NHLBI Pro­gram Project

NHLBI Mitochon­drial Bio­logy Project

Ping Lab Main Research Projects

Proteome Biology of Cardiac Mitochondria

Pro­teome Bio­logy of Car­diac Mitochondria

Mitochon­dria play essen­tial roles in car­diac pathophy­sio­logy and the murine model has been exten­si­vely used to inves­ti­gate car­dio­vas­cu­lar disea­ses. In the pre­sent study, we cha­rac­te­ri­zed murine car­diac mitochon­dria using an LC/​​MS/​​MS approach. We extrac­ted and puri­fied car­diac mitochon­dria; vali­da­ted their func­tio­na­lity to ensure the final pre­pa­ra­tion con­tains neces­sary com­po­nents to sus­tain their nor­mal func­tion; and sub­jec­ted these vali­da­ted orga­ne­lles to LC/​​MS/​​MS-​​​​based pro­tein iden­ti­fi­ca­tion. A total of 940 dis­tinct pro­teins were iden­ti­fied from murine car­diac mitochon­dria, among which, 480 pro­teins were not pre­viously iden­ti­fied by major pro­teo­mic pro­fi­ling stu­dies. Read more →

Cardiac Protein Degradation

Map­ping the Murine Car­diac 26S Pro­tea­some Complexes

The impor­tance of pro­tea­so­mes in gover­ning the intra­ce­llu­lar pro­tein degra­da­tion pro­cess has been inc­rea­singly recog­ni­zed. Recent inves­ti­ga­tions indi­cate that pro­tea­some com­ple­xes may exist in a spe­cies– and cell-​​​​type-​​​​specific fashion. To date, des­pite evi­dence lin­king impai­red pro­tein degra­da­tion to car­diac disease phe­noty­pes, vir­tually nothing is known regar­ding the mole­cu­lar com­po­si­tion, func­tion, or regu­la­tion of car­diac pro­tea­so­mes. We have taken a func­tio­nal pro­teo­mic approach to cha­rac­te­rize 26S pro­tea­so­mes in the murine heart. Read more →

Cardiac Organelle-​​specific Peptide Spectral Library

The rapid deve­lop­ment of high accu­racy and high sen­si­ti­vity mass spec­tro­metry tech­no­lo­gies has revo­lu­tio­ni­zed our unders­tan­ding of pro­teins and their con­tri­bu­tion to cellu­lar func­tion. Howe­ver, there is an inc­rea­singly appa­rent dis­con­nect bet­ween these state-​​​​of-​​​​the-​​​​art tools and their effec­tive appli­ca­tions to advance car­dio­vas­cu­lar bio­logy and medi­cine. Des­pite pro­gress made in cer­tain areas of inves­ti­ga­tion, car­dio­vas­cu­lar pro­teo­mic research faces three major cha­llen­ges: the exces­sive cost of ins­tru­men­ta­tion; the limi­ted acces­si­bi­lity of advan­ced pro­teo­mic tech­no­logy to the car­dio­vas­cu­lar com­mu­nity at large; and the overwhel­ming quan­tity and frag­men­ted nature of mass spec­tra data­sets lac­king func­tio­nal anno­ta­tions. Read more →