Anny Xiaobo Zhou, PhD
PRIMARY APPOINTMENT:
Professor, Department of Medicine, Division of Pulmonary and Critical Care
CONTACT:
Aurbach Bldg, 450 Ray C Hunt Drive
Room 1234
Charlottesville, Virginia 22903
Telephone: 434-924-5946
Email: zhou1@virginia.edu
EDUCATION AND TRAINING:
- BS, Pharm.D, Clinical Pharmacy, Sichuan University
- PhD, Cell Biology, Peking Union Medical College
- Post-doctoral Fellow, Virology, Harvard Medical School
RESEARCH
Research Disciplines: Biochemistry, Biology, Cell and Developmental Biology, Epigenetics, Genetics, Metabolism, Molecular and Cellular Physiology, Molecular Biology, Translational Science
Research Interests: Genetics, Functional Genomics, Epigenetics, Lung repair/regeneration, Metabolic regulation, Alveolar stem cells, Chromatin interaction, Innate immune response, Live-cell imaging
During the development of chronic lung disease, repetitive environmental insults/injuries, such as cigarette smoke, respiratory viruses infection and allergy lead to ineffective repair in the genetically susceptible subjects. Molecular understanding on how such genetic factors modulate lung repair/regeneration process will potentially facilitate the identification of novel drug targets for treating complex lung disease in susceptible patients who carry risk alleles of common variants identified from genome-wide association studies (GWAS).
Our lab aims to address the missing knowledge gap between human genetic discoveries in GWAS and better understanding of lung biology especially during the development of chronic obstructive pulmonary disease ( COPD), idiopathic pulmonary fibrosis (IPF) and asthma by integrative and multidisciplinary approaches, including CRISPRi followed by single cell RNA screening for functional variants identification, and using lineage tracing mouse models, ex vivo organoid models and single live cell imaging to capture dynamic changes of various pathways regulating metabolic reprograming, exosome production and secretion, CD8+ T cells activation, innate immune response, alveolar niche-stem cell interaction to shape the fate of alveolar repair to either homeostasis or aberrant fibrosis or alveolar destruction seen in COPD lungs.
We hope to identify the converged pathways co-regulated by multiple GWAS genes in lung diseases as prioritized drug targets and also shared mechanism regulated by pleiotropy GWAS genes identified in multiple human complex traits to indicate possible re-purpose of existing drug to treat lung diseases.
Liu T, Prescott WG, Zhou X. Advances in Non-Type 2 Asthma in the Severe Cases: from molecular insights to novel treatment strategies. Eur Respir J. 2024 May 2:2300826. Epub ahead of print. PMID: 38697650
Liu T, Hecker J, Liu S, Rui X, Boyer N, Wang J, Yu Y, Zhang Y, Mou H, Gomez-Escobar LG, Choi AMK, Raby BA, Weiss ST, Zhou X. The Asthma Risk Gene, GSDMB, Promotes Mitochondrial DNA-induced ISGs Expression. J Respir Biol Transl Med. 2024 Mar;1(1):10005. PMID: 38737375
Liu T, Liu S, Rui X, Cao Y, Hecker J, Guo F, Zhang Y, Gong L, Zhou Y, Yu Y, Krishnamoorthyni N, Bates S, Chun S, Boyer N, Xu S, Park JA, Perrella MA, Levy BD, Weiss ST, Mou H, Raby BA, Zhou X. Gasdermin B, an asthma-susceptibility gene, promotes MAVS-TBK1 signaling and airway inflammation. Eur Respir J. 2024 Mar 21:2301232. PMID: 38514093
Guo F*, Zhang L*, Yu Y, Gong L, Tao S, Werder RB, Mishra S, Zhou Y, Anamika WJ, Lao T, Inuzuka H, Zhang Y, Pham B, Liu T, Tufenkjian TS, Richmond BW, Wei W, Mou H, Wilson AA, Hu M, Chen W, Zhou X. Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells. EBioMedicine. 2024 Mar;101:105026. PMID: 38417378; PMCID: PMC10944180. (*Co-first author)
Gong L, Bates S, Li Y, Lin X, Wei W, and Zhou X. AKT 1 Phosphorylates FAM13A and Promotes Its Degradation via CUL4A/DDB1/DCAF1 E3 Complex. Am J Respir Cell Mol Biol. 2023 May;68(5):577-590.
Yun JH, Lee C, Liu T, Liu S, Kim EY, Xu S, Curtis JL, Pinello L, Bowler RP, Silverman EK, Hersh CP, Zhou X. Hedgehog interacting protein-expressing lung fibroblasts suppress lymphocytic inflammation in mice. JCI Insight. 2021 Sep 8;6(17):e144575. PMID: 34375314; PMCID: PMC8492352.
Gong L, Bates S, Li J, Qiao D, Glass K, Wei W, Hsu VW, Zhou X, Silverman EK. Connecting COPD GWAS genes: FAM13A controls TGFβ2 secretion by modulating AP-3 transport. Am J Respir Cell Mol Biol. 2021 Nov;65(5):532-543. PMID: 34166600.
Benway CJ, Liu J, Guo F, Du F, Randell SH, Cho MH, Silverman EK, Zhou X; International COPD Genetics Consortium. Chromatin Landscapes of Human Lung Cells Predict Potentially Functional Chronic Obstructive Pulmonary Disease Genome-Wide Association Study Variants. Am J Respir Cell Mol Biol. 2021 Jul;65(1):92-102. PMID: 33788674.
Lin X, Li Y, Gong L, Yun JH, Xu S, Tesfaigzi Y, Qiao D, Zhou X. Tempo-spatial regulation of the Wnt pathway by FAM13A modulates the stemness of alveolar epithelial progenitors. EBioMedicine. 2021 Jul 2;69:103463. PMID: 34224973.
Lin X, Liou YH, Li Y, Gong L, Li Y, Hao Y, Pham B, Xu S, Jiang Z, Li L, Peng Y, Qiao D, Lin H, Liu P, Wei W, Zhang G, Lee CH, Zhou X. FAM13A Represses AMPK Activity and Regulates Hepatic Glucose and Lipid Metabolism. iScience. 2020 Mar 27;23(3):100928. PMID: 32151973
Hao Y, Bates S, Mou H, et al. GWAS Functional Variant rs2076295 Regulates Desmoplakin (DSP) Expression in Airway Epithelial Cells. Am J Respir Crit Care Med. 2020;10.1164/rccm.201910-1958OC. PMID: 32551799
Parker MM, Hao Y, Guo F, Pham B, Chase R, Platig J, Cho MH, Hersh CP, Thannickal VJ, Crapo J, Washko G, Randell SH, Silverman EK, San José Estépar R, Zhou X#, Castaldi PJ#. Identification of an emphysema-associated genetic variant near TGFB2 with regulatory effects in lung fibroblasts. Elife. 2019 Jul 25;8. (#, Co-corresponding author)
Castaldi P*, Guo F*, Qiao D*, Du F1, Naing Z, Li Y1, Pham B, Mikkelsen T, Cho MH, Silverman EK, Zhou X. Identification of Functional Variants in the FAM13A Chronic Obstructive Pulmonary Disease Genome-Wide Association Study Locus by Massively Parallel Reporter Assays.Am J Respir Crit Care Med. 2019 Jan 1;199(1):52-61. (*, Co-first author)
Lao T, Jiang Z, Yun J, Qiu W, Guo F, Huang C, Mancini JD, Gupta K, Laucho-Contreras ME, Naing ZZ, Zhang L, Perrella MA, Owen CA, Silverman EK, Zhou X. Hhip haploinsufficiency sensitizes mice to age-related emphysema. Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):E4681-7.
Jiang Z, Polverino F, Lao T, Qiu W, Gupta K, Mancini J.D, Cho MH, Castaldi PJ, Guo F, Sun Y, Yu J, Laucho-Contreras ME, Kobzik L, Raby BA, Choi AMK, Perrella MA, Owen CA., Silverman EK and Zhou XA. Chronic Obstructive Pulmonary Disease Susceptibility Gene, FAM13A, Regulates Protein Stability of β-Catenin. Am J Respir Crit Care Med. 2016, Jul 15;194(2):185-97.
McGeachie MJ*, Yates KP*, Zhou X, Guo F, Sternberg AL, Van Natta M, Wise RA, Szefler S, Sharma S, Kho AT, Cho MH, Croteau-Chonka DC, Castaldi PJ, Jain G, Sanyal A, Zhan Y, Lajoie BR, Dekker J, Stamatoyannopoulos J, Covar RA, Zeiger RS, Adkinson NF, Williams PV, Kelly HW, Grasemann H, Vonk JM, Koppelman G, Postma D, Raby B, Houston I, Lu Q, Fuhlbrigge A, Tantisira K, Silverman EK, Tonascia J, Weiss ST, Strunk RC. Patterns of Lung Function Growth and Decline in Persistent Childhood Asthma. N Engl J Med. 2016 May 12;374(19):1842-52.
LaoT, Glass K, QiuW, GuptaK, MorrowJ, ManciniJD, VuongL, PerrellaMA, HershCP, OwenCA, QuackenbushJ, YuanG, Silverman EK, and ZhouX*. Haploinsufficiency of Hedgehog interacting protein causes increased emphysema induced by cigarette smoke through network rewiring. Genome Med. 2015 Feb 14;7(1):12.
Sharma S*, Zhou X*, Thibault DT, Himes BE, Liu A, Szefler SJ, Strunk R, Castro M, Hansel N, DietteGB, Vonakis BM, Adkinson NF, Avila L, Soto-Quiros M, Barraza-Villareal A, Lemanske RF, Solway J, Krishnan J, White SR, Cheadle C, Berger AE, Fan J, Boorgula MP, Nicolae D, Gilliland F, Barnes K,. London SJ, Martinez F, OberC, Celedón J, Carey VJ, Weiss ST, Raby RA. A genome-wide survey of CD4+ lymphocyte regulatory genetic variants identifies novel asthma genes. J Allergy Clin Immunol. 2014 Nov;134(5):1153-62.
Zhou X#, Baron RM, Hardin M, Cho MH, Zielinski J, Hawrylkiewicz I, Sliwinski,P, Hersh CP, Mancini JD, Lu K, Thibault D, Donahue AL, Klanderman BJ, Rosner B, Raby BA, Lu Q, Geldart AM, Layne MD, Perrella MA, Weiss ST, Choi AMK, Silverman EK#. Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP. Human Molecular Genetics, 2012, Mar 15;21(6):1325-35. (#corresponding author)