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Rong Li, Ph.D.

Rong Li, Ph.D.

Academic Titles: 
Bloomberg Distinguished Professor
Position Title: 
Director, Center for Cell Dynamics, Institute for Basic Biomedical Sciences

Department of Cell Biology, The Johns Hopkins University School of Medicine
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University Whiting School of Engineering
BCMB Graduate Program

410-955-9938 (office)
443-287-7667 (lab)

855 N. Wolfe Street
451 Rangos
Baltimore, MD 21205

The goal of our research is to understand how eukaryotic cells polarize, divide, move, and vary their genomes to adapt to the changing environment.  We strive for integrated analyses on the systems level that combines whole-cell quantitative observation and mathematical modeling with cutting-edge molecular genetics approaches. We are intrigued about how cells generate patterns through self-organization in response to environmental signals, accomplish division or motility through coordinated structural rearrangements and force production, and, when challenged with hostile environments or genetic perturbations, evolve innovative solutions to maintain vitality and functionality.  In addition to the goal of identifying fundamental principles, we actively seek opportunities to apply basic-research insights to the improvement of human health.  Our research areas include:       

I.  Cell polarization and segregation of aging determinants  

Cell polarity is the simplest form of whole-cell pattern beyond spherical symmetry, from which more complex developmental and multicellular patterns emerge.  Our ongoing work attempts to explain how molecular components of distinct functional modules interact in time and space to establish cell polarity that is robust to noise but sensitive to physiological inputs.  A functional consequence of cell polarity in the unicellular organism, the budding yeast, is asymmetric segregation of aging determinants such that cell division generates a young cell with renewed replicative potential from an aged mother cell.  We use live-cell imaging to observe the generation and transmission of recessive determinants that are beneficial but poorly renewed, as well as dominant determinants resulting from accumulated damages.  We use these data to build models that not only explain the finite replicative life span but also predict its modification by environmental or genetic changes.   

II. Spindle positioning and asymmetric meiotic cell division

The development of mammalian organisms starts with two rounds of asymmetric meiotic division of the oocyte.  Our recent work has uncovered novel roles of the actin cytoskeleton in the acentric positioning of the meiotic spindle and of the chromatin in setting up cortical polarity required for extrusion of the polar body.  Our ongoing study is designed to elucidate the mechanism of the chromatin-based signal, its transmission through the cytoplasm to the cortex, and consequent changes in cytoskeletal dynamics to produce the forces that drive oocyte symmetry breaking with the potential to impact early zygotic development. 

III. Motility of differentiated mammalian cells in diverse environments

Cell motility is crucial for the development and physiology of diverse cell types and tissues, yet mechanistic insights have come mainly from transformed cell lines moving on 2D surfaces.  An emerging line of research in our lab is to study the motility of cells of well-defined tissue origins in mechanical and geometrical environments that mimic physiological conditions.  We isolate primary cells from genetically modified animals and then apply high-resolution biophysical techniques to observe and parameterize their motility in vitro in engineered environments that provide tissue-mimetic tests of environmental inputs.  Our ultimate goals are to identify context-dependent design principles in the cytoskeletal machine that drives cell movement and to use this insight to develop cancer-specific therapies against tumor spreading and metastasis.

IV. Cellular adaptation through variation of chromosome copy numbers

Aneuploidy, the state of having unequal numbers of different chromosomes, is a frequent genetic alteration due to errors in mitosis and meiosis and can drive rapid adaptive changes in unicellular organisms and cancer.  Our recent work has demonstrated dramatic ways in which aneuploidy alters gene expression and cell behavior.  We are currently investigating how aneuploidy affects the epigenetic state of cells and which cellular pathways may be particularly sensitive to modification by an unbalanced chromosome dosage.  Metazoans have evolved powerful surveillance mechanisms to prevent aneuploidy, most 

notably the p53 system that is so often mutated in cancer cells.  Our ongoing study aims to uncover how p53 senses numerical abnormalities of the genome in mammalian somatic cells.  We are also exploring an evolution-based strategy for eradicating karyotypically heterogeneous cell population, with the goal of using it to design combinatorial drug therapies for the treatment of cancer and certain infectious diseases. 

V. Epithelial morphogenesis and polycystic kidney disease

Cells that constitute mammalian epithelial tissues have the ability to detect and adjust to significant environmental stress to maintain their proper differentiated state and multicellular organization.  In polarized renal epithelial cells, a mechanosenory pathway is mediated by a transmembrane complex, consisting of polycystin-1 and polycystin-2 proteins.  Mutations in these proteins result in autosomal dominant polycystic kidney disease (ADPKD), a highly prevalent human hereditary disease. We are using a combination of mouse genetics and live-cell analysis to understand how loss of polycystin function alters the growth control and morphogenetic fate of epithelial cells in ADPKD.


Research Interest: 
Cellular dynamics in space, time, and adaptation
Lab Members:
Namesort descending Classification Email Phone
Akshay Narkar Student anarkar1@jhu.edu 443-287-7667
Albert Liu Student aliu53@jhmi.edu 443-287-7667
Alexis Tomaszewski Student atomasz3@jhmi.edu 443-287-7667
Arthur Wang Student ywang401@jhmi.edu 443-287-7667
Blake Johnson Student bjohn134@jhmi.edu 443-287-7667
Dina Youngblood Administrative Coordinator dyoungb2@jhmi.edu 410-614-7864
Haiyang Wang, Ph.D. Postdoctoral Fellow hwang168@jhmi.edu 443-287-7667
Jin Zhu, Ph.D. Postdoctoral Fellow jzhu51@jhmi.edu 443-287-7667
Josh McNamara Student mcnamara@jhmi.edu 443-287-7667
Linhao Ruan Student lruan1@jhmi.edu 443-287-7667
Molly Gordon Student mgordo34@jhmi.edu 443-287-7667
Sree Ramachandran Sr. Laboratory Manager sramach5@jhu.edu 443-287-7667
Xi Zhang, Ph.D. Postdoctoral Fellow xzhan141@jhu.edu 443-287-7667
Yi Dong Student yi@jhmi.edu 443-287-7667

Dysfunction of cellular mechanisms maintaining proteostasis leads to accumulation of misfolded proteins and their aggregates, which often results in debilitating human diseases, such as neurodegenerative diseases (ND). Interestingly, those diseases are also frequently coupled with mitochondrial defects. Although proteostasis and mitochondria are individually studied intensively in the context of ND, the relationship between those two are poorly understood.

Selected Publications:
Wang H, Li Y, Yang J, Duan X, Kalab P, Sun S, and Li R. Symmetry breaking in hydrodynamic forces drive meiotic spindle rotation in mammalian oocyte. Sci Adv Advance In press  
Pei-Hsun Wu*, Daniele M. Gilkes, Jude M. Phillip, Akshay Narkar, Thomas Wen-Tao Cheng, Jorge Marchand, Meng-Horng Lee, Rong Li, Denis Wirtz*. 2020. Single-cell morphology encodes metastatic potential. Sci. Adv. 6, eaaw6938 (2020) DOI: 10.1126/sciadv.aaw6938
Duan X, Li Y, Yi K, Guo F, Wang H, Wu PH, Yang J, Mair DB, Morales EA, Kalab P, Wirtz D, Sun SX, Li R. Dynamic organelle distribution initiates actin-based spindle migration in mouse oocytes. Nat Commun. 2020 Jan 14;11(1):277. doi: 10.1038/s41467-019-14068-3.  
Ruan L, Wang Y, Zhang X, Tomaszewski A, McNamara JT, Li R. 2020. Mitochondria-associated proteostasis. Ann Rev Biophys. 2020 Jan 13. doi: 10.1146/annurev-biophys-121219-081604. [Epub ahead of print].  
Yang J, Duan X, Fraser AK, Choudhury MI, Ewald AJ, Li R, Sun SX. Microscale Pressure Measurements Based on an Immiscible Fluid/Fluid Interface. Sci Rep. 2019 Dec 27;9(1):20044. doi: 10.1038/s41598-019-56573-x.  
Thompson DJ et al. Genetic predisposition to mosaic Y chromosome loss in blood. Nature. 2019 Nov;575(7784):652-657. doi: 10.1038/s41586-019-1765-3. Epub 2019 Nov 20.
Li R. I am an American scientist of the world. Mol Biol Cell. 2019 Nov 1;30(23):2865-2866. doi: 10.1091/mbc.E19-07-0389.
Drutovic D, Duan X, Li R, Kalab P, Solc P. RanGTP and Importin β Regulate Meiosis I Spindle Assembly and Function in Mouse Oocytes. EMBO J. 2020 Jan 2;39(1):e101689. doi: 10.15252/embj.2019101689. Epub 2019 Oct 16.  
Puddu F, Herzog M, Selivanova A, Wang S, Zhu J, Klein-Lavi S, Gordon M, Meirman R, Millan-Zambrano G, Ayestaran I, Salguero I, Sharan R, Li R, Kupiec M, Jackson SP. Genome Architecture and Stability in the Saccharomyces Cerevisiae Knockout Collection. Nature 2019 Sep;573(7774):416-420. doi: 10.1038/s41586-019-1549-9. Epub 2019 Sep 11.      
Paul P, Ramachandran S, Xia S, Unruh JR, Conkright-Fincham J, Li R. 2019. Dopamine receptor antagonists as potential therapeutic agents for ADPKD. PLoS One. 2019 May 6;14(5):e0216220. doi: 10.1371/journal.pone.0216220. eCollection 2019  
Tsai H-J, Nelliat AR, Choudhury MI, Kucharavy A, Bradford WD, Cook ME, Kim J, Mair DB, Sun SX, Schatz MC & Li R. 2019. Hypo-osmotic-like stress underlies general cellular defects of aneuploidyNature (2019) https://doi.org/10.1038/s41586-019-1187-2.  
Mair, Devin B., Heather M. Ames, and Rong Li. “Mechanisms of invasion and motility of high-grade gliomas in the brain.” Molecular biology of the cell 29.21 (2018): 2509-2515
McDonald NALind ALSmith SELi RGould KL. Nanoscale architecture of the Schizosaccharomyces pombecontractile ring. Elife. 2017 Sep 15; 6. pii: e28865. doi: 10.7554/eLife.28865.  
Chou FS , Li R, Wang PS. Molecular components and polarity of radial glial cells during cerebral cortex development. 2018. Cell Mol Life Sci. 2018 Mar;7 5(6):1027-1041. doi: 10.1007/s00018-017-2680-0.    
Jin Zhu, Hung-Ji Tsai, Molly R. Gordon, Rong Li. Cellular Stress Associated with Aneuploidy; Dev Cell. 2018 Feb 26;44(4):420-431. doi: 10.1016/j.devcel.2018.02.002.  
Linhao Ruan, Xi Zhang, Rong Li. Recent insights into the cellular and molecular determinants of aging. J Cell Sci. 2018 Feb 2; 131(3). pii: jcs210831. doi: 10.1242/jcs.210831
Pushpendra Singh, Rong Li. Emerging roles for sphingolipids in cellular aging. Curr Genet. 2017 Dec 19. doi: 10.1007/s00294-017-0799-z.   
Mulla WA, Seidel CW, Zhu J, Tsai HJ, Smith SE, Singh P, Bradford WD, McCroskey S, Nelliat AR, Conkright J, Peak A, Malanowski KE, Perera AG, Li R. 2017. Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast. Elife. 2017 Aug 25; 6. pii: e27991. doi: 10.7554/eLife.27991.
McDonald NALind ALSmith SELi RGould KL. 2017.  Nanoscale architecture of the Schizosaccharomyces pombe contractile ring. Elife. 2017 Sep 15; 6. pii: e28865. doi: 10.7554/eLife.28865.
Anderson KL, Page C, Swift MF, Suraneni P, Janssen MEW, Pollard TD, Li R, Volkmann N, Hanein D. 2017. Nano-scale actin-network characterization of fibroblast cells lacking functional Arp23 complex. Journal of structural biology, 197 (3) 312-321.
McDonald NALind ALSmith SELi RGould KL. Nanoscale architecture of the Schizosaccharomyces pombecontractile ring. Elife. 2017 Sep 15; 6. pii: e28865. doi: 10.7554/eLife.28865.
Ruan L, Zhou C, Jin E, Kucharavy A, Zhang Y, Wen Z, Florens L, Li R. 2017. Cytosolic proteostasis through importing of misfolded proteins into mitochondriaNature; Mar 16; 543, 443–446; doi:10.1038/nature21695
Potapova TA, Seidel CW, Box AC, Rancati G, Li R. 2016. Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53. Mol Biol Cell. 2016 Oct 15;27(20):3065-3084. Epub 2016 Aug 24.
Wang PS, Chou FS, Ramachandran S, Xia S, Chen HY, Guo F, Suraneni P, Maher B,  Li R. 2016. Crucial Roles of the Arp2/3 Complex during Mammalian Corticogenesis.  Development 2016; Aug 1 143(15): 2741-2752
Swaney KF, Li R. Function and regulation of the Arp2/3 complex during cell migration in diverse environments. Curr Opin Cell Biol. 2016 May 7;42:63-72.
P Vargas, P Maiuri, M Bretou,  P Sáez, P Pierobon, M Maurin, M Chabaud, D Lankar, D Obino, E Terriac, M Raab, H R Thiam,  HR2, T Brocker, S M Kitchen-Goosen, A Alberts, P Sunareni, S  Xia, R Li , R Voituriez, M Piel, A M Lennon-Duménil. Innate Control of Actin Nucleation Determines Two Distinct Migration Behaviours In Dendritic Cells. Nat Cell Bio.  doi: 10.1038/ncb3284.  2015 Dec 7. [Epub ahead of print]
Potapova TA, Unruh JR, Box AC, Bradford WD, Seidel CW, Slaughter BD, Sivagnanam S, Wu Y, Li RKaryotyping human and mouse cells using probes from single-sorted chromosomes and open source software. Biotechniques. 2015 Dec 1;59(6):335-46. doi: 10.2144/000114362. eCollection 2015.
Zhu J, Heinecke D, Mulla W, Bradford WD, Rubinstein B, Box A, Haug JS and Li R.  Single-cell based quantitative assay of chromosome transmission fidelity. G3. 2015;5:1043-56
Chen G, Mulla WA, Kucharavy A, Tsai HJ, Rubinstein B, Conkright J, McCroskey S, Bradford WD, Weems L, Haug JS, Seidel CW, Berman J, Li R. Targeting the Adaptability of Heterogeneous Aneuploids. Cell. 2015;160:771-784. 
Suraneni P, Fogelson B, Rubinstein B, Noguera P, Volkmann N, Hanein D, Mogilner A, Li R. A Mechanism of Leading Edge Protrusion in the absence of Arp2/3 Complex. Mol Biol Cell. 2015;26:901-12. 
Zhou C, Slaughter BD, Unruh JR, Guo F, Yu Z, Mickey K, Narkar A, Ross RT, McClain M, Li R. Organelle-based aggregation and retention of damaged proteins in asymmetrically dividing cells. Cell. 2014;159:530-542.   
Smith SE, Rubinstein B, Mendes Pinto I, Slaughter BD, Unruh JR, Li R. Independence of symmetry breaking on Bem1-mediated autocatalytic activation of Cdc42.  J Cell Biol. 2013;202:1091-1106. 
Li R. The art of choreographing asymmetric cell division. Dev Cell. 2013;25:439-450. 
Yi K, Rubinstein B, Unruh JR, Guo F, Slaughter BD, Li R. Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes. J Cell Biol. 2013;200:567-576. 
Li R, Albertini DF. The road to maturation: somatic cell interaction and self-organization of the mammalian oocyte. Nat Rev Mol Cell Biol.2013;14:141-152. 
Slaughter BD, Unruh JR, Das A, Smith SE, Rubinstein B, Li R. Non-uniform membrane diffusion enables steady-state cell polarization via vesicular trafficking. Nat Commun. 2013;4:1380. 
Pinto IM, Rubinstein B, Kucharavy A, Unruh J, Li R. Actin Depolymerization Drives Actomyosin Ring Contraction during Budding Yeast Cytokinesis. Dev Cell. 2012;22:1247-1260. 
Chen G, Bradford WD, Seidel CW, Li R. Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy. Nature. 2012;482:246-250. 
Das A, Slaughter BD, Unruh JR, Bradford WD, Alexander R, Rubinstein B, Li R. Flippase-mediated phospholipid asymmetry promotes fast Cdc42 recycling in dynamic maintenance of cell polarity. Nat Cell Biol. 2012;14:304-310. 
Suraneni P, Rubinstein B, Unruh JR, Durnin M, Hanein D, Li R. The Arp2/3 complex is required for lamellipodia extension and directional fibroblast cell migration. J Cell Biol. 2012;197:239-251. 
Zhu J, Pavelka N, Bradford WD, Rancati G, Li R. Karyotypic Determinants of Chromosome Instability in Aneuploid Budding Yeast. PLoS Genet. 2012;8:e1002719. 
Zhou C, Slaughter BD, Unruh JR, Eldakak A, Rubinstein B, Li R. Motility and segregation of hsp104-associated protein aggregates in budding yeast. Cell. 2011;147:1186-1196. 
Yi K, Unruh JR, Deng M, Slaughter BD, Rubinstein B, Li R. Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3-complex-driven cytoplasmic streaming in mouse oocytes. Nat Cell Biol. 2011;13:1252-1258. 
Gao JT, Guimera R, Li H, Pinto IM, Sales-Pardo M, Wai SC, Rubinstein B, Li R. Modular coherence of protein dynamics in yeast cell polarity system. Proc Natl Acad Sci U S A. 2011;108:7647-7652. 
Pavelka N, Rancati G, Zhu J, Bradford WD, Saraf A, Florens L, Sanderson BW, Hattem GL, Li R. Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature. 2010;468:321-325. 
Xia S, Li X, Johnson T, Seidel C, Wallace DP, Li R. Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development. 2010;137:1075-1084. 
Slaughter BD, Das A, Schwartz JW, Rubinstein B, Li R. Dual modes of cdc42 recycling fine-tune polarized morphogenesis. Dev Cell. 2009;17:823-835.   
Rancati G, Pavelka N, Fleharty B, Noll A, Trimble R, Walton K, Perera A, Staehling-Hampton K, Seidel CW, Li R. Aneuploidy Underlies Rapid Adaptive Evolution of Yeast Cells Deprived of a Conserved Cytokinesis Motor. Cell. 2008;135:879-893.