{"id":2350,"date":"2018-12-02T17:54:30","date_gmt":"2018-12-02T23:54:30","guid":{"rendered":"https:\/\/restruct-lgmd-2021.pantheonsite.io\/?p=2350"},"modified":"2023-10-06T16:14:49","modified_gmt":"2023-10-06T16:14:49","slug":"researcher-qi-lu","status":"publish","type":"post","link":"https:\/\/www.lgmd-info.org\/tr\/lgmd2i\/2018\/12\/02\/researcher-qi-lu\/","title":{"rendered":"LGMD ARA\u015eTIRMACISI: Qi Lu"},"content":{"rendered":"

\"LGMD ARA\u015eTIRMAYA I\u015eIK TUTUYOR\"<\/strong><\/p>\n

LGMD ARA\u015eTIRMACISI:\u00a0 <\/strong>\u00a0\u00a0Dr. Qi Lu\u00a0\u00a0\"\"<\/a><\/p>\n

Ba\u011fl\u0131l\u0131k:\u00a0 \u00a0<\/strong>McColl Lockwood Musk\u00fcler Distrofi Ara\u015ft\u0131rma Laboratuvar\u0131<\/p>\n

Rol veya Pozisyon:\u00a0\u00a0<\/strong>Direkt\u00f6r, McColl Lockwood kas distrofisi ara\u015ft\u0131rma laboratuvar\u0131, Carolinas T\u0131p Merkezi, Atrium Health, Charlotte<\/p>\n

\u015eu anki pozisyonunuza gelmek i\u00e7in hangi e\u011fitim ve \u00f6\u011fretimi ald\u0131n\u0131z?<\/strong><\/p>\n

\u00c7in'de t\u0131p e\u011fitimi ald\u0131m ve \u0130ngiltere'deki Londra \u00dcniversitesi'nden doktora derecesi ald\u0131m.<\/p>\n

Sizi ara\u015ft\u0131rma alan\u0131nda kariyer yapmaya ve \u00f6zellikle kas distrofisi \u00fczerine \u00e7al\u0131\u015fmaya y\u00f6nlendiren neydi?<\/strong><\/p>\n

Londra'daki doktora \u00e7al\u0131\u015fmamdan \u00f6nce uzun y\u0131llar patolog olarak e\u011fitim alm\u0131\u015ft\u0131m ve do\u011fal olarak kas distrofisinden kaynaklanan kas dokular\u0131n\u0131n histopatolojisiyle ilgileniyordum. Duchenne musk\u00fcler distrofisinin hastal\u0131kl\u0131 kaslar\u0131ndaki \"revertant lifler\" beni b\u00fcy\u00fcleyene kadar musk\u00fcler distrofi ara\u015ft\u0131rmalar\u0131yla pek ilgilenmiyordum. DMD kaslar\u0131 distrofin ekspresyonundan yoksundur, ancak kas liflerinin k\u00fc\u00e7\u00fck bir k\u0131sm\u0131 asl\u0131nda neredeyse normal distrofin seviyelerine sahiptir. Liflerin distrofin yoklu\u011fundan normal distrofin seviyelerine d\u00f6nmesinin arkas\u0131ndaki mekanizmalar\u0131 anlamaya \u00e7al\u0131\u015fmak i\u00e7in \u00e7ok zaman harcad\u0131m ve mekanizmay\u0131 bilirsek tedavinin geli\u015ftirilebilece\u011fini d\u00fc\u015f\u00fcnd\u00fcm. Londra'daki MRC Klinik Ara\u015ft\u0131rma Merkezi'nde Profes\u00f6r Terrence Partridge'in g\u00f6zetiminde Kas H\u00fccresi Biyolojisi Laboratuvar\u0131'nda yapt\u0131\u011f\u0131m \u00e7al\u0131\u015fmalar, DMD kaslar\u0131ndaki bu geri d\u00f6n\u00fc\u015fl\u00fc liflerin b\u00fcy\u00fck olas\u0131l\u0131kla kendili\u011finden olu\u015fan \"ekzon atlamas\u0131ndan\" kaynakland\u0131\u011f\u0131, ba\u015fka mutasyonlardan kaynaklanmad\u0131\u011f\u0131 sonucuna vard\u0131. O d\u00f6nemde DMD tedavisi i\u00e7in \"ekzon atlama\" kavram\u0131 rapor edilmekteydi. Bu, geri d\u00f6n\u00fc\u015f\u00fcml\u00fc lifler hakk\u0131ndaki anlay\u0131\u015f\u0131mla birlikte beni DMD modeli olan MDX farelerinde ekzon atlama y\u00f6ntemini kullanmaya y\u00f6neltti. \u00c7ok heyecan verici bir \u015fekilde, \u00e7al\u0131\u015fmam ilk kez antisens oligon\u00fckleotidin DMD modelinde terap\u00f6tik distrofin seviyelerinin restorasyonunu sa\u011flayabildi\u011fini \u015f\u00fcpheye yer b\u0131rakmayacak \u015fekilde g\u00f6sterdi ve sonu\u00e7 2003 y\u0131l\u0131nda Nature Medicine dergisinde yay\u0131nland\u0131. K\u0131sa s\u00fcre sonra \u0130ngiltere'de Dr. Francesco Muntoni'nin PI olarak DMD'ye oligon\u00fckleotid tedavisinin klinik denemeleri i\u00e7in haz\u0131rl\u0131klara ba\u015flamak \u00fczere bir grup olu\u015fturduk. Bir ara\u015ft\u0131rma sonucunun do\u011frudan klinik uygulamalara d\u00f6n\u00fc\u015ft\u00fcr\u00fclebilece\u011fi ger\u00e7e\u011fi ilgimi b\u00fcy\u00fck \u00f6l\u00e7\u00fcde art\u0131rd\u0131 ve beni sonsuza dek kas distrofisi ara\u015ft\u0131rmalar\u0131na itti. Tesad\u00fcf eseri, Carolinas T\u0131p Merkezi o s\u0131rada yeni tan\u0131mlanm\u0131\u015f bir genetik kusur olan FKRP gen mutasyonlar\u0131 ile bir t\u00fcr ekstremite ku\u015fa\u011f\u0131 musk\u00fcler distrofisini (LGMD) incelemek i\u00e7in yeni bir laboratuvar kuracak birini ar\u0131yordu. Ben de 2004 y\u0131l\u0131nda Carolinas T\u0131p Merkezi'nde McColl Lockwood Musk\u00fcler Distrofi Ara\u015ft\u0131rma Laboratuvar\u0131'n\u0131 kurmak \u00fczere Direkt\u00f6r olarak i\u015fe al\u0131nd\u0131m.<\/p>\n

Hangi konular \u00fczerinde \u00e7al\u0131\u015f\u0131yorsunuz?<\/strong><\/p>\n

McColl Lockwood laboratuvar\u0131 \u00f6zellikle FKRP genindeki mutasyonlar\u0131n neden oldu\u011fu LGMD2I'yi hedeflemektedir. Bu spesifik kas distrofisi t\u00fcr\u00fc distroglikanopati olarak da adland\u0131r\u0131l\u0131r \u00e7\u00fcnk\u00fc do\u011frudan kas g\u00fc\u00e7s\u00fczl\u00fc\u011f\u00fcne neden olan ana kusur, normalde distroglikan ad\u0131 verilen kas lifi y\u00fczey proteinlerinden birinde bulunan spesifik bir \u015fekerin (glikan) eksikli\u011fidir. Distroglikan \u00fczerindeki bu \u015feker, kas liflerini tek tek hareket etmek yerine g\u00fc\u00e7l\u00fc bir halat olu\u015fturacak \u015fekilde birbirine ba\u011flamak ve b\u00f6ylece kas\u0131n\u0131z kas\u0131ld\u0131\u011f\u0131nda olas\u0131 hasar\u0131 en aza indirmek i\u00e7in kritik \u00f6neme sahiptir. \u015eeker eksikli\u011fi bu ba\u011flant\u0131y\u0131 bozar ve ilerleyen kas hasar\u0131na neden olur ve yava\u015f yava\u015f yara olu\u015fumuna ve i\u015flev kayb\u0131na yol a\u00e7ar. \u0130lk birka\u00e7 y\u0131l boyunca, laboratuvar\u0131m iki ana program y\u00fcr\u00fctt\u00fc; biri DMD i\u00e7in ekson atlama tedavisinin daha fazla kullan\u0131lmas\u0131 (ilk ara\u015ft\u0131rmalar\u0131mdan kalan bir proje) ve di\u011feri FKRP ile ili\u015fkili kas distrofisi i\u00e7in hem h\u00fccre k\u00fclt\u00fcr\u00fc hem de fare modelleri model sistemlerinin olu\u015fturulmas\u0131. Son 6 y\u0131l boyunca, neredeyse t\u00fcm projeler LGMD2I ve baz\u0131 konjenital musk\u00fcler distrofi vakalar\u0131n\u0131 i\u00e7eren FKRP musk\u00fcler distrofisine deneysel tedavi geli\u015ftirmeye y\u00f6nelik olmu\u015ftur. Terap\u00f6tik geli\u015ftirme i\u00e7in bug\u00fcne kadar \u00fcstlendi\u011fimiz ana projeler \u015funlard\u0131r: 1) Fonksiyonel glikozilasyonu geri getirebilen\/geli\u015ftirebilen bile\u015fikleri tan\u0131mlamak i\u00e7in ila\u00e7 taramas\u0131; 2) FKRP genindeki mutasyonlardan kaynaklanan fonksiyon kayb\u0131n\u0131 telafi etmek i\u00e7in AAV gen tedavisi. 3) Musk\u00fcler distrofi i\u00e7in terap\u00f6tik potansiyellerini de\u011ferlendirmek \u00fczere mevcut ila\u00e7lar\u0131n de\u011ferlendirilmesi; ve son zamanlarda 4) distroglikan\u0131n glikozilasyonunu eski haline getirmek i\u00e7in \u015feker terapisi. T\u00fcm bu terapi \u00e7al\u0131\u015fmalar\u0131, hastalarda tan\u0131mlanan mutasyonlar\u0131 i\u00e7eren ve klinikte g\u00f6zlemlenene benzer hastal\u0131k belirtilerine sahip FKRP mutant fare modellerimizde ger\u00e7ekle\u015ftirilmi\u015ftir.<\/p>\n

\u00c7al\u0131\u015fman\u0131z hastalara nas\u0131l yard\u0131mc\u0131 olacak? Do\u011fas\u0131 gere\u011fi daha bilimsel mi yoksa LGMD i\u00e7in bir tedavi olabilir mi?<\/strong>s veya MD<\/strong>genel olarak?<\/strong><\/p>\n

Yukar\u0131da da belirtti\u011fim gibi, ara\u015ft\u0131rma programlar\u0131m\u0131z \u00f6zellikle terapi geli\u015ftirmeye odaklanan translasyonel bir yap\u0131ya sahiptir. Son birka\u00e7 y\u0131lda yapt\u0131\u011f\u0131m\u0131z yay\u0131nlardan da anla\u015f\u0131laca\u011f\u0131 \u00fczere, \u00fc\u00e7 t\u00fcr tedavi ile terap\u00f6tik potansiyeller g\u00f6sterilmi\u015ftir: 1) Tamoksifen ve raloksifen gibi mevcut ila\u00e7larla hastal\u0131\u011fa \u00f6zg\u00fc olmayan bir tedavi, FKRP fare modelinde kas patolojisi ve i\u015flevine \u00f6nemli uzun vadeli fayda sa\u011flamaktad\u0131r. Bu tedavi potansiyel olarak t\u00fcm LGMD'lere uygulanabilir; 2) FKRP mutasyonuna ba\u011fl\u0131 musk\u00fcler distrofiye \u00f6zg\u00fc AAV gen tedavisi. Bu tedavinin hastal\u0131\u011f\u0131n ilerlemesini neredeyse tamamen \u00f6nleme potansiyeli oldu\u011fu g\u00f6sterilmi\u015ftir; ve 3) normalde v\u00fccudumuzda bulunan bir metabolit olan ribitol ile tedavi. Bu tedavi de hastal\u0131\u011fa \u00f6zg\u00fcd\u00fcr ve distroglikan\u0131n glikozilasyonunu etkili bir \u015fekilde art\u0131rarak kas patolojisi ve i\u015flevinde \u00f6nemli iyile\u015fme sa\u011flad\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir. T\u00fcm bu deneysel tedaviler FKRP fare modelimiz kullan\u0131larak ger\u00e7ekle\u015ftirilmi\u015ftir ve klinik denemelere ge\u00e7ilebilir.<\/p>\n

Hastalar\u0131n ve LGMD ile ilgilenen di\u011fer ki\u015filerin ara\u015ft\u0131rma hakk\u0131nda (kendi projeleriniz ve genel olarak alan hakk\u0131nda) ne bilmelerini istersiniz?<\/strong><\/p>\n

Bireysel hastal\u0131klar\u0131n\u0131n do\u011fas\u0131n\u0131n ne oldu\u011funu a\u00e7\u0131k\u00e7a bilmelerini istiyoruz. Daha da \u00f6nemlisi, hastalar ve ebeveynler i\u00e7in, hangi genin hangi mutasyonlar\u0131na sahip olduklar\u0131n\u0131. Bireyselle\u015ftirilmi\u015f t\u0131bb\u0131n heyecan verici \u00e7a\u011f\u0131na girerken bu bilgilerin hepsi kritik \u00f6nem ta\u015f\u0131yor. Ba\u015flang\u0131\u00e7ta bu kula\u011fa zor gelebilir, ancak denemeye devam ederseniz herkes bunu kavrayabilir. Prensipte neredeyse t\u00fcm kas distrofilerinin hastal\u0131k mekanizmas\u0131, duydu\u011fumuz \u00e7o\u011fu hastal\u0131ktan \u00e7ok daha basittir ve anla\u015f\u0131lmas\u0131 kolayd\u0131r. Bu bilgi ile ara\u015ft\u0131rmalar\u0131 anlaman\u0131z ve mevcut tedavileri kendinize g\u00f6re yorumlaman\u0131z kolay olacakt\u0131r. Bu ayn\u0131 zamanda siz ve ara\u015ft\u0131rmac\u0131lar aras\u0131ndaki ileti\u015fimi de geli\u015ftirecektir.<\/p>\n

Bu alanda \u00e7al\u0131\u015fmaya devam etmek i\u00e7in size ilham veren nedir? <\/strong><\/p>\n

Burada \u00f6zellikle iki fakt\u00f6rden bahsetmek istiyorum: Birincisi, her g\u00fcn ayn\u0131 ya da benzer \u015feyleri tekrarlamaktan s\u0131k\u0131lmayan bir ya\u015fam. Herhangi bir zamanda yapt\u0131\u011f\u0131n\u0131z deneylerin \u00e7o\u011funda arayaca\u011f\u0131n\u0131z yeni y\u00f6nler olacakt\u0131r. Bu, \u00e7o\u011fu insan\u0131n iyi bir ya\u015fam olarak kabul edece\u011fi t\u00fcrden bir umut ve arzudur! \u0130kinci olarak, DMD i\u00e7in oligon\u00fckleotid tedavisinin tan\u0131mlanmas\u0131ndaki ilk ba\u015far\u0131, ara\u015ft\u0131rmalar\u0131m sayesinde do\u011frudan hasta tedavisine y\u00f6nelik bile yararl\u0131 bir \u015fey elde edilebilece\u011fi konusunda bana ilham veriyor. Carolinas Sa\u011fl\u0131k Vakf\u0131'n\u0131n ve ebeveynlerimin, ara\u015ft\u0131rma yapmama ve ara\u015ft\u0131rma oda\u011f\u0131mda ve hatta kariyerimde zorunlu sapmalardan ka\u00e7\u0131nmama izin veren sars\u0131lmaz deste\u011fine sahip olmam da \u00f6nemli.<\/p>\n

Hastalar sizi nas\u0131l te\u015fvik edebilir ve \u00e7al\u0131\u015fmalar\u0131n\u0131za nas\u0131l yard\u0131mc\u0131 olabilir?<\/strong><\/p>\n

Bizler, ara\u015ft\u0131rmac\u0131lar, hastalar ve ebeveynler, b\u00fcy\u00fck toplumun bir ba\u015fka katman\u0131y\u0131z. Daha iyi ya\u015famak ve daha h\u0131zl\u0131 ilerleme kaydetmek i\u00e7in birbirimizin te\u015fvikine, cesaretlendirmesine ve deste\u011fine ihtiyac\u0131m\u0131z var. Bir ara\u015ft\u0131rmac\u0131 olarak, tedavi sa\u011flayamay\u0131z, ancak hastal\u0131k ve potansiyel tedaviler hakk\u0131nda baz\u0131 \u00f6zel ve yararl\u0131 bilgilere sahip oldu\u011fumuza inan\u0131yoruz. Hastal\u0131kla ilgili her t\u00fcrl\u00fc soruyu i\u00e7eren hasta\/ebeveyn g\u00f6r\u00fc\u015flerini almaktan memnuniyet duyar\u0131z. \u00d6rne\u011fin, bir tedavinin sizin i\u00e7in uygun olup olmayaca\u011f\u0131 ve nas\u0131l \u00e7al\u0131\u015ft\u0131\u011f\u0131 hakk\u0131nda bir sorunuz varsa, sorun. Bir ba\u015fka \u00f6rnek, belirli bir semptomunuz varsa, ancak bunun hastal\u0131kla ilgili olup olmad\u0131\u011f\u0131n\u0131 bilmiyorsan\u0131z, bize de sorabilirsiniz ve net bir cevap veya \u00e7\u00f6z\u00fcme yol a\u00e7masa da olas\u0131l\u0131\u011f\u0131 d\u00fc\u015f\u00fcnebiliriz. Bu t\u00fcr temaslar kula\u011fa \u00f6zel gelmeyebilir, ancak kar\u015f\u0131l\u0131kl\u0131 takdiri g\u00f6sterir ve ara\u015ft\u0131rmac\u0131lar\u0131n merak\u0131n\u0131 ve sorumlulu\u011funu te\u015fvik eder.<\/p>\n

* * * LGMD konusunda fark\u0131ndal\u0131k yaratmaya yard\u0131mc\u0131 olmak i\u00e7in l\u00fctfen bu g\u00f6nderiyi BE\u011eEN\u0130N, YORUM YAPIN ve PAYLA\u015eIN!<\/p>\n

* Limb Girdle Muscular Dystrophy (LGMD) hakk\u0131nda daha fazla bilgi edinmek veya daha fazla \"Spotlight Interviews\" okumak i\u00e7in l\u00fctfen web sitemizi ziyaret edin https:\/\/lgmd-info.org<\/a><\/p>\n<\/div><\/div><\/div><\/div><\/div>","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":4245,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[91,35,92],"tags":[],"class_list":["post-2350","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-researcher-interview","category-lgmd2i","category-researcher"],"acf":[],"yoast_head":"\nLGMD RESEARCHER: Qi Lu - LGMD Awareness Foundation<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.lgmd-info.org\/tr\/lgmd2i\/2018\/12\/02\/researcher-qi-lu\/\" \/>\n<meta property=\"og:locale\" content=\"tr_TR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"LGMD RESEARCHER: Qi Lu - 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