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.
- 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
- IU Press Release: http://news.indiana.edu/releases/iu/2014/02/hundley-messenger-rna.shtml
- Featured on the NSF website News from the Field:http://www.nsf.gov/news/news_summ.jsp? cntn_id=130446&org=NSF&from=news
- 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.
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
- 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