December 2011

Advice for new assistant professors

Peter Kennelly writes that he has observed many newly minted faculty over the years and offers some sage advice to make their transition less painful. Here then, is a list of twelve suggestions that young assistant professors wisely should consider for the achievement of tenure and success in their careers.



Although expensive, the ‘cleaning’ of blood (apheresis) is a viable option for people with severe hypercholesterolemia

Familial hypercholesterolemia is characterized by very high concentrations of low-density lipoprotein (LDL) in the blood. In such cases where drug-mediated cholesterol regulation is ineffective, LDL-apheresis might prove the only remedy if effective. Orsoni and colleagues tested the ability of LDL-apheresis over a two-year period. In addition to removing LDL subparticles and apoproteins, the treatment also removed apoE-high density lipoprotein HDL (apoE-HDL), which can adhere to vessel walls, promoting the growth of plaques. Thus, the findings suggest that although an expensive treatment option, such apheresis is effective at lowering the concentration of circulating lipoproteins in those patients who do not respond to other therapies.



Chemical proteomic method reveals new target for treating head and neck cancers

Head-and-neck cancer is an aggressive cancer in need of an identifiable Achilles’ heel. Feller and Kuster used a chemical proteomics approach to identify possible therapeutic targets. Studying 146 protein kinases, they identified EPHA2, a transmembrane protein kinase receptor known to bind ephrins, as a possible target for further investigation. The researchers will determine how EPHA2 expression correlates with prognosis and may begin to develop small-molecule inhibitors of the protein kinase.



Creating your own path: a bioinformatics case study

Like all of us, Ewy Mathé sought out the position that fulfilled her interests. Unlike many of us, she found it. Mathé tells of her initial interests in brain surgery and forensics and how a job in a yeast genetics lab gave her sufficient time to realize that bench work wasn’t her greatest interest either. She landed in a Ph.D. program in bioinformatics where she specialized in protein-structure folding. Now a staff scientist at the NIH, she’s sure she has found her life’s interest.



Enzyme controls fatty acid oxidation based on environmental cues

Carnitine palmitoyltransferase 1, an enzyme whose activity is required for proper cell metabolism, controls the rate-limiting step in fatty acid β-oxidation. In a recent “Paper of the Week,” Ulmer and colleagues have determined that CPT1 is inhibited by the presence of malonyl-CoA and is additionally regulated by the curvature of the outer mitochondrial membrane (in which it resides) and by the lipid compostion in the same membrane. Because CPT1’s function depends on the presence of environmental cues, the protein may make an excellent drug target for disorders from diabetic ketoacidosis to fatty liver disease.



New protein sensors to quantify phosphoinositides in situ

Phospholipids are involved in cellular metabolism and homeostasis, and some of these molecules regulate the activity of various enzymes and ion channels. Within the phospholipid family exists a subgroup known as the phosphoinositides. The concentration, distribution, and movement of these within the cell have not been amenable to quantitation until now. A new, chemically modified lipid domain has been created that binds phospholipids and undergoes a fluorescent blue shift. This probe promises to quantify the amount of phosphoinositides required for specific functions within the cell.


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