Guangyu Wang

Guangyu Wang, PhD

Assistant Professor of Cardiovascular Sciences, Academic Institute
Assistant Member, Research Institute
Houston Methodist


Biography

Dr. Guangyu Wang is an Assistant Professor of Cardiovascular Sciences at Houston Methodist Research Institute (HMRI), Weill Cornell Medical College. He started his research group in July of 2021. The overarching goal of his research is to utilize high-throughput multi-omics datasets, mostly based on DNA and RNA sequencing, to develop models that explain how cell state is regulated. He is especially interested in endothelial cells (ECs), covering various aspects of their biology, such as their differentiation and transdifferentiation, and the stability/plasticity of their chromatin structure and histone modification.

Description of Research

The broad goals of the research in the Wang lab are to understand:

  • How epigenetics regulates transcriptome
  • How transcriptional shifts affect cell states and cell/tissue level phenotypes

To achieve our goal, we are motivated by modulating the causes of transcriptional shifts and the translational potential of identifying. We develop and apply computational tools to integrate and interpret large biomedical and molecular datasets that can uncover the regulation mechanism and the effects of the transcriptional process.

Specifically, we aim to utilize high-throughput multi-omics datasets, mostly based on DNA and RNA sequencing, to develop models that explain how cell state is regulated. We are especially interested in endothelial cells (ECs), covering various aspects of their biology, such as their differentiation and trans-differentiation, and the stability/plasticity of their chromatin structure and histone modification.

?Single-cell dynamics

Single-cell transcriptomics (scRNA-seq) and single-cell epigenomics (scATAC-seq) data revolutionize the field of regulatory genomics. We combine cutting-edge computational approaches with state-of-the-art single-cell profiling to better understand cell state transitions, decode cis-regulatory programs, and predict the effect of TF perturbations in single-cell datasets and their effect on cell identity in contexts such as cell trans-differentiation and reprogramming.

?Chromatin structure & Histone modification:

The Wang lab seeks to understand the chromatin folding of genomic DNA, which is one of the most basic and important genomic regulations in dynamic processes such as differentiation or cellular state switching. We have developed computational methods to investigate cell identity-associated TADs (topological associated domains), stripes, and loops. We initially detected split and merging of TADs comparing fibroblast to ECs and suggested these TAD splitting and merging may play important role in cell differentiation and are highly associated with histone modification alternation (Wang et al, Genome Biology, 2020). We also developed computational methods that decipher open chromatin, histone modification, and transcription factor binding genome-wide in sub-populations of cells undergoing dynamic processes such as differentiation or stochastic state switching (Wang et al, Nature Communication, 2020; Wang et al, GPB, 2021).

?AI & Machine learning

Data-driven research in Wang lab is powered by artificial intelligence (AI) and machine learning that guide us to understand more about biological systems and processes. We are currently working on:

  • Deep learning for transcriptome to predict cell state transition and pseudo-time based on the RNA velocity model.
  • Transferring learning for scRNA-seq and scATAC-seq to predict therapy choice and patient outcome.
  • Web-based workflows of single-cell multi-omics to efficiently implement data preparation, advanced analysis, and integrative analysis of scRNA-seq and scATAC-seq.

Publications

Epigenetic Induction of Smooth Muscle Cell Phenotypic Alterations in Aortic Aneurysms and Dissections
Chakraborty, A, Li, Y, Zhang, C, Li, Y, Rebello, KR, Li, S, Xu, S, Vasquez, HG, Zhang, L, Luo, W, Wang, G, Chen, K, Coselli, JS, Lemaire, SA & Shen, YH 2023, , Circulation, vol. 148, no. 12, pp. 959-977. https://doi.org/10.1161/CIRCULATIONAHA.123.063332

Aerobic Exercise Alters the Melanoma Microenvironment and Modulates ERK5 S496 Phosphorylation
Savage, H, Pareek, S, Lee, J, BallarĂ², R, Minussi, DC, Hayek, K, Sadullozoda, M, Lochmann, BS, McQuade, JL, LaVoy, EC, Marmonti, E, Patel, H, Wang, G, Imanishi, M, Kotla, S, Abe, JI & Schadler, K 2023, , Cancer immunology research, vol. 11, no. 9, pp. 1168-1183. https://doi.org/10.1158/2326-6066.CIR-22-0465

An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis
Abe, J-I, Imanishi, M, Li, S, Zhang, A, Ko, KA, Samanthapudi, VSK, Lee, L-L, Bojorges, AP, Gi, YJ, Hobbs, BP, Deswal, A, Herrmann, J, Lin, SH, Chini, EN, Shen, YH, Schadler, KL, Nguyen, T-H-M, Gupte, AA, Reyes-Gibby, C, Yeung, S-CJ, Abe, RJ, Olmsted-Davis, EA, Krishnan, S, Dantzer, R, Palaskas, NL, Cooke, JP, Pownall, HJ, Yoshimoto, M, Fujiwara, K, Hamilton, DJ, Burks, JK, Wang, G, Le, N-T & Kotla, S 2023, , Circulation Research, vol. 133, no. 1, pp. 25-44. https://doi.org/10.1161/CIRCRESAHA.122.322017

Dynamic changes in P300 enhancers and enhancer-promoter contacts control mouse cardiomyocyte maturation
Zhou, P, VanDusen, NJ, Zhang, Y, Cao, Y, Sethi, I, Hu, R, Zhang, S, Wang, G, Ye, L, Mazumdar, N, Chen, J, Zhang, X, Guo, Y, Li, B, Ma, Q, Lee, JY, Gu, W, Yuan, GC, Ren, B, Chen, K & Pu, WT 2023, , Developmental Cell, vol. 58, no. 10, pp. 898-914.e7. https://doi.org/10.1016/j.devcel.2023.03.020

Publisher Correction: Epigenetic landscape reveals MECOM as an endothelial lineage regulator
Lv, J, Meng, S, Gu, Q, Zheng, R, Gao, X, Kim, JD, Chen, M, Xia, B, Zuo, Y, Zhu, S, Zhao, D, Li, Y, Wang, G, Wang, X, Meng, Q, Cao, Q, Cooke, JP, Fang, L, Chen, K & Zhang, L 2023, , Nature Communications, vol. 14, no. 1, 2842, pp. 2842. https://doi.org/10.1038/s41467-023-38708-x

Epigenetic landscape reveals MECOM as an endothelial lineage regulator
Lv, J, Meng, S, Gu, Q, Zheng, R, Gao, X, Kim, JD, Chen, M, Xia, B, Zuo, Y, Zhu, S, Zhao, D, Li, Y, Wang, G, Wang, X, Meng, Q, Cao, Q, Cooke, JP, Fang, L, Chen, K & Zhang, L 2023, , Nature Communications, vol. 14, no. 1, 2390, pp. 2390. https://doi.org/10.1038/s41467-023-38002-w

A relay velocity model infers cell-dependent RNA velocity
Li, S, Zhang, P, Chen, W, Ye, L, Brannan, KW, Le, NT, Abe, JI, Cooke, JP & Wang, G 2023, , Nature Biotechnology, vol. 42, no. 1, pp. 99-108. https://doi.org/10.1038/s41587-023-01728-5

Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors
Banerjee, P, Rosales, JE, Chau, K, Nguyen, MTH, Kotla, S, Lin, SH, Deswal, A, Dantzer, R, Olmsted-Davis, EA, Nguyen, H, Wang, G, Cooke, JP, Abe, JI & Le, NT 2023, , Frontiers in Cardiovascular Medicine, vol. 10, 1186679, pp. 1186679. https://doi.org/10.3389/fcvm.2023.1186679

CRAT links cholesterol metabolism to innate immune responses in the heart
Mao, H, Angelini, A, Li, S, Wang, G, Li, L, Patterson, C, Pi, X & Xie, L 2023, , Nature Metabolism, vol. 5, no. 8, pp. 1382-1394. https://doi.org/10.1038/s42255-023-00844-5

Endothelial activation and fibrotic changes are impeded by laminar flow-induced CHK1-SENP2 activity through mechanisms distinct from endothelial-to-mesenchymal cell transition
Nguyen, MTH, Imanishi, M, Li, S, Chau, K, Banerjee, P, Velatooru, LR, Ko, KA, Samanthapudi, VSK, Gi, YJ, Lee, LL, Abe, RJ, McBeath, E, Deswal, A, Lin, SH, Palaskas, NL, Dantzer, R, Fujiwara, K, Borchardt, MK, Turcios, EB, Olmsted-Davis, EA, Kotla, S, Cooke, JP, Wang, G, Abe, JI & Le, NT 2023, , Frontiers in Cardiovascular Medicine, vol. 10, 1187490, pp. 1187490. https://doi.org/10.3389/fcvm.2023.1187490

Premature senescence and cardiovascular disease following cancer treatments: mechanistic insights
Jain, A, Casanova, D, Padilla, AV, Paniagua Bojorges, A, Kotla, S, Ko, KA, Samanthapudi, VSK, Chau, K, Nguyen, MTH, Wen, J, Hernandez Gonzalez, SL, Rodgers, SP, Olmsted-Davis, EA, Hamilton, DJ, Reyes-Gibby, C, Yeung, SCJ, Cooke, JP, Herrmann, J, Chini, EN, Xu, X, Yusuf, SW, Yoshimoto, M, Lorenzi, PL, Hobbs, B, Krishnan, S, Koutroumpakis, E, Palaskas, NL, Wang, G, Deswal, A, Lin, SH, Abe, JI & Le, NT 2023, , Frontiers in Cardiovascular Medicine, vol. 10, 1212174, pp. 1212174. https://doi.org/10.3389/fcvm.2023.1212174

TNIK regulation of interferon signaling and endothelial cell response to virus infection
Chau, KM, Dominic, A, Davis, EL, Kotla, S, Berrios, ET, Fahim, A, Arunesh, A, Li, S, Zhao, D, Chen, K, Davis, AR, Nguyen, MTH, Wang, Y, Evans, SE, Wang, G, Cooke, JP, Abe, JI, Huston, DP & Le, NT 2023, , Frontiers in cardiovascular medicine, vol. 10, 1213428, pp. 1213428. https://doi.org/10.3389/fcvm.2023.1213428, https://doi.org/10.3389/fcvm.2023.1213428

TNIK regulation of interferon signaling and endothelial cell response to virus infection
Chau, KM, Dominic, A, Davis, EL, Kotla, S, Berrios, ET, Fahim, A, Arunesh, A, Li, S, Zhao, D, Chen, K, Davis, AR, Nguyen, MTH, Wang, Y, Evans, SE, Wang, G, Cooke, JP, Abe, JI, Huston, DP & Le, NT 2023, , Frontiers in cardiovascular medicine, vol. 10, 1213428. https://doi.org/10.3389/fcvm.2023.1213428

StripeDiff: Model-based algorithm for differential analysis of chromatin stripe
Gupta, K, Wang, G, Zhang, S, Gao, X, Zheng, R, Zhang, Y, Meng, Q, Zhang, L, Cao, Q & Chen, K 2022, , Science advances, vol. 8, no. 49, abk2246, pp. eabk2246. https://doi.org/10.1126/sciadv.abk2246

StripeDiff: Model-based Algorithm for Differential Analysis of Chromatin Stripe
Wang, G 2022, , Science Advances.

StripeDiff: Model-based algorithm for differential analysis of chromatin stripe
Gupta, K, Wang, G, Zhang, S, Gao, X, Zheng, R, Zhang, Y, Meng, Q, Zhang, L, Cao, Q & Chen, K 2022, , Science advances, vol. 8, no. 49, abk2246. https://doi.org/10.1126/sciadv.abk2246

Telomerase therapy reverses vascular senescence and extends lifespan in progeria mice
Mojiri, A, Walther, BK, Jiang, C, Matrone, G, Holgate, R, Xu, Q, Morales, E, Wang, G, Gu, J, Wang, R & Cooke, JP 2021, , European heart journal, vol. 42, no. 42, pp. 4352-4369. https://doi.org/10.1093/eurheartj/ehab547

Role of Endothelial and Mesenchymal Cell Transitions in Heart Failure and Recovery Thereafter
Wang, G, Cruz, AS, Youker, K, Marcos-Abdala, HG, Thandavarayan, RA, Cooke, JP, Torre-Amione, G, Chen, K & Bhimaraj, A 2021, , Frontiers in Genetics, vol. 11, 609262, pp. 609262. https://doi.org/10.3389/fgene.2020.609262

MACMIC Reveals A Dual Role of CTCF in Epigenetic Regulation of Cell Identity Genes
Wang, G, Xia, B, Zhou, M, Lv, J, Zhao, D, Li, Y, Bu, Y, Wang, X, Cooke, JP, Cao, Q, Lee, MG, Zhang, L & Chen, K 2021, , Genomics, Proteomics and Bioinformatics, vol. 19, no. 1, pp. 140-153. https://doi.org/10.1016/j.gpb.2020.10.008

Broad genic repression domains signify enhanced silencing of oncogenes
Zhao, D, Zhang, L, Zhang, M, Xia, B, Lv, J, Gao, X, Wang, G, Meng, Q, Yi, Y, Zhu, S, Tomoiaga, AS, Lee, MG, Cooke, JP, Cao, Q & Chen, K 2020, , Nature Communications, vol. 11, no. 1, 5560, pp. 5560. https://doi.org/10.1038/s41467-020-18913-8