Jay Brenman, PhD

Brenman

 Associate Professor

Research Description

All cells and organisms must monitor and maintain their energy levels for survival. One particular protein kinase, AMP-activated protein kinase (AMPK) plays a central role in energy balance. AMPK consists of a protein complex encoded by three subunits, a serine-threonine kinase catalytic subunit (α) and two regulatory subunits (ß, γ). When AMPK signaling is disrupted cells undergo cell death and organisms can not survive limited starvation.

AMPK has many potential biomedically-relevant functions. AMPK is proposed to be a therapeutic target for Type 2 diabetes and Metabolic syndrome (obesity, insulin resistance, cardiovascular disease). In addition, since cancer cells have larger energetic requirements than non-dividing cells, targeting AMPK might be an attractive approach for attacking cancer.

We identified mutations in the AMPK kinase domain (AMPKα) during a genetic screen looking for "neurodegeneration mutants" in Drosophila. Inactivation of AMPK leads to neurodegeneration-like phenotypes in neurons and abnormal metabolism in other cells. Our lab uses combinations of genetics, biochemistry/proteomics and cell culture models to try to further identify new molecules involved in AMPK signaling. We are particularly interested in how AMPK signaling and molecules it regulates are relevant to:

  • Neurodegeneration

    • Metabolism (Type 2 Diabetes/Cardiac Disease)
    • Cancer

Many of our studies use Drosophila melanogaster (the fruit fly) due to the powerful genetics of this assay system and conserved molecules in AMPK signaling. However, we also use mouse genetics to explore AMPK function  in two contexts: 1) In brains of knockout mice to explore the role of AMPK in normal nervous system function; 2) In brain tumor cancer models (in collaboration with Dr. R. Miller).

Other studies use differential proteomics (in collaboration with Dr. O. Alzate) in combination with AMPK knockout cells and tissues to elaborate new AMPK signaling targets/components.

Finally, human mutations in the gamma subunit of AMPK cause the fatal cardiac syndrome, Wolf-Parkinson-White. We are trying to use Drosophila to develop an animal model with these mutations to allow us to use powerful genetic analyses to better understand this disease and regulation of AMPK signaling.

A joint project (with Dr. J. Sexton, NCCU) involves developing new cell based assays for new compounds that could become thereapeutics for metabolic disease (particularly Type 2 Diabetes and fatty liver). We are also developing novel small molecule drugs to modulate AMPK activity.


    Contact Information

    Email
    Office: (919) 843-3637
    Lab: (919) 843-3638


    Affiliations