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UF Health University of Florida
Department of Molecular Genetics & Microbiology College of Medicine
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Lien T Nguyen

Lien T Nguyen,

Assistant Professor

Department: Molecular Genetics & Microbiology
Business Phone: (352) 273-5112
Business Email: lien.nguyen@ufl.edu

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About Lien T Nguyen

My research group is interested in understanding the roles of repetitive elements or “genomic dark matter” in disease and health. Our research focuses are: 1] Detecting novel pathogenic or functional tandem repeats and repeat expansions. 2] Studying pathogenic roles of novel repeat expansion mutations. 3] Studying functions of tandem repeats in the central nervous system. We use molecular, genetic, and repeat enrichment; advanced sequencing and computational tools; animal models, patient samples and patient-derived models to identify and study pathogenic or functional tandem repeats. Disease focus: Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and diseases with unknown etiologies. Hobbies: Outside the lab, I enjoy cooking, handmaking, and reading. Two books that I find the most impressive and helpful are Dế Mèn Phiêu Lưu ký by Tô Hoài and the 7 Habits of Highly Effective People by Stephen Covey. I also like doing Yoga, Pilates, and Tennis. Favorite sentences: “Nothing in life is to be feared, it is only to be understood” – Marie Curie. “Expect nothing – Appreciate everything” – Zen proverb.

Related Links:
Lab Website

Teaching Profile

Courses Taught

  1. GMS6012 – Human Genetics

    College of Medicine

  2. GMS7980 – Research for Doctoral Dissertation

    College of Medicine

  3. BMS6003 – Genetics and Health

    College of Medicine

  4. GMS6001 – Fundamentals of Biomedical Sciences I

    College of Medicine

  5. GMS7979 – Advanced Research

    College of Medicine

Research Profile

We study the roles of tandem repeats and repeat expansions in disease and cellular function. Repetitive elements or “genome dark matter” make up > 50% of the human genome. Among the various types of repetitive DNAs, short tandem repeats, which account for > 3% of the genome, exhibit a high mutagenic rate and are a large source of genetic variation and their expansion is the cause of > 60 diseases. However, technical difficulties with sequencing through repetitive DNAs and mapping tandem repeats back to specific sites in the genome have limited our understanding of repeat expansion mutations in biology and disease. Recent findings and our discovery that novel repeat-associated non-AUG (RAN) polymeric proteins accumulate in autopsy tissue from AD and sporadic ALS patients strongly suggests that novel disease-causing expanded repeats remain to identify. Interestingly, native functions of a set of tandem repeats including the regulation of responses to environmental changes and the expression of brain-specific transcripts were also described. We use molecular, genetic, and repeat enrichment, advanced sequencing and computational tools, animal models, patient samples and patient-derived models to identify and study pathogenic or functional tandem repeats and repeat expansions. Our research focuses on three areas: 1) detecting novel pathogenic or functional tandem repeats and repeat expansions, 2) studying pathogenic roles of novel repeat expansion mutations, and 3) studying functions of tandem repeats in the central nervous system.

Open Researcher and Contributor ID (ORCID)

0000-0001-5237-2576

Areas of Interest

  • Alzheimer’s disease
  • Amyotrophic Lateral Sclerosis
  • Diseases with unknown genetic etiologies
  • Frontotemporal dementia
  • Repeat Expansion Diseases
  • Retrotransposable elements

Publications

Academic Articles

  1. CASP8 intronic expansion identified by poly-glycine-arginine pathology increases Alzheimer’s disease risk

    Journal
    Proceedings of the National Academy of Sciences.
    Volume/Issue
    122(7)
    [DOI]
    10.1073/pnas.2416885122.
    Publisher’s Site

  2. Updates on Disease Mechanisms and Therapeutics for Amyotrophic Lateral Sclerosis

    Journal
    Cells.
    Volume/Issue
    13(11)
    [DOI]
    10.3390/cells13110888.
    Publisher’s Site

  3. RAN proteins in neurodegenerative disease: Repeating themes and unifying therapeutic strategies.

    Journal
    Current opinion in neurobiology.
    Volume/Issue
    72:160-170
    [DOI]
    10.1016/j.conb.2021.11.001.
    [PMID]
    34953315.
    15 citations PubMed Publisher’s Site

  4. The alternative initiation factor eIF2A plays key role in RAN translation of myotonic dystrophy type 2 CCUG•CAGG repeats.

    Journal
    Human molecular genetics.
    Volume/Issue
    30(11):1020-1029
    [DOI]
    10.1093/hmg/ddab098.
    [PMID]
    33856033.
    20 citations PubMed Publisher’s Site

  5. Repeat length increases disease penetrance and severity in C9orf72 ALS/FTD BAC transgenic mice.

    Journal
    Human molecular genetics.
    Volume/Issue
    29(24):3900-3918
    [DOI]
    10.1093/hmg/ddaa279.
    [PMID]
    33378537.
    13 citations PubMed Publisher’s Site

  6. Survival and Motor Phenotypes in FVB C9-500 ALS/FTD BAC Transgenic Mice Reproduced by Multiple Labs.

    Journal
    Neuron.
    Volume/Issue
    108(4):784-796.e3
    [DOI]
    10.1016/j.neuron.2020.09.009.
    [PMID]
    33022226.
    34 citations PubMed Publisher’s Site

  7. Metformin inhibits RAN translation through PKR pathway and mitigates disease in C9orf72 ALS/FTD mice.

    Journal
    Proceedings of the National Academy of Sciences of the United States of America.
    Volume/Issue
    117(31):18591-18599
    [DOI]
    10.1073/pnas.2005748117.
    [PMID]
    32690681.
    108 citations PubMed Publisher’s Site

  8. Antibody Therapy Targeting RAN Proteins Rescues C9 ALS/FTD Phenotypes in C9orf72 Mouse Model.

    Journal
    Neuron.
    Volume/Issue
    105(4):645-662.e11
    [DOI]
    10.1016/j.neuron.2019.11.007.
    [PMID]
    31831332.
    76 citations PubMed Publisher’s Site

Grants

  1. Novel repeat associated non-AUG (RAN) proteins in sALS, sFTD and SBMA: shared pathological features and unifying therapeutic opportunities

    Active

    Role:
    Principal Investigator
    Funding:
    NATL INST OF HLTH NINDS

  2. Studying roles of CASP8 SVA GGGAGA repeat expansions in Alzheimer’s disease

    Active

    Role:
    Principal Investigator
    Funding:
    NATL INST OF HLTH NIA

  3. Contribution of CASP8 GGGAGA repeat expansion in Alzheimer’s disease

    Active

    Role:
    Principal Investigator
    Funding:
    ALZHEIMERS ASSO

  4. Identifying and understanding the role of repeat RNAs and RAN proteins in Alzheimer’s disease

    Active

    Role:
    Principal Investigator
    Funding:
    NATL INST OF HLTH NIA

  5. Identifying and targeting novel repeat associated non-AUG (RAN) proteins in sporadic ALS

    Active

    Role:
    Co-Investigator
    Funding:
    US ARMY MED RES ACQUISITION

  6. Novel repeat associated non-AUG (RAN) proteins in sALS, sFTD and SBMA: shared pathological features and unifying therapeutic opportunities

    Role:
    Principal Investigator
    Funding:
    NATL INST OF HLTH NINDS

  7. Identifying and understanding the role of repeat RNAs and RAN proteins in Alzheimer’s disease

    Role:
    Principal Investigator
    Funding:
    NATL INST OF HLTH NIA

Contact Details

Phones:
Business:
(352) 273-5112
Emails:
Business:
lien.nguyen@ufl.edu
Addresses:
Business Mailing:
PO BOX 103610
 GAINESVILLE FL 326110001
Business Street:
2033 MOWRY RD RM 225
 GAINESVILLE FL 32610