Muge N. Kuyumcu-Martinez received her Ph.D. at Baylor College of Medicine studying mechanisms by which positive-strand RNA viruses utilize to target RNA binding proteins involved in host mRNA translation. She pursued her post-doctoral training at Baylor College of Medicine working on alternative splicing regulation by RNA binding proteins during heart development and in cardiac complications of muscular dystrophy. She was promoted to an Instructor position at Baylor College of Medicine. In 2010, she was recruited as a tenure track Assistant Professor to the University of Texas Medical Branch. Since then, she has received the prestigious March of Dimes Basil O'Connor Starter Scholar Award and obtained numerous federal and private grants. She has published several high impact research papers and review articles regarding the role of RNA binding proteins in human heart diseases. She has served as an ad hoc member of study sections for American Heart Association and NIH. She is currently a member of American Heart Association and RNA society.
Our laboratory’s main focus is to understand the regulation of alternative splicing (AS) networks in the heart and how dysregulation of AS impacts heart function and development. Specifically, we are interested in identifying signaling pathways that control differential expression of alternatively spliced variants in the heart.
We are currently pursuing two different aspects of AS regulation.
1. Regulation of AS networks by PKC in developing heart
Our data indicate that the protein kinase C (PKC) signaling is critical for AS transitions during rat and mouse heart development. We are systematically investigating a cause and effect relationship between PKC and synchronized AS networks during murine heart development. We are also testing RNA binding protein substrates of PKC in developing heart. Our aim is to identify a regulatory circuitry that controls gene expression via AS during heart development and cardiac differentiation.
AS can alter expression of genes drastically by removing or including alternative exons that correspond to the sequences responsible for mRNA stability and translatability. It can also modify the function of proteins by eliminating exons that code for essential domains. Even though AS is critical for gene regulation, the mechanisms that coordinate AS events in the heart is not well understood. Identifying AS events with direct impact on gene function may provide ways to treat congenital and adult heart diseases, which can be caused by mutations that affect proper splicing.
2. Dysregulation of AS in diabetes
Since chronic activation of PKC is a major contributor to cardiovascular complications of diabetes, we are testing whether PKC causes misregulation of AS in diabetic hearts. Our data show that aberrantly spliced isoforms of genes are expressed in diabetic heart tissues. We are further pursuing the consequences of AS defects in diabetes and analyzing the RNA binding proteins involved in this process.
Diabetes is a costly health care problem affecting 8.3% of the US population. The majority of the diabetes patients die from cardiovascular complications. Defining AS events that promote abnormal gene expression in diabetic hearts may reveal novel ways such as oligo-based therapy to correct splicing defects and ultimately prevent/treat cardiovascular complications of diabetes.
In the laboratory, we use several different model systems including cultured cells, transgenic and knockout mouse models, and rat models to understand the fundamental questions about AS regulation in the heart.
- Muge received a collaborative CPRIT grant titled "Targeting ARNT and RBFOX2 Alternative Splicing as a Novel Treatment Modality in Lymphoid Malignancies" (August 2019).
- Congrats to KarryAnne. Her paper is published in BBRC (Sep 2018).
- Congratulations to Dr. Jun Cao for receiving an American Heart Association post-doctoral fellowship (April 2018)
- Congratulations to Dr. Sunil Verma for receiving the best abstract award for his talk at the 6th Cardiovascular Research Institute Symposium held at Baylor College of Medicine (April 2018)
- Curtis’s review has just been published in WIREs RNA (December 2017).
- KarryAnne has received the “Jane Welsh Award for Excellence in Cardiovascular Research Graduate Student Award” and the “Elferink Scholarship for Academic Excellence” (December 2017).
- Curtis’s paper is published in Muscle and Nerve (April 2017).
- Muge received an NIH R01 grant (January 2017).
- Muge’s review has just been published in Development (November 2016).
- Curtis Nutter received the prestigious Kempner Scholarship (Sep 2016).
- Sunil Verma's recent paper is in press at Scientific Reports (July 2016)
- A collaborative paper with the Garg lab is in press at International Journal of Proteomics (May 2016)
- Our recent paper on Rbfox2 is in press at Cell Reports (May 2016).
- Curtis Nutter received the best student poster at the Clinical and Translational Research Forum (April 2016).
- Our collaborative paper with Dr. Fujise is published in Scientific Reports (Jan 2016).
- Ela and high school student Yareli in the lab got the "Team Science Award" for the best Mentor/Student pair in the Ball High School Bench Tutorials Program.
- Muge received the BMB pilot grant. (April 2015)
- Muge received the American Heart Association Grant in Aid Award (January 2015)
- Curtis was awarded the Arthur V. Simmang Scholarship. (November 2014)
- Curtis received the BSCO Award for his contribution to graduate student organization. (October 2014)
- Muge received the Institute of Infections and Immunity Mini Center Grant as one of the project leaders together with Dr. Nisha Garg, Dr. Ken Fujise and Dr. Whitney Yin. (September 2014)
- Curtis received the prestigious Levin Presidential Scholar Award (August 2014).