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Heather Hundley Lab

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Current Hundley Lab Members:

Heather A. Hundley, Ph.D.- Principal Investigator (click here to view Dr. Hundley’s faculty webpage)

Mike C. Washburn- Genome, Cell and Developmental Biology Ph.D. student

Eimile Oakes- Genome, Cell and Developmental Biology Ph.D. student

Ellen Hallberg- Undergraduate researcher, Biology Honors Thesis

 

Current Research Interests:

Active research projects ongoing in my lab are focused on understanding the biological impact of double-stranded RNA and RNA editing on post-transcriptional regulation of gene expression in both normal and cancerous cells. We use a combination of biochemistry, genomics/genetics and molecular biology in both the model organism Caenorhabditis elegans (microscopic worms) and human cell lines to address our questions.

Proper control of gene expression is critical for the normal development of all organisms. Errors in regulating mRNA (post-transcriptional gene expression) account for over 20% of all human genetic diseases, including many types of cancer. Post-transcriptional gene regulation is governed by the interactions of trans-acting factors with cis-acting elements, which are typically found within the noncoding or untranslated regions (UTRs) of mRNA. Our lab is interested in understanding how a family of proteins called ADARs recognize and modifies double-stranded regions within UTRs to regulate gene expression. 

ADARs are highly expressed in the nervous system of both worms and humans. ADARs bind to double-stranded RNA (dsRNA) and convert adenosine (A) to inosine (I), a process called RNA editing. Current estimates range from over 400,000 to 1 million A-to-I editing events in noncoding regions of the human transcriptome. Global hypoediting of these events has been reported in many neuropathological diseases, including epilepsy, schizophrenia, amyotrophic lateral sclerosis, and many types of cancer, including glioblastomas (brain tumors). However the levels of the ADAR proteins are not altered in disease, implying that other mechanisms to regulate ADAR-mediated RNA editing exist. We have recently utilized next generation sequencing and molecular biology approaches to identify a major regulator of noncoding editing in C. elegans. Current efforts in the lab are focused on dissecting the regulatory mechanism and determining the conservation of this regulatory protein in human cells. 

In addition to RNA editing, our lab is interested in how both ADARs and dsRNA elements affect post-transcriptional gene regulation. We have previously shown that C. elegans ADR-1 regulates translation of neuronal mRNAs in an editing independent manner. Furthermore, our work has provided the first data that double-stranded structures within UTRs affect translation of human mRNAs in many cancer cell lines and the C. elegans nervous system. Our current goal is to dissect the mechanisms that both ADR-1 and double-stranded RNA structures utilize to repress translation in neurons, by both determining co-factors required for the translational repression and identifying the endogenous neuronal mRNAs regulated by this mechanism.

 

Publications

Wheeler EC, Washburn MC, Major F, Rusch DB, Hundley HA(2015) Noncoding regions of C. elegans mRNA undergo selective adenosine to inosine deamination and contain a small number of editing sites per transcript, RNA Biology, 2015 Feb;12(2):162-74. doi:10.1080/15476286.2015.1017220.

Washburn MC and Hundley HA(in press) Controlling the editor: the many roles of RNA binding proteins in regulating A-to-I RNA editing, in RNA processing: disease and genome-wide probing, G. Yeo ed. (Springer Press)

Washburn MC, Kakaradov B, Sundararaman B, Wheeler E, Hoon S, Yeo GW, Hundley HA (2014) The dsRBP and Inactive Editor, ADR-1, Utilizes dsRNA Binding to Regulate A-to-I RNA Editing accross the C. elegans Transcriptome, Cell Reports, 2014 Feb 4; pii:S2211-1247(14)00028-X

Hundley HA (2013) Regulation of gene expression through inosine-containing UTRs, In RNA Editing: Current Research and Future Trends, S. Maas, ed. (2013)   http://www.horizonpress.com/rna-editing

Bass B, Hundley H, Li JB, Peng Z, Pickrell J, Xiao XG, Yang L. (2012) The difficult calls in RNA editing, Nature Biotechnology, Dec 7;30(12):1207-9.

Capshew CR, Dusenbury KL and Hundley HA (2012) Inverted Alu dsRNA structures do not affect localization but can alter translation efficiency of human mRNAs independent of RNA editing, Nuc. Acids Res. , 2012 Sep 1;40(17):8637-8645.

Hundley HA and Bass BL (2010) RNA editing in double-stranded UTRs and other noncoding RNA sequences, TIBS, 2010 Jul;35(7):377-83. 

Hundley HA, Krauchuk AA, Bass BL (2008) C. elegans and H. sapiens mRNAs with edited 3’ UTRs are present on polysomes, RNA, 2008 Oct;14(10):2050-2060.

Bass BL, Hellwig S, Hundley HA. (2005) A nuclear RNA is cut out for Translation, Cell, 2005 Oct21;123(2):181-183.

Rauch T, Hundley HA, Pfund C, Wegrzyn RD, Walter W, Kramer G, Kim SY, Craig EA, Deuerling E (2005) Dissecting functional similarities of ribosome-associated chaperones from Saccharomyces cerevisiae and Escherichia coli, Molecular Microbiology, 2005 Jul;57(2):357-65.

Hundley HA, Walter W, Bairstow S, Craig, EA. (2005) Human Mpp11 J-protein: Ribosome- tethered Molecular Chaperones Are Ubiquitous, Science, 2005 May 13; 308(5724):1032-4. (Science Express 2005 Mar 31).

Craig EA, Eisenman HE, Hundley HA. (2003) Ribosome-tethered molecular chaperones: the first line of defense against protein misfolding? Current Opinion in Microbiology 2003 Apr; 6(2):157-62.

Hundley H, Eisenman H, Walter W, Evans T, Hotokezaka Y, Wiedmann M, Craig E. (2002) The in vivo function of the ribosome-associated Hsp70, Ssz1, does not require its putative peptide-binding domain. Proc Natl Acad Sci 2002 Apr 2;99(7):4203-8.

  • NEWS
  • SEMINARS
  • EVENTS
  • Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis

    Apr 28th, 2015

    Anirban K Mitra, Assistant Professor of Medical and Molecular Genetics has recently published his research in Oncogene. His study links paracrine signals from the microenvironment to the regulation of a key miRNA - miR-193b - in ovarian cancer cells, which promotes metastatic colonization.

    New link between motor proteins and breast cancer

    Apr 21th, 2015

    Collaborative work between Claire Walczak (Medical Sciences) and Ritu Aneja (Georgia Tech) reveals that overexpression of the mitotic kinesin, HSET, promotes tumor progression.

    American Cancer Society awards Research Scholar Grant to Dr. Heather Hundley

    Apr 21th, 2015

    Heather A. Hundley, Assistant Professor of Biochemistry and Molecular Biology, has been awarded a $775,000 grant from the American Cancer Society to support her project “Mechanisms Regulating RNA Editing at Specific Sites in the Transcriptome.”

    PUBLICATION

    Comparison of MAPK specificity across the ETS transcription factor family identifies a high-affinity ERK interaction required for ERG function in prostate cells

    Selvaraj N, Kedage V, Hollenhorst PC

    ERK signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration

    Selvaraj N, Budka JA, Ferris MW, Plotnik JP, Hollenhorst PC

    Regulatory mechanisms that control mitotic kinesins

    Yount AL, Zong H, Walczak CE

  • Peter Hollenhorst, PhD

    Aug. 31, 4pm JH 009

    Assistant Professor of Biochemistry and Molecular Biology Medical Sciences Program,
    Indiana University Bloomington, IN

    Lindsey D. Mayo, PhD

    Sept. 14, 4pm JH 009

    Associate Professor of Pediatrics
    Associate Professor of Biochemistry and Molecular Biology Wells Center for Pediatric Research
    Indianapolis, IN

    Charles N. Landen Jr, MD

    Sept. 21, 4pm JH 009

    Associate Professor
    Department of Obstetrics and Gynecology
    University of Virginia Cancer Center

    Qianben Wang, PhD

    Sept. 28, 4pm JH 009

    Associate Professor
    Department of Molecular Virology, Immunology and Medical Genetics and the Comprehensive Cancer Center
    College of Medicine the Ohio State University

  • CME conference

    Ethical Decisions for End of Life Care

    Wednesday, Jul 8th

    Shawn Gerber, M.Div.
    BCC Director, Spiritual Care & Chaplaincy IU Health Bloomington
    Bloomington, IN

    Pediatric Trauma

    Friday, Jul 10th

    Yueh Chang Ho, MD
    Assistant Prof. of Radiology
    IUSOM
    Indianapolis, IN

    Carpal Tunnel Syndrome

    Wednesday, Jul 15th

    Otto Wickstrom, MD
    IU Health Southern Indiana Physicians
    Orthopedics & Sports Medicine
    Bloomington, IN

    Personalized Medicine: Challenges to Patients & their Physicians

    Friday, Jul 24th

    Kenneth Cornetta, MD
    IU Dept. of Medical & Molecular Genetics

    The Increasing Complexity of Venous Thromboembolic Disease

    Friday, Jul 31st

    Kenneth Cornetta, MD
    David Hedrick, MD

    Indiana Hemophilia & Thrombosis Center
    Indianapolis, IN

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