Heather Hundley, Ph.D.
1001 E. 3rd Street
Bloomington, IN 47405
Phone: (812) 855-0675
Fax: (812) 855-4436
Research Program Membership
Department of Biochemistry and Molecular Biology
IU School of Medicine
The overall goal of my research program is to understand the biological impact of double-stranded RNA and RNA editing on post-transcriptional regulation of gene expression in both normal and cancerous cells. 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. ADARs highly expressed in the nervous system of both worms and humans. Alterations in editing occur in a number of diseases, including epilepsy, schizophrenia, amyotrophic lateral sclerosis, and many types of cancer, including glioblastomas. Despite their biological importance, the role of ADARs in regulating gene expression is unclear. Our work characterizing mammalian mRNAs with edited double-stranded structures has challenged the existing paradigm that RNA editing of endogenous dsRNA results in nuclear retention. In addition, we have recently determined that double-stranded 3' UTR structures alter translation of human mRNAs in many cancer cell lines, such as HeLa (cervical), U87 (glioblastoma), T98G (glioblastoma). As a provocative question in cancer biology is to understand how RNA processing affects tumor development and RNA editing is tightly linked to brain tumor progression, we are currently monitoring editing levels and the effects of double-stranded 3' UTRs on protein expression in normal brain matter and glioblastomas.
Post-doctoral Fellowship - University of Utah, Salt Lake City, UT 2009
Ph.D. - University of Wisconsin, Madison, WI 2005