Clara L. Kielkopf, Ph.D.

Clara L. Kielkopf, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, NY 14642

Office: (585) 273-4799
Fax: (585) 275-6007
Lab: (585) 276-3681

Research Bio

My laboratory determines and leverages the three-dimensional structures of pre-mRNA splice site assemblies to understand and potentially treat human genetic diseases and hematologic malignancies. We focus on the structural and molecular basis for 3ยด splice site recognition by the essential splicing factors U2AF65, U2AF35, and SF1. Our recent structures of U2AF65 bound to a range of splice site signals provide a basis for understanding disease-causing mutations in the splice sites of gene transcripts. Towards a view of the higher order splice site assembly, we have revealed phosphorylation-induced conformational changes in the splicing factor subunit SF1 bound to U2AF65, and demonstrated that the phosphorylated interface is essential in vivo. Now, an immediate goal of my laboratory is to determine roadmaps of the key interactions among higher order 3' splice site complexes, and in future phases of the project, assist the development of therapeutics targeted at the level of pre-mRNA splicing.
Our work is enhanced by collaborations with leading researchers in the field of RNA biology and has been documented by peer-reviewed publications in respected journals (including publications in Molecular Cell and Nature Structural & Molecular Biology, impact factors 12.9 and 12.1). I am co-director of the Structural Biology and Biophysics Facility, which supports X-ray crystallographic and biomolecular interaction equipment at the University of Rochester, including a BIAcore T200 that I obtained via an S10 grant from the NIH.

I take pride in the education and placement of members from my group, including graduate students (for example, Karen Thickman, who was an F32 recipient and is now an Assistant Professor at Carnegie Mellon, and Krystle McLaughlin, who was an SPIRE postdoctoral scholar at UNC-Chapel Hill and is now an Assistant Professor at LeHigh University), undergraduate students (for example, Jason Heath, who completed post baccalaureate training at the NIH), and postdoctoral scholars (for example, Allen Sickmier, who is now a Senior Scientist at Amgen, Inc.).
Please visit our lab website for more information.

Awards & Honors (National)

Edward P. Evans Foundation Award 2014
Prostate Cancer Foundation Award 2005
March of Dimes Basil O'Connor Award 2004
Kimmel Scholar Cancer Research Award 2004
NSF Pre-Doctoral Fellowship 1994 - 1997

Awards & Honors (Local)

'Feature' article for 'Nucleic Acids Research' journal 2013
'Hot' article for 'Biochemistry' journal 2012
Invited Chapter in Molecular Cloning 4th Ed. 2011
Press release for 'Molecular Cell' article in URMC news 2010
Cover illustration for CSHL mRNA processing meeting abstract book 2009
'Hot' article and cover illustration for 'Biochemistry' journal 2008
Faculty Research Initiative Award, Johns Hopkins University 2005
Faculty Innovation Award, Johns Hopkins University 2003
Faculty Development Award, Johns Hopkins University 2002
Hilldale Fellowship, University of Wisconsin-Madison 1993

Recent Journal Articles

Showing the 5 most recent journal articles. 32 available »

2015 Sep 25
Loerch S, Kielkopf CL. "Dividing and Conquering the Family of RNA Recognition Motifs: A Representative Case Based on hnRNP L." Journal of molecular biology. 2015 Sep 25; 427(19):2997-3000. Epub 2015 Jun 20.
2015 Apr
Okeyo-Owuor T, White BS, Chatrikhi R, Mohan DR, Kim S, Griffith M, Ding L, Ketkar-Kulkarni S, Hundal J, Laird KM, Kielkopf CL, Ley TJ, Walter MJ, Graubert TA. "U2AF1 mutations alter sequence specificity of pre-mRNA binding and splicing." Leukemia. 2015 Apr; 29(4):909-17. Epub 2014 Oct 14.
2014 Jun 20
Loerch S, Maucuer A, Manceau V, Green MR, Kielkopf CL. "Cancer-relevant splicing factor CAPER? engages the essential splicing factor SF3b155 in a specific ternary complex." The Journal of biological chemistry. 2014 Jun 20; 289(25):17325-37. Epub 2014 May 02.
Agrawal AA, McLaughlin KJ, Jenkins JL, Kielkopf CL. "Structure-guided U2AF65 variant improves recognition and splicing of a defective pre-mRNA." Proceedings of the National Academy of Sciences of the United States of America. 2014 111(49):17420-5. Epub 2014 Nov 24.
2013 Apr 1
Jenkins JL, Agrawal AA, Gupta A, Green MR, Kielkopf CL. "U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs." Nucleic acids research. 2013 Apr 1; 41(6):3859-73. Epub 2013 Feb 01.

Current Appointments

Associate Professor - Department of Biochemistry and Biophysics (SMD) - Primary
Associate Professor - Cancer Center


PhD | Biology | California Inst of Tech1999
BS | Molecular Biology | University of Wisconsin-Madison1994