Dr. Yukimatsu (Sean) Toh, Ph.D.
Assistant Professor, Center for Translational Cancer Research
Email Address: Yukimatsu.Toh@uth.tmc.edu
Phone Number: 713-500-3611
Room Number: SRB 330-14
Narrative
Dr. Toh received his Ph.D. in structural biology from the University of Tokyo, Japan. Dr. Toh researches advanced therapeutic options like targeted therapy – antibody-drug conjugates (ADCs). He focused on cutting-edge research and development in peptibody-drug conjugates (PDCs), which is attached the toxic payload via a cleavable linker to a chimeric protein comprising a biologically/pharmacologically active RSPOs fused to the constant region (Fc)of antibody. R-spondins are a group of four related secreted proteins (RSPO1-4) that play critical roles in the normal development and survival of adult stem cells. RSPOs function as ligands of LGR4-6 to potentiate Wnt signaling and support stem cell growth. RNA seq analysis shows that LGR4 was upregulated in most colorectal cancers, and LGR5 was also highly upregulated in most GI cancer cases. His work also is developing immunoconjugates that can be used for Dual-targeting with antibody engineering with tumor immunotherapy as well as for the treatment of other diseases by bispecific antibodies, making novel strategies and innovative therapeutics for the treatment of cancers.
RESEARCH PROJECTS
Development of anti-LGR4-6 peptibody-drug conjugates
Bispecific antibody (BsAb) ADC development
Mechanistic understanding of the Wnt signaling in human Wnt-related diseases
Selected Publications:
Cui J, Toh Y, Park S, Yu W, Tu J, Wu L, Li L, Jacob J, Pan S, Carmon KS, Liu QJ.: Drug Conjugates of Antagonistic R-Spondin 4 Mutant for Simultaneous Targeting of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors 4/5/6 for Cancer Treatment. J Med Chem. 64:12572–12581, 2021
Park S, Wu L, Tu J, Yu W, Toh Y, Carmon KS, Liu QJ.: Unlike LGR4, LGR5 potentiates Wnt-β-catenin signaling without sequestering E3 ligases. Sci Signal. 13:eaaz4051, 2020
Zhang W, Zheng W, Toh Y, Betancourt-Solis MA, Tu J, Fan Y, Vakharia VN, Liu J, McNew JA, Jin M, Tao YJ.: Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association. Proc Natl Acad Sci USA. 114:8550-8555, 2017
Toh Y, Harper J, Dryden KA, Yeager M, Arias CF, Méndez E, Tao YJ.: Crystal Structure of the Human Astrovirus Capsid Protein. J Virol. 29:9008-9017, 2016
Toh Y, Takeshita D, Nagaike T, Numata T, Tomita K.: Mechanism for the alteration of the substrate specificities of template-independent RNA polymerases. Structure. 19:232-243, 2011
Toh Y, Takeshita D, Numata T, Fukai S, Nureki O, Tomita K.: Mechanism for the definition of elongation and termination by the class II CCA-adding enzyme. EMBO J. 28:3353-3365, 2009
Toh Y, Numata T, Watanabe K, Takeshita D, Nureki O, Tomita K.: Molecular basis for maintenance of fidelity during the CCA-adding reaction by a CCA-adding enzyme. EMBO J. 27:1944-1952, 2008
Watanabe K*, Toh Y*, Suto K, Shimizu Y, Oka N, Wada T, Tomita K. (*–equal first author): Protein-based peptide-bond formation by aminoacyl-tRNA protein transferase. Nature. 449:867-871, 2007 (*–equal first author)
