Academic Title:
Professor
Primary Appointment:
Medicine
Secondary Appointment(s):
Physiology
Additional Title:
Director, Center for Precision Disease Modeling
Email:
Location:
670 West Baltimore St, Baltimore, MD 21201
Phone (Primary):
410-706-4047
Phone (Secondary):
734-355-2700 (Cell)
Fax:
410-706-4060
Education and Training
- Peking University, Beijing, China, B.S., Cell Biology and Genetics, 1991-1996
- University of Michigan, Ann Arbor, Michigan, Ph.D, Molecular, Cellular and Developmental Biology,1996-2002
- University of Texas Southwestern Medical Center, Dallas, Texas, Postdoc Fellow, Molecular Biology and Developmental Biology, 2002-2006
Biosketch
Dr. Han is a developmental biologist with a research program focused on using Drosophila and human cells to model human diseases and to identify precision medicine-based therapeutics. Dr. Han's lab is focused on using fruit flies and human cells to provide functional validation for novel genetic variants associated with heart, kidney, muscle, blood, and metabolic diseases.
An independent PI since 2006, Dr. Han has made seminal contributions to establish the fruit fly Drosophila as an important model system for heart and kidney diseases. His lab established the Drosophila heart as a high-throughput functional validation platform for genetic variants associated with Congenital Heart Disease, the most common birth defect. His lab is also the first to discover that the Drosophila nephrocyte is the functional equivalent of human podocyte and renal proximal tubule (by combining filtration and protein reabsorption), and can be used to model many types of kidney diseases. Dr. Han's lab found that over 85% of known Neprhotic Syndrome genes are conserved in flies and required for nephrocyte function. Dr. Han designed a novel "Gene Replacement" approach and used it to identify and validate many heart and renal disease genes and variants. In one of these studies, his lab identified a dietary supplement as an effective therapeutic treatment using a personalized Drosophila renal disease model carrying the exact COQ2 gene variant from patient. This dietary supplement is now a top-choice precision medicine treatment for renal diseases caused by genetic variants in the COQ pathway genes. Dr. Han's lab is also the first to establish a fly model of APOL1 nephropathy, a kidney disease that affects many African Americans. Recently, Dr. Han's lab used Drosophila and human cells to study the genes of the SARS-CoV-2 virus that causes COVID-19, and identified three highly pathogenic SARS-CoV-2 proteins, their host interactions, as well as potential drugs that could inhibit their pathogenicity.
See the Contributions to Science section below for more information.
Research/Clinical Keywords
Drosophila, Human Disease Models, heart, kidney, blood, muscle, metabolic diseases, nephrocyte, congenital heart disease, leukemia, nephrotic syndrome, genetic kidney diseases, drug screen, APOL1 nephropathy, COVID-19, SARS-CoV-2, viral protein host interaction
Highlighted Publications
Zhao, Y., van de Leemput, J., and Han, Z.* (2023) The opportunities and challenges of using Drosophila to model human cardiac diseases. Frontiers in Physiology (E-published on April 12, 2023) PMID: 37123266. (*Corresponding author).
Zhu, J.Y., Wang, G., Huang, X., Lee, H., Lee, J.G., Yang, P, van de Leemput, J., Huang, W., Kane, M.A., Yang, P., and Han, Z.* (2022) SARS-CoV-2 Nsp6 causes cardiac defects through MGA/MAX complex-mediated increased glycolysis. Communications Biology (E-published on September 30, 2022). 5 (1):1039. PMID: 36180527. (*Corresponding author).
Huang, W., Zhu, J.Y., Fu, Y., van de Leemput, J., and Han, Z.* (2022) Lpt, trr and Hcf regulate histone mono- and dimethylation that are essential for Drosophila heart development. Developmental Biology (E-published on July 16, 2022). PMID: 35853502. (*Corresponding author).
van de Leemput, J., Wen, P., and Han, Z.* (2022) Using Drosophila nephrocytes to understand the formation and maintenance of the podocyte slit diaphragm. Frontiers in Cell and Developmental Biology (E-published on Feb. 21, 2022). PMID: 35265622. (*Corresponding author).
Zhu, J.Y., Huang, X., Fu, Y., Wang, Y., Zheng, P., Liu, Y., and Han, Z.* (2022) Pharmacological or genetic inhibition of hypoxia signaling attenuates oncogenic RAS-induced cancer phenotypes. Disease Model & Mechanisms (E-published on September 28, 2021). PMID: 34580712. (*Corresponding author).
van de Leemput, J., and Han, Z.* (2021) Drosophila, a powerful model to study virus-host interactions and pathogenicity in the fight against SARS-CoV-2. Cell & Bioscience (E-published on June 13, 2021). PMID: 34120640. (*Corresponding author).
van de Leemput, J., and Han, Z.* (2021) Understanding individual SARS-CoV-2 proteins for targeted drug development against COVID-19. Molecular & Cellular Biology (E-published on June 14, 2021). PMID: 34124934. (*Corresponding author).
Lee, J.G., Huang, W., Lee, H., van de Leemput, J., Kane, M.A., and Han Z.* (2021) Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor. Cell & Bioscience (E- published on March 25, 2021). PMID: 33766124. (*Corresponding author).
Zhu, J.Y., Lee, J.G., van de Leemput, J., Lee, H., and Han, Z.* (2021) Functional analysis of SARS-CoV-2 proteins in Drosophila identifies Orf6-induced pathogenic effects with Selinexor as an effective treatment. Cell & Bioscience (E-published on March 25, 2021). PMID: 33766136. (*Corresponding author).
Wen, P., Zhang, F., Fu, Y., Zhu, J.Y., Richman A., Han, Z.* (2020) Exocyst Genes Are Essential for Recycling Membrane Proteins and Maintaining Slit Diaphragm in Drosophila Journal of the American Society of Nephrology 31(5): 1024-1034 (E-pub on April 1st, 2020) PMID: 32238475. (*Corresponding author).
Fu, Y., Huang, X., Zhang, P., van de Leemput, J., and Han, Z.* (2020) Single-cell RNA sequencing identifies novel cell types in Drosophila Journal of Genetics and Genomics (E-pub on March 9, 2020) PMID: 32487456. (*Corresponding author).
Zhao, F., Zhu, J.Y., Richman, A., Fu, Y., Huang, W., Chen, N., Pan, X., Yi, C., Ding, X., Wang, S., Ma, Y., Nie, X., Huang, J., Yang, Y., Yu, Z., and Han, Z. *(2019) Mutations in NUP160are implicated in Steroid-Resistant Nephrotic Syndrome. Journal of the American Society of Nephrology (E-pub on March 25, 2019). PMID: 30910934. (*Corresponding author).
Zhu, J.Y., Fu, Y., Richman, A., Zhao, Z., Ray, P.E., and Han, Z.*(2017) A personalized Drosophila model of COQ2 nephropathy rescued by the wild-type human COQ2 allele and dietary Q10 supplementation. Journal of the American Society of Nephrology 28(9): 2607 – 2617. PMID: 28428331. (Featured on the cover of JASN for the September 2017 issue). (*Corresponding author).
Fu, Y., Zhu, J.Y., Richman, A., Zhao, Z., Zhang, F., Ray, P.E., Han, Z.*(2017) A Drosophila model system to assess the function of human monogenic podocyte mutations that cause nephrotic syndrome. Human Molecular Genetics 26(4): 768-780. E-published on Feb. 6, 2017. PMID: 28164240. (*Corresponding author).
Zhu, J.Y., Fu, Y., Nettleton, M., Richman, A., and Han, Z.*(2017). High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila. eLife(E-published on Jan. 20, 2017). PMID: 28084990; PMCID: PMC5300701. (*Corresponding author).
Fu, Y., Zhu, J.Y., Richman, A., Zhang, Y., Xie, X., Das, J.R., Li, J., Ray, P.E., and Han, Z.*(2017) APOL1-G1 in nephrocytes induces hypertrophy and accelerates cell death. Journal of the American Society of Nephrology 28(4): 1106-1116.E-published on Nov. 18, 2016. PMID: 27864430; PMCID: PMC5373456. (Featured by editorial “Mechanisms of APOL1-associated renal disease”, Nature Review Nephrology13, page 62, 2017.) (*Corresponding author).
Patel, M.V., Zhu, J.Y., Jiang, Z., Richman, A., VanBerkumF. and Han, Z.*(2016) Gia/Mthl5 is an aorta specific GPCR required for Drosophilaheart tube morphology and normal pericardial cell positioning. Developmental Biology 414, 100-107. PMID: 26994946; PMCID: PMC4875858. (*Corresponding author).
Chen, Z. Zhu, J.Y., Fu, Y., Richman, A., and Han, Z.*(2016) Wnt4 is required for ostia development in Drosophila. Developmental Biology 413, 188-198. PMID: 26994311; PMCID: PMC4857614.(*Corresponding author).
Zhang, F., Zhao, Y., Chao, Y., Muir, K., and Han, Z.*(2013). Cubilin and Amnionless mediate protein reabsorption in Drosophila Journal of the American Society of Nephrology24(2): 209-216. Epub Dec. 20, 2012. PMID: 23264686; PMCID: PMC3559489. (This paper was featured in commentary: “The Drosophila nephrocyte: Back on stage”, Na, J. and Cagan, R., Journal of the American Society of Nephrology 24, 161-163, 2013.) (*Corresponding author).
Zhang, F., Zhao, Y., and Han, Z.*(2013). An in vivofunctional analysis system for renal gene discovery in Drosophilapericardial nephrocytes. Journal of the American Society of Nephrology24(2): 191-197. Epub Jan. 4, 2013. PMID: 23291470; PMCID: PMC3559487. (This paper was featured as “This Month’s Highlights” in JASN: “Drosophila facilitate study of podocytes”, by JASN editors)(*Corresponding author).
Chen, Z., Liang, S., Zhao, Y., and Han, Z.*(2012). MiR-92b regulates Mef2 levels through a negative feedback circuit during Drosophila muscle development. Development139(19): 3543-3552. Epub Aug. 16, 2012. PMID: 22899845; PMCID: PMC3436111. (*Corresponding author).
Yi, P.*, Han, Z.*#, Li, X., and Olson, E.N.# (2006). The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1. Science 313 (5791): 1301 – 1303. (E-pub on July 20, 2006). PMID: 16857902. (*Co-first author and # co-corresponding author).
Additional Publication Citations
Han, Z., Fujioka, M., Su, M., Liu, M., Jaynes, J.B., and Bodmer, R. (2002). Transcriptional integration of competence modulated by mutual repression generates cell-type specificity within the cardiogenic mesoderm. Developmental Biology252(2), 225-240. PMID: 12482712; PMCID: PMC2693947.
Han, Z., Bodmer, R. (2003). Myogenic cells fates are antagonized by Notchonly in asymmetric lineages of the Drosophilaheart, with or without cell division. Development130(13), 3039-3051.PMID: 12756185.
Han, Z., Li, X., Wu, J. and Olson, E.N. (2004). A myocardin-related transcription factor regulates activity of serum response factor in Drosophila. Proceedings of the National Academy of Sciences101(34), 12567-12572. PMID: 15314239; PMCID: PMC515097.
Han, Z., Olson, E.N. (2005). Hand is a direct target of Tinman and GATA factors during Drosophilacardiogenesis and hematopoiesis. Development132(15): 3525-3536. PMID: 15975941.
Fujioka, M., Wessells, R. J., Han, Z., Liu, J., Fitzgerald, K., Yusibova, G. L., Zamora, M., Ruiz-Lozano, P., Bodmer, R., Jaynes, J. B. (2005). Embryonic even-skipped-Dependent Muscle and Heart Cell Fates Are Required for Normal Adult Activity, Heart Function, and Lifespan. Circulation Research97(11), 1108-1114. PMID: 16239588; PMCID: PMC2726805.
Kwon, C.*, Han, Z.*, Olson, E.N., Srivastava, D. (2005). DrosophilamicroRNA1 regulates Notch signaling during cardiac lineage determination and differentiation. Proceedings of the National Academy of Sciences 102(52), 18987-18991 (*Co-first author). PMID: 16357195; PMCID: PMC1315275.
Han, Z., Yi, P., Li, X., Olson, E.N.(2006). Hand, an evolutionarily conserved bHLH transcription factor required for Drosophilacardiogenesis and hematopoiesis. Development133 (6): 1175-1182.PMID: 16467358.
Yi, P.*, Han, Z.*,#, Li, X., Olson, E. N#. (2006). The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1. Science313(5791): 1301 – 1303. PMID: 16857902. (*Co-first author and #co-corresponding author).(This paper was featured in Editor’s Choice titled “Holding the heart together”, Science Signaling351, p307, 2006)
Liotta, D., Han, J., Elgar, S., Garvey, C., Han, Z., and Taylor, M.V. (2007). The Him gene reveals a balance of inputs controlling muscle differentiation in Drosophila Current Biology. 17(16):1409-1413. PMID: 17702578; PMCID: PMC1955682.
Liu, J., Qian, L., Han, Z., Wu, X, Bodmer, R. (2008). Spatial specificity of mesodermal even-skipped expression relies on multiple repressor sites. Developmental Biology313(2), 876-886. PMID: 18067885;PMCID: PMC2245897.
Elalayli, M., Hall, J. D., Fakhouri, M., Neiswender, H., Ellison, T., Han, Z., Roon, P., LeMosy, E. K. (2008).Palisade is required in the Drosophilaovary for assembly and function of the protective vitelline membrane. Developmental Biology319(2), 359-369. PMID: 18514182; PMCID: PMC2536644.
Yi, P., Johnson A. N., Han, Z., Wu, J., and Olson, E. N. (2008). Heterotrimeric G proteins regulate a noncanonical function of septate junction proteins to maintain cardiac integrity in Drosophila. Developmental Cell, 15(5): 704 – 713. PMID: 19000835; PMCID: PMC2736786.
Chen, Z., Liang, S., Zhao, Y., and Han, Z. (2012). MiR-92b regulates Mef2 levels through a negative feedback circuit during Drosophila muscle development. Development139(19): 3543-3552. Epub Aug. 16, 2012. PMID: 22899845; PMCID: PMC3436111.
Zhang, F., Zhao, Y., and Han, Z. (2013). An in vivofunctional analysis system for renal gene discovery in Drosophilapericardial nephrocytes. Journal of the American Society of Nephrology24(2): 191-197. Epub Jan. 4, 2013. PMID: 23291470; PMCID: PMC3559487. (This paper was featured as “This Month’s Highlights” in JASN: “Drosophila facilitate study of podocytes”, by JASN editors.)
Zhang, F., Zhao, Y., Chao, Y., Muir, K., and Han, Z. (2013). Cubilin and Amnionless mediate protein reabsorption in Drosophila Journal of the American Society of Nephrology24(2): 209-216. Epub Dec. 20, 2012. PMID: 23264686; PMCID: PMC3559489. (This paper was featured in commentary: “The Drosophila nephrocyte: Back on stage”, Na, J. and Cagan, R., Journal of the American Society of Nephrology24, 161-163, 2013.)
Gee, H.Y., Saisawat, P., Ashraf, S., Hurd, T.W., Vega-Warner, V., Fang, H., Beck, B.B., Gribouval, O., Zhou, W., Diaz, K.A., Natarajan, S., Wiggins, R.C., Lovric, S., Chernin, G., Schoeb, D.S., Ovunc, B., Frishberg, Y., Soliman, N.A., Fathy, H.M., Goebel, H., Hoefele, J., Webernn, J.W., Faul, C., Han, Z., Washburn, J., Antignac, C., Levy, S., Otto, E.A., Hildebrandt, F. (2013). ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling. Journal of Clinical Investigation123, 3243 - 3253. PMID: 23867502.
Ashraf S., Gee H. Y., Woerner, S., Vega-Warner, V., Lovric, S., Fang, H., Xie, L., Song, X., Cattran, D.C., Paterson, A., Nitschké, P., Cochat, P., Zhou, W., Airik, R., Allen, S., Otto, E., Kari, J., Böckenhauer, D., Kleta, R., Gok, F., Washburn, J., Wiggins, R.C., Choi, M., Lifton R.P., Levy S., Han, Z.,Salviati L., William, D.S.,Pollak, M., Pei, Y., Antignac, C., Hildebrandt., F. (2013). Exome resequencing reveals ADCK4 mutations as a novel cause of steroidresistant nephrotic syndrome. Journal of Clinical Investigation123(12), 5179-5189. PMID: 24270420; PMCID: PMC3859425
Gee, H.Y., Zhang F., Ashraf, S., Kohl, S., Sadowski C., Vega-Warner, V., Zhou, W., Fang H., Lovric, S., Hoefele, J., Weber, L., Podracka, L., Boor, A., Innis, J., Washburn, J., Salviati L., William, D.S., Levy, S., Otto, E., Han, Z.*, and Hildebrandt, F.* (2015) KANK deficiency leads to defective podocyte function and nephrotic syndrome. Journal of Clinical Investigation125(6), 2375-2384. PMID: 25961457; PMCID: PMC4497755. (*Co-corresponding author).
Fulga T.A., McNeill, E.M., Binari, R., Yelick, J., Blanche, A., Booker, M., Zhao, Y., Bejarano, F., Han, Z.,Lai, E.C., Wall, D.P., Perrimon, N., Van Vactor, D. (2015) A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs. Nature Communication.6: 7279, E-published on June 17, 2015). PMID:26081261; PMCID: PMC4471878
Chen, Z. Zhu, J.Y., Fu, Y., Richman, A., and Han, Z.(2016) Wnt4 is required for ostia development in the Drosophila Developmental Biology 413, 188-198. PMID: 26994311; PMCID: PMC4857614.
Patel, M.V., Zhu, J.Y., Jiang, Z., Richman, A., VanBerkumF. and Han, Z.(2016) Gia/Mthl5 is an aorta specific GPCR required for Drosophilaheart tube morphology and normal pericardial cell positioning. Developmental Biology 414, 100-107. PMID: 26994946; PMCID: PMC4875858
Jiang, Z., Li, F., Wan, Y., Han, Z.,Yuan, W., Cao, L., Deng, Y., Peng, X., Chen, F., Fan, X., Liu, X., Dai, G., Wang, Y., Zeng, Q., Shi, Y., Zhou, Z., Chen, Y., Xu, W., Luo, S., Chen, S., Ye, X., Mo, X., Wu, X., and Li, Y. (2016) LASS5 Interacts with SDHB and Synergistically Represses p53 and p21 Activity. Current Molecular Medicine16(6):582-90. PMID: 27280497; PMCID: PMC5280074.
Li, J., Das, J.R., Tang, P., Han, Z.,Jaiswal, J.K., Ray, P.E. (2016) Transmembrane TNF-α Facilitates HIV-1 Infection of Podocytes Cultured from Children with HIV-Associated Nephropathy. Journal of the American Society of Nephrology28(3): 862-875. E-published on Nov. 3, 2016. PMID: 27811066; PMCID: PMC5328167.
Fu, Y., Zhu, J.Y., Richman, A., Zhang, Y., Xie, X., Das, J.R., Li, J., Ray, P.E., and Han, Z. (2017) APOL1-G1 in nephrocytes induces hypertrophy and accelerates cell death. Journal of the American Society of Nephrology 28(4): 1106-1116.E-published on Nov. 18, 2016. PMID: 27864430; PMCID: PMC5373456. (Featured by editorial “Mechanisms of APOL1-associated renal disease”, Nature Review Nephrology13, page 62, 2017.)
Zhu, S., Han, Z.,Luo, Y., Chen, Y., Zeng, Q., Wu, X., and Yuan, W. (2016) Molecular mechanisms of heart failure: insights from Drosophila. Heart Failure Review22(1): 91-98. E-published on Dec. 1, 2016. PMID: 27904993; PMCID: PMC5222906.
Zhu, J.Y., Fu, Y., Nettleton, M., Richman, A., and Han, Z.(2017). High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila. eLife(E-published on Jan. 20, 2017). PMID: 28084990; PMCID: PMC5300701.
Fu, Y., Zhu, J.Y., Richman, A., Zhao, Z., Zhang, F., Ray, P.E., Han, Z.(2017) A Drosophila model system to assess the function of human monogenic podocyte mutations that cause nephrotic syndrome. Human Molecular Genetics 26(4): 768-780. E-published on Feb. 6, 2017. PMID: 28164240.
Fu, Y., Zhu, J.Y., Zhang, F., Richman, A., Zhao, Z., and Han, Z.(2017) Comprehensive functional analysis of Rab GTPase genes in Drosophila nephrocytes. Cell and Tissue Research368(3): 615-627. E-published on Feb. 8, 2017. PMID: 28180992; PMCID: PMC5429992.
Zhu, J.Y., Heidersbach, A., Kathiriya, I.S., Garay, B.I., Ivey, K.N., Srivastava, D., Han, Z.*,and King, I.N.* (2017) The E3 ubiquitin ligase Nedd4/Nedd4L is directly regulated by microRNA-1. Development144, 866-875. (*Co-corresponding author, E-published on Mar. 1, 2017). PMID: 28246214; PMCID: PMC5374346.
Zhu, J.Y., Fu, Y., Richman, A., and Han, Z*.(2017). Validating candidate congenital heart disease genes in Drosophila.Bio Protocol(E-published on June 20, 2017), Vol 7, Issue 12. PMID: 29276722. (*Corresponding author).
Zhu, J.Y., Fu, Y., Richman, A., Zhao, Z., Ray, P.E., and Han, Z.(2017) A personalized Drosophila model of COQ2 nephropathy rescued by the wild-type human COQ2 allele and dietary Q10 supplementation. Journal of the American Society of Nephrology 28(9): 2607 – 2617. PMID: 28428331; PMCID: PMC5576924. (Featured on the cover of JASN for the September 2017 issue).
Basu, M., Zhu, J.Y., LaHaye, S., Majumdar, U., Jiao, K., Han, Z.*,and Garg, V.* (2017) Epigenetic mechanisms underlying maternal diabetes-associated risk of congenital heart disease. JCI Insight2(20), E-published on Oct. 19, 2017. PMID: 29046480. (*Co-corresponding author).
Okamoto, K., Rausch, J.W., Wakashin, H., Fu, Y., Chung, J.Y., Dummer, P.D., Shin, M., Chandra, P., Suzuki, K., Shrivastav, S., Rosenberg, A.Z., Hewitt, S.M., Ray, P., Noiri, E., Grice, S.F., Hoek, M., Han, Z.,Kopp, J.B. (2018) APOL1 risk allele RNA contributes to renal toxicity injury by activating protein kinase R. Communications Biology1, 188. E-published on Nov. 7, 2018. PMID: 30417125.
Zhao, F., Zhu, J.Y., Richman, A., Fu, Y., Huang, W., Chen, N., Pan, X., Yi, C., Ding, X., Wang, S., Ma, Y., Nie, X., Huang, J., Yang, Y., Yu, Z., and Han, Z*.(2019) Mutations in NUP160are implicated in Steroid-Resistant Nephrotic Syndrome. Journal of the American Society of Nephrology (E-pub on March 25, 2019). PMID: 30910934.
Cina, D., Ketela, T., Brown, K.R., Chandrashekhar, M., Mero, P., Li, C., Onay, T., Fu, Y., Han, Z., Saleem, M.A., Moffat, J., and Quaggin, S.E. (2019) Forward genetic screen in human podocytes identifies diphthamide biosynthesis genes as regulators of adhesion. American Journal of Physiology-Renal Physiology (E-pub on Sep. 30, 2019) PMID: 31566424.
Harsh, S., Fu, Y., Kenney, E., Han, Z., and Eleftherianos, I. (2020) Zika virus non-structural protein NS4A restricts eye growth in Drosophila through regulation of JAK/STAT signaling. Disease Model & Mechanisms 13 (4): dmm040816. (E-pub on March 9, 2020) PMID: 32152180.
Fu, Y., Huang, X., Zhang, P., van de Leemput, J., and Han, Z.* (2020) Single-cell RNA sequencing identifies novel cell types in Drosophila Journal of Genetics and Genomics (E-pub on March 9, 2020) PMID: 32487456. (*Corresponding author).
Wen, P., Zhang, F., Fu, Y., Zhu, J.Y., Richman A., Han, Z.* (2020) Exocyst Genes Are Essential for Recycling Membrane Proteins and Maintaining Slit Diaphragm in Drosophila Journal of the American Society of Nephrology 31(5): 1024-1034 (E-pub on April 1st, 2020) PMID: 32238475. (*Corresponding author).
Manivannan S.N., Darouich, S., Masmoudi, A., Fordon, D., Zender, G., Han, Z., White, P., McBride, K., and Garg, V. (2020) Novel frameshift variant in MYL2 reveals molecular differences between dominant and recessive forms of hypertrophic cardiomyopathy. PLoS Genetics (E-pub on May 26, 2020) PMID: 32453731.
Ekure, E.N., Adeyemo, A., Liu, H., Sokunbi, O., Kalu, N., Martinez, A.F., Owosela, B., Tekendo-Ngongang, C., Addissie, Y.A., Olusegun-Joseph, A., Ikebude, D., Berger, S.I., Muenke, M., Han, Z. and Kruszka, P. (2020) Exome Sequencing and Congenital Heart Disease in Sub-Saharan Africa. Circulation: Genomic and Precision Medicine (E- published on Dec. 31, 2020). PMID: 33448881.
Zhu, J.Y., Hannan, S.B., Dräger, N.M., Vereshchagina, N., Krahl, A.C., Fu, Y., Elliott, C.J., Han, Z., Jahn, T.R., and Rasse, T.M. (2021) Autophagy inhibition rescues structural and functional defects caused by the loss of mitochondrial chaperone Hsc70-5/mortalin in Drosophila. Autophagy (E- published on Jan. 6, 2021). PMID: 33404278.
Wan, X., Perry, J., Zhang, H., Jin, F., Ryan, K.A., Van Hout, C., Reid, J., Overton, J., Baras, A., Han, Z., Streeten, E., Li, Y., Mitchell, B.D., Shuldiner, A.R. and Fu, M. (2021) Heterozygosity for a Pathogenic Variant in SLC12A3 That Causes Autosomal Recessive Gitelman Syndrome Is Associated with Lower Serum Potassium. Journal of the American Society of Nephrology 32 (3): 756 – 765. (E-published on March 1, 2021). PMID: 33542107.
Yu, R., Cao, X., Sun, L., Zhu, J.Y., Wasko, B.M., Liu, W., Crutcher, E., Liu, H., Jo, M.C., Qin, L., Kaeberlein, M., Han, Z., and Dang, W. (2021) High-throughput yeast replicative lifespan screen shows that histone deacetylase complex HDA regulates aging. Nature Communications (E-published on March 31, 2021). PMID: 33790287.
For a complete list of Dr. Han's published work, visit: MyBibliography
Research Interests
The main research interest of Dr. Han is to use the fruit fly Drosophila and human cells to model human diseases, to provide functional data for human genetic variants, and to discovery disease mechanisms and develop targeted treatments. Dr. Han’s lab has developed many types of Drosophila disease models. As a developmental biologist, he is particularly interested in genetic variants that affect the development and function of heart, kidney, blood, muscle and metabolism, as well as cancer and COVID-19.
For heart diseases, his lab developed the first high-throughput variant function validation system for Congenital Heart Disease. His lab also discovered many new genes required for heart development in flies.
For kidney diseases, his lab developed the first in vivo functional assay for Drosophila nephrocytes, which share striking similarities with human glomerular podocytes. His lab is the first to use nephrocytes to model and study human genetic kidney diseases.Work done in Dr. Han’s lab has led to the discovery of several new kidney disease genes, as well as a targeted treatment for a specific type of genetic kidney disease.
For blood, muscle and metabolic diseases, Dr. Han’s lab developed novel functional assays and fly models to study genetic variants involved in leukemia, congenital muscular dystrophy, and different types of metabolic diseases.
For cancer, Dr. Han's lab estabolished a series of novel leukemia models using Drosophila, and used these leukemia models for genetic screen and drug screen.
For COVID-19, Dr. Han's lab used Drosophila and human cells to study the function of all 29 proteins in the SARS-CoV-2 virus that causes the COVID-19 pandemic, and identified the three most pathogenic SARS-CoV-2 proteins and their host interactions, as well as potential drugs that could inhibit their pathogenicity.
The long-term goal of Dr. Han’s research is to establish Drosophila as a primary model system for providing the much-needed functional data for large number of genetic variants identified from patient sequencing, and to use Drosophila precision disease models to discover underlying mechanism, and to develop mechanism-based targeted treatment using fly models and human cells.
Awards and Affiliations
Society Memberships
- 1998 – present: Genetic Society of America
- 1999 – present: American Heart Association
- 2006 – present: Society of Chinese Bioscientists in America
- 2011 – present: American Society of Nephrology
- 2016 – present: American Society of Human Genetics
Academic Honors
- 1997: University of Michigan Horace H. Rackham School of Graduate Studies, Pre-Doctorial Fellowship
- 2001: American Heart Association, Council on Cardiovascular Disease, Weinstein Cardiovascular Development Research Conference, Travel Award
- 2003: Pathways to Cardiac Development and Regeneration Conference, Young Investigator Award
- 2006: Genetics Society of America, 47th Annual Drosophila Research Conference, Best presentation Award
- 2006: University of Michigan Biomedical Sciences Scholar
- 2015: First Sino-US-Japan Pediatric Translational Medicine Forum, Lecture Award
- 2017: Children’s National Health System, Children’s Research Institute 2017 Major Scientific Advances
- 2019: University of Maryland School of Medicine (UMSOM) Special Trans-Disciplinary Recruitment Award Program (STRAP) awardee
Major Research Awards
- 2001: American Heart Association Midwest Affiliate, Pre-doctorial Fellowship
- 2003: American Heart Association Texas Affiliate Post-doctorial Fellowship
- 2006: American Heart Association National Center, National Scientist Development Award
- 2007: University of Michigan McKay Cardiovascular Research Grant Award
- 2008: National Institute of Health (NIH) R01 Award, R01-HL090801: “A novel G protein signaling pathway controlling Drosophila cardiac morphogenesis”. Role: Principle Investigator.
- 2009: National Institute of Health (NIH), American Reinvestment and Recovery Act Administration (ARRA) Supplement Award, R01-HL090801S: “Secretion pathway genes in Drosophila cardiac morphogenesis”, Role: Principle Investigator.
- 2014: National Institute of Health (NIH) R01 Award, R01-DK098410: “Drosophila, a new genetic model for glomerular diseases and drug discovery”. Role: Principle Investigator.
- 2017: National Institute of Health (NIH) R01 Award, R01-HL134940: “Ancestral roles of histone-modifying genes in heart development and disease”. Role: Principle Investigator.
- 2017: National Institute of Health (NIH) R01 Award, R01- DK105055: “Anti-fibrotic action of SARA”.Role: Site PI.
- 2018: National Institute of Health (NIH) R01 Award, R01-DK098410: “Modeling Nephrotic Syndrome in Drosophila nephrocytes”. Role: Principle Investigator.
- 2018: National Institute of Health (NIH) R01 Award, R01-DK115968: Novel mechanisms and Drosophila model of APOL1-HIV-1 nephropathies in children”. Role: Multi PI.
- 2019: National Institute of Health (NIH) R01 Award, R01- DK120908: “Integrating Drosophila and human podocyte studies to discover APOL1 renal toxicity”. Role: Principle Investigator.
- 2019: National Institute of Health (NIH) INCLUDE Supplement Award, R01-HL134940S: “Using Drosophila heart to map candidate genes associated with Down Syndrome Congenital Heart Disease”. Role: Principle Investigator.
- 2020: National Institute of Health (NIH), R01-DK119380: “Whole Genome Sequencing for Nephrotic Syndrome Discovery”. Role: Site PI.
Community Service Award
- 2017: Thomas Jefferson High School for Science and Technology, Mentorship Program Award
Grants and Contracts
Active Grants
Han, Zhe (single PI) R01-HD111480 4/04/2023 – 3/31/2028
Screen and functional validation of Pediatric Cardiomyopathy genetic variants in Drosophila
National Institute of Health (NIH), National Institute of Child Health and Human Development (NICHD)
Pediatric cardiomyopathies (PCM) are devastating disorders of the heart muscle with most children diagnosed before one year of age with limited treatment options. The genetic underpinnings remain poorly understood. We develop bioinformatic tools to prioritize the recently identified 343 PCM candidate genetic variants for modeling in the Drosophila, followed by efficient “gene-level” and “variant-level” functional validation in the fly heart, to provide the much-needed in vivo data to confirm the causality of the candidate variants.
Total Award Amount (including Indirect cost): $3,251,755.
Yearly Direct Costs of Award: $420,939.00
Role: PI (single-PI)
Han, Zhe (single PI) R01-DK098410
4/10/2014 – 7/31/2024
Modeling Nephrotic Syndrome in Drosophila nephrocytes
National Institute of Health (NIH), National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)
Yearly Direct Costs of Award: $225,000
Role: PI (single-PI)
Percent Effort: 20%
The goal of this project is to establish the Drosophila nephrocyte as a primary model system for modeling nephrotic syndrome caused by genetic mutations in humans.
Han, Zhe (multi-PI) R01-DK115968
9/15/2018 – 6/30/2024
Novel mechanisms and Drosophila model of APOL1-HIV-1 nephropathies in children
National Institute of Health (NIH), National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)
Yearly Direct Costs of Award (to the Han lab): $178,000
Role: Multi-PI, with Dr. Patricio Ray at the University of Virginia
Percent Effort: 20%
The goal of this project is to develop the Drosophila HIV-1 nephropathy models and use it to study the molecular mechanism of HIV-associated nephropathy.
Han, Zhe (single PI) R01- DK120908
3/1/2019 – 12/31/2024
Integrating Drosophila and human podocyte studies to discover APOL1 renal toxicity mechanism and therapeutic targets
National Institute of Health (NIH), National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)
Yearly Direct Costs of Award: $225,000
Role: PI (single-PI)
Percent Effort: 20%
The goal of this project is to develop the Drosophila model APOL1 nephropathy model and use it to study the molecular mechanism of APOL1-associated nephropathy.
Han, Zhe (Site-PI) R01- DK119380
9/18/2019 – 8/31/2024
Whole Genome Sequencing for Nephrotic Syndrome Discovery
National Institute of Health (NIH), National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)
Yearly Direct Costs of Award: $102,676
Role: Site PI, with Dr. Matthew Sampson from the Harvard University
Percent Effort: 5%
The goal of this project is to use Drosophila to test the function of novel genetic variants identified from nephrotic syndrome patients.
In the News
NEWS RELEASES About the Han Lab Research
1. APOL1 linked to reduced nephrocyte function, increased cell size, accelerated cell death
(Public Release: November 18, 2016)
Links:
https://www.eurekalert.org/pub_releases/2016-11/cnhs-alt111816.php
2. High-throughput, in vivo validation of candidate congenital heart disease genes
(Public Release: February 9, 2017)
Links:
https://www.eurekalert.org/pub_releases/2017-02/cnhs-hiv020917.php
https://www.sciencedaily.com/releases/2017/02/170209163824.htm
3. Drosophila effectively models human genes responsible for genetic kidney diseases (Public Release: March 17, 2017)
Links:
https://www.eurekalert.org/pub_releases/2017-03/cnhs-dem031717.php
https://www.sciencedaily.com/releases/2017/03/170317180606.htm
4. Studying fruit flies to better understand human kidneys
(Public Release: April 6, 2017)
Link:
https://innovationdistrict.childrensnational.org/tag/rab-proteins
5. Supplement can lessen kidney damage linked to genetic mutations in transgenic fruit flies (Public Release: April 20, 2017)
Links:
https://www.eurekalert.org/pub_releases/2017-04/cnhs-scl042017.php
6. Lab led by Zhe Han, Ph.D., receives $1.75 million from NIH to continue pioneering research (Public Release: July 31, 2017)
Link:
https://eurekalert.org/pub_releases/2017-07/cnhs-llb073117.php
7. Research led by Zhe Han featured on cover of JASN, leading kidney disease journal (Public Release: December 5, 2017)
Link:
8. $2 million NIH grant for treating disease linked to APOL1
(Public Release: April 2, 2019)
Links:
https://www.eurekalert.org/pub_releases/2019-04/cnhs-ng040219.php
https://innovationdistrict.childrensnational.org/2m-nih-grant-for-treating-disease-linked-to-apol1/
9. NUP160 genetic mutation linked to steroid-resistant nephrotic syndrome
(Public Release: March 26, 2019)
Links:
https://www.eurekalert.org/pub_releases/2019-03/cnhs-ngm032019.php
https://innovationdistrict.childrensnational.org/nup160-genetic-mutation-linked-to-steroid-resistant-nephrotic-syndrome/
10. UM School of Medicine Scientist Receives NIH Award to Study Heart Disease Related to Down Syndrome (Public Release: September 25, 2019)
Links:
11. UM School of Medicine Researchers Identify Mechanism to Explain Role of Certain Gene Mutations in Kidney Disease (Public Release: April 03, 2020)
Links:
12. Cancer Drug Lessens the Toxicity of a Protein from the Virus that Causes Covid-19 (Public Release: March 29, 2021)
Links:
https://www.sciencedaily.com/releases/2021/03/210326151339.htm
13. University of Maryland Study shockingly finds that SARS-CoV-2 Nsp6 proteins can induce morphological and functional defects in the heart (Public Release: June 7, 2022)
Links:
14. How a SARS-CoV-2 Virus Protein Damages the Heart (Public Release: November 4, 2022)
Links:
https://www.medschool.umaryland.edu/news/2022/How-a-SARS-CoV-2-Virus-Protein-Damages-the-Heart.html
15. Scientists ID Heart-Damaging SARS-CoV-2 Protein (Public Release: November 22, 2022)
Links:
https://www.the-scientist.com/news-opinion/scientists-id-heart-damaging-sars-cov-2-protein-70782
Community Service
- 2015 – 2019: Member, Mentorship Program, Thomas Jefferson Magnet High School for Science & Technology (TJHSST)
- 2016 – 2017: Chair, Scientific Committee, Society of Chinese Bioscientists in America (SCBA) DC-Baltimore Chapter
- 2017 – 2019: Chair, National Membership Committee, Society of Chinese Bioscientists in America (SCBA)
- 2017: Organizer, 2017 SCBA DC-Baltimore Chapter Scientific Symposoium
- 2020: Organizer, 2020 SCBA DC-Baltimore Chapter Scientific Symposoium
- 2020 - present: Webmaster, Society of Chinese Bioscientists in America (SCBA)
- 2020 - 2021: President-Elect, SCBA DC-Baltimore Chapter
- 2021 - present: President, SCBA DC-Baltimore Chapter
Professional Activity
EDITORIAL ACTIVITIES
2006 – Manuscript Reviewer, Developmental Biology
2007 – Manuscript Reviewer, Genetics
2008 – Manuscript Reviewer, PLOS One
2009 – Manuscript Reviewer, Journal of Cell Science
2009 – Manuscript Reviewer, Journal of Cell Biology
2010 – Manuscript Reviewer, Development
2010 – Manuscript Reviewer, Genesis
2010 – Manuscript Reviewer, PLOS Biology
2011 – Manuscript Reviewer, Cell and Tissue Research
2012 – Manuscript Reviewer, Current Biology
2013 – Manuscript Reviewer, Circulation Research
2013 – Manuscript Reviewer, PLOS Genetics
2014 – Manuscript Reviewer, Cell and Biosciences
2014 Guest Associate Editor, PLOS Genetics
2015 – Manuscript Reviewer, Developmental Cell
2015 – Manuscript Reviewer, Aging Cell
2016 Guest Associate Editor, PLOS Genetics
2016 – Manuscript Reviewer, JASN
2016 – Manuscript Reviewer, eLife
2017 – Manuscript Reviewer, Human Molecular Genetics
2017 – Manuscript Reviewer, Scientific Reports
2017 – Manuscript Reviewer, Frontiers in Pediatrics
2017 – Manuscript Reviewer, Journal of Child Science
2018 – Manuscript Reviewer, Kidney International
2018 – Manuscript Reviewer, Nature Communications
2018 – Guest Associate Editor, Frontiers in Genetics
2019 – Manuscript Reviewer, Nature Review Nephrology
2019 – Manuscript Reviewer, The FASEB Journal
2020 – Manuscript Reviewer, Trends in Genetics
2020 – Manuscript Reviewer, Experimental Cell Research
2020 – Manuscript Reviewer, Disease Model & Mechanism
2021 – Manuscript Reviewer, Marine Drugs
2021 – Manuscript Reviewer, Genome Biology
2021 – Editorial Board: Cell and Bioscience
2022 – Associate Editor: Cell and Bioscience
GRANT REVIEW ACTIVITIES
2009–2012 Reviewer, University of Michigan, Cardiovascular Center, McKay Grants
2011–2012 Reviewer, University of Michigan, Organogenesis Center grants
2012–2013 Reviewer, Italian Ministry of Health (MOH) grants
2013 Reviewer, University of Michigan, O’Brien Kidney Center, Internal kidney research grant
2013 Ad Hoc Reviewer, National Institute of Health (NIH), Cardiovascular Development and Differentiation (CDD) Study Section
2014 Ad Hoc Reviewer, NASA International Life Science Research Program
2014 Ad Hoc Reviewer, National Institute of Health (NIH), U54 O’Brien Center Grant Special Review Panel
2014 Ad Hoc Reviewer, National Institute of Health (NIH), Diabetic Complications Consortium (DiaComp) Pilot Grant
2015 Ad Hoc Reviewer, National Institute of Health (NIH), Cardiovascular Development and Differentiation (CDD) Study Section
2015 Ad Hoc Reviewer, National Institute of Health (NIH), Center for Scientific Review, Special Emphasis Panel on Small Business Grants (ZRG1 DKUS-L11)
2016 Ad Hoc Reviewer, National Institute of Health (NIH), Diabetic Complications Consortium (DiaComp) Pilot Grant
2017 Ad Hoc Reviewer, United Kingdom Kidney Foundation Grant
2018 Ad Hoc Reviewer, National Institute of Health (NIH), Center for Scientific Review (CSR), CSR Anonymization Project for R01 reviews
2019 Scientist Reviewer, Department of Defense, Congressionally Directed Medical Research Programs (CDMRP), Urologic Disease panel
2020 Ad Hoc Reviewer, National Institute of Health (NIH), Diabetic Complications Consortium (DiaComp)
SCIENTIFIC MEETING ORGANIZED
2017 Meeting Organizer: SCBA DC-Baltimore Chapter 2017 Annual Scientific Symposium, Johns Hopkins University Rockville Campus, Gaithersburg, MD
2020 Meeting Organizer: SCBA DC-Baltimore Chapter 2020 Annual Scientific Symposium, University of Maryland College Park, Silver Spring, MD (changed to online conference due to COVID-19)
Links of Interest
1. Flybase:
2. DIOPT Fly Ortholog Finder:
https://www.flyrnai.org/cgi-bin/DRSC_orthologs.pl
3. Disease and Gene Network (DisGeNET):
4. GeneMatcher
https://genematcher.org/?tab=submissionsTab
5. Jane: Journal/Author Name Estimator:
https://jane.biosemantics.org/
6. GTExPortal: