2019 Sc ie ntific Re tre a t F RI DAY, APRI L 26, 2019 DI SCOVE RY WORL D PAVI L I ON T URNI NG CANCE R DI SCOVE RI E S I NT O T RE AT ME NT S Brian F. Volkman, PhD T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
DI SCL OSURE S – BRI AN VOL K MAN T o g e the r, T a king o n Ca nc e r’ s T o ug he st SFI in Protein Foundry, LLC, Cha lle ng e s manufacturer of recombinant proteins for research use 2019 Sc ie ntific Re tre a t Inventor on multiple issued and pending patents on engineered proteins as potential therapeutic agents mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
DI SCOVE RY AND DE VE L OPME NT AL T HE RAPE UT I CS PROGRAM BUI L D DDT = OPPORT UNI T Y L I NK PROPE L CANCE R COL L ABORAT I VE mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
DRUG DI SCOVE RY AND DE VE L OPME NT T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s 2019 Sc ie ntific Re tre a t TRANSLATIONAL RESEARCH mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
DRUG DI SCOVE RY AND DE VE L OPME NT T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s BUIL D the foundation 2019 MCW excels at Sc ie ntific basic science Re tre a t TARGET VALIDATION research TARGET IDENTIFICATION TRANSLATIONAL RESEARCH mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
DRUG DI SCOVE RY AND DE VE L OPME NT T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s MCW excels at 2019 basic science Sc ie ntific Re tre a t research TARGET VALIDATION Blake Hill, Francis Peterson, Davin Jensen, Brian Smith, Brian Volkman, Dan Sprague, Mike Olp, John Egner, Liza Lanum, Sarah Rolli TARGET IDENTIFICATION TRANSLATIONAL RESEARCH mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
T ARGE T I DE NT I F I CAT I ON – F YN SH2 T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s 2019 Sc ie ntific Re tre a t Subramaniam Malarkannan, PhD MCWCC Cancer Biology Program mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
T ARGE T I DE NT I F I CAT I ON – F YN SH2 T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s 2019 Sc ie ntific Re tre a t Subramaniam Malarkannan, PhD MCWCC Cancer Biology Program mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
T ARGE T VAL I DAT I ON – F YN SH2 T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s 2019 pY peptide Sc ie ntific Re tre a t binding site mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
T ARGE T VAL I DAT I ON – F YN SH2 T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s Computational solvent mapping 2019 Sc ie ntific identifies ligand Re tre a t binding hot spots mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
T ARGE T VAL I DAT I ON – F YN SH2 T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s 2019 Sc ie ntific Re tre a t Fyn SH2 for NMR screening of chemical fragment libraries mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
MCW I NVE ST ME NT S I N DRUG DI SCOVE RY CAPABI L I T I E S mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
MCW I NVE ST ME NT S I N DRUG DI SCOVE RY CAPABI L I T I E S Translational Accelerator Program mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
DRUG DI SCOVE RY AND DE VE L OPME NT T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s 2019 Sc ie ntific Re tre a t TARGET VALIDATION TARGET IDENTIFICATION TRANSLATIONAL RESEARCH mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
DRUG DI SCOVE RY AND DE VE L OPME NT T o g e the r, T a king o n Ca nc e r’ s T o ug he st The Translational Cha lle ng e s Research Unit helps MCW deliver the 2019 latest treatments to Sc ie ntific checkpoint inhibitors Re tre a t more patients CAR-T cell therapy mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
DRUG DI SCOVE RY AND DE VE L OPME NT T o g e the r, T a king o n Ca nc e r’ s LI N K T o ug he st Cha lle ng e s 2019 CHALLENGE : Promising Sc ie ntific new drug candidates Re tre a t are stranded TRANSLATIONAL RESEARCH mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
DRUG DI SCOVE RY AND T o g e the r, DE VE L OPME NT : MCWD3 T a king o n Ca nc e r’ s Goal: first-in-human clinical trials at MCW with MCW- T o ug he st Cha lle ng e s derived discoveries Inception: Formed in 2017, led by Bill Clarke, MCW’s 2019 first Director of Research Commercialization Sc ie ntific Re tre a t Portfolio approach: • Identify MCW-derived discoveries with therapeutic potential • Meet with PIs to assess commercial promise, identify gaps in preclinical development • Facilitate next steps toward IND mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
ST RAT E GI CAL L Y MANAGE D PORT F OL I O 2019 Sc ie ntific Re tre a t______T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s
ST RAT E GI CAL L Y MANAGE D PORT F OL I O 2019 Sc ie ntific Re tre a t______T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s
MCWD3: ST RAT E GI CAL L Y T o g e the r, MANAGE D PORT F OL I O T a king o n Target Ca nc e r’ s Cancer Indication MCWD3 T o ug he st Honokiol Head and Neck Members Cha lle ng e s Hippo Breast Bill Clarke (OTD) Mortalin Thyroid Blake Hill CRR9 Pancreatic 2019 John Imig p38G Pancreatic and Colon Sc ie ntific Mike Dwinell Glucosidase II Breast Re tre a t MitoMetformin Pancreatic and Colon Nita Salzman PBRM1 Gall bladder and Breast Ravit Boger Fyn Leukemias Jim Thomas Drp1 Breast and Testicular Ben George NAMPT Breast and Esophageal Paul Ornstein Lif Ovarian, Lung, Melanoma Matt Lasokowski K-Ras Lung, Pancreas, Colon Brian Volkman Fis1 Breast, Pancreas, Esophageal mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
MCWD3: ST RAT E GI CAL L Y T o g e the r, MANAGE D PORT F OL I O T a king o n Ca nc e r’ s MCWD3 T o ug he st Members Cha lle ng e s Bill Clarke (OTD) Blake Hill 2019 John Imig Sc ie ntific Mike Dwinell Re tre a t Nita Salzman Ravit Boger Jim Thomas Ben George Paul Ornstein Brian Volkman Matt Lasokowski mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
CXCR4: VAL I DAT E D T ARGE T F OR T o g e the r, ME T AST AT I C CANCE R T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s 2019 Sc ie ntific Re tre a t Murphy, PM (2001) NEJM 345, 833-835.
CXCR4: VAL I DAT E D T ARGE T F OR T o g e the r, ME T AST AT I C CANCE R T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s 2019 Sc ie ntific Re tre a t Murphy, PM (2001) NEJM 345, 833-835. Involvem emen ent o t of chem emokine r ne recep eptors in breast c cancer metastasi sis ( s (2001) 2001) Müller er A A et et al. Nature 410, 410, 50 50-56 56 mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
CXCR4: VAL I DAT E D T ARGE T F OR T o g e the r, ME T AST AT I C CANCE R T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s 2019 Sc ie ntific Re tre a t Murphy, PM (2001) NEJM 345, 833-835. Involvem emen ent o t of chem emokine r ne recep eptors in breast c cancer metastasi sis ( s (2001) 2001) Müller er A A et et al. Nature 410, 410, 50 50-56 56 mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
E PI GE NE T I C RE GUL AT I ON OF CHE MOK I NE E XPRE SSI ON CB program 2019 Sc ie ntific Re tre a t______T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s
E PI GE NE T I C RE GUL AT I ON OF CHE MOK I NE E XPRE SSI ON 2019 Sc ie ntific Re tre a t______T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s
CXCR4 I NDUCE S DI ME RI ZAT I ON T o g e the r, OF I T S L I GAND CXCL 12 T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s Fluorescence 2019 Polarization Sc ie ntific Re tre a t [CXCL12] (mM) Veldkamp, CT et al (2006) J Mol Biol Veldkamp, CT et al (2008) Science Signaling 1: RA4 mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r
PROT E I N E NGI NE E RI NG: CXCL 12 L OCK E D DI ME R CXCL12 2 dimer 10 nM wt CXCL12 THP-1 cells IC 50 ~ 5 nM Veldkamp, CT et al (2008) Science Signaling 1:RA4 CXCL12 L36C/A65C [CXCL12] (mM) 2019 Sc ie ntific Re tre a t______T o g e the r, T a king o n Ca nc e r’ s T o ug he st Cha lle ng e s
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