Medicine - Pulmonary, Critical Care, and Sleep Medicine

2008 Recipient

Nitric oxide and autophagy in inflammation and immunity

Dr. Eissa received the award for his studies related to critical cellular and immunological processes. Dr. Eissa's laboratory demonstrated that cells regulate inducible nitric oxide synthase (iNOS), an important host defense protein, through aggresome formation. Their studies indicated that aggresome formation in response to misfolded proteins may merely represent an acceleration of an established physiologic regulatory process for specific proteins whose regulation by aggresome formation is deemed necessary by the cell. These findings established the presence of the "physiologic aggresome", that is, aggresome formation not associated with misfolded proteins, and defined a new paradigm for cellular regulation of protein processing.

Dr. Eissa's laboratory has also shown that Toll-like receptor 4 (TLR4) serves as a previously unrecognized environmental sensor for autophagy. These studies unraveled an important aspect of autophagy regulation and provided a link between stimulation of autophagy and pattern recognition receptors of innate immunity. This work opened a new window for potential therapeutic interventions for modulation of autophagy through the TLRs. These new therapeutic strategies may be able to outsmart pathogens, some of which rely on suppressing autophagy for their survival.

Dr. Eissa's nomination was based on the following publications:

Kolodziejska KE, Burns AR, Moore RH, Stenoien DL, Eissa NT. 2005. Regulation of inducible nitric oxide synthase by aggresome formation. Proc Natl Acad Sci U S A. 102(13):4854-9. 

Xu Y, Jagannath C, Liu XD, Sharafkhaneh A, Kolodziejska KE, Eissa NT. 2007. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27(1):135-44. 

Sha Y, Pandit L, Zeng S, Eissa NT. 2009. A critical role for CHIP in the aggresome pathway. Mol Cell Biol 29(1):116-28. Epub 2008 Oct 27.