I have been studying kidney diseases since 2010. My graduate work focused on developing new therapeutic options for chronic kidney diseases. I am currently deploying cutting-edge technologies to deeply understand how the kidney goes awry after injuries.
My research centers around the use of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to understand the complex dynamics of kidney injury. By employing these advanced technologies, I am dissecting the intricate cellular interactions and molecular pathways that contribute to progression of kidney diseases. Single-cell RNA sequencing allows for an in-depth analysis of cellular heterogeneity, revealing unique gene expression patterns within individual cells. In parallel, spatial transcriptomics offers a comprehensive view of these cellular expressions in situ. This integrative approach is pivotal in unraveling the multifaceted nature of kidney injury. My goal is to leverage these insights to develop innovative diagnostic and therapeutic strategies that can significantly improve patient outcomes in nephrology.
I benchmarked the performance of various snRNA-seq techniques against the scRNA-seq technique, and found that snRNA-seq achieved comparable gene detection to scRNA-seq in adult kidney, and it also had substantial advantages, including reduced dissociation bias, compatibility with frozen samples, elimination of dissociation-induced transcriptional stress responses, and successful performance on inflamed fibrotic kidney.
Using a high throughput scRNA-seq technique called Drop-seq, I identified that all kidney cell types are immature in the kidney organoid. Importantly, non-kidney cell types – principally neurons and muscle cells – are also present within kidney organoids. As a proof of concept, I have identified a simple approach to reduce the number of the off-target cells in kidney organoids by inhibiting the pathway that drives neuronal differentiation.
Using both in vitro and in vivo approaches, I found that BM-MSCs exerted a significant beneficial effect in attenuating tubular inflammation and tubular fibrotic changes in models of protein overload. I further observed a strong reduction in ADR-induced acute and chronic kidney injury by iPS-MSCs. I also showed that the secretory factors, such as HGF and TSG-6, contributed to the anti-apoptotic and anti-fibrotic effects exerted by MSCs.
I completed my undergraudate thesis in Dr. Lin Liu's lab, where I worked on establishing embryonic stem cell lines from blastocysts of various species such as mouse, bovine and human.
Wu H, Dixon EE, Xuanyuan Q, Guo J, Yoshimura Y, Debashish C, Niesnerova A, Xu H, Rouault M, Humphreys BD. High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing. Nat Commun. 2024 Feb 15;15(1):1396.
Wu H, Humphreys BD. Immune cell heterogeneity in a mouse model of diabetic kidney disease. Kidney Int. 2022 Dec;102(6):1215-1216.
Wu H, Gonzalez VR, Yao X, Reilly D, Chen T, Rankin M, Myshkin E, Breyer MD, Humphreys BD. Mapping the Single Cell Transcriptomic Response of Murine Diabetic Kidney Disease in Therapies. Cell Metab. 2022 Jul 5;34(7):1064-1078.e6. → Journal Cover
Wu H, Humphreys BD. Single Cell Sequencing and Kidney Organoids Generated from Pluripotent Stem Cells. Clin J Am Soc Nephrol. 2020 15(4):550-556.
Wu H*, Lai CF*, Chang-Panesso M, Humphreys BD. Proximal Tubule Translational Profiling during Kidney Fibrosis Reveals Proinflammatory and Long Noncoding RNA Expression Patterns with Sexual Dimorphism. J Am Soc Nephrol. 2020 31(1):23-38. → Journal Cover
Wu H, Kirita Y, Donnelly EL, Humphreys BD. Advantages of Single-Nucleus over Single-Cell RNA Sequencing of Adult Kidney: Rare Cell Types and Novel Cell States Revealed in Fibrosis. J Am Soc Nephrol. 2019 30(1):23-32.
Wu H*, Uchimura K*, Donnelly EL, Kirita Y, Morris SA, Humphreys BD. Comparative Analysis and Refinement of Human PSC-Derived Kidney Organoid Differentiation with Single-Cell Transcriptomics. Cell Stem Cell 2018 23(6):869-881.e8. → Best of Cell Stem Cell 2018
Wu H*, Malone AF*, Donnelly E, Kirita Y, Uchimura K, Ramakrishnan SM, Gaut J, Humphreys BD. Single-Cell Transcriptomics of a Human Kidney Allograft Biopsy Specimen Defines a Diverse Inflammatory Response. J Am Soc Nephrol. 2018 29(8):2069-2080 → Journal Cover and Top JASN Articles 2018
Wu H and Humphreys BD. The promise of single-cell RNA sequencing for kidney disease investigation. Kidney Int. 2017 92(6)1334-1342
Wu H, Yiu WH, Wong DW, Li RX, Chan LY, Leung JC, Zhang Y, Lian Q, Lai KN, Tse HF, Tang SC. Human Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Prevent Adriamycin Nephropathy in Mice. Oncotarget. 2017 8;103640-103656
Wu H, Yiu WH, Li RX, Wong DW, Chan LY, Leung JC, Zhang Y, Lian Q, Lin M, Tse HF, Lai KN, and Tang SC. Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis. PLoS ONE 2014 9(3).
Moderator in session: "Podocytopathy: Novel Insights and Emerging Therapeutic Targets". Kidney Week 2023. Philadelphia, PA. November 03, 2023.
High resolution spatially resolved transcriptomic atlas of kidney injury and repair with direct RNA hybridization-based in situ sequencing. Kidney Week 2022. Orlando, FL. November 04, 2022.
Moderator in session: "One Cell at a Time: Application of Single-Cell RNA Sequencing in Kidney Transplantation". Kidney Week 2021. San Diego, CA. November 04, 2021.
Unravelling kidney fibrosis using single-nucleus transcriptomics. KSN 2021. Seoul, Republic of South Korea. September 03, 2021.
Murine Diabetic Nephropathy at Single Cell Resolution. Kidney Week 2019. Washington, DC. November 07, 2019.
Comparative analysis of kidney organoid and adult human kidney by single cell RNA-seq. Kidney Week 2018. San Diego, CA. October 26, 2018.
Comparison of single cell and single nucleus RNA-seq methodologies for creating kidney cell atlas. HCA Science Retreats. Woods Hole, MA. October 24, 2018.
Defining Kidney Organoid Cell Diversity by scRNA-Seq. Kidney Week 2017. New Orleans, LA. November 03, 2017.
Towards Single Cell RNA-Sequencing of Tubular Epithelium in AKI. Kidney Week 2017. New Orleans, LA. November 02, 2017.
| Journal | Times | Dates |
|---|---|---|
| Nephrology Dialysis Transplantation | 6 | 2023-01 | 2022-09 | 2020-03 | 2019-10 | 2018-05 | 2017-10 |
| Nature Communications | 7 | 2024-02 | 2023-08 | 2023-06 | 2022-10 | 2021-11 | 2021-09 | 2021-07 |
| Stem Cells Translational Medicine | 2 | 2019-03 | 2018-12 |
| Kidney International | 8 | 2024-02 | 2023-09 | 2022-12 | 2022-10 | 2022-09 | 2022-07 | 2022-06 | 2022-04 |
| Developmental Dynamics | 1 | 2021-01 |
| Science Translational Medicine | 1 | 2020-04 |
| Journal of the Formosan Medical Association | 1 | 2021-06 |
| Journal of the American Society of Nephrology | 3 | 2023-10 | 2023-05 | 2020-08 |
| Journal of Molecular Cell Biology | 1 | 2020-12 |
| Clinical Journal of the American Society of Nephrology | 1 | 2020-06 |
| Translational Research | 1 | 2018-08 |
| Communications Biology | 3 | 2023-03 | 2022-08 | 2021-12 |
| Scientific Reports | 1 | 2021-01 |
| Journal of Pathology | 1 | 2023-11 |
Total cites
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