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Genetics Faculty


Kristian Baker
Associate Professor
Department of Genetics
School of Medicine
Case Western Reserve University
Biomedical Research Building 629
2109 Adelbert Road
Cleveland, Ohio 44106-4955
Tel: (216) 368-0277
Fax: (216) 368-3432
E-mail: kristian.baker@case.edu


About Kristian Baker

Kristian Baker received her Ph.D. in Genetics from the University of British Columbia (UBC) in Vancouver, Canada in 2002. She completed post-doctoral training at the Howard Hughes Medical Institute at the University of Arizona under the mentorship of Dr. Roy Parker, a pioneer in the study of RNA regulation and metabolism. She joined the faculty at Case Western Reserve University in 2005 and is currently a tenured Associate Professor in the Department of Genetics & Genome Sciences where her lab investigates molecular mechanisms that regulate the interplay between mRNA translation and degradation, and how RNA quality control is maintained in the cell. Outside of the lab, she is an engaged mentor and enthusiastic educator, and serves the greater RNA scientific community as Chair of the Membership Committee for the international RNA Society.


Research

Nonsense-mediated mRNA decay (NMD) denotes the remarkable cellular surveillance system in eukaryotic cells that recognizes and eliminates mRNA encoding nonsense codons within their protein-coding region (Figure 1). Nonsense codons direct premature termination of translation and, as a consequence, the synthesis of incomplete polypeptides. The prompt degradation of nonsense-containing mRNA by the NMD pathway assures that the mRNA does not accumulate as a substrate for translation, thereby protecting cells from amassing truncated polypeptides that might confer deleterious dominant-negative or gain-of-function phenotypes to the cell.

The NMD pathway represents a conserved and essential biological process necessary for protecting cells from transmitting faulty genetic information. In spite of almost three decades of study, a number of fundamental questions central to this process remain poorly resolved, including how cells discriminate between normal and premature translation termination and what molecular events occur subsequently to cause accelerated decay of the nonsense codon-containing mRNA. The Baker lab uses molecular, biochemical, and genetic approaches to study the underlying mechanisms of NMD, with the ultimate goal of developing therapeutics which could modulate NMD and be applied for the treatment of patients with a vast array of genetic diseases caused by nonsense mutations.


Selected Publications

Purification of Transcript-Specific mRNP Complexes Formed In Vivo from Saccharomyces cerevisiae.
Smith JE, Baker KE
Methods Mol Biol (2017);1648:201-220
See PubMed abstract

ATP hydrolysis by UPF1 is required for efficient translation termination at premature stop codons.
Serdar LD, Whiteside DL, Baker KE
Nat Commun (2016);7:14021
See PubMed abstract

Nonsense-mediated RNA decay--a switch and dial for regulating gene expression.
Smith JE, Baker KE
Bioessays (2015);37(6):612-23
See PubMed abstract

Codon optimality is a major determinant of mRNA stability.
Presnyak V, Alhusaini N, Chen YH, Martin S, Morris N, Kline N, Olson S, Weinberg D, Baker KE, Graveley BR, Coller J
Cell (2015);160(6):1111-24
See PubMed abstract

Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae.
Smith JE, Alvarez-Dominguez JR, Kline N, Huynh NJ, Geisler S, Hu W, Coller J, Baker KE
Cell Rep (2014);7(6):1858-66
See PubMed abstract

Decapping of long noncoding RNAs regulates inducible genes.
Geisler S, Lojek L, Khalil AM, Baker KE, Coller J
Mol Cell (2012);45(3):279-91
See PubMed abstract

The Centrality of RNA, Then and Now
Baker KE, Nilsen TW
Cell (2011);147: 962-963

Nonsense-mediated mRNA decapping occurs on polyribosomes in Saccharomyces cerevisiae.
Hu W, Petzold C, Coller J, Baker KE
Nat Struct Mol Biol (2010);17(2):244-7
See PubMed abstract

Co-translational mRNA decay in Saccharomyces cerevisiae.
Hu W, Sweet TJ, Chamnongpol S, Baker KE, Coller J
Nature (2009);461(7261):225-9
See PubMed abstract

Nonsense-mediated mRNA decay in yeast does not require PAB1 or a poly(A) tail.
Meaux S, van Hoof A, Baker KE
Mol Cell (2008);29(1):134-40
See PubMed abstract

Conventional 3' end formation is not required for NMD substrate recognition in Saccharomyces cerevisiae.
Baker KE, Parker R
RNA (2006);12(8):1441-5
See PubMed abstract

Under the Tucson sun: a meeting in the desert on mRNA decay.
Baker KE, Condon C
RNA (2004);10(11):1680-91
See PubMed abstract

Nonsense-mediated mRNA decay: terminating erroneous gene expression.
Baker KE, Parker R
Curr Opin Cell Biol (2004);16(3):293-9
See PubMed abstract