Jia Yi Fong

National University of Singapore

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Diana Low

Institute of Molecular and Cell Biology

Cheryl M. Koh

APA Corporation (United States)

Ernesto Guccione

Icahn School of Medicine at Mount Sinai

Heike Wollmann

Agency for Science, Technology and Research

Cheng Mun Wun

Peter MacCallum Cancer Centre

Yudao Shen

Shanghai Jiao Tong University

Luca Pignata

University of Naples Federico II

Tiziana Bonaldi

European Institute of Oncology

Jerald Yoo

Seoul National University

Ari Melnick

Cornell University

Cooperative Institutions

Agency for Science, Technology and Research

National University of Singapore

Institute of Molecular and Cell Biology

Experimental Drug Development Centre

Icahn School of Medicine at Mount Sinai

National University Cancer Institute, Singapore

University of Toronto

Memorial Sloan Kettering Cancer Center

Duke-NUS Medical School

Princess Margaret Cancer Centre

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A 1.96Vpp Input-Range 3rd-order Noise-Shaping Pipelined-SAR ADC with Self-Boosted Impedance and Active Charge Sharing for Biosignal Acquisition

2022 IEEE Asian Solid-State Circuits Conference (A-SSCC) (2024)

Rucheng Jiang Chne-Wuen Tsai Bo Yin Jia Yi Fong Jerald Yoo

Biosignal

Successive approximation ADC

10.1109/a-sscc60305.2024.10848701

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A head-to-head comparison of the inhibitory activities of 15 peptidomimetic SARS-CoV-2 3CLpro inhibitors

Bioorganic & Medicinal Chemistry Letters (2021)

Subramanyam Vankadara Yun Xuan Wong Bo Liu Yi Yang See Li Tan

Peptidomimetic

10.1016/j.bmcl.2021.128263

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Citations (27)

Abstract 4731: Therapeutic targeting of RNA splicing through inhibition of protein arginine methylation

Experimental and Molecular Therapeutics (2019)

Jia Yi Fong Diana Low Luca Pignata Kimihito C. Kawabata Stanley Chun-Wei Lee

Mutations in RNA splicing factors commonly occur in myeloid leukemia and solid tumors. These mutations occur in a heterozygous manner and confer dependency on the wild-type allele. Studies have shown that splicing factor mutant cancers are vulnerable to further perturbation of splicing, by pharmacological intervention that directly targets core splicing factors. Our project identifies the use of PRMT inhibitors, as plausible alternative therapeutic strategy to treat spliceosomal mutant leukemia. The data show that splicing factor mutant leukemia exhibit greater sensitivity to the use of inhibitors against Type I PRMTs and PRMT5, in comparison to their wild-type counterparts. As the need for new therapeutic strategies in cancer treatment increases, this study identifies PRMT inhibitors as a potential therapeutic intervention against cancers with splicing factor mutations.Citation Format: Jia Yi Fong, Diana Low, Luca Pignata, Kimihito Cojin Kawabata, Stanley CW Lee, Cheryl Koh, Daniele Musiani, Enrico Massignani, Cheng Mun Wun, Pierre-Alexis V. Goy, Yudao Shen, Heike Wollmann, Florence PH Gay, Genna Luciani, Dalia Barsyte, Jian Jin, Ari M. Melnick, Tiziana Bonaldi, Omar Abdel-Wahab, Ernesto Guccione. Therapeutic targeting of RNA splicing through inhibition of protein arginine methylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4731.

Splicing factor

Wild type

10.1158/1538-7445.sabcs18-4731

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Biomedical System-on-Chip Design with Integrated Body-Coupled Powering

2022 IEEE Biomedical Circuits and Systems Conference (BioCAS) (2023)

Ying‐Jie Zhu Jia Yi Fong Longyang Lin Jerald Yoo Jiamin Li

Capacitive Body-Coupled Powering (BCP) has been demonstrated as an effective power delivery solution for wearable biomedical system-on-chips (SoC), thanks to its improved path loss compared to the RF-based transmission in the body area, and its insusceptibility to the body shadowing effect. Integrating BCP with biomedical SoCs could unlock potentials for a power-sustainable and long-lasting system design. In this paper, starting from the motivation for BCP, we will identify the challenges in the integration of BCP with other building blocks of the SoC (e.g., sensing front-end, transceiver). After reviewing and analyzing the existing techniques for BCP and a BCP-compatible SoC design, the design considerations and optimizations will be discussed.

Transceiver

10.1109/biocas58349.2023.10388567

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Abstract 4731: Therapeutic targeting of RNA splicing through inhibition of protein arginine methylation

Cancer Research (2019)

Jia Yi Fong Diana Low Luca Pignata Kimihito C. Kawabata Stanley CW Lee

Abstract Mutations in RNA splicing factors commonly occur in myeloid leukemia and solid tumors. These mutations occur in a heterozygous manner and confer dependency on the wild-type allele. Studies have shown that splicing factor mutant cancers are vulnerable to further perturbation of splicing, by pharmacological intervention that directly targets core splicing factors. Our project identifies the use of PRMT inhibitors, as plausible alternative therapeutic strategy to treat spliceosomal mutant leukemia. The data show that splicing factor mutant leukemia exhibit greater sensitivity to the use of inhibitors against Type I PRMTs and PRMT5, in comparison to their wild-type counterparts. As the need for new therapeutic strategies in cancer treatment increases, this study identifies PRMT inhibitors as a potential therapeutic intervention against cancers with splicing factor mutations. Citation Format: Jia Yi Fong, Diana Low, Luca Pignata, Kimihito Cojin Kawabata, Stanley CW Lee, Cheryl Koh, Daniele Musiani, Enrico Massignani, Cheng Mun Wun, Pierre-Alexis V. Goy, Yudao Shen, Heike Wollmann, Florence PH Gay, Genna Luciani, Dalia Barsyte, Jian Jin, Ari M. Melnick, Tiziana Bonaldi, Omar Abdel-Wahab, Ernesto Guccione. Therapeutic targeting of RNA splicing through inhibition of protein arginine methylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4731.

Splicing factor

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SR protein

10.1158/1538-7445.am2019-4731

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A Warhead Substitution Study on the Coronavirus Main Protease Inhibitor Nirmatrelvir

ACS Medicinal Chemistry Letters (2022)

Subramanyam Vankadara Monique Danielle Dawson Jia Yi Fong Qin Yao Oh Qi An Ang

The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antiviral activities against human alphacoronavirus 229E was also investigated along with a cell-based assay. We discovered that the hydroxymethylketone and ketobenzothiazole warheads were equipotent to the nitrile warhead, suggesting that these analogs can also be used for treating coronavirus infections.

Warhead

Vero cell

Protease inhibitor (pharmacology)

Coronavirus

10.1021/acsmedchemlett.2c00260

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Citations (27)

PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis

Nature Communications (2020)

Slim Mzoughi Jia Yi Fong David Papadopoli Cheryl M. Koh Laura Hulea

Abstract PRDM (PRDI-BF1 and RIZ homology domain containing) family members are sequence-specific transcriptional regulators involved in cell identity and fate determination, often dysregulated in cancer. The PRDM15 gene is of particular interest, given its low expression in adult tissues and its overexpression in B-cell lymphomas. Despite its well characterized role in stem cell biology and during early development, the role of PRDM15 in cancer remains obscure. Herein, we demonstrate that while PRDM15 is largely dispensable for mouse adult somatic cell homeostasis in vivo, it plays a critical role in B-cell lymphomagenesis. Mechanistically, PRDM15 regulates a transcriptional program that sustains the activity of the PI3K/AKT/mTOR pathway and glycolysis in B-cell lymphomas. Abrogation of PRDM15 induces a metabolic crisis and selective death of lymphoma cells. Collectively, our data demonstrate that PRDM15 fuels the metabolic requirement of B-cell lymphomas and validate it as an attractive and previously unrecognized target in oncology.

Cell metabolism

10.1038/s41467-020-17064-0

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Citations (29)

Elucidating host cell response pathways and repurposing therapeutics for SARS-CoV-2 and other coronaviruses

Scientific Reports (2022)

Zhewei Shen Anna Halberg Jia Yi Fong Jingyu Guo Gavin Song

Abstract COVID-19, first reported in late 2019, is an ongoing pandemic that has been causing devastation across the globe. Although there are multiple vaccines that can prevent severe symptoms, effective COVID-19 therapeutics are still of importance. Using our proprietary in silico engine, we screened more than 22,000 unique compounds represented by over half a million gene expression profiles to uncover compounds that can be repurposed for SARS-CoV-2 and other coronaviruses in a timely and cost-efficient manner. We then tested 13 compounds in vitro and found three with potency against SARS-CoV-2 with reasonable cytotoxicity. Bortezomib and homoharringtonine are some of the most promising hits with IC 50 of 1.39 μM and 0.16 μM, respectively for SARS-CoV-2. Tanespimycin and homoharringtonine were effective against the common cold coronaviruses. In-depth analysis highlighted proteasome, ribosome, and heat shock pathways as key targets in modulating host responses during viral infection. Further studies of these pathways and compounds have provided novel and impactful insights into SARS-CoV-2 biology and host responses that could be further leveraged for COVID-19 therapeutics development.

Homoharringtonine

Repurposing

Coronavirus

Drug repositioning

Eosinopenia

10.1038/s41598-022-21984-w

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Citations (5)

Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation

Cancer Cell (2019)

Jia Yi Fong Luca Pignata Pierre-Alexis Goy Kimihito C. Kawabata Stanley Chun-Wei Lee

10.1016/j.ccell.2019.07.003

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Citations (229)

Concurrent Body-Coupled Powering and Communication ICs With a Single Electrode

IEEE Journal of Solid-State Circuits (2024)

Jiamin Li Yilong Dong Longyang Lin Joanne Si Ying Tan Jia Yi Fong

Body-coupled powering (BCP) and body-coupled communication (BCC) utilize the human body channel as the wireless transmission medium, which shows less path loss around the body area. However, integrating both BCP and BCC requires multiple electrodes or alternating the uplink and downlink in the time domain, due to signal interferences and backflow between different paths. To address this issue, we propose a base station (BS) IC and a sensor node (SN) IC with BCP and BCC concurrency. At the BS, the adaptive self-interference cancellation (SI-C) structure suppresses the output signals that are coupled at the data receiver, enabling the concurrent uplink data recovery and downlink power delivery. At the SN, the ground domain of the uplink data path is separated from that of the downlink power/data path to suppress leakage between the paths. For regulated power supply in different ground domains, the cross-ground-domain power converter is designed with 89.1% efficiency. The ICs are implemented in a 40-nm 1P8M standard CMOS process, and BCC

$+$

BCP concurrent operations are successfully validated.

10.1109/jssc.2024.3353386

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