PhD: inganta gyaran fata a cikin JEB

Masu bincike sun tabbatar da cewa αvβ6 integrin yana samuwa a cikin blisters a cikin kwayoyin cutar fata na JEB da kuma a cikin samfurin su. Sun katange αvβ6 integrin aiki a cikin samfurin kuma sun nuna cewa wannan yana inganta lafiyar fata da kuma gyara tare da ƙananan kumburi da rage kumburi.

Jagoran bincike:

Dr Emanuel Rognoni babban malami ne a Cibiyar Blizard. A lokacin da PhD ya mayar da hankali kan EB subtype Kindler Syndrome inda ya bayyana wani sabon aiki na integrin daure protein Kindlin-1 don epithelial stem cell homeostasis ta inganta αvβ6 integrin-mediated canza girma factor-β (TGFβ) kunnawa da epithelial Wnt sigina. A lokacin postdoc ɗinsa ya ƙara ƙwarewa a cikin binciken fata, yana bincikar yadda ƙungiyoyin fibroblast dermal daban-daban ke tsarawa da tasiri juna yayin haɓakawa da warkar da rauni a cikin Lab ɗin Farfesa Fiona Watt (KCL). Yin amfani da fasahohin jeri-fadi na genome, sabbin dandamali na al'adun 2D / 3D da samfuran transgenic / cuta, ƙungiyarsa a QMUL yanzu tana buɗe hanyoyin ƙwayoyin ƙwayoyin cuta da abubuwan da ke tattare da fibroblast iri-iri a cikin lafiyar fata, sabuntawa da cuta.

Masu bincike:

Dokta Matthew Caley babban malami ne a cikin Halittar Halittu a Cibiyar Blizard tare da gogewa fiye da shekaru goma a cikin binciken fata, ilimin halitta na matrix da kuma samar da samfuran fata a cikin vitro. Yana aiki a cikin al'ummomin binciken fata na Biritaniya da Turai, memba na kungiyar British Society for Investigative Dermatology (BSID) da kuma wanda ya kafa cibiyar sadarwa ta Skin Microbiome in Healthy Aging (SMiHA). Ƙungiyarsa tana amfani da nau'ikan fata don fahimtar ilimin kwayoyin halitta na tsufa na fata, cututtukan fata da ba kasafai ba da kuma ciwon daji na fata. Ya mayar da hankali na musamman kan laminin 332 da kuma yadda wannan furotin ya wuce kawai gina jiki.

Farfesa John Marshall Farfesa ne na Tumor Biology wanda bincikensa ya mayar da hankali kan aikin masu karɓar mannewar cell, integrins, a cikin mamayewar ƙwayoyin tumo tare da wallafe-wallafe sama da 130. Shi babban ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararru ne na ƙwanƙwasa ƙwanƙwasa αvβ6 wanda ke haɓakawa sosai yayin gyaran nama a cikin raunuka na yau da kullun da ciwon daji. Bincikensa ya ƙunshi haɗin gwiwar masana'antu da yawa da gwaji na asibiti.

"Manufarmu ita ce inganta fatar marasa lafiya na JEB, inganta warkar da raunuka don haka rage haɗarin cututtuka da za su iya haifar da sepsis da mutuwa da wuri."

- Dr Rognoni

Sunan baiwa: Inganta farfadowar fata a cikin JEB ta hanyar niyya ga integrin αvβ6.

Junctional epidermolysis bullosa (JEB) cuta ce ta fata da ba kasafai ba ke haifar da kumburi mai yaduwa da raunin rauni. Wannan yana faruwa ne ta hanyar asarar mahimman sunadaran da ke ɗaure murfin fata zuwa sauran jiki. Mafi tsanani nau'i, JEB mai tsanani, yana faruwa ne ta hanyar asarar aikin laminin-332 wani mahimmin sashi na tsarin ƙulla fata. Marasa lafiya tare da JEB suna fama da gazawar ci gaba, rashin warkar da rauni, matsanancin ciwon fata da haɗarin guba na jini (sepsis). Yaran da aka gano suna da JEB mai tsanani kusan duk suna mutuwa kafin cikarsu ta biyu kuma ya zuwa yanzu babu wasu ingantattun magunguna don dakatarwa ko warkar da wannan cuta mai kisa. Mun gano cewa hanyar siginar haɓakar haɓakar beta (TGFβ) tana da ƙarfi a cikin fata na JEB. Mun yi imanin wannan ya faru ne saboda yawancin matakan integrin αvβ6, babban mai kula da siginar TGFβ a cikin fata, wanda kuma aka lura a cikin raunuka na kullum, fibrosis da halayen rigakafi na fata. Za mu bincika ayyukan αvβ6 a cikin fata na JEB ta amfani da samfuran al'adun mu na in vitro cell (Aim-1 & 2) kuma muyi amfani da samfurin cutar mu na JEB don fahimtar rawar αvβ6 a cikin fata na yau da kullun da warkar da rauni (Aim-3). A ƙarshe, za mu toshe αvβ6 integrin a cikin samfurin mu na JEB kuma muyi nazarin yadda yake hana yawan aiki na TGFβ kuma da fatan inganta gyaran fata na JEB (Aim-4). Binciken mu na farko na asibiti zai ƙayyade idan zaɓin αvβ6 integrin zai iya ba da dama na warkewa a cikin JEB da yuwuwar sauran nau'ikan EB tare da siginar αvβ6 da TGFβ da aka soke.

JEB ba a iya warkewa a halin yanzu kuma jiyya na yanzu suna mayar da hankali kan sarrafa blisters, sarrafa cututtuka da hana rikitarwa. Tushen cutar shine asarar furotin mai suna laminin-332 daga fata. Bayananmu sun gano cewa takamaiman mai karɓa na mannewa tantanin halitta, mai suna αvβ6 integrin, yana haɓaka sosai a cikin fata na JEB, wanda kuma ana lura dashi a cikin raunuka na yau da kullun, fibrosis da ciwace-ciwacen daji. αvβ6 integrin ba wai kawai yana taimakawa ƙwayoyin fata don mannewa da ƙaura ba amma kuma yana sarrafa ayyukan abubuwan haɓaka mai ƙarfi, gami da TGFβ. Yawan aiki na TGFβ yana haifar da lahani na warkar da rauni da kumburin fata. Yin amfani da samfuran mu na musamman na JEB, za mu ƙayyade rawar αvβ6 integrin a cikin fata na JEB. Za mu bincika idan toshe aikin αvβ6 integrin yana da yuwuwar inganta warkar da rauni a cikin JEB. Yin niyya αvβ6 integrin bazai zama magani mai warkewa ba, duk da haka, tsarinmu yana da yuwuwar kula da siginar haɓakar cututtukan cututtuka kamar TGFβ da goyan bayan warkar da fatar fata, inganta ingancin rayuwa da rayuwar marasa lafiya na JEB. Saboda αvβ6 integrin da TGFβ kuma an soke su a cikin nau'ikan nau'ikan EB da yawa, bincikenmu zai tallafawa ci gaban warkewa don wasu cututtukan fata.

Manufar wannan aikin shine bincika idan an yi niyya ta takamaiman mai karɓar mannewar tantanin halitta, mai suna αvβ6 integrin zai iya inganta fata a cikin cututtukan fata na ƙwayoyin cuta Junctional epidermolysis bullosa (JEB). Shirin mu shine bincika ayyukan αvβ6 a cikin fata na JEB ta amfani da samfuran al'adun mu na in vitro cell (Aim-1 & 2) da kuma amfani da tsarin cututtukan mu na JEB don fahimtar rawar αvβ6 a cikin fata na yau da kullun da warkar da rauni (Aim-3). A ƙarshe, za mu toshe αvβ6 integrin a cikin samfurin mu na JEB kuma mu yi nazarin yadda yake hana overactivation na canza hanyar siginar beta (TGFβ) kuma inganta gyaran fata na JEB (Aim-4).

A farkon aikin mun dauki wani dalibi mai hazaka na PhD wanda nan take ya tsunduma aikin bayan ya kammala dukkan kwasa-kwasan horon da ya kamata. Saboda sake fasalin kayan aikin QMUL mun yanke shawarar ba da fifiko ga gwaje-gwajen vivo (Aim-3 da Aim-4). Anan mun fara ta hanyar ƙarin nazarin kasancewar integrin αvβ6 a cikin fata masu rauni da marasa rauni a cikin nau'in cutar mu na JEB wanda ke da girma musamman a cikin fata. Mun kuma tabbatar da cewa αvβ6 integrin kuma an bayyana shi a cikin blisters a cikin kwayoyin cutar fata na JEB. Mun kammala gwaje-gwajen farko na toshe aikin integrin na αvβ6 a cikin tsarin cutar mu na JEB na tsawon makonni biyu kuma mun sami damar ganin ci gaba mai yawa na lafiyar fata da gyara JEB. Abin ban sha'awa, fatar JEB ba ta kasance ƙasa da fibrotic da kumburi ba amma kuma mun lura da raguwar blisters na fata da tsananin su. Yanzu muna ci gaba da bincike don gano yadda hanawar αvβ6 ke canza kumburin fata da inganta lafiyar fata. Muna da sha'awar gwada ƙarin jiyya na dogon lokaci na toshe αvβ6 integrin da kuma yadda zai inganta warkar da raunukan buɗe ido.

Yayin da a cikin wannan shekarar ta farko ɗalibin PhD ya mai da hankali kan nazarin gwaje-gwajen in vivo, ta kuma fara bincika aikin ƙwayoyin cuta na integrin αvβ6 integrin (Aim-1&2) ta hanyar kafa kayan aikin gwaji da yawa a cikin lab. Mahimmanci, dalibar PhD ta yi nasarar ƙaddamarwa kuma ta sami ci gaba na PhD na watanni 9 na viva. Wani muhimmin mahimmanci ga ɗalibin shine gabatar da sakamakonta mai ban sha'awa daga shekararta ta farko a ɗaya daga cikin manyan tarukan fata na Burtaniya a cikin Afrilu na wannan shekara, inda nan da nan aka zaɓi zaɓenta don gabatar da baki. Bugu da ƙari kuma ɗalibin PhD da PI sun samar da labarin DEBRA UK guda biyu (https://www.debra.org.uk/repairing-skin-cells/ da https://www.debra.org.uk/improving-eb-wound-healing/) game da wannan aikin kuma mu duka biyu mun kuma tsunduma cikin ayyukan PPI daga sauran ƙungiyoyin agaji na EB kamar su CureEB don ci gaba da gudanar da bincike na yau da kullun. (Daga rahoton ci gaba na 2025.)