Contact

Location: STRF 2.292.4

Department

Cell Systems and Anatomy

Lizhen Chen, PhD

Assistant Professor

Education

Year Degree Discipline Institution
2000 BS Biochemistry Lanzhou University
Lanzhou, Gansu , P.R. China
2008 PhD Genetics University of Georgia,
Athens , GA

Research

The goal of our research is to discover molecular pathways involved in aging and diseases, and to translate such findings into potential therapeutic targets. Specifically, our research focuses on genetic and epigenetic regulation of neuronal aging, age-dependent axon regeneration and cancer. We use C. elegans, mouse and cell culture models in our research. We are also collaborating with translational and clinical investigators.

Genetic and epigenetic regulation in axon regeneration

In the mature mammalian CNS, axons regenerate poorly after injury, accounting for permanent functional deficits. In contrary, embryonic and early postnatal animals show a remarkable ability to regenerate axons. Characterization of the mechanisms underlying this inability to regrow is of great interest to human health. It has been shown that injured mature CNS axons can regrow into sciatic nerve grafts transplanted into the lesion site, prompting the notion that successful axon regeneration requires a permissive environment. Research in recent years has also supported the emerging recognition that the intrinsic growth ability of adult neurons is as important as the extrinsic inhibitory factors. We are combining genetic screen and genomic approaches to identify novel regulators, especially intrinsic regulators, which will then be functionally validated.

Microtubule dynamics and aging

Aging impacts the function of the nervous system and is the major risk factor for neurodegenerative diseases and is a fundamental problem in basic neuroscience and in human health. On the other hand, the nervous system corporate the organism’s overall metabolism and affect homeostasis and longevity. Microtubules (MTs) are essential cytoskeleton involved in cell division, shaping the cell and intracellular transport. MT regulation is involved on several levels in neuronal function and maintenance of neuronal structure, and also appears to be a general downstream indicator and effector in age-dependent neurodegeneration. Drugs targeting MT dynamics have been shown to ameliorate the pathogenic symptoms in animal models of neurodegenerative diseases. Mutations in tubulin genes or MT associated proteins have also been reported to affect neuronal integrity during aging. We are interested in understanding the effects of aging on MT organization and testing whether stabilizing neuronal microtubule can delay neuronal aging and promotes longevity.

Role of CELF RNA binding proteins in neuronal development and aging

RNA binding proteins (RBPs) are critical players in gene regulation and are at center stage in our understanding of cellular function in both normal and disease processes. Dysfunction of RBPs and the subsequent disruption of RNA processing are increasingly implicated in neurological disorders including age-associated neurodegneration. CELF RBPs regulate alternative splicing and RNA stability and are expressed in the nervous system. Mutations in CELF genes have been linked to various neuronal disorders, including autism spectrum disorders, schizophrenia and seizures. CELF1 and CEFL2 have been recently identified as a risk factor associated with AD in several independent GWAS analyses. We are interested in the molecular mechanisms by which CELF RBPs regulate neurodevelopment and neurodegeneration.

Enhancer regulation in axon regeneration and cancer

Enhancers are essential distal DNA regulatory elements that control temporal- or spatial-specific gene expression patterns during development and other biological processes. Dysregulation of enhancer function is involved in many diseases including cancer. Enhancer function is regulated by combinations of transcription factors (TFs) and cofactors. Cofactors, including Mediator complex (Mediator), chromatin-remodeling complexes (CRCs), and histone-modifying complexes (HMCs), are recruited to enhancers by pioneer TFs to form combinatorial enhancer complexes. We are investigating the enhancers that are activated or inactivated in response to neuronal injury and during axon regeneration. We are also studying the component changes in enhancer complexes in response to different signals during cancer progression.

Publications

Neuronal microtubules impact lifespan.
Apple E, Chen L
Aging (Albany NY). 2019 Sep 6;11(17):6616-6617. doi: 10.18632/aging.102224. Epub 2019 Sep 6.
PMCID: PMC6756882

A Non-canonical Role of YAP/TEAD Is Required for Activation of Estrogen-Regulated Enhancers in Breast Cancer.
Zhu C, Li L, Zhang Z1 Bi M, Wang H, Su W, Hernandez K, Liu P, Chen J, Chen M, Huang TH, Chen L*, Liu Z*
Molecular Cell. 2019 Aug 22;75(4):791-806.e8. doi: 10.1016/j.molcel.2019.06.010. Epub 2019 Jul 11.
PMCID: PMC6707877 [Available on 2020-08-22], *co-corresponding authors

Cell-autonomous and non-autonomous roles of daf-16 in muscle function and mitochondrial capacity in aging C. elegans.
Wang H#, Webster P#, Chen L, Fisher AL
Aging (Albany NY). 2019 Apr 24;11(8):2295-2311. doi: 10.18632/aging.101914.
PMCID: PMC6520005, #contributed equally

Microtubule regulators regulate neuronal aging and organismal longevity through DAF-16 in C. elegans.
Xu A, Zhang Z, Ko S, Fisher L, Liu Z, Chen L
Aging Cell. 2019 Apr;18(2):e12884. doi: 10.1111/acel.12884. Epub 2019 Jan 14.
PMCID: PMC6413656

Microtubules and axon regeneration in C. elegans.
Chen L
Molecular and Cellular Neurosciences. 2018 Sep;91:160-166. doi: 10.1016/j.mcn.2018.03.007. Epub 2018 Mar 16.
PMID: 29551667

CELF RNA binding proteins promote axon regeneration in C. elegans and mammals through alternative splicing of Syntaxins.
Chen L, Liu Z, Zhou B, Wei C, Zhou Y, Rosenfeld MG, Fu XD, Chisholm AD, Jin Y
eLife. 2016 Jun 2;5. pii: e16072. doi: 10.7554/eLife.16072.
PMCID: PMC4946901

Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase.
Chen L, Chuang M, Koorman T, Boxem M, Jin Y, Chisholm AD
eLife. 2015 Sep 4;4. doi: 10.7554/eLife.08695.
PMCID: PMC4596636

RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans.
Grill B, Chen L, Tulgren ED, Baker ST, Bienvenut W, Anderson M, Quadroni M, Jin Y, Garner CC
Journal of Neuroscience. 2012 Feb 22;32(8):2628-36. doi: 10.1523/JNEUROSCI.2901-11.2012.
PMCID: PMC3302171

Axon regeneration pathways identified by systematic genetic screening in C. elegans.
Chen L, Wang Z, Ghosh-Roy A, Hubert T, Yan D, O’Rourke S, Bowerman B, Wu Z, Jin Y, Chisholm AD
Neuron. 2011 Sep 22;71(6):1043-57. doi: 10.1016/j.neuron.2011.07.009. Epub 2011 Sep 21.
PMCID: PMC3183436

Axon regeneration mechanisms: insights from C. elegans.
Chen L, Chisholm AD
Trends in Cell Biology. 2011 Oct;21(10):577-84. doi: 10.1016/j.tcb.2011.08.003. Epub 2011 Sep 8.
PMCID: PMC3183269

Mouse and zebrafish Hoxa3 orthologues have nonequivalent in vivo protein function.
Chen L, Zhao P, Wells L, Amemiya CT, Condie BG, Manley NR
PNAS. 2010 Jun 8;107(23):10555-60. doi: 10.1073/pnas.1005129107. Epub 2010 May 24.
PMCID: PMC2890846

Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions.
Liu Z, Farley A, Chen L, Kirby BJ, Kovacs CS, Blackburn CC, Manley NR
PLoS Genetics. 2010 Dec 23;6(12):e1001251. doi: 10.1371/journal.pgen.1001251.
PMCID: PMC3009658

Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner.
Chen L, Xiao S, Manley NR
Blood. 2009 Jan 15;113(3):567-74. doi: 10.1182/blood-2008-05-156265. Epub 2008 Oct 31.
PMCID: PMC2628364

Evidence for an additional base-pairing element between the telomeric repeat and the telomerase RNA template in Kluyveromyces lactis and other yeasts.
Wang ZR, Guo L, Chen L, McEachern MJ
Molecular and Cellular Biology. 2009 Oct;29(20):5389-98. doi: 10.1128/MCB.00528-09. Epub 2009 Aug 17.
PMCID: PMC2756879

Synergistically therapeutic effects of VEGF165 and angiopoietin-1 on ischemic rat myocardium.
Liu X, Chen Y, Zhang F, Chen L, Ha T, Gao X, Li C
Scandinavian Cardiovascular Journal. 2007 Apr;41(2):95-101.
PMID: 17454834

Clinical cellular cardiomyoplasty: technical considerations.
Zhang F, Yang Z, Chen Y, Qin J, Zhu T, Xu D, Xu Z, Xu Q, Qian Y, Ma W, Chen L, Gao X, Li C, Ha T, Kao RL
Journal of Cardiac Surgery. 2003 May-Jun;18(3):268-73.
PMID: 12809404

Neuronal apoptosis induced by endoplasmic reticulum stress.
Chen L, Gao X
Neurochemical Research. 2002 Sep;27(9):891-8.
PMID: 12396099

Novel zinc fluorescent probe bearing dansyl and aminoquinoline groups.
Jiang P, Chen L, Lin J, Liu Q, Ding J, Gao X, Guo Z
Chemical Communications. 2002 Jul 7;(13):1424-5.
PMID: 12125585