Megan Stan­i­fer, Ph.D.

m.stanifer@dkfz.de

Phone: ++49-(0)6221–56-7858

Impact of cel­lu­lar polar­i­ty on virus sensing

Projects

Intesti­nal epithe­lial cells are in con­stant con­tact with the ever-present com­men­sal flo­ra. This leaves them with a com­plex task of main­tain­ing a fine bal­ance between tol­er­at­ing the micro­bio­ta and being ready to respond to invad­ing pathogens. Intesti­nal cells are polar­ized with an api­cal side fac­ing the lumen of the gut and a baso­lat­er­al side fac­ing the ster­ile lam­i­na pro­pria. Our work has uncov­ered that one method used by human intesti­nal epithe­lial cells (hIECs) to avoid over stim­u­la­tion is that they polar­ize the pathogen-recog­ni­tion recep­tor TLR‑3 to the baso­lat­er­al side of hIECs to avoid over detec­tion of the com­men­sal bac­te­ria. Our group con­tin­ues to inves­ti­gate the mol­e­c­u­lar mech­a­nisms used by hIECs to main­tain immune-home­osta­sis and how these mech­a­nisms are mis-reg­u­lat­ed in patients with inflam­ma­to­ry bow­el dis­ease. Addi­tion­al­ly, we are now extend­ing our obser­va­tions in hIECs to addi­tion­al mucos­al tis­sues (e.g. the lung and gen­i­tal tract) to deter­mine if all tis­sues that act as a pro­tect bar­ri­er use sim­i­lar mech­a­nisms to detect and fight invad­ing pathogens while tol­er­at­ing the pres­ence of the com­men­sal flora.

Selected Publications

Stan­i­fer, ML, Muken­hirn, M, Muen­chau, S,  Per­volara­ki, K,  Kanaya, T, Albrecht, D,  Oden­dall, C, Kagan, J,  Bart­feld, S,  Ohno, H Boulant, S. Asym­met­ric dis­tri­b­u­tion of TLR3 leads to a polar­ized immune response in human intesti­nal epithe­lial cells Nature Micro­bi­ol­o­gy. 2019 Nov 4. doi.org/10.1038/s41564-019‑0594‑3.

Rihn, S; Aziz, M; Stew­art, D; Hugh­es, J; Turn­bull, M; Varela, M; Sug­rue, E; Herd, C; Stan­i­fer, M; Sink­ins, S; Pal­mari­ni, M and Wil­son, S. TRIM69 inhibits Vesic­u­lar Stom­ati­tis Indi­ana Virus (VSIV). Jour­nal of Virol­o­gy. 2019 Aug 2. pii: JVI.00951–19.

Per­volara­ki, K, Guo, C, Albrecht, D, Stan­i­fer, ML, Boulant, S. Inter­de­pen­dence of type I and type III inter­fer­ons. J. of Inter­fer­on and Cytokine Research 2019 Jun 13. 

Muen­chau, S; Deutsch, R; Albrecht, D; Niesler, B, Stan­i­fer, ML, Boulant, S. miR­NA 16 and 340 reg­u­late bar­ri­er func­tion in human intesti­nal epithe­lial cells under low oxy­gen con­di­tions. Mol­e­c­u­lar Cell Biol­o­gy 2019 May 6.

Stan­i­fer, ML, Per­volara­ki, K, Boulant, S. Dif­fer­en­tial reg­u­la­tion of type I and type III inter­fer­on sig­nal­ing, Inter­na­tion­al Jour­nal of Mol­e­c­u­lar Sci­ences 2019 Mar 21;20(6).

Fakhiri, J; Schnei­der, M; Puschhof, J; Stan­i­fer, M; Schildgen,V; Holderbach,S; Voss, Y; El Andari, J; Schild­gen, O; Boulant, S; Meis­ter, M; Clevers, H Qiu,Y; Grimm, D. Nov­el chimeric gene ther­a­py vec­tors based on Ade­no-asso­ci­at­ed virus (AAV) and four dif­fer­ent mam­malian bocavirus­es (BoV). Mol­e­c­u­lar Ther­a­py — Meth­ods & Clin­i­cal Devel­op­ment, 2019 Jan 18;12:202–222.

Per­volakari, K; Rast­gou, S; Albrecht, D; Bor­mann, F; Hoe­fer, T; Stan­i­fer, ML; Boulant, S. Kinet­ics of antivi­ral action of type III inter­fer­on is inde­pen­dent of recep­tor lev­el. Plos Pathogen 2018 Nov 28;14(11).

Stan­i­fer, ML, Kischnick, C, Boulant, S. MRV ISVPs coun­ter­act immune induc­tion by block­ing cel­lu­lar tran­scrip­tion. Sci­en­tif­ic Reports, 2017 Sep 7;7(1):10873.

Shah, NM; Stan­i­fer, ML; Höhn, K; Engel, U; Hasel­mann, U; Barten­schlager, R; Kräus­slich, HG; Kri­jnse-Lock­er, J; Boulant S. Genome pack­ag­ing of reovirus is medi­at­ed by the scaf­fold­ing prop­er­ty of the micro­tubule net­work. Cell Micro­bi­ol. 2017 Dec;19(12).

Stan­i­fer, ML, Per­volar­ki, K, Muen­chau, S, Grimm, D, Renn, L, Rabin, R, Boulant, S. Type I and type III inter­fer­ons dis­play dif­fer­ent depen­den­cy on MAPKs to mount an antivi­ral state in the human gut. Fron­tiers Immunol­o­gy, 2017.

Kim, IS; Jen­ni, S; Stan­i­fer, ML; Roth, E; Whe­lan SPJ; van Oijen, A; Har­ri­son, SC. Mech­a­nisms of mem­brane fusion induced by vesic­u­lar stom­ati­tis virus G pro­tein. PNAS. 017 Jan 3;114(1):E28-E36.

Mar­tinez, C; Rodi­no-Janeiro, B; Lobo, B; Stan­i­fer, ML; Klaus, B; Gransow, M; Alon­so-Coton­er, C; Pigrau, M; Roeth, R; Rap­pold, G; Huber, W; Gon­za­lez Siloz, R; Loren­zo, J’ Azpiroz, F; Boulant, S; Vic­ario, M; Niesler, B; Snatos, J. miR16 and miR-125b are involved in bar­ri­er func­tion dys­reg­u­la­tion through the mod­u­la­tion of claudin‑2 and cin­gulin expres­sion in the jejunum in irri­ta­ble bow­el syn­drome with diar­rhea. Gut, 2017 Jan 12

Stan­i­fer ML, Rip­pert A, Kaza­kov A, Willem­sen J, Buch­er D, Ben­der S, Barten­schlager R, Binder M, Boulant S. Reovirus inter­me­di­ate sub­vi­ral par­ti­cles con­sti­tute a strat­e­gy to infect intesti­nal epithe­lial cells by exploit­ing TGF‑β depen­dent pro-sur­vival sig­nal­ing. Cell Micro­bi­ol. 2016 Jun 8

Boulant S, Stan­i­fer M, Lozach PY. Dynam­ics of virus-recep­tor inter­ac­tions in virus bind­ing, sig­nal­ing, and endo­cy­to­sis. Virus­es. 2015 Jun 2;7(6):2794–815

Boulant S, Stan­i­fer M, Kur­al C, Cure­ton DK, Mas­sol R, Nib­ert ML, Kirch­hausen T. Sim­i­lar uptake but dif­fer­ent traf­fick­ing and escape routes of reovirus viri­ons and infec­tious sub­viri­on par­ti­cles imaged in polar­ized Madin-Dar­by canine kid­ney cells. Mol Biol Cell. 2013 Apr;24(8):1196–207

Stan­i­fer, ML; Cure­ton, DK; Whe­lan SPJ. A recom­bi­nant vesic­u­lar stom­ati­tis virus bear­ing a lethal muta­tion in the gly­co­pro­tein gene, uncov­ers a sec­ond site sup­pres­sor that restores fusion. J.Virology. 2011 Aug;85(16):8105–15.

Gee, GV; Stan­i­fer, ML; Chris­tensen, BC; Atwood, WJ, Ugoini,I; Nel­son, HH, Mar­sit, CJ; Kelsey, KT. SV40 asso­ci­at­ed miR­NA is not detectable in mesothe­liomas. British Jour­nal of Can­cer. 2010 Sep 7;103(6):885–8.

Gas­parovic, ML; Mag­in­nis, MS; O’Hara, B; Dugan, AS; and Atwood, WJ. Mod­u­la­tion of PML pro­tein expres­sion both neg­a­tive­ly and pos­i­tive­ly reg­u­lates JCV infec­tion. Virol­o­gy. 2009 Aug 1;390(2):279–88.

Gas­parovic, ML; Gee, GV; Atwood, WJ. The JC Virus (JCV) Minor Cap­sid Pro­teins Vp2 and Vp3 are Essen­tial for Virus Prop­a­ga­tion. J Virol. 2006 Nov; 80(21):10858–61.

Elph­ick, G.F.; Querbes, W.; Jor­dan, J.A.; Gee, G.V.; Eash, S.; Man­ley, K.; Dugan, A.; Stan­i­fer, M.; Roth, B.L.; and W.J. Atwood. The Human Poly­omavirus, JCV, Uses Sero­tonin Recep­tors to Infect Cells. Sci­ence 2004 Nov 19; 306 (5700): 1380–3.