Dr. Hu Huang's primary focus involves studying the retina. The retina is a metabolically active nervous tissue that senses and converts light into electrical signals for visual perception in the brain. The normal visual function requires retinal homeostasis primarily maintained by blood-retinal barrier (BRB) and neuroglia-mediated surveillance. Retinal pigment epithelium (RPE) and vascular endothelial cells (ECs) comprise the outer (o) and inner (i)BRB, respectively. Pericytes, photoreceptors, glial, and ganglion cells reinforce BRB structure and function. Retinal diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), impair BRB integrity and reactivate neuroglia.
Dr. Huang's primary research interest is deciphering the molecular and cellular mechanisms of BRB integrity and neuroglial reactivation in retinal health and disease. One active project elaborates on the placental growth factor (PlGF)’s role in iBRB function using human retinal ECs, iPSC-derived vascular organoids, and transgenic mice. New mechanisms include regulation of glucose-6-phosphate dehydrogenase (G6PD), crosstalk with Angiopoietin/Tie2 and TGF-β, and epigenetic mechanism by histone deacetylase. G6PD’s antioxidant function via oxidative pentose phosphate pathway (oxPPP) is essential for retinal cell survival during oxidative stress.
Another project explores the roles of mitochondrial abnormality, autophagy dysfunction, and epithelial-mesenchymal transition in RPE dysfunction and AMD pathogenesis. Evidence suggests that CXCR5 is involved in microglial activation, RPE homeostasis, and oBRB function by regulating the Forkhead-box transcription factors. New projects include transcription control of glial activation and exosome-mediated cell (mis)communications in retinal health and diseases using genomics, proteomics, CRISPR-Cas9 gene editing, and genetically-modified mouse models. Together, Dr. Huang's research aims to understand pathophysiology, design therapy, and restore vision for retinal neurodegenerative and microvascular diseases.
1 Hospital Dr
Columbia, MO 65212
- Blood retinal barrier
- Diabetic retinopathy
- Retinal degeneration
- Cytokine and chemokine
- Pathological angiogenesis
Areas of Expertise
- Gene expression
- Retinal cell cultures
- Stem cells & iPSCs
- Mouse models
Education & Training
PhD, Shanghai Institute of Biochemistry
Johns Hopkins University
Awards & Honors
- Active NIH/NEI R01 Research Grant
- NIH/NEI Travel Grant (ARVO, Florida)
- BrightFocus Foundation-MD Research Award
- Wilmer Research Grant Award, Johns Hopkins University
- Knights Templar Eye Foundation Research Fellowship Award
- Huang H, Saddala MS, Mukwaya, A, Mohan RR, Lennikov A. Association of placental growth factor and angiopoietin in human retinal endothelial cell-pericyte co-cultures and iPSC-derived vascular organoids. Cur Eye Res. 2022. Cur Eye Res. 2022 Dec 2;1-15. doi: 10.1080/02713683.2022.2149808.
- Yang X, Diaz V, Huang H. The role of interferon regulatory factor 1 in regulating microglial activation and retinal inflammation. Int J Mol Sci. 2022. Int J Mol Sci. 2022. 23(23),14664. http://doi.org/10.3390/ijms232314664.
- Balne PK, Gupta S, Keele L, Landon KM, Sinha NR, Hoffman AC, Hauser N, Sinha PR, Huang H, Kempuraj D, Mohan RR. Characterization of C-X-C chemokine receptor type 5 (CXCR5) in the cornea and role in the inflammatory response after corneal injury. Exp Eye Res. doi:10.1016/j.exer.2022.109312. PMID: 36400287.
- Saddala MS, Yang X, Tang S, Huang H. Transcriptome-wide analysis reveals core sets of transcription factors of retinal microglial sensome and inflammatory genes in retinal microglia. Genomics. 2021, 113:3058-3071.
- Saddala MS, Lennikov A, Mukwaya A, Yang X, Tang S, Huang H. Data mining and network analysis reveal C-X-C chemokine receptor type 5 is involved in the pathophysiology of age-related macular degeneration. J Biomol Struct Dyn. 2021. Jul 9:1-10. Doi: 10.1080/07391102.2021.1949391. PMID: 34243690.
- Hikage F, Lennikov A, Mukwaya A, Lachota M, Ida Y, Utheim TP, Chen D-F, Huang H, Ohguro H. NF-κB activation in retinal microglia is involved in the inflammatory and neovascularization signaling in laser-induced choroidal neovascularization in mice. Exp Cell Res. 2021. 403:112581. doi:10.1016/j.yexcr.2021.12581. PMID: 33811906.
- Lennikov A, Mukwaya A, Saddala MS, Fan L, Sandro D, Huang H. Synergistic interactions of PlGF and VEGF contribute to blood-retinal barrier breakdown through canonical NFκB activation. Exp Cell Res. 2020. 397(2):112347. PMID: 33130176. DOI: 10.1016/j.yexcr.2020.112347.
- Huang H. Pericyte-Endothelial Interaction in the Retinal Microvasculature. Int. J. Mol. Sci. 2020, 21(19), 7413; doi: 103390/ijms21197413. (Review)
- Lennikov A, Mukwaya A, Saddala MS, Mukwaya A, Huang H. Deficiency of C-X-C chemokine receptor type 5 (CXCR5) gene causes dysfunction of retinal pigment epithelium cells. Lab Invest. 2020. PMID: 3299482. DOI: 10.1038/s41374-020-00491-4.
- Huang H, Saddala M, Lennikov A, Mukwaya, A., Fan F. RNA-seq reveals placental growth factor regulates the human retinal endothelial cell barrier integrity by transforming growth factor (TGF-β) signaling. Mol Cell Biochem. 2020. PMID: 32813141. DOI: 10.1007/s11010-020-03862-z
- Saddala MS, Lennikov A, Huang H. RNA-seq data from C-X-C chemokine receptor type 5 (CXCR5)gene knockout aged mice with retinal degeneration phenotype. Bata Brief. 2020. 31:105915. PMID: 32642521. DOI: 10.1016/j.dib.2020.105915.
- Saddala MS, Lennikov A, Mukwaya, A. Huang H. Transcriptome-wide analysis of CXCR5 deficient retinal pigment epithelial (RPE) cells reveals molecular signatures of RPE homeostasis. Biomedicines. 2020. 8(6),147. DOI: 10.3390/biomedicines8060147.
- Huang H, Lennikov A. CXCR5/NRF2 double knockout mice develop age-related macular degeneration-like phenotypic features at early ages. Exp. Eye Res. 2020.196:108061. DOI: 10.1016/j.exer.2020.108061.
- Saddala MS, Lennikov A, Mukwaya A, Huang H. Anti-inflammatory and anti-angiogenic effects of novel L-VGCC blockers in microglia cell culture and ocular angiogenesis models. J. Neuroinflammation. 2020. 17:132.
- Saddala MS, Lennikov A, Huang H. Discovery of Small-Molecule Activators for Glucose-6-Phosphate Dehydrogenase (G6PD) Using Machine Learning Approaches. Int J Mol Sci. 2020 Feb 23;21(4). doi: 10.3390/ijms21041523. PMID: 32102234.
- Saddala MS, Lennikov A, Huang H. Placental Growth Factor Regulates the Pentose Phosphate Pathway and Antioxidant Defense Systems in Human Retinal Endothelial Cells. J. Proteomics. 2020:10;217:103682.
- Saddala MS, Lennikov A, Huang H. RNA-Seq reveals expression profile of genes involved in retinal degeneration in Pde6c mutant Danio rerio. BMC Genomics. 2020. 21(1). DOI:10.1186/s12864-020-6550-z.
- Huang H, Lennikov A, Saddala M, Grab JD, Gozal, D, Khalyfa, A, Fan F. Placental growth factor negatively regulates endothelial cell barrier function through suppression of glucose-6-phosphate dehydrogenase and anti-oxidant defense systems. FASEB Journal. 2019: 33(12). PMID: 31585507. DOI: 10.1096/fj.201901353.
- Lennikov A, Saddala MS, Mukwaya A, Tang S, Huang H. Autoimmune-mediated retinopathy in CXCR5-deficient mice as the result of accumulation of age-related macular degeneration associated proteins. Front Immunol. 2019:10:1903. PMID: 31474986. doi: 10.3389/fimmu.2019.01903.
- Saddala MS, Huang H. Identification of novel inhibitors for TNF-α, TNF receptor-1 and TNF-α, TNF receptor-1 complex using pharmacophore-based approaches. J Transl Med. 2019: 17(1): 215. PMID: 31266509. doi: 10.1186/s12967-019-1965-5.
- Cao X, Li W, Liu Y, Huang H, Ye C. The anti-inflammatory effects of Cxcr5 in the mouse retina following acute ocular hypertension. Biomed Res Int. 2019: 3487607. doi: 10.1155/2019/3487607.
- Saddala MS, Lennikov A, Anthony M, Huang H. Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs and SSRs in the age-related macular degeneration. Human Genomics. 2019.13:15.