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Clara L. Kielkopf, Ph.D.

Contact Information

Phone Numbers

Fax: (585) 275-6007

Office: (585) 273-4799

Research Labs

Biography

Research

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 3´ 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.

Credentials

Faculty Appointments

Education

1994
BS | University of Wisconsin-Madison
Molecular Biology

1999
PhD | California Inst of Tech
Biology

Awards

2014
Edward P. Evans Foundation Award

2013
'Feature' article for 'Nucleic Acids Research' journal

2012
'Hot' article for 'Biochemistry' journal

2011
Invited Chapter in Molecular Cloning 4th Ed.

2010
Press release for 'Molecular Cell' article in URMC news

2009
Cover illustration for CSHL mRNA processing meeting abstract book

2008
'Hot' article and cover illustration for 'Biochemistry' journal

2005
Faculty Research Initiative Award, Johns Hopkins University

2005
Prostate Cancer Foundation Award

2004
Kimmel Scholar Cancer Research Award

2004
March of Dimes Basil O'Connor Award

2003
Faculty Innovation Award, Johns Hopkins University

2002
Faculty Development Award, Johns Hopkins University

1994 - 1997
NSF Pre-Doctoral Fellowship

1993
Hilldale Fellowship, University of Wisconsin-Madison

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Publications

Journal Articles

5/2017
Jenkins JL, Kielkopf CL. "Splicing Factor Mutations in Myelodysplasias: Insights from Spliceosome Structures." Trends in genetics : TIG.. 2017 May 0; 33(5):336-348. Epub 2017 Mar 31.

12/20/2016
Chatrikhi R, Wang W, Gupta A, Loerch S, Maucuer A, Kielkopf CL. "SF1 Phosphorylation Enhances Specific Binding to U2AF(65) and Reduces Binding to 3'-Splice-Site RNA." Biophysical journal.. 2016 Dec 20; 111(12):2570-2586.

12/2016
Loerch S, Kielkopf CL. "Unmasking the U2AF homology motif family: a bona fide protein-protein interaction motif in disguise." RNA.. 2016 Dec 0; 22(12):1795-1807.

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