systemic delivery. These findings have therapeutic implications beyond STAT3 to other “undruggable” targets in human cancers. <i>Cancer Discov; 2(8); 694–705. ©2012 AACR.</i></p><p>Read the Commentary on this article by Koppikar et al., p. 670.</p><p>This article is highlighted in the In This Issue feature, p. 653.</p></div>

  PublisherDOI

• Supplementary Figure 7 from First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy

  2023-04-03

  preprintOpen access

  <p>PDF file - 107K, Systemic delivery of cyclic STAT3 decoy does not affect total or pSTAT3 expression levels</p>

  PublisherDOI

Recent grants

• Development of JB Recognition Codes for Manipulation of RNA Structures and Functions

  NSF · $540k · 2016–2020

• NIH Grant R01GM077261

  NIH · $1.1M · 2012

• A Rational Approach to Targeting Unstable RNA Repeats

  NIH · $425k · 2017–2020

• Development of Nucleic Acid Platform for Targeting DNA

  NSF · $525k · 2010–2013

Frequent coauthors

• Srinivas Rapireddy

  55 shared

• Joanne I. Yeh

  36 shared

• Sufi M. Thomas

  University of Kansas Medical Center

  35 shared

• Sonali Joyce

  University of Pittsburgh Medical Center

  29 shared

• Jennifer R. Grandis

  29 shared

• Bruce A. Armitage

  Carnegie Mellon University

  29 shared

• Malabika Sen

  28 shared

• Simion I. Chiosea

  University of Pittsburgh Medical Center

  28 shared

Labs

• Ly GroupPI

Education

• Ph.D.

  Georgia Institute of Technology

  1999

• Other

  University of California at Berkeley

  2000

• Other

  The Scripps Research Institute

  2001

Awards & honors

• Julius Ashkin Teaching Award, Mellon College of Science (201…
• Innovative Research Award (2002)
• The Berkman Faculty Development Award (2002)
• Cosmetic Society for Chemists Aging Research Breakthrough of…
• National Institute of Aging Emerging Researcher (2000)