NAME: Wen, He

POSITION TITLE: Assistant Professor; Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine

EDUCATION/TRAINING

A.   Personal Statement

My principal research interests are metabolomics and nuclear magnetic resonance (NMR) bioanalysis. A new “omics” approach, called metabolomics, has recently emerged as a promising tool to differentiate patients with different conditions. Compared to other omics approaches, metabolomics analyses small molecular metabolites that are present in the body and change status according to environmental state. Metabolomics and pattern recognition techniques can be used for several different aims, such as disease diagnosis, toxic marker investigation, natural product classification and basic metabolism analysis.

Recent studies have shown that histone modification can modulate cancer metabolism, as well as metabolites can also regulate the occurrence and development of tumors by modulating histone modifications, becoming hot issue. Using a metabolomics approach, we aim to reveal the mechanisms of histone-modifying enzymes that regulate cancer metabolic reprogramming to provide new ideas and targets for cancer therapy.

B.   Positions and Honors

Positions and Employment

0 1 /201 0 – 0 3 /201 0       Visiting Scientist, The Urological Diseases Research Center, Boston Children’s

Hospital, Harvard Medical School, Boston , USA

0 9 /2016 – present       Assistant Professor, Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine, Shenzhen, China

C.   Contributions to Science (*: first /co- first author)

A full list of my publications (in a total of 24) is enclosed at the end of this document.

1.    Application of metabolomics in disease diagnosis

The sensitivity and specificity of gold standard approaches for disease diagnosis, such as biliary tract cancer or leptomeningeal carcinomatosis are poor. Therefore, it is important to develop new methods that improve on diagnostic sensitivity and specificity. The NMR-based metabolomics approach performs well in discriminating between cancerous and benign disease samples. In addition, the prediction models generate significantly improved diagnostic results compared with canonical diagnostic tools.

1)    Wen H*, Lee T*, You S, Park SH, Song H, Eilber KS, Anger JT, Freeman MR, Park S, Kim J. Urinary Metabolite Profiling Combined with Computational Analysis Predicts Interstitial Cystitis-Associated Candidate Biomarkers. J Proteome Res. 2015 Jan 2; 14: 541−8.

2)    Cho HR*, Wen H*, Ryu YJ, An YJ, Kim HC, Moon WK, Han MH, Park S, Choi SH. An NMR metabolomics approach for the diagnosis of leptomeningeal carcinomatosis. Cancer Res. 2012 Oct 15;72(20):5179-87.

3)    Wen H*, Yoo SS*, Kang J, Kim HG, Park JS, Jeong S, Lee JI, Kwon HN, Kang S, Lee DH, Park S. A new NMR-based metabolomics approach for the diagnosis of biliary tract cancer. J Hepatol. 2010 Feb;52(2):228-33. (cover introduction)

2.    NMR bioanalysis

We developed an NMR-based assay (HCACO, HNCO) combined with stable isotopes to evaluate enzyme activity. This assay can be performed in a complex mixture without extraction, can generate time-dependent absolute quantitative data, and can be applied to enzyme inhibitor screening. In addition, a novel approach, termed “in-cell metabolomics”, has been developed and can be applied to real-time monitoring of live cell metabolism to compare the metabolic differences between cancerous and normal cells or to identify new therapeutic targets and anti-cancer drugs.

1)    Wen H, Yun T, Xu WJ, Choi SH, Kim H, Park CK, Lee SH, Park SW, Lee SK, Park S. A highly facile and specific assay for cancer-causing isocitrate dehydrogenase mutant using 13C4-labeled α-ketoglutarate and heteronuclear NMR. Anal Chem. 2013 Dec 17;85(24):11987-92.

2)    Wen H*, An YJ*, Xu WJ, Kang KW, Park S. Real-Time Monitoring of Cancer Cell Metabolism and Effects of an Anticancer Agent using 2D In Cell NMR Spectroscopy. Angew Chem Int Ed Engl. 2015 Apr 27;54(18):5374-7.

3)    Lee S*, Wen H*, Cha JW, Park S. Specific Detection of Cellular Glutamine Hydrolysis in Live Cells Using HNCO Triple Resonance NMR. ACS Chem Biol. 2016 Nov 18;11(11):3140-3145.

3.    Application of metabolomics in basic metabolism

Dietary restriction (DR) is a reduction in food consumption that can increase the lifespan of many species, including yeast, fruit flies, rats, dogs and monkeys. Many studies have identified some of the genes and proteins involved in the aging pathways, but the downstream pathways regarding how these genes and proteins regulate aging are unknown. DR is a form of dieting where the diet directly influences metabolic pathways, indicating that DR may mediate metabolism directly. Consequently, we have used a multi-platform metabolomics approach to directly investigate metabolism and understand the mechanisms underlying these beneficial effects of DR. From our findings, we propose Phase II detoxification as one of the mechanisms underlying the beneficial effects of DR.

1. Wen H*, Xu WJ*, Jin X, Oh S, Phan CH, Song J, Lee SK, Park S. The roles of IP3 receptor in energy metabolic pathways and reactive oxygen species homeostasis revealed by metabolomic and biochemical studies. Biochim Biophys Acta. 2015 Nov;1853(11 Pt A):2937-44.

2)     Wen H*, Cho HR*, Yun T, Kim H, Park CK, Lee SH, Choi SH, Park S. Metabolomic comparison between cells over-expressing isocitrate dehydrogenase 1 and 2 mutants and the effects of an inhibitor on the metabolism. J Neurochem. 2015 Jan;132(2):183-93.

3)     Wen H*, Yang HJ*, An YJ, Kim JM, Lee DH, Jin X, Park SW, Min KJ, Park S. Enhanced phase II detoxification contributes to beneficial effects of dietary restriction as revealed by multi-platform metabolomics studies. Mol Cell Proteomics. 2013 Mar;12(3):575-86.  

D.   Research Support

Ongoing Research Support

NSFC (China) (31701099)                                                               01/01/2018 to 12/31/2020

He Wen, PI                                                                                       ￥220,000 (direct cost)

The study of mechanism of histone methyltransferase GLP in regulation of cancer metabolic reprogramming

NSF of Guangdong Province (2017A030310459)                    05/01/2017 to 04/30/2020

He Wen, PI                                                                                       ￥100,000 (direct cost)

Study on the molecular mechanism of beneficial effects of dietary restriction using systems biology

Science and Technology Foundation of Shenzhen City (JCYJ20170302144650949)                                                                                                                                                          06/01/2017 to 05/31/2019

He Wen, PI                                                                                       ￥300,000

Study on the molecular mechanism of dietary restriction delaying aging using system biology

E.    Peer-reviewed publications (*: first/co-first author)

1.      Lee S, Wen H, An YJ, Cha JW, Ko YJ, Hyberts SG, Park S. Carbon Isotopomer Analysis with Non-Unifom Sampling HSQC NMR for Cell Extract and Live Cell Metabolomics Studies. Anal Chem. 2017 Jan 17;89(2):1078-1085.

2.      Lee S*, Wen H*, Cha JW, Park S. Specific Detection of Cellular Glutamine Hydrolysis in Live Cells Using HNCO Triple Resonance NMR. ACS Chem Biol. 2016 Nov 18;11(11):3140-3145.

3.      Wen H*, Xu WJ*, Jin X, Oh S, Phan CH, Song J, Lee SK, Park S. The roles of IP3 receptor in energy metabolic pathways and reactive oxygen species homeostasis revealed by metabolomic and biochemical studies. Biochim Biophys Acta. 2015 Nov;1853(11 Pt A):2937-44.

4.      Wen H*, An YJ*, Xu WJ, Kang KW, Park S. Real-Time Monitoring of Cancer Cell Metabolism and Effects of an Anticancer Agent using 2D In Cell NMR Spectroscopy. Angew Chem Int Ed Engl. 2015 Apr 27;54(18):5374-7.

5.      Wen H*, Lee T*, You S, Park SH, Song H, Eilber KS, Anger JT, Freeman MR, Park S, Kim J. Urinary Metabolite Profiling Combined with Computational Analysis Predicts Interstitial Cystitis-Associated Candidate Biomarkers. J Proteome Res. 2015 Jan 2; 14: 541−8.

6.      Wen H*, Cho HR*, Yun T, Kim H, Park CK, Lee SH, Choi SH, Park S. Metabolomic comparison between cells over-expressing isocitrate dehydrogenase 1 and 2 mutants and the effects of an inhibitor on the metabolism. J Neurochem. 2015 Jan;132(2):183-93.

7.      Wen H*, Kwon HN*, Park S. A new mechanism in the binding between Homer3 EVH1 domain and inositol 1,4,5 trisphosphate receptor suppressor domain. Biochem Cell Biol. 2014 Jun;92(3):163-71.

8.      An YJ, Cho HR, Kim TM, Keam B, Kim JW, Wen H, Park CK, Lee SH, Im SA, Kim JE, Choi SH, Park S. An NMR metabolomics approach for the diagnosis of leptomeningeal carcinomatosis in lung adenocarcinoma cancer patients. Int J Cancer. 2015 Jan 1;136(1):162-71.

9.      Wen H, Yun T, Xu WJ, Choi SH, Kim H, Park CK, Lee SH, Park SW, Lee SK, Park S. A highly facile and specific assay for cancer-causing isocitrate dehydrogenase mutant using 13C4-labeled α-ketoglutarate and heteronuclear NMR. Anal Chem. 2013 Dec 17;85(24):11987-92.

10.   Um S, Kim YJ, Kwon H, Wen H, Kim SH, Kwon HC, Park S, Shin J, Oh DC. Sungsanpin, a lasso peptide from a deep-sea streptomycete. J Nat Prod. 2013 May 24;76(5):873-9.

11.   Yu SL, An YJ, Yang HJ, Kang MS, Kim HY, Wen H, Jin X, Kwon HN, Min KJ, Lee SK, Park S. Alanine-metabolizing enzyme Alt1 is critical in determining yeast life span, as revealed by combined metabolomic and genetic studies. J Proteome Res. 2013 Apr 5;12(4):1619-27.

12.   Wen H*, Yang HJ*, An YJ, Kim JM, Lee DH, Jin X, Park SW, Min KJ, Park S. Enhanced phase II detoxification contributes to beneficial effects of dietary restriction as revealed by multi-platform metabolomics studies. Mol Cell Proteomics. 2013 Mar;12(3):575-86.

13.   An YJ, Xu WJ, Jin X, Wen H, Kim H, Lee J, Park S. Metabotyping of the C. elegans sir-2.1 mutant using in vivo labeling and (13)C-heteronuclear multidimensional NMR metabolomics. ACS Chem Biol. 2012 Dec 21;7(12):2012-8.

14.   Cho HR*, Wen H*, Ryu YJ, An YJ, Kim HC, Moon WK, Han MH, Park S, Choi SH. An NMR metabolomics approach for the diagnosis of leptomeningeal carcinomatosis. Cancer Res. 2012 Oct 15;72(20):5179-87.

15.   Wen H, Kang S, Song Y, Song Y, Yang HJ, Kim MH, Park S. Characterization of the binding sites for the interactions between FKBP12 and intracellular calcium release channels. Arch Biochem Biophys. 2012 Jan 1;517(1):37-42.

16.   Wen H*, Lee MY*, Song Y, Moon S, Park S. Combined genomic-metabolomic approach for the differentiation of geographical origins of natural products: deer antlers as an example. J Agric Food Chem. 2011 Jun 22;59(12):6339-45.

17.   Yang HJ*, Choi MJ*, Wen H*, Kwon HN, Jung KH, Hong SW, Kim JM, Hong SS, Park S. An effective assessment of simvastatin-induced toxicity with NMR-based metabonomics approach. PLoS One. 2011 Feb 22;6(2):e16641.

18.   Kang S, Kwon H, Wen H, Song Y, Frueh D, Ahn HC, Yoo SH, Wagner G, Park S. Global dynamic conformational changes in the suppressor domain of IP3 receptor by stepwise binding of the two lobes of calmodulin. FASEB J. 2011 Mar;25(3):840-50.

19.   Kwon HN*, Kim M*, Wen H*, Kang S, Yang HJ, Choi MJ, Lee HS, Choi D, Park IS, Suh YJ, Hong SS, Park S. Predicting idiopathic toxicity of cisplatin by a pharmacometabonomic approach. Kidney Int. 2011 Mar;79(5):529-37.

20.   Wen H*, Jeon B*, Moon S*, Song Y, Kang S, Yang HJ, Song Y, Park S. Differentiation of antlers from deer on different feeds using an NMR-based metabolomics approach. Arch Pharm Res. 2010 Aug;33(8):1227-34.

21.   Wen H*, Yoo SS*, Kang J, Kim HG, Park JS, Jeong S, Lee JI, Kwon HN, Kang S, Lee DH, Park S. A new NMR-based metabolomics approach for the diagnosis of biliary tract cancer. J Hepatol. 2010 Feb;52(2):228-33. (cover introduction)

22.   Wen H, Kang S, Song Y, Song Y, Sung SH, Park S. Differentiation of cultivation sources of Ganoderma lucidum by NMR-based metabolomics approach. Phytochem Anal. 2010 Jan-Feb;21(1):73-9.

23.   Kang J, Choi MY, Kang S, Kwon HN, Wen H, Lee CH, Park M, Wiklund S, Kim HJ, Kwon SW, Park S. Application of a 1H nuclear magnetic resonance (NMR) metabolomics approach combined with orthogonal projections to latent structure-discriminant analysis as an efficient tool for discriminating between Korean and Chinese herbal medicines. J Agric Food Chem. 2008 Dec 24;56(24):11589-95.

24.   Kang J, Kang S, Kwon HN, He W, Park S. Distinct interactions between ubiquitin and the SH3 domains involved in immune signaling. Biochim Biophys Acta. 2008 Sep;1784(9):1335-41.