An NCI-designated Comprehensive Cancer Center
Michael Kahn | City of Hope

Michael Kahn, Ph.D.

Professor and Chair, Department of Molecular Medicine; Co-leader, Developmental Cancer Therapeutics Program
Research Focus
  • Chemical genomics
  • Wnt signaling

Research Teams

Michael Kahn, Ph.D., is professor and chair in the Department of Molecular Medicine and co-leader in the Developmental Cancer Therapeutics Program at City of Hope's comprehensive cancer center. He comes to City of Hope from University of Southern California, where he was the first appointed provost professor, with joint appointments in the Department of Biochemistry and Molecular Biology at Keck School of Medicine of USC and the Department of Molecular Pharmacology and Toxicology in the School of Pharmacy. He was also the co-leader of the GI-Oncology Program at the USC Norris Comprehensive Cancer Center, as well as the Center for Drug Discovery and Development at USC.
 
After completing his postdoctoral training at Columbia University with Professor Gilbert Stork, Dr. Kahn subsequently did a second postdoctoral fellowship at the Roche Institute for Molecular Biology, where he first became interested in utilizing novel chemistry to complement and enhance the investigation of complex biological signaling pathways.
 
Dr. Kahn’s research program is focused on the integration of basic science (biochemistry, cell and molecular biology and chemistry) with translational medicine. His lab utilizes a forward chemical genomic strategy to identify and validate novel pharmacologic tools to study complex signaling pathways in development and disease. Utilizing a proprietary chemical library, his lab identified the first specific CBP/β-catenin antagonist ICG-001, which has been fundamental in studies involving both normal somatic stem cell and cancer stem cell biology. From a translational perspective, these studies led to the development of the second-generation CBP/β-catenin antagonist, Wnt modulating drug, PRI-724. These efforts resulted in the clinical trials of PRI-724 in colon and pancreatic cancer, leukemia and liver fibrosis.
 
His lab is currently continuing basic research investigations concerning differential Kat3 coactivator usage (i.e., CBP versus p300) in somatic stem cell biology and cancer, regenerative medicine and aging. The lab is also investigating modulation of Wnt/β-catenin in the immune response. CBP/ β-catenin inhibitors in combination with immunotherapy may provide a significant benefit. Another area of interest to his lab is the endogenous mechanisms that control the differential usage of these coactivators and the role that the N-termini play as a nexus for the integration of a number of additional signaling pathways (e.g., STAT1/2, nuclear receptor family, RAR/RXR, Vit D) with the Wnt signaling cascade. Dr. Kahn is applying this forward chemical genomic strategy to additional critical signaling cascades with the broader goal of developing novel small molecule therapeutics.

Locations

City of Hope Comprehensive Cancer Center, 1500 East Duarte Road

Duarte, CA 91010

Nuclear receptor/Wnt beta-catenin interactions are regulated via differential CBP/p300 coactivator usage. PLoS One, 2018, 13(7):e0200714, Ono, M., Lai, K.K.Y., Wu, K., Nguyen, C., Lin, D.P., Murali, R., Kahn, M.

Differentiation Therapy Targeting the B-Catenin/CBP Interaction in Pancreatic Cancer, Cancers, 2018, 10(4), Manegold, P., Lai, K.K.Y., Wu, Y., Teo, J.L., Lenz, H.J., Genyk, Y.S., Pandol, S.J., Wu, K., Lin, D.P., Chen, Y., Nguyen, C., Zhao, Y., Kahn, M.

Characterization of Imatinib Resistant CML Leukemic Stem/Initiating Cells and Their Sensitivity to CBP/Catenin Antagonists, Current molecular pharmacology, 2018, 11(2): 113-121, Zhao, Y., Wu, K., Wu, Y., Melendez, E., Smbatyan, G., Massiello, D., Kahn, M.
 
Wnt/B-catenin activation and macrophage induction during liver cancer development following steatosis, Oncogene, 2017, 36(43): 6020-6029, Debebe, A., Medina, V., Chen, C.Y., Mahajan, I.M., Jia, C., Fu, D., He, L., Zeng, N., Stiles, B.W., Chen, C.L., Wang, M., Aggarwal, K.R., Peng, Z., Huang, J., Chen, J., Li, M., Dong, T., Atkins, S., Borok, Z., Yuan, W., Machida, K., Ju, C., Kahn, M., Johnson, D., Stiles, B.L.
 
CBP/Catenin antagonists: Targeting LSCs’ Achilles heel, Experimental hematology, 2017, 52:1-11, Kim, Y.M., Gang, E.J., Kahn, M.
 
Small molecule p300/catenin antagonist enhances hematopoietic recovery after radiation, PLoS One, 2017, 12(5):e0177245 Zhao, Y., Wu, K., Nguyen, C., Smbatyan, G., Melendez, E., Higuchi, Y., Chen, Y., Kahn, M.
 
Specific Inhibition of CBP/Catenin Signaling Safely Eliminates Drug Resistant Leukemia Initiating Cells
Oncogene, 2016, 35(28): 3705-3717, Zhao, Y., Masiello, D., McMillian, M., Nguyen, C., Wu, Y., Melendez, E., Smbatyan, G., Kida, A., He, Y., Teo, J.L., Kahn, M.
 
Differential /b-catenin/coactivator ineractions regulate adult stem/progenitors
J. Biol. Chem, 2016, 291(12): 6569-6582, Rieger, M.E., Zhou, B., Solomon, N., Sunohara, M., Li, C., Nguyen, C., Liu, Y., Pan, J.H., Minoo, P., Crandall, E.D., Brody, S.L., Kahn, M., Borok, Z.
 
Kat3 Coactivators in Somatic Stem Cells and cancer Stem Cells: Biological Roles, Evolution and Pharmacologic Manipulation, Cell Biol. Toxicol., 2016, 32(1): 61-81, Thomas, P.D., Kahn, M.
 
Can we safely target the Wnt pathway? Nature Reviews - Drug Discovery, 2014, 13(7): 513-532, Kahn, M.
 
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Michael Kahn | City of Hope

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