Doctor of Philosophy, University of Houston, Pharmacological and Pharmaceutical Sciences (2021)
Master of Science, North Dakota State Univ, Ag & Appl Sci (2015)
Bachelor of Science, North Dakota State Univ, Ag & Appl Sci (2012)
Michael Lim, Postdoctoral Faculty Sponsor
Bin Guo, Gomika Udugamasooriya, Satya Prakash Shukla, Kwang Bog Cho, Shuang Zhou. " Patent Serial No. PCT/US2020/40324 Inhibitors of IL-15 and their use in treating autoimmune/inflammatory disorders"
Gomika Udugamasooriya, Bin Guo, Satya Prakash Shukla, Kwang Bog Cho. " Patent Serial No. PCT/US2021/26218 Novel peptoid compounds that bind to cell receptor ACE2 and prevent virus entry into cells"
Bin Guo, Gomika Udugamasooriya, Xinli Liu, Satya Prakash Shukla, Kwang Bog Cho, Xue Zhou. " Patent Serial No. PCT/US2021/38408 Compounds for Drug Delivery Across Blood-Brain Barrier"
A peptoid interleukin-15 receptor antagonist suppresses inflammation and arthritis in mice.
Clinical & translational immunology
2022; 11 (11): e1432
To discover a novel peptoid antagonist that targets the interleukin-15 (IL-15) receptor and to evaluate its therapeutic efficacy in the treatment of inflammation and arthritis.A new compound (IFRA3, interleukin-15 receptor antagonist 3) was discovered using a unique on-bead two-colour combinatorial cell screening of a peptoid library. The interaction of IFRA3 with IL-15 receptor was assessed by in vitro pull-down and thermal shift assays. The efficacy of IFRA3 in treating inflammation and arthritis was evaluated in mouse models.IFRA3Q1 (a tetrameric derivative of IFRA3) inhibited the activity of IL-15 and suppressed CTLL-2 cell proliferation (which depends on IL-15 activity). IFRA3Q1 exhibited strong in vivo anti-inflammatory activity in carrageenan-induced inflammation in mice. Furthermore, IFRA3Q1 inhibited collagen-induced arthritis in DBA/1J mice.By binding to and inhibiting the function of IL-15 receptor, IFRA3Q1 exhibited significant anti-arthritis activity. Our findings suggest that IFRA3Q1 represents a new paradigm for arthritis therapy by targeting IL-15 signalling.
View details for DOI 10.1002/cti2.1432
View details for PubMedID 36439637
View details for PubMedCentralID PMC9686008
- Inhibitors of il-15 and their use in treating autoimmune/inflammatory disorders US Patent App. 17/624,523, US 2022/0242907 A1 . 2022
"Molecular Masks" for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2021; 22 (16)
Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor angiotensin-converting enzyme 2 (ACE2), which allows the virus to enter the human body. Using our unique cell screening technology, we identified two ACE2-binding peptoid compounds and developed dimeric derivatives (ACE2P1D1 and ACE2P2D1) that effectively blocked spike protein-ACE2 interaction, resulting in the inhibition of SARS-CoV-2 pseudovirus entry into human cells. ACE2P1D1 and ACE2P2D1 also blocked infection by a D614G mutant pseudovirus. More importantly, these compounds do not decrease ACE2 expression nor its enzyme activity (which is important in normal blood pressure regulation), suggesting safe applicability in humans.
View details for DOI 10.3390/ijms22168963
View details for Web of Science ID 000689201200001
View details for PubMedID 34445669
View details for PubMedCentralID PMC8396575
A CRISPR-Cas9 repressor for epigenetic silencing of KRAS
2021; 164: 105304
KRAS is one of the most frequently mutated oncogenes in cancers. Currently no direct and effective anti-KRAS therapies are available. Using the powerful CRISPR-Cas9 technology to target the mutant KRAS promoter, we designed an epigenetic repressor to silence KRAS through epigenome editing. Catalytically dead Cas9 (dCas9) functioned as a DNA binding device, which was fused with a transcriptional repressor histone deacetylase 1 (HDAC1). We designed a panel of three CRISPR RNAs (crRNAs) covering 1500-bp range of the KRAS promoter and identified that crRNA1 and crRNA2 efficiently silenced KRAS. The suppression of K-Ras resulted in a significant inhibition of cell growth, suppression of colony formation in soft agar and induction of cell death in cancer cells with KRAS mutations. In addition, the chromatin immunoprecipitation (ChIP) assay demonstrated dCas9-HDAC1 modified histone acetylation on the KRAS promoter. Furthermore, transfection of dCas9-HDAC1 protein and gRNA ribonucleoprotein complex also inhibited K-Ras and suppressed cell proliferation. In summary, we have developed a new strategy that combines CRISPR-Cas9 technology with HDAC1 epigenetic silencing to target cancers driven by KRAS mutations.
View details for DOI 10.1016/j.phrs.2020.105304
View details for Web of Science ID 000615153300004
View details for PubMedID 33202255
View details for PubMedCentralID PMC8422974
Chemopreventive Agent 3,3 '-Diindolylmethane Inhibits MDM2 in Colorectal Cancer Cells
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2020; 21 (13)
3,3'-Diindolylmethane (DIM) is a naturally derived chemopreventive compound. It comes from glucobrassicin, an indole glucosinolate enriched in cruciferous vegetables, and is formed in the acidic environment of the stomach after ingestion. Mouse double minute 2 homolog (MDM2) is an important, multi-functional oncogenic protein and it has been well recognized for its negative regulation of the tumor suppressor protein p53. We discovered a novel mechanism of action of DIM, that it directly inhibits MDM2 in multiple colorectal cancer (CRC) cell lines. Treatment with DIM decreased MDM2 at messenger RNA (mRNA) and protein levels, inhibited cancer cell proliferation, and induced cell cycle arrest and apoptosis. DIM-induced decrease of MDM2 is p53-independent and is partly mediated by proteasome degradation of MDM2, as blocking of the proteasome activity reversed MDM2 protein inhibition. Overexpression of MDM2 blocked DIM's effects in growth suppression and apoptosis induction. When combined with imidazoline MDM2 inhibitors (Nutlin-3a and Idasanutlin/RG-7388), synergism was observed in cancer cell growth inhibition. In summary, our data support a new mechanism of action for DIM in direct inhibition of MDM2. The identification of MDM2 as a novel DIM target may help develop a new strategy in CRC prevention.
View details for DOI 10.3390/ijms21134642
View details for Web of Science ID 000550262200001
View details for PubMedID 32629830
View details for PubMedCentralID PMC7370074
Long Noncoding RNA (lncRNA)-Mediated Competing Endogenous RNA Networks Provide Novel Potential Biomarkers and Therapeutic Targets for Colorectal Cancer
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2019; 20 (22)
Colorectal cancer (CRC) is the third most common cancer and has a high metastasis and reoccurrence rate. Long noncoding RNAs (lncRNAs) play an important role in CRC growth and metastasis. Recent studies revealed that lncRNAs participate in CRC progression by coordinating with microRNAs (miRNAs) and protein-coding mRNAs. LncRNAs function as competitive endogenous RNAs (ceRNAs) by competitively occupying the shared binding sequences of miRNAs, thus sequestering the miRNAs and changing the expression of their downstream target genes. Such ceRNA networks formed by lncRNA/miRNA/mRNA interactions have been found in a broad spectrum of biological processes in CRC, including liver metastasis, epithelial to mesenchymal transition (EMT), inflammation formation, and chemo-/radioresistance. In this review, we summarize typical paradigms of lncRNA-associated ceRNA networks, which are involved in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the competitive crosstalk among RNA transcripts and the novel targets for CRC prognosis and therapy.
View details for DOI 10.3390/ijms20225758
View details for Web of Science ID 000502786800240
View details for PubMedID 31744051
View details for PubMedCentralID PMC6888455
Suppression of Mammary Carcinogenesis Through Early Exposure to Dietary Lipotropes Occurs Primarily In Utero
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
2015; 67 (8): 1276-1282
The study determined whether feeding during lactation affects the suppressive effect of maternal dietary lipotropes (i.e., methionine, choline, folate, and vitamin B12) on mammary carcinogenesis. Pregnant Sprague-Dawley rats were randomly allocated to the control diet during pregnancy and lactation (CC), lipotropes-fortified diet during pregnancy (LC), lipotropes-fortified diet during pregnancy plus lactation (LL), or lipotropes-fortified diet during lactation (CL). Randomly selected female offspring from each group were injected intraperitoneally with 50 mg/kg body weight of N-nitroso-N-methylurea at 50 days of age to induce mammary tumors. The LC and LL diets significantly increased tumor latency and survival (P < 0.05). Tumor volumes were significantly suppressed in LC and LL offspring as compared with the CC and CL pups (3759.1 ± 563.0 and 3603.7 ± 526.1 vs. 7465.0 ± 941.1 and 5219.3 ± 759.8 mm(3), respectively; P < 0.05). Both LC and LL lowered tumor multiplicity as compared with CC and CL (P < 0.05). The LC and LL diets repressed transcription of histone deacetylase (HDAC) 1 as well as total HDAC enzyme activity as compared with CC and CL diets (P < 0.05). Data suggest that the tumor suppressive effect of maternal dietary lipotropes is primarily in utero and may be linked to regulation of proteins involved in chromatin remodeling.
View details for DOI 10.1080/01635581.2015.1087039
View details for Web of Science ID 000365670700010
View details for PubMedID 26474214
In utero exposure to dietary lipotropes affects DNA methylation and gene expression in mammary glands of offspring
FEDERATION AMER SOC EXP BIOL. 2014
View details for Web of Science ID 000346651000229