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Clara L. Kielkopf, Ph.D.

Contact Information

Phone Numbers

Office: (585) 273-4799

Fax: (585) 275-6007

Research Labs

Faculty Appointments

Biography

Research

The Kielkopf lab investigates the molecular structures and interactions among key pre-mRNA splicing factors in human genetic diseases and hematologic malignancies (Trends Genetics 2017). Our recent structures of U2AF2 bound to a range of splice site signals provide a basis for understanding disease-causing mutations in the splice sites of gene transcripts (PNAS 2014; Nature Commun. 2016). As a step towards viewing the architecture of multi-subunit pre-mRNA splicing factor complexes, we revealed phosphorylation-induced conformational changes in the splicing factor subunit SF1 bound to U2AF2, and demonstrated that the phosphorylated interface is essential in vivo (Structure 2013). We have further shown that recurrent, cancer-associated mutations of U2AF1 alter its RNA interactions (Leukemia 2014; PLOS Genetics 2017). Now, our immediate goal 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.

We are grateful to the following organizations for research funding:

National Institutes of Health:
R01 GM070503: Molecular Recognition During pre-mRNA Splicing
R01 GM117005: Structural Control of Human Co-factors for Retroviral Gene Expression

Edward P. Evans Foundation:
Research Discovery Grant: Structural mechanisms & targeting of MDS-relevant pre-mRNA splicing factors

Credentials

Education

1994
B.S. | University of Wisconsin-Madison
Molecular Biology (summa cum laude)

2000
Ph.D. | California Institute of Technology
Biology and Chemistry

Post-doctoral Training & Residency

2000 - 2001
Post-doctoral Training | The Rockefeller University

Awards

2017
Edward P. Evans Foundation Research Award

2014
Edward P. Evans Foundation Research Award

2009
Cover illustration for CSHL mRNA processing meeting abstract book

2005
Prostate Cancer Foundation Award

2004
Kimmel Scholar Cancer Research Award

2004
March of Dimes Basil O'Connor Award

2000 - 2002
American Cancer Society Postdoctoral fellowship

1994 - 1997
NSF Pre-Doctoral Fellowship

1993
Hilldale Fellowship, University of Wisconsin-Madison

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Publications

Journal Articles

11/7/2019
Maji D, Grossfield AM, Kielkopf CL. "Structures of SF3b1 reveal a dynamic Achilles heel of spliceosome assembly: Implications for cancer-associated abnormalities and drug discovery." Biochimica et biophysica acta. Gene regulatory mechanisms.. 2019 Nov 7; :194440. Epub 2019 Nov 07.

8/2019
Talkish J, Igel H, Hunter O, Horner SW, Jeffery NN, Leach JR, Jenkins JL, Kielkopf CL, Ares M. "Cus2 enforces the first ATP-dependent step of splicing by binding to yeast SF3b1 through a UHM-ULM interaction." RNA.. 2019 Aug 0; 25(8):1020-1037. Epub 2019 May 20.

2/20/2019
Kennedy SD, Bauer WJ, Wang W, Kielkopf CL. "Dynamic stacking of an expected branch point adenosine in duplexes containing pseudouridine-modified or unmodified U2 snRNA sites." Biochemical and biophysical research communications.. 2019 Feb 20; Epub 2019 Feb 20.

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