WIMM PI Curriculum Vitae

Personal Data Name Nationality Email

Ahmed Ashour Ahmed UK/Egypt ahmed.ahmed@obs-gyn.ox.ac.uk

Present Position 2 ! -present "onorary #onsultant in $ynaecological %ncology and &'( lead )or $ynaecological %ncolgy*%x)ord (rust+ 2 !2-present ,ro)essor o) $ynaecological %ncology *Uni-ersity o) %x)ord+ 2 !2-present ./&& &0# 1enior #linical 0esearch 2ello3 *./&&+

Previous Positions !445 0esident6 'epartment o) %bstetrics and $ynaecology6 Ain 1hams Uni-ersity6 #airo6 Egypt. !447 Assistant 8ecturer6 'epartment o) %bstetrics and $ynaecology6 Ain 1hams Uni-ersity6 #airo6 Egypt. !449 1"%6 %bstetrics and $ynaecology6 :ed)ord "ospital. !44; 2 2 East Anglia 1pecialist 0egistrar (raining in %bstetrics and $ynaecology.

2 &0# #linical 0esearch 2ello36 'epartment o) %ncology6 Uni-ersity o) #ambridge6 "utchison/&0# 0esearch #entre. < #ancer 0esearch UK #linician 1cientist6 #ambridge 0esearch /nstitute6 'epartment o) %ncology6 Uni-ersity o) #ambridge. "onorary #onsultant $ynaecologist = $ynaecological %ncology 1ubspecialty (rainee6 $ynaecological %ncology 0egional #entre6 Addenbrooke>s "ospital6 #ambridge. #ancer 0esearch UK #linician 1cientist and ,ostdoctoral 2ello36 %-arian #ancer 0esearch 8aboratory6 'epartment o) Experimental (herapeutics6 &' Anderson #ancer #enter6 "ouston6 (?6 U1A. #ancer 0esearch UK #linician 1cientist and @isiting 1cientist6 "utchison/&0# 0esearch #entre6 'epartment o) %bstetrics and $ynaecology and 'epartment o) %ncology6 Uni-ersity o) #ambridge. "onorary #onsultant $ynaecologist = $ynaecological %ncology 1ubspecialty (rainee6 $ynaecological %ncology 0egional #entre6 Addenbrooke>s "ospital6 #ambridge. #linical 0eader and #onsultant $ynaecological %ncologist6 Nu))ield 'epartment o) %bstetrics and $ynaecology6 Uni-ersity o) %x)ord. ,rincipal /n-estigator6 %-arian #ancer 0esearch 8aboratory6 %ld 0oad #ampus 0esearch :uilding. ,ro)essor o) $ynaecological %ncology6 Uni-ersity o) %x)ord and &0# 1enior #linical 0esearch 2ello3 at the ./&&.

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Research Achievements A- %ur laboratory has disco-ered that a 57-kb intergenic region do3nstream o) the stem cell regulator SOX2 is )reAuently *< B+ mutated in high grade serous o-arian cancers. /n collaboration 3ith our industrial partner Complete Genomics 3e per)ormed 3hole genome seAuencing o) o-arian cancer minimal residual disease *C! to 2 cells+ and identi)ied an intergenic signature o) single nucleotide polymorphisms that is strongly associated 3ith cell di))erentiation. 'o3nstream analysis using targeted deep seAuencing o) a 2&b region )lanking the SOX2 gene con)irmed that a 57-kb region )reAuently harbors no-el and rare -ariants in high grade serous o-arian cancers. 2unctional characteriDation o) this region con)irmed that it is an area o) open chromatin that is most probably in-ol-ed in the regulation o) stem cell di))erentiation. :- %-arian cancer metastasis targets6 almost exclusi-ely6 adipocyte-rich destinations 3ithin the abdominal ca-ity e-en at end-stage terminal disease..e ha-e disco-ered a pre-iously unrecogniDed role o) 1/K2 in mediating adipocyte sur-i-al signals at the o-arian cancer mental metastatic niche and -alidated on-target acti-ity o) no-el 1/K2 inhibitors in cells. %ngoing 3ork aims to establish the role o) such inhibitors in pre-enting o-arian cancer metastasis. What are the Future Aims of Your Current Group? %ur group is )ocused on in-estigating the causes and the possible mechanisms o) eliminating microscopic residual chemotherapy-resistant disease *&0#'+. .e are taking se-eral approaches to address this problem. First6 to characteriDe the genetic basis o) &0#'6 3e 3ill extend our 3ork on 3hole genome seAuencing o) paired samples6 be)ore and a)ter chemotherapy6 in patients 3ith ad-anced stage o-arian cancer 3ho sho3ed complete clinical response to chemotherapy but still had &0#'. Using intraoperati-e -ideo-assisted tumour mapping */%@(+ be)ore and a)ter chemotherapy 3e aim to compare regions o) extreme sensiti-ity *that undergo complete pathological response+ and extreme resistance *&0#'+ )rom the same patient to unra-el no-el therapeutic strategies in patients 3ith o-arian cancer. Second6 to in-estigate the mechanisms o) lipid-based acti-ation o) o-arian cancer cells at the metastatic niche6 3e are conducting detailed analysis o) the metabolic regulator 1/K2 in o-arian cancer. .e are using genetic analysis6 chemical biology and timelapse microscopy to in-estigate 3hy 1/K2 is essential )or the sur-i-al o) o-arian cancer cells and )or its metastasis to adipocyte-rich en-ironment. .e are also collaborating 3ith 1te)an Knapp6 %x)ord6 and Nathanael $ray6 "ar-ard6 to de-elop no-el 1/K inhibitors.

o! do "hese Aims Contri#ute to the $nderstandin% and&or Mana%ement of Disease

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%-arian "igh-grade serous cancers *"$1#c+ are kno3n to be highly sensiti-e to chemotherapy. "o3e-er6 achie-ing complete pathological response in these tumours is rare. E-en in the absence o) clinically identi)iable residual tumour6 &0#' at the end o) primary therapy is responsible )or early recurrences 3ith a median progression )ree sur-i-al o) approximately 2 months. (he detailed genomic characteriDation o) &0#' is likely to lead to important -aluable insights into clinically rele-ant mechanisms o) resistance in patients. /n addition6 it is possible that &0#' )oci may ha-e uni)ying genetic alterations that become e-ident )ollo3ing chemotherapy-induced death o) the bulk o) the tumour and this may gi-e -aluable opportunities to consolidate treatment using therapies targeted to such uni)ying
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alterations. /n addition to taking such hypothesis generating in-estigations6 our laboratory is interested in identi)ying clinically rele-ant mechanisms o) response to taxane as one o) the most commonly used chemotherapeutic agents. .e ha-e identi)ied 1/K2 as a no-el target )or therapy that is reAuired )or adipocyte-mediated o-arian cancer cell proli)eration at the metastatic niche and 3e 3ill continue to in-estigate the mechanisms by 3hich this target modulates cancer cell sur-i-al and chemotherapy response. (he aim is to gain insights into ho3 such modulation could be exploited therapeutically )or patients.

'a( Summar( of Research E-ery year about 2 6 3omen are diagnosed 3ith o-arian cancer 3orld3ide o) 3hom about hal) die o) their disease 3ithin )i-e years o) diagnosis. (his makes o-arian cancer the most )atal tumour o) the )emale genital system. %-arian cancers are characteriDed by being highly sensiti-e to drugs such as carboplatin and taxol. "o3e-er6 in spite o) excellent tumour shrinkage the tumour rarely goes a3ay completely. /nstead6 small number o) cancer cells are le)t behind that can only be seen by a microscope *microscopic residual tumour+. Un)ortunately such cells retain the capacity to di-ide and gro3 leading to recurrence o) cancers that are6 then6 -ery resistant to treatment. %ur laboratory is taking steps to o-ercome this problem. (o be able to identi)y these cancer cells at surgery 3e ha-e de-eloped special imaging systems in collaboration 3ith physicists. .ith the aid o) special dyes6 it is possible to make these cells EshineF during surgery i) exposed to particular lasers and this helps to identi)y and characteriDe them. %nce these cells are identi)ied6 3e extract 'NA material that is used to conduct extensi-e genetic analyses using state o) the art seAuencing technology to determine the complete genetic )ingerprint o) these cells. 1tudying the genetic makeup o) these cells in this detailed 3ay can then help us understand ho3 such cancer cells e-aded chemotherapy. %ur laboratory has also disco-ered that inter)ering 3ith the )unction o) an important cancer enDyme called 1/K2 can enhance the therapeutic bene)it o) standard cancer drugs such as taxol. .e belie-e that 1/K2 controls important aspects o) the li)e cycle o) the cancer cell such as metabolism and cell di-ision. .e are6 there)ore6 in-estigating the role o) 1/K2 in detail to be able to identi)y and de-elop ne3 chemical inhibitors o) its acti-ity that could be used )or cancer treatment. /n the )uture6 3e hope to be able to treat patients 3ith drug combinations that 3ill increase the e))iciency o) standard drugs and decrease the chance o) lea-ing behind microscopic tumour at the end o) treatment.

All Pu#lications )ver the Past * Years 13anton #6 &arani &6 ,ardo %6 .arne ,"6 Kelly $6 1ahai E6 Elustondo 26 #hang G6 (emple G6 Ahmed AA6 :renton G'6 'o3n3ard G6 Nicke :. 0egulators o) mitotic arrest and ceramide metabolism are determinants o) sensiti-ity to paclitaxel and other chemotherapeutic drugs. #ancer #ell 2 9H!!IJ4;K<!2. *2;.2+ Krypuy &6 Ahmed AA6 Etemadmoghadam '6 "yland 1G6 Australian %-arian #ancer 1tudy $roup6 'e2aDio A6 2ox 1:6 :renton G'6 :o3tell ''6 'obro-ic A. "igh resolution melting )or mutation scanning o) (,<5 exons <-;. :&# #ancer 2 9H 9I!7;. *5+ Ahmed AA6 &ills A'6 /brahim AEK6 (emple G6 :lenkiron #6 @ias &6 &assie #E6 /yer N$6 &c$eoch A6 #ra3)ord 06 Nicke :6 'o3n3ard G6 13anton #6 :ell 1'6 Earl "&6 8askey 0A6 #aldas #6 :renton G'. (he extracellular matrix protein ($2:/ induces microtubule stabiliDation and sensitiDes o-arian cancers to paclitaxel. #ancer #ell 2 9H!2I<!JK<29. *2;.2+ $ri))in N6 $rant 8A6 2reeman 1G6 GimeneD-8inan &6 :erman 8"6 Earl "6 Ahmed AA6 #ra3)ord 06 :renton G6 1ala E. /mage-guided biopsy in patients 3ith suspected o-arian carcinomaI a sa)e and e))ecti-e techniAueL Eur 0adiol 2 4H!4I25 K25<. *5.2+ Ahmed AA6 Etemadmoghadam '6 (emple G6 8ynch A$6 0iad &6 1harma 06 1te3art #6 2ereday 16 #aldas #6 :o3tell '6 :renton G'. 'ri-er mutations in (,<5 are ubiAuitous in high grade serous carcinoma o) the o-ary. G ,athol 2 ! H22!IJ4K<7. *7.5+ Ahmed AA6 8u M6 Gennings N:6 Etemadmoghadam '6 #apalbo 86 Gacamo 0%6 :arbosa&orais N6 A%#16 @i-as-&eNia ,6 8opeD-:erestein $6 $randNean $6 :artholomeusD $6 8iao .6 Andree)) &6 :o3tell '6 $lo-er '&6 1ood AK6 :ast 0# Gr. 1/K2 is a centrosome kinase reAuired )or bipolar mitotic spindle )ormation that pro-ides a potential target )or therapy in o-arian cancer. #ancer #ell 2 ! H!;I! 4K2!. *2;.2+ Ahmed AA6 $oldsmith G6 2okt /6 8e ?26 KrDysko KA6 8esyng :6 :ast 0# Gr6 ,riebe .. A genistein deri-ati-e6 /(:-5 !6 induces microtubule depolymeriDation and mi- totic arrest in multidrug-resistant o-arian cancer. #ancer #hemother ,harmacol 2 !!H 7;I! 55KJJ. *2.;+ #hen &O6 8iao .16 8u M6 :ornmann .$6 "ennessey @6 .ashington &N6 0osner $86 Ou O6 Ahmed AA6 :ast 0# Gr. 'ecitabine and suberoylanilide hydroxamic acid *1A"A+ inhibit gro3th o) o-arian cancer cell lines and xenogra)ts 3hile inducing expression o) imprinted tumor suppressor genes6 apoptosis6 $2& arrest and autophagy. #ancer 2 !!H!!9IJJ2JK5;. *J.;+ :adg3ell '6 8u M6 1uh $6 :ao GG6 'as ,6 Andree)) &6 #hen .6 Ou O6 Ahmed AA6 8iao .6 :ast 0# Gr. (he tumor suppressor gene A0"/ *'/0A15+ suppresses o-arian cancer cell migration through inhibition o) the 1tat5 and 2AK/0ho signaling path- 3ays. %ncogene 2 !!H5!I7;K94. *7.J+ Ahmed AA6 .ang ?6 8u M6 $oldsmith G6 8e ?26 $randNean $6 :artholomeusD $6 :room :6 :ast 0# Gr. &odulating microtubule stability enhances the cytotoxic response o) cancer cells to paclitaxel. #ancer 0es 2 !!H9!I<; 7K!9. *9.4+ 8e ?26 &ao .6 "e $6 #laret 2?6 ?ia .6 Ahmed AA6 "ung &#6 1iddik M"6 :ast 0# Gr. (he 0ole o) p29Kip! in 'asatinib-Enhanced ,aclitaxel #ytotoxicity in "uman %-arian #ancer #ells. G Natl #ancer /nst 2 !!H! 5I!J 5K22. *!5.;+

Ahmed AA6 :ecker #6 :ast 0# Gr. (he origin o) o-arian cancer. :G%$ 2 !2H !!4I!5JK7. *5.<+ ?ie ?6 :artholomeusD #6 Ahmed AA6 KaDansky A6 'iao 86 :aggerly KA6 "ortobagyi $N6 Ueno N(. :isphosphorylated ,EA-!< 1ensitiDes %-arian #ancer #ells to ,aclitaxel by /mpairing the &icrotubule-'estabiliDing E))ect o) 1#8/,. &ol #ancer (her. 2 !5 &ar 24. PEpub ahead o) printQ ,ub&ed ,&/'I 25<J557J. *<.2+ +e( Pu#lications "hrou%hout (our Career Ahmed AA6 @ias &6 /yer N$6 #aldas #6 :renton G'. &icroarray segmentation methods signi)icantly in)luence data precision. Nucleic Acids 0es 2 JH52Ie< . Ahmed AA6 &ills A'6 /brahim AEK6 (emple G6 :lenkiron #6 @ias &6 &assie #E6 /yer N$6 &c$eoch A6 #ra3)ord 06 Nicke :6 'o3n3ard G6 13anton #6 :ell 1'6 Earl "&6 8askey 0A6 #aldas #6 :renton G'. (he extracellular matrix protein ($2:/ induces microtubule stabiliDation and sensitiDes o-arian cancers to paclitaxel. #ancer #ell 2 9H!2I<!JK<29. Ahmed AA6 Etemadmoghadam '6 (emple G6 8ynch A$6 0iad &6 1harma 06 1te3- art #6 2ereday 16 #aldas #6 :o3tell '6 :renton G'. 'ri-er mutations in (,<5 are ubiAuitous in high grade serous carcinoma o) the o-ary. G ,athol 2 ! H22!IJ4K<7. Ahmed AA6 8u M6 Gennings N:6 Etemadmoghadam '6 #apalbo 86 Gacamo 0%6 :arbosa&orais N6 A%#16 @i-as-&eNia ,6 8opeD-:erestein $6 $randNean $6 :artholomeusD $6 8iao .6 Andree)) &6 :o3tell '6 $lo-er '&6 1ood AK6 :ast 0# Gr. 1/K2 is a centrosome kinase reAuired )or bipolar mitotic spindle )ormation that pro-ides a potential target )or therapy in o-arian cancer. #ancer #ell 2 ! H!;I! 4K2!. Ahmed AA6 .ang ?6 8u M6 $oldsmith G6 8e ?26 $randNean $6 :artholomeusD $6 :room :6 :ast 0# Gr. &odulating microtubule stability enhances the cytotoxic re- sponse o) cancer cells to paclitaxel. #ancer 0es 2 !!H9!I<; 7K!9. Mar,ers of -steem 2 2 2 2 2 < ; 4 4 4 :lair :ell priDe )or an oral presentation. Egyptian National Encouragement ,riDe )or &edicine under the category RAd-anced 1cienti)ic (echnologiesR. (he Egyptian &edical 1yndicate 1hield )or distinguished scienti)ic research. (he Ain 1hams Uni-ersity 1hield )or distinguished scienti)ic research. AA#0-:ristol-&yers 1Auibb 1cholar-in-(raining A3ard )or best oral presentation. ,ersonal #hair in $ynaecological %ncology6 Uni-ersity o) %x)ord. $ynaecological %ncology &'( 8ead )or the regional cancer specialist centre.

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Current Grant Support ./&& &0# 1enior #linical 0esearch *2 !2-2 !9+ CS!.2& (arget %-arian #ancer *2 !2-2 !<+ S!; K "elen #larke 2und *2 !J-2 !9+ S!< 6 :0# )unding )or a translational study *2 !2-2 !9+ CS! &. #o-,/ )or the #ancer (heme

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application. #ancer 0esearch UK/E,10#6 %x)ord #ancer /maging #entre *#ollaborator 3ith @oNno-ic and 'obson+ CS2 K. #o-,/ )or ,rogramme 2. 2or current )unding round. #amella 1amuel 2und S<<K %-arian #ancer Action ,rogramme $rant *2 !J-2 !9+ S7 K.