Tons of damages from various sources hampering DNA every day and therefore repairing DNA damages is the fundamental mechanism for the adequate maintenance of genome stability. We are interested in understanding the DNA repair mechanism in the germline. We have focused on investigating the epigenetic regulation of DNA damage response and repair. This includes the role of conserved Epigenetic regulators in DNA damage repair and the role of novel genes of DNA repair and damage response. Students interested in working in Genetics or Molecular biology in my lab, send an E-mail to me.
News
Torenia sp. extracts contain multiple potent antitumor compounds with nematocidal activity, triggering an activated DNA damage checkpoint and defective meiotic progression
Qinghao Meng, Robert P. Borris and Hyun-Min Kim*
Pharmaceuticals (impact factor 4.9), 2024, 17(5), 611; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11124231/.
Abstract
Previously, we analyzed 316 herbal extracts to evaluate their potential nematocidal properties in Caenorhabditis elegans. In this study, our attention was directed towards Torenia sp., resulting in reduced survival and heightened larval arrest/lethality, alongside a noticeable decrease in DAPI-stained bivalent structures and disrupted meiotic progression, thus disrupting develop-mental processes. Notably, Torenia sp. extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways, hindering germline development. LC‒MS analysis revealed 13 compounds in the Torenia sp. extracts, including flavonoids, terpenoids, tanshinones, an analog of resveratrol, iridoids, carotenoids, fatty acids, and alkaloids. Of these, 10 are known for their anti-tumor activity, suggesting the potential of Torenia species beyond traditional gardening, extending into pharmaceutical and therapeutic applications.
Keywords: Torenia species; DNA repair; meiosis; germline development; medicinal plants; herbs
LSD2 Is an Epigenetic Player in Multiple Types of Cancer and Beyond
Hyun-Min Kim* and Zifei Liu
Abstract
Exploring the Impact of Onobrychis cornuta and Veratrum lobelianum Extracts on C. elegans: Implications for MAPK Modulation, Germline Development, and Antitumor Properties
December 4, 2023
Qinghao Meng, Nishit Pathak, Ren Xiaojing and Robert P. Borris and Hyun-Min Kim*
Nutrients (Impact factor 6.6), 2023 Dec 19. https://pubmed.ncbi.nlm.nih.gov/38201838/
Abstract
In an era of increasing interest in the potential health benefits of medicinal foods, the need to assess their safety and potential toxicity remains a critical concern. While these natural remedies have garnered substantial attention for their therapeutic potential, a comprehensive understanding of their effects on living organisms is essential. We examined 316 herbal extracts to determine their potential nematocidal attributes in Caenorhabditis elegans. Approximately 16% of these extracts exhibited the capacity to induce diminished survival rates and larval arrest, establishing a correlation between larval arrest and overall worm viability. Certain extracts led to an unexpected increase in male nematodes, accompanied by a discernible reduction in DAPI-stained bivalent structures and perturbed meiotic advancement, thereby disrupting the conventional developmental processes. Notably, Onobrychis cornuta and Veratrum lobelianum extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways, thus hindering germline development. Our LC-MS analysis revealed jervine in V. lobelianum and nine antitumor compounds in O. cornuta. Interestingly, linoleic acid replicated phenotypes induced by O. cornuta exposure, including an increased level of pCHK-1 foci, apoptosis, and the MAPK pathway. Mutants in the MAPK pathway mitigated the decline in worm survival, underscoring its importance in promoting worm viability. This study reveals complex interactions between herbal extracts and C. elegans processes, shedding light on potential antitumor effects and mechanisms. The findings provide insights into the complex landscape of herbal medicine’s impact on a model organism, offering implications for broader applications.
Keywords: DNA repair; O. cornuta; V. lobelianum; germline; linoleic acid; meiosis.
Experimental Insights into the Interplay between Histone Modifiers and p53 in Regulating Gene Expression
July 6, 2023
,Int. J. Mol. Sci.(impact factor 6.2) 3 July 2023. https://pubmed.ncbi.nlm.nih.gov/37446210/
Hyun-Min Kim*, Xiaoyu Zheng and Ethan Lee
Abstract
Chromatin structure plays a fundamental role in regulating gene expression, with histone modifiers shaping the structure of chromatin by adding or removing chemical changes to histone proteins. The p53 transcription factor controls gene expression, binds target genes, and regulates their activity. While p53 has been extensively studied in cancer research, specifically in relation to fundamental cellular processes, including gene transcription, apoptosis, and cell cycle progression, its association with histone modifiers has received limited attention. This review explores the interplay between histone modifiers and p53 in regulating gene expression. We discuss how histone modifications can influence how p53 binds to target genes and how this interplay can be disrupted in cancer cells. This review provides insights into the complex mechanisms underlying gene regulation and their implications for potential cancer therapy.
A Decade of CRISPR-Cas Gnome Editing in C. elegans
December 15, 2022
Hyun-Min Kim*, Yebin Hong and Jiani Chen
Int. J. Mol. Sci.(impact factor 6.2), 2022, 23(24), 15863
https://pubmed.ncbi.nlm.nih.gov/36555505/
Abstract
CRISPR-Cas allows us to introduce desired genome editing, including mutations, epitopes, and deletions, with unprecedented efficiency. The development of CRISPR-Cas has progressed to such an extent that it is now applicable in various fields, with the help of model organisms. C. elegans is one of the pioneering animals in which numerous CRISPR-Cas strategies have been rapidly established over the past decade. Ironically, the emergence of numerous methods makes the choice of the correct method difficult. Choosing an appropriate selection or screening approach is the first step in planning a genome modification. This report summarizes the key features and applications of CRISPR-Cas methods using C. elegans, illustrating key strategies. Our overview of significant advances in CRISPR-Cas will help readers understand the current advances in genome editing and navigate various methods of CRISPR-Cas genome editing.
Keywords: C. elegans; CRISPR; Cas; genome editing; genome engineering.
杜克昆山大学Hyun Min Kim教授实验室招收硕士研究生、博士后、科研专家 Application for the Master of Science Program at Duke Kunshan University
杜克昆山大学Hyun Min Kim教授实验室招收硕士研究生、博士后、科研专家
Kim教授在杜克昆山大学的实验室,主要研究秀丽隐杆线虫 (C. elegans) 遗传和DNA损伤修复机制。
Hyun Min Kim 教授曾在哈佛医学院完成博士后的研究工作,在Nature、Cell等高水平学术期刊上发表数十篇学术论文。成功应聘者能在较短时间内发表高水平学术论文,并有机会到国外高水平学术机构继续深造。
杜克昆山大学为武汉大学和杜克大学联合办学的高等国际学校,学校具有优秀的实验环境,强大的科研背景,汇聚了世界各地高水平教授。
杜克昆山大学自2022年8月起开放招收硕士研究生通道,链接:https://globalhealth.dukekunshan.edu.cn
Kim Lab网站:https://sites.duke.edu/kimlab/
e-mail:hm.k at dukekunshan. edu. cn
由于Professor Kim为外籍全职在华教授,因此非常青睐有英语交流能力的学生,如果你的英语能力不强也不要担心,随着不断的练习你的英语能力也会有非常大的提升,这将对你今后的个人发展有非常大的助益。
英文原版招生信息如下,欢迎大家报名:
Application for the Master of Science Program at Duke Kunshan University
Dear students,
We are recruiting Graduate students for the Master of Science program in my lab.
Advantages
1. This program offers a degree from Duke therefore, you will receive a Duke degree in the USA after graduation. Duke is one of the top-class universities in the world. This is a three-year course for MS degree. Please find more details at the website
https://globalhealth.dukekunshan.edu.cn
2. The program offers the world’s top-class level of faculties and education.
3. Duke Kunshan, located at Kushan Suzhou, provides a very modern and high-tech environment. Kunshan is a beautiful city located in Suzhou.
4. Once you get admitted, you may be eligible for the support of the full tuition fee.
5. You will be appointed to my lab and receive my research guidance. You are expected to work in the lab and to research for publication. Please find more information at Professor Kim lab https://sites.duke.edu/kimlab/
6. Application starts in August 2022. Since the schedule is very tight, you must prepare the application soon. Please see more details at https://globalhealth.dukekunshan.edu.cn
If you want to apply for the my lab for the MS study, e-mail your 1) transcript and 2) Resume/CV to me at hm.k @ dukekunshan. edu. cn
FYI, we are also looking for Research Assistant.
Xiaojing Ren published her first paper about histone demethylase AMX-1
2022 June
Histone demethylase AMX-1 regulates fertility in a p53/CEP-1 dependent manner, 2022
Xiaojing Ren, Sisi Tian, Qinghao Meng, Hyun-Min Kim*.
https://pubmed.ncbi.nlm.nih.gov/35846143/
Abstract
Histone methylation shapes the epigenetic configuration and adjusts multiple fundamental nuclear processes, including transcription, cell cycle control and DNA repair. The absence of histone demethylase LSD1/SPR-5 leads to progressive fertility defects as well as a reduction in brood size. Similarly, C. elegans LSD2 homolog AMX-1 has been implicated in regulating H3K4me2 and maintaining interstrand crosslinks (ICL) susceptibility. However, the mechanisms of how lack of AMX-1 induces sterility have not been addressed so far. This study investigated the histone demethylase AMX-1 in C. elegans and uncovered how amx-1 contributes to sterility in a p53/CEP-1 dependent manner. We show that while sterility in spr-5 mutants exhibited progressive over generations, amx-1 mutants displayed non-transgenerational fertility defects. Also, amx-1 mutants exhibited a reduced number of sperms and produced low brood size (LBS) or sterile worms that retain neither sperms nor germline nuclei, suggesting that fertility defects originated from germline development failure. Surprisingly, sterility exhibited in amx-1 was mediated by p53/CEP-1 function. Consistent with this result, upregulation of Piwi expression in amx-1 mutants suggested that AMX-1 is essential for germline development by regulating Piwi gene expressions. We propose that AMX-1 is required for proper Piwi expression and transposon silencing in a p53/CEP-1 dependent manner; thus, the absence of AMX-1 expression leads to defective meiotic development and sterility. This study elucidates how LSD2/AMX-1 contributes to sterility, therefore, expanding the boundaries of histone demethylase function.
Keywords: CEP-1; LSD2; Piwi; fertility; histone methylation; p53; sterility; transposon.
People in the lab
- Duke University – Associate Professor of the Practice Duke University, Durham, USA (2024-)
- Duke Kunshan University – Associate Professor of Biology, Kunshan China (2022-)
- Tianjin University – Associate Professor of School of Pharmaceutical Science and Technology (2016-2021)
- Harvard Medical School, USA – Postdoc Research Fellow
- Georgia Tech – Ph.D
Links
Lab Resources
Organizations
Monica lab (Harvard Medical School)
Summer Research
Kim lab supports Summer research students. Students who want to work in the lab are encouraged to contact me.
Summer Journal Club
We organizes Summer Journal clubs for the students. Due to the pandemic spread, we currently operate online presentations only. Journal clubs start at 8:30 PM to include students located in foreign countries. Please find the presentation materials at either the links site or MS-teams.
Weekly Presentation: Thursday 8:30-9:30pm. Shanghai time
Join Zoom Meeting https://duke.zoom.us/j/6866647729?pwd=T0dSanhFTXV0V2FJMTE0SDNPZTZLUT09
PDF resources https://people.dukekunshan.edu.cn/~hk284/Papers
Bioscience Data Club
Kim lab organizes Bioscience Data Club since 2018. This is a monthly meeting aimed for the departmental seminar among Bioscience oriented laboratories. Presenters will discuss their research to assist any scientific issue. All students and faculties are welcome. For more information, contact me or my students on the ‘people’ link. Free snacks and beverages served.
AMX-1 publication on PLOS Genetics Zhang et al., 2021
Histone demethylase AMX-1 is necessary intercrosslink repair. 2021. Xiaojuan Zhang, Sisi Tian, Sara E. Beese-Sims, Jingjie Chen, Nara Shin, Monica P. Colaiácovo and Hyun-Min Kim*.
CRISPR-Cas publication 2021-5-27
CRISPR-Cas Publication accepted in Springer Nature publisher.
▪ Hyun-Min Kim* and Xiaojuan Zhang. Design of repair templates for CRISPR-Cas9-triggered homologous recombination in Caenorhabditis elegans. CRISPR-Cas methods, volume2, Springer Nature. Jul 2021 (*Correspondence). Editors: M. Tofazzal Islam and Kutubuddin A Molla
From Yogurt to Genetic Scissors: Nobel Recognition for CRISPR 2020-10-12
From Yogurt to Genetic Scissors: Nobel Recognition for CRISPR
October 7th 2020, Posted in Tianjin University
Hyun M. Kim
The Nobel Prize in Chemistry was jointly awarded to Emmanuelle Charpentier and Jennifer Doudna for their CRISPR work. It is the first time a science Nobel has been awarded to two women. The function of CRISPR was first identified in 2007 by researchers at the Danish yogurt company DANISCO. Lactobacillus responsible for yogurt fermentation are susceptible to viral infection, but they discovered that certain lactic acid bacteria behave as if they were resistant to viruses. Genomic analysis these bacteria revealed that CRISPR genes defeat the viral infection.
How CRISPR-Cas protects the immune system was not exactly known until Jennifer Doudna and Emmanuelle Charpentier elucidated CRISPR’s mechanism (Science 2012, 337:816–821. doi: 10.1126/science.1225829). In brief, bacteria cut the invading virus’s nucleotide sequence and store it in the CRISPR genes. When the virus bacteriophage re-invades, the viral nucleotide sequence stored in the CRISPR genes is transcribed to RNA and binds to the Cas9 protein to cleave invading viral DNA.
During viral infections, the effector complex recognizes short motifs near the target sequence in the virus and binds with sequences complementary to crRNA, initiating the Cas protein to break the viral genome by causing a double-stranded break (See figure). The double-stranded break caused by the Cas can be repaired with its repair mechanisms, such as non-homologous end joining (deletion or insertion) or homologous recombination (error-free recombination) pathway.
These findings enabled CRISPR as a new genetic scissors that could replace the existing lower efficiency and specificity genetic-scissor technologies such as ZFNs and TALENs. With CRISPR it is easy to engineer specific sequence binding, and simple to effect gene deletions, insertions and modifications. Numerous studies using various experimental models have contributed significantly to the high efficiency of CRISPR genome editing (Current Protocols in Molecular Biology. 2019, Sept 24. https://doi.org/10.1002/cpmb.106). Moreover, the simplicity and robustness of CRISPR have extended its application from basic sciences to translational research and medicine within a relatively short time (Biomedicines. 2018, Nov 12;6(4):105. doi: 10.3390/biomedicines6040105).
Gene editing using the CRISPR/Cas9 offers the potential to alter humankind in ways yet not feasible; it is imperative to ensure international standards for its ethical use. With proper cautions, CRISPR technology holds the promise to correct genetic diseases and enhance current therapies beyond imagination, the perfect harmony with Alfred Nobel’s bequest.
Nobel Prize 2019 adaptation mechanism of cells to oxygen concentration 2020-10-12
The Nobel Assembly of the Karolinska Institute of Sweden announced the co-winners of the 2019 Nobel Prize in Physiology or Medicine in recognition of their contributions to the adaptation mechanism of cells to oxygen concentration. Three co-winners found HIF-1α molecules affect ~ 300 genes, as well as the hypoxia response element, which acts as a switch in various genes when our bodies are in hypoxia.
These changes can lead to multiple human diseases such as anemia, infections, myocardial infarction, tumors, and strokes. In particular, cancer cells grow even in a hypoxic state because the HIF-1α protein induces angiogenesis factors expression.
When patients undergoing chemotherapy or radiation therapy, cancer is often in a low-oxygen state, so it was not clear why or how the drug is not working”. Answers to such problems open significant pathways on how to improve the treatment’s effectiveness in the future. Thanks to their research contributions, the protein is now the target of targeted anticancer drugs.
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A new research article published in 3Biotech Journal. 2020-7-12
Our new publication accepted in 3BIOTECH. This research focuses on Genome editing, which was initiated by Prof. Kim and Shouyue. https://pubmed.ncbi.nlm.nih.gov/32728517/
New publication on Current Protocols in Molecular Biology 2019-9-25
Current Protocols in Molecular Biology is considered as the top level. I am happy to published our article once again.
Kim, H.-M., & Colaiácovo, M. P. (2019). CRISPR-Cas9-guided genome engineering in caenorhabditis elegans. Current Protocols in Molecular Biology, Sept 24 129, e106. doi: 10.1002/cpmb.106