.jpg "Kim M. Keeling, PhD photo")
Assistant Professor
University of Alabama at Birmingham
My name is Kim Keeling. I am currently an Assistant Professor of Biochemistry & Molecular Genetics at the University of Alabama at Birmingham (UAB).
I obtained a Bachelors of Science degree in Chemistry at UAB in 1990. I then worked at NASA as a biochemist where I performed work in protein cystallography and supported microgravity experiments flown on the Space Shuttle. I then attended graduate school at UAB where, in 2000, I obtained a PhD in Medical Genetics. I performed postdoctoral work in the UAB Department of Microbiology under Dr. David Bedwell and was appointed as an Instructor in 2003. In 2007, I was promoted to Assistant Professor. In 2019, I earned a Bachelors of Arts degree in English/Professional Writing at UAB.
My research involves the development of therapies that alleviate protein deficiencies caused by premature termination codons (PTCs). One approach that I have been investigating is the pharmacological suppression of translation termination at PTCs, which restores partial levels of deficient protein function. I have developed immortalized cell lines and/or animal models to evaluate this approach for two different genetic diseases, mucopolysaccharidosis I-Hurler and cystic fibrosis. I have also developed an array of therapeutic endpoints that can be used to evaluate the efficiency of PTC suppression drugs both in vitro and in vivo. I have been a Principal Investigator or Co-Investigator on fourteen different grants (both internal and external) to explore this approach. Four of these grants were NIH-funded. The establishment of these model systems has also been the basis of collaborations with several research groups and pharmaceutical companies to characterize new PTC suppression compounds. I have successfully administered or co-administered these projects and have co-authored fifteen peer-reviewed publications on this approach.
I have also begun examining whether attenuating nonsense-mediated mRNA decay (NMD) is another way to overcome gene expression deficiencies attributable to PTCs. Using funds from a Pilot and Feasibility Grant that was awarded to me by the UAB Cystic Fibrosis Research Center and with the aid of the UAB CF Center Animal Models Core (Core B), I generated inducible NMD-deficient transgenic mice. I was awarded an R21 grant from NIH (OD019922) to examine whether in vivo NMD attenuation is a safe and effective way to enhance PTC suppression using these NMD-deficient mice. With the aid of the CF Center Animal Models Core, the NMD-deficient transgenic mice were crossed with Cftr-G542X knock-in mice in order to examine how NMD attenuation affects the ability of CFTR modifier drugs to restore CFTR protein function. I received a grant from the Cystic Fibrosis Foundation (KEELIN15XX0) to carry out this study. More recently, I obtained funding from the Cystic Fibrosis Foundation (KEELIN20G0) to explore how CFTR mRNAs are targeted to NMD.