Yuet-Kin Leung, PhD

Research Program: Cancer Biology Faculty Rank: Associate Professor Campus: University of Arkansas for Medical Sciences College: College of Medicine Department: Pharmacology & Toxicology

Cancer Research Interest

• Disease Site Focus: Gynecology, Prostate
• Research Focus Area: Informatics, Carcinogenesis
• Type of Research: Basic
• Research Interest Statement: My research has been focused on understanding gene dysregulation in hormone-related cancers, topics ranging from epigenetic gene regulation to post-transcriptional spliced variant expression. Normal cells would not spontaneously turn into cancer cells without external stimuli/triggers. Using rodent models, we identified a class of endocrine disrupting chemicals that reprogram transcriptomeMember Application Question Response via epigenetic mechanisms at specific windows of exposure (e.g. prenatal, neonatal and pubertal period). Cancer cells may take advantage of the epigenetic control to re-wire all necessary gene networks and pathways to survive. Our laboratory has been working on dissecting the relationship between DNA methylation as well as non-coding RNAs and cis-acting elements during gene transcription using global and gene-specific approaches. Besides, cancer cells could express protein decoy or isoforms with novel functions to facilitate cancer progression. We were one of the first groups to identify a novel CYP1A1 spliced variant that could augment oxidative stress and promote progression of ovarian cancer cells. We also revealed estrogen receptor beta isoforms may act as protein decoys to negate the tumor suppressive function of the wild type receptor during prostate carcinogenesis.

Contact Information

• Email Address: RICKYLEUNG@UAMS.EDU
• Profiles Research Networking Software: View Profile

Active Grants

• National Science Foundation – Contract # AWD30000-260
  “RII Track-2 FEC: Facilitating Ubiquitous Technology Utilizing Resilient Eco-friendly Sensors (FUTURE Sensors)”
  Co-Investigator
  8/1/2022 – 7/31/2028

Recent Publications

• Leung YK, Lee SG, Wang J, [et al.]. The Loss of an Orphan Nuclear Receptor NR2E3 Augments Wnt/β-catenin Signaling via Epigenetic Dysregulation that Enhances Sp1-β catenin-p300 Interactions in Hepatocellular Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2024 11(29):e2308539. PMID: 38790135. PMCID: PMC11304255.
• Shahror RA, Shosha E, Ji MH, [et al., including Leung YK]. Proteomic Analysis of Aqueous Humor in Central Retinal Artery Occlusion: Unveiling Novel Insights Into Disease Pathophysiology. Translational vision science & technology. 2024 13(8):30. PMID: 39163016. PMCID: PMC11343007.
• Cortes-Ramirez SA, Ho SM, Leung YK. Endocrine-Disrupting Chemicals: A Looming Threat to Current and Future Generations. International journal of molecular sciences. 2024 25(15). PMID: 39125790. PMCID: PMC11311772.
• Puvvula J, Braun JM, DeFranco EA, [et al., including Leung YK]. Gestational exposure to environmental chemicals and epigenetic alterations in the placenta and cord blood mononuclear cells. Epigenetics communications. 2024 4(1):4. PMID: 38962689. PMCID: PMC11217138.
• Puvvula J, Manz KE, Braun JM, [et al., including Leung YK]. Maternal and newborn metabolomic changes associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations at delivery: an untargeted approach. Metabolomics : Official journal of the Metabolomic Society. 2023 20(1):6. PMID: 38095785.
• Wang X, DeFilippis RA, Weldemichael T, [et al., including Leung YK]. An imidazo[1,2-a]pyridine-pyridine derivative potently inhibits FLT3-ITD and FLT3-ITD secondary mutants, including gilteritinib-resistant FLT3-ITD/F691L. European journal of medicinal chemistry. 2023 264:115977. PMID: 38056299. PMCID: PMC11590664.
• Tu SM, Chen JZ, Singh SR, [et al., including Leung YK]. Stem Cell Theory of Cancer: Clinical Implications of Epigenomic versus Genomic Biomarkers in Cancer Care. Cancers. 2023 15(23). PMID: 38067237. PMCID: PMC10705798.
• Wang X, DeFilippis RA, Leung YK, [et al.]. N-(3-Methoxyphenyl)-6-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl)pyridin-2-amine is an inhibitor of the FLT3-ITD and BCR-ABL pathways, and potently inhibits FLT3-ITD/D835Y and FLT3-ITD/F691L secondary mutants. Bioorganic chemistry. 2023 143:106966. PMID: 37995643. PMCID: PMC11586108.
• Leung YK. A Silent Threat: Exploring the Impact of Endocrine Disruption on Human Health. International journal of molecular sciences. 2023 24(12). PMID: 37372939. PMCID: PMC10298293.
• Zhang L, Moccia M, Briggs DC, [et al., including Leung YK]. Discovery of N-Trisubstituted Pyrimidine Derivatives as Type I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose. Journal of medicinal chemistry. 2022 65(2):1536-1551. PMID: 35081714. PMCID: PMC10536133.
• McDermott A, Kim K, Kasper S, [et al., including Leung YK]. The androgen receptor inhibits transcription of GPER1 by preventing Sp1 and Sp3 from binding to the promoters in prostate cancer cells. Oncotarget. 2022 13:46-60. PMID: 35018219. PMCID: PMC8741193.
• Ho SM, Rao R, Ouyang B, [et al., including Leung YK]. Three-Generation Study of Male Rats Gestationally Exposed to High Butterfat and Bisphenol A: Impaired Spermatogenesis, Penetrance with Reduced Severity. Nutrients. 2021 13(10). PMID: 34684636. PMCID: PMC8541510.
• Zhang L, Lakkaniga NR, Bharate JB, [et al., including Leung YK]. Discovery of imidazo[1,2-a]pyridine-thiophene derivatives as FLT3 and FLT3 mutants inhibitors for acute myeloid leukemia through structure-based optimization of an NEK2 inhibitor. European journal of medicinal chemistry. 2021 225:113776. PMID: 34479037. PMCID: PMC8585723.
• Kharbanda A, Tran P, Zhang L, [et al., including Leung YK]. Discovery of 4-aminoquinolines as highly selective TGFβR1 inhibitors with an attenuated MAP4K4 profile for potential applications in immuno-oncology. European journal of medicinal chemistry. 2021 225:113763. PMID: 34419892.
• Kharbanda A, Zhang L, Saha D, [et al., including Leung YK]. Discovery and biological evaluation of phthalazines as novel non-kinase TGFβ pathway inhibitors. European journal of medicinal chemistry. 2021 223:113660. PMID: 34246853. PMCID: PMC9472513.
• Padala KP, Padala PR, Leung YK, [et al.]. Untangling the Complex Interactions of Open Burn Pit Exposure and Health Outcomes: Response to Brumage et al. The primary care companion for CNS disorders. 2021 23(2). PMID: 34000124.
• Leung YK, Biesiada J, Govindarajah V, [et al.]. Low-Dose Bisphenol A in a Rat Model of Endometrial Cancer: A CLARITY-BPA Study. Environmental health perspectives. 2020 128(12):127005. PMID: 33296240. PMCID: PMC7725436.
• Padala KP, Padala PR, Leung YK, [et al.]. Open Burn Pit Exposure and Concern About the COVID-19 Pandemic. The primary care companion for CNS disorders. 2020 22(6). PMID: 33166097.
• Lakkaniga NR, Gunaganti N, Zhang L, [et al., including Leung YK]. Pyrrolo[2,3-d]pyrimidine derivatives as inhibitors of RET: Design, synthesis and biological evaluation. European journal of medicinal chemistry. 2020 206:112691. PMID: 32823007. PMCID: PMC10536156.
• Wongsurawat T, Jenjaroenpun P, De Loose A, [et al., including Leung YK]. A novel Cas9-targeted long-read assay for simultaneous detection of IDH1/2 mutations and clinically relevant MGMT methylation in fresh biopsies of diffuse glioma. Acta neuropathologica communications. 2020 8(1):87. PMID: 32563269. PMCID: PMC7305623.
• Liu X, Zhang E, Kopras EJ, [et al., including Leung YK]. Estrogen activates pyruvate kinase M2 and increases the growth of TSC2-deficient cells. PloS one. 2020 15(2):e0228894. PMID: 32078667. PMCID: PMC7032738.