Maselo a chitetezo chamthupi ndi mabala a RDEB (2022)

Covid adasokoneza kwambiri polojekitiyi, motero ofufuzawo adapanga njira ina yoyesera kuti ayankhe mafunso oyambilira a kafukufukuyu. Amafotokoza kupita patsogolo kwakukulu pakumvetsetsa momwe chitetezo chamthupi chimagwirira ntchito pakhungu ndipo amakhulupirira kuti zomwe apeza m'nkhani zotsatirazi zitha kukhala zothandiza kwa odwala omwe ali ndi RDEB:

• Epidermal mammalian chandamale cha rapamycin complex 2 chimayang'anira lipid synthesis ndi filaggrin processing mu epidermal chotchinga mapangidwe - Journal of Allergy and Clinical Immunology 
• Glutamine Metabolism Imalamulira Stem Cell Fate Reversibility ndi Kusamalira Kwanthawi yayitali mu Follicle Ya Tsitsi - Cell Metabolism
• Kuwongolera Mayankho Ochiritsa Mabala pa Ukalamba - Journal of Investigative Dermatology
• Kagayidwe ka Mitochondrial imagwirizanitsa njira zokonzetsera siteji mu macrophages panthawi yakuchira kwa bala - Cell Metabolism
• Udindo wa mTOR Signaling Cascade mu Epidermal Morphogenesis ndi Skin Barrier Formation 

Wofufuza wamkulu:

Sabine Eming: Pulofesa ndi Dokotala Wotsogola ku Dept. of Dermatology, University of Cologne, amatsogolera ndondomeko ya ntchito mu kuwonongeka kwa minofu ndi kukonzanso komwe kumaphatikizapo kusanthula koyambirira kwa kamangidwe ka ntchito, kupyolera mu zitsanzo za vivo, mpaka ku matenda a anthu. Gulu lake likufuna kumvetsetsa momwe khungu limamverera kuwonongeka kwa minofu ndi momwe zochitikazi zimasinthira kuyankhanso, kupanga zipsera kapena matenda. Cholinga chimodzi cha gululi ndikugawanitsa kuyanjana pakati pa mphamvu yobwezeretsanso minofu ndi kuyankha kwa chitetezo chamthupi. Iye ndi Wofufuza Wamkulu wa mapulojekiti ofufuza omwe amathandizidwa ndi gulu lachitatu ndi mayesero azachipatala, akuvumbulutsa mabala a mabala m'matenda osiyanasiyana oyambira ndikumasulira chidziwitsochi kuti chithandizire chisamaliro chabala kwa odwala. Adzagwirizanitsa ntchitoyo ndi kuyanjana ndi ogwira nawo ntchito ku Freiburg. Adzakhala ndi udindo wokwaniritsa bwino ntchitoyi, atsogolere wophunzira wa PhD pakupanga zoyesera, kuwunika kwasayansi zotsatira, kulemba pamanja, ndi kumasulira.

Ofufuza nawo:

Dimitra Kiritsi: Consultant dermatologist ndi Junior Group Leader, wagwira ntchito kwa zaka 9 monga dokotala-wasayansi ku Dipatimenti ya Dermatology ndi EB-Center Freiburg. Amaphatikizidwa muzofufuza, kasamalidwe ndi chisamaliro chambiri cha odwala omwe ali ndi EB. Kafukufuku wake amayang'ana kwambiri ma pathomechanisms ndi chitukuko cha njira zatsopano zochizira matenda obadwa nawo akhungu, makamaka EB ndi skin mosaicism. Ali ndi chidziwitso chambiri monga wotsogolera wamkulu komanso wofufuza m'mayesero 11 azachipatala omwe ali ndi vuto la matuza (autoimmune ndi EB). Panopa ndi Mutu wa Immunofluorescence Laboratory, "Fragile Skin Clinical Trial Unit" ndi Wound Care Unit ya Dept. Dermatology ku Freiburg. Adzapereka zinthu za odwala ndi zidziwitso zofunika pa maphunziro omwe aperekedwa, ndikuthandizira kuwunika kwa zotsatira pambuyo pomaliza phunzirolo ndi kulemba nkhanizo.

Alexander Nyström: ndi mtsogoleri wa gulu ku Dipatimenti ya Dermatology, Medical Center - University of Freiburg. Ali ndi chidziwitso chochuluka ndi zitsanzo za preclinical za RDEB, ndipo adzagawana zomwe adakumana nazo ndi maphunziro ochiritsa bala.

"M'kafukufukuyu timvetsetsa bwino za kuwonongeka kwa mabala kwa odwala a RDEB komanso momwe mavuto omwe amadzatsatira angadziwikire msanga komanso kupewedwa."

Prof Dr Sabine Eming

Grant Title: Kuwunika chitetezo chamthupi muzovuta zochiritsa mabala mwa odwala a RDEB

M'lingaliro ili ndilofunika kwambiri kuti tidziwe zomwe tikuchita ndi maselo omwe amachititsa kuti pakhale zovuta zochiritsa bala (kuchuluka kwa zipsera ndi carcinogenesis) mwa odwala a RDEB ndikubweretsanso chidziwitso kwa wodwalayo kuti athandizire kuchiza mabala am'deralo komanso kupita patsogolo kwa matenda.

Maselo a chitetezo cha m'thupi ndi gawo lofunika kwambiri la mphamvu yachibadwa ya thupi yobwezeretsa ntchito ya minofu pambuyo povulala. Pambuyo pa mitundu yambiri ya kuwonongeka kwa minofu kuphatikizapo matuza mu odwala EB, maselo enieni a chitetezo cha mthupi makamaka monocytes / macrophages amagwira ntchito ziwiri zofunika: kuyankha mofulumira ku tizilombo toyambitsa matenda ndi zowonongeka zomwe zimagwirizanitsidwa ndi maselo a maselo ndikuthandizira kukonza kuwonongeka kwa minofu.

Izi zimafuna kuti macrophages ayambe kutengera pro-inflammatory phenotype ndiyeno pambuyo pake pamene ngozi yofulumira yadutsa kuti ipeze anti-inflammatory phenotype kulimbikitsa kuthetsa ndi kukonza.

Tsopano zikuwonekeratu kuti mphamvu zoyendetsedwa mwamphamvu pakati pa pro-inflammatory and resolution activation phenotype mu macrophages ndizofunikira pakuyankha kothandiza kwa machiritso. Tikupangira kuti tivumbulutse ntchito ya macrophages pakuchiritsa mabala mwa odwala a RDEB ndikuzindikira njira zosinthira magwiridwe antchito a macrophage m'mabala a odwala a RDEB.

Macrophages amalumikizidwanso kwambiri pakupangika kwa khansa ndipo mwamakina amatha kuyikidwa pamalo olumikizirana pakati pa bala lomwe silimachira lomwe limalumikizidwa ndi RDEB komanso kusintha kwapang'onopang'ono kwa bala kukhala carcinoma. Timakhulupirira kwambiri kuti pofotokozera njira zofunika zomwe maselo a chitetezo cha mthupi amawonongera machiritso mwa odwala a RDEB sikungopititsa patsogolo chitukuko cha mankhwala atsopano omwe amachititsa kuti mabala atsekeke (monga kuvala mabala omwe amachepetsa kutupa kosatha) komanso kungathandizenso kukulitsa matenda. zida zowunika ngati chilonda chosachiritsika chimakhala chowopsa.

Zoyeserera zayambika monga zafotokozedwera mu pulani yoyambirira ya polojekiti. Kuphatikiza apo, mogwirizana ndi zoyeserera zomwe zaperekedwa mu dongosolo loyambirira la polojekitiyi, labotale ya wopemphayo yapita patsogolo kwambiri pakumvetsetsa momwe chitetezo chamthupi chimakhudzira kukonza ntchito yotchinga khungu la epidermal, pamapulojekiti okhudzana ndi omwe akupitilira mu gulu la wopemphayo. . Tikukhulupirira kuti zomwe zapezedwazi zithandizira kumvetsetsa momwe chitetezo chobadwa nacho chimakhudzira zovuta zamachiritso mwa odwala a RDEB, ndikuti odwala a RDEB apindula ndi zomwe apezazi. Apa tikuwona mwayi wofufuza mwatsopano kuti athandize odwala a RDEB. (Kuchokera ku lipoti la 2019.)

Kuyesera kunayambika monga momwe zafotokozedwera mu dongosolo loyambirira la polojekiti. Poyamba panali kuchedwa kupanga mtundu wina wa chibadwa, womwe tidawaganizira kuti tathetsedwa pofika koyambirira kwa 2020. Komabe, mosayembekezereka koyambirira kwa 2020 moyo wamaphunziro ndi malo oyesera zidatsekedwa chifukwa cha ziletso za mliri wa COVID-19 ku Yunivesite. Mu 2020 ndi 2021 moyo waku yunivesite udayima pang'ono. Zida ndi ma laboratories sakanatha kugwiritsidwa ntchito monga momwe zidapangidwira komanso kusinthana kwasayansi ndi zokambirana zinali zoletsedwa kwambiri. Zotsatira za izi, kusukulu komweko komanso padziko lonse lapansi (kuchedwa kuyitanitsa ndi kutumiza kuchokera kuzinthu za labotale, kuchepa kwa ogwira ntchito chifukwa cha matenda), sikunathetsedwebe. Ponseponse, kuchepa kwa mliri wakhudza kwambiri ntchito yathu komanso dongosolo loyambirira la polojekitiyi. Chifukwa chake, monga tafotokozera mu lipoti lanthawi yayitali kuyambira pa 25 Disembala 2019, wopemphayo wapanga njira ina yoyesera yomwe ikuyembekezeka kukwaniritsa dongosolo loyambirira la polojekitiyo ndikuyankha mafunso oyambilira a kafukufukuyo. Laboratory ya wopemphayo yapita patsogolo kwambiri pakumvetsetsa momwe chitetezo chamthupi chimakhudzira ntchito yotchinga khungu la epidermal, pamapulojekiti okhudzana ndi omwe akupitilira gulu la wopemphayo. Tikukhulupirira kuti zomwe zapezedwazi zithandizira kumvetsetsa momwe chitetezo chamtundu wa 2 chimakhudzira zovuta zamachiritso mwa odwala a RDEB, ndikuti odwala a RDEB apindula ndi zomwe apeza. Apa tikuwona mwayi wofufuza mwatsopano kuti athandize odwala a RDEB. (Kuchokera ku lipoti lomaliza la 2022.)