Yuet-Kin Leung, PhD
University of Arkansas for Medical Sciences
College of Medicine
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.
- Email Address: RICKYLEUNG@UAMS.EDU
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- US Department of Defense – W81XWH2210152“DNA methylation markers associated with exposure ”Co-Investigator05/01/22 – 04/30/26
- NIH/Nat. Inst. of Environmental Health Sciences – 1R01ES032675“RNA modifications by paternal exposure to arsenic ”Principal Investigator04/29/22 – 01/31/27
- 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.
- 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 TGF?R1 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 TGF? 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.
- 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.
- Khanal T, Leung YK, Jiang W, [et al.]. NR2E3 is a key component in p53 activation by regulating a long noncoding RNA DINO in acute liver injuries. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 33(7):8335-8348. PMID: 30991008. PMCID: PMC6593879.
- Langevin SM, Kuhnell D, Niu L, [et al., including Leung YK]. Comprehensive mapping of the methylation landscape of 16 CpG-dense regions in oral and pharyngeal squamous cell carcinoma. Epigenomics. 2019 11(9):987-1002. PMID: 31215230. PMCID: PMC7132784.
- Xie C, Leung YK, Chen A, [et al.]. Differential methylation values in differential methylation analysis. Bioinformatics (Oxford, England). 2019 35(7):1094-1097. PMID: 30184051. PMCID: PMC6449748.
- Dworatzek E, Mahmoodzadeh S, Schriever C, [et al., including Leung YK]. Sex-specific regulation of collagen I and III expression by 17?-Estradiol in cardiac fibroblasts: role of estrogen receptors. Cardiovascular research. 2019 115(2):315-327. PMID: 30016401. PMCID: PMC6933535.
- Leung YK, Chan QK, Ng CF, [et al.]. Correction: Hsa-miRNA-765 as a Key Mediator for Inhibiting Growth, Migration and Invasion in Fulvestrant-Treated Prostate Cancer. PloS one. 2019 14(3):e0214184. PMID: 30883603. PMCID: PMC6422296.
- Leung YK, Ouyang B, Niu L, [et al.]. Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort. Epigenetics. 2018 13(3):290-300. PMID: 29560787. PMCID: PMC5997167.
- Alexander J, Teague AM, Chen J, [et al., including Leung YK]. Offspring sex impacts DNA methylation and gene expression in placentae from women with diabetes during pregnancy. PloS one. 2018 13(2):e0190698. PMID: 29470513. PMCID: PMC5823368.
- Khanal T, Choi K, Leung YK, [et al.]. Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer. Scientific reports. 2017 7(1):10662. PMID: 28878246. PMCID: PMC5587550.
- Chen T, Lu L, Xu C, [et al., including Leung YK]. Inhibition Role of Atherogenic Diet on Ethyl Carbamate Induced Lung Tumorigenesis in C57BL/6J Mice. Scientific reports. 2017 7(1):4723. PMID: 28680122. PMCID: PMC5498653.
- Leung YK, Govindarajah V, Cheong A, [et al.]. Gestational high-fat diet and bisphenol A exposure heightens mammary cancer risk. Endocrine-related cancer. 2017 24(7):365-378. PMID: 28487351. PMCID: PMC5488396.
- Ho SM, Cheong A, Adgent MA, [et al., including Leung YK]. Environmental factors, epigenetics, and developmental origin of reproductive disorders. Reproductive toxicology (Elmsford, N.Y.). 2017 68:85-104. PMID: 27421580. PMCID: PMC5233640.
- Tarapore P, Hennessy M, Song D, [et al., including Leung YK]. High butter-fat diet and bisphenol A additively impair male rat spermatogenesis. Reproductive toxicology (Elmsford, N.Y.). 2017 68:191-199. PMID: 27658648. PMCID: PMC5357593.
- Zhou Z, Kennell C, Leung YK, [et al.]. Calcium phosphate-polymer hybrid nanoparticles for enhanced triple negative breast cancer treatment via co-delivery of paclitaxel and miR-221/222 inhibitors. Nanomedicine : nanotechnology, biology, and medicine. 2017 13(2):403-410. PMID: 27520723.
- Tarapore P, Hennessy M, Song D, [et al., including Leung YK]. Data on spermatogenesis in rat males gestationally exposed to bisphenol A and high fat diets. Data in brief. 2016 9:812-817. PMID: 27872877. PMCID: PMC5107686.
- Xu Z, Taylor JA, Leung YK, [et al.]. oxBS-MLE: an efficient method to estimate 5-methylcytosine and 5-hydroxymethylcytosine in paired bisulfite and oxidative bisulfite treated DNA. Bioinformatics (Oxford, England). 2016 32(23):3667-3669. PMID: 27522082. PMCID: PMC5181539.
- Miller M, Bailey B, Govindarajah V, [et al., including Leung YK]. A community survey on knowledge of the impact of environmental and epigenetic factors on health and disease. Perspectives in public health. 2016 136(6):345-352. PMID: 26941233. PMCID: PMC5367049.
- Cheong A, Zhang X, Cheung YY, [et al., including Leung YK]. DNA methylome changes by estradiol benzoate and bisphenol A links early-life environmental exposures to prostate cancer risk. Epigenetics. 2016 11(9):674-689. PMID: 27415467. PMCID: PMC5048723.
- Rizzardi AE, Zhang X, Vogel RI, [et al., including Leung YK]. Quantitative comparison and reproducibility of pathologist scoring and digital image analysis of estrogen receptor ?2 immunohistochemistry in prostate cancer. Diagnostic pathology. 2016 11(1):63. PMID: 27401406. PMCID: PMC4940862.