In some ways, Lingrel is still the curious, small-town Midwestern boy who was fascinated with science and nature. Some of it may arise from the fact that he never really left Ohio. Except for his two-year postdoc at Caltech and a one-year sabbatical at the MRC laboratory in Cambridge, England, Lingrel has been a steady fixture in the Buckeye state, from growing up in Byhalia, to his college years at Otterbein College in Westerville, to his graduate studies at The Ohio State University and finally his long and impressive professorship at the University of Cincinnati.
It’s that continued connection with his youth, spending countless hours trying to understand how things work, that has shaped his research path, be it his globin or Na,K-ATPase studies, or even his more recent foray into KLF2 (Krüppel-like factor).
These studies began as an offshoot of his research with globin expression, but, as in the case of the Na,K-ATPase, Lingrel notes, “I’ve managed to make second careers out of what I thought would just be side projects.”
Other researchers had discovered a transcription factor, called the erythroid Krüppel-like factor, that was critical in orchestrating the switch from fetal to adult hemoglobin expression, and Lingrel used some cDNA from EKLF as a clone to screen for other proteins that bound to hemoglobin genes.
What he uncovered was not just a protein that shared a similar gene-binding region, but one that closely resembled EKLF, ushering in a new Krüppel-like protein family.
Jerry Lingrel’s group recently has shown that KLF2 is involved in making blood vessels. Here, stained sagittal sections of wild type (A) and knock-out (B) mouse aorta highlight the vascular defects that occur when KLF2 is deficient. Wu, J., Bohanan, C. S., Neumann, J. C., and Lingrel, J. B., J. Biol. Chem. (2008) 283, 3942–3950.
He named this new transcription factor LKLF (for lung Krüppel-like factor, although it was later renamed KLF2) and began pursuing its role. He found that it was vital for proper development of the lung and other tissues in embryos but also had a role in the formation, maturation and integrity of blood vessels.
The most interesting aspect of KLF2 function, though, was that it was induced in endothelial cells by fluid shear stress. “That caught my eye,” Lingrel says, “because it’s in areas of low-shear stress, like bifurcations, where you get plaque buildups and atherosclerosis; so KLF2 might be an atheroprotective agent.” His group is currently developing transgenic mice that overexpress KLF2 in low-stress areas and testing their resistance to plaque buildup when fed a high-fat diet.