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Dr. Heather Hundley

Assistant Professor of Biochemistry and Molecular Biology

Dr. Hundley is interested in post-transcriptional mechanisms of regulating gene expression. Gene expression is the movement of information from genomic DNA to mRNA to protein. 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. The 3’ untranslated region (3’ UTR) of mRNAs is a “hotspot” for regulatory elements that direct post-transcriptional gene regulation. My lab is currently focusing on how long double-stranded structures present in 3’ UTRs affect gene expression both in human cell lines and in the microscopic worm,Caenorhabditis elegans


Double-stranded RNA (dsRNA) structures are present in over 5% of human protein coding genes. These regions are targets of the Adenosine deaminase that act on RNA (ADAR) family of enzymes. ADARs bind to dsRNA and catalyze a hydrolytic deamination of adenosine to result in inosine-a process is referred to as RNA editing. Alterations in editing occur in a number of diseases, including epilepsy, schizophrenia, amyotrophic lateral sclerosis, and many types of cancer. Despite their biological importance, the role of ADARs in regulating gene expression is unclear.


Our main goals are to determine the mechanism of how double-stranded structures, and the inosines within them, affect gene expression and elucidate the biological function of ADARs. We use a combination of biochemistry, genetics, and molecular and cellular biology in both worm and human systems to identify the cellular factors and conditions that allow RNA structures and ADARs to regulate gene expression.

   

Selected 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. (Horizon Press )
  • 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.

PubMed

Awards and Honors

  • American Cancer Society Institutional Research Grant
  • Ralph W. and Grace M. Showalter Research Trust Grant
  • IUSM Biomedical Research Enhancement Grant
  • Helen Hay Whitney Post-doctoral Fellowship, 2006-2009

Affiliations

  • Member, IUPUI Signature Center for the Cure of Glioblastoma
  • Associate Member, Indiana University Simon Cancer Center
  • Adjunct Assistant Professor of Biology, Indiana University
  • Trainer, Genome, Cell and Developmental Biology Graduate Program
  • Trainer, Biochemistry Interdisciplinary Graduate Program
  • Fellow, Indiana Molecular Biology Institute

  • 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

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    Shawn Gerber, M.Div.
    BCC Director, Spiritual Care & Chaplaincy IU Health Bloomington
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    Friday, Jul 10th

    Yueh Chang Ho, MD
    Assistant Prof. of Radiology
    IUSOM
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    Otto Wickstrom, MD
    IU Health Southern Indiana Physicians
    Orthopedics & Sports Medicine
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    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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