Marcus A. Tius, PhD, MS

Marcus Antonius Tius, PhD, MS

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Full Member, Cancer Biology Program, University of Hawaiʻi Cancer Center
University of Hawaiʻi Cancer Center Special Liaison to University of Hawaiʻi at Mānoa

Academic Appointment(s):
Professor, Department of Chemistry, College of Natural Sciences, University of Hawaiʻi at Mānoa
Joanna L. Sullivan Chair for Cancer Research, University of Hawaiʻi Cancer Center

Degree(s):
1980 - PhD, Chemistry, Harvard University
1977 - MS, Chemistry, Harvard University

Fellowships
2001 - CREST Fellowship (Japan)
1998 - Japan Society for the Promotion of Science Fellowship
1987 - 1991 - Fellow of the Alfred P. Sloan Foundation

Honors

11/18/2002 - Roche Distinguished Lecturer, Colorado State University
2000 - Faculty Performance Award
1996 - Honolulu City Council Honoree (research)
1993 - Mortar Board Honoree (teaching)
1991 - Regents' Medal for Excellence in Teaching

Research Focus

My research group works on the development of methodology in organic synthesis and applications of natural products synthesis. The targeted natural products are characterized by structural novelty and pharmacological activity that is relevant to cancer (e.g. cryptophycins, madindolines, rocaglamide, terpestacin). My group collaborates with the groups of Dr. James Turkson (Cedars-Sinai Medical Center, L.A., STAT3 inhibitors), Dr. Joe Ramos (UH Cancer Center, rocaglamide), and Dr. Peiwen Fei (UH Cancer Center, P53 inhibitors). My research group also has interests in the synthesis and medicinal chemistry of cannabinoids, primarily classical-nonclassical hybrid structures. I have collaborated with Dr. Alex Makriyannis (Director, Center for Drug Discovery, Northeastern University) on a number of projects. My research group has developed very efficient methods for stereo- and enantioselective synthesis of cannabinoids and we have developed the means to modify all the known pharmacophoric regions of these molecules. This work was initiated before the connection between activation of the endocannabinoid system and cancer had been established, so now all my research has some cancer relevance.

The process team at Eli Lilly Company modified the cryptophycin total synthesis that was developed in my group, and used the method to prepare material for clinical trial.  I am a co-inventor on the cryptophycin patent.  Although Lilly dropped the compound during Phase II, the IP has been licensed to Sanofi-Aventis that is pursuing its development as a targeted therapy against solid tumors.

My participation in Dr. Turkson's the STAT3 project goes back approximately four years when a collaborator with organic synthesis expertise was needed in order to provide materials.  We have prepared the first sub-nanomolar specific STAT3 inhibitor.

Selected Publications

Brotherton-Pleiss C, Yue P, Zhu Y, Nakamura K, Chen W, Fu W, Kubota C, Chen J, Alonso-Valenteen F, Mikhael S, Medina-Kauwe L, Tius MA, Lopez-Tapia F, Turkson J. (2021). Discovery of Novel Azetidine Amides as Potent Small-Molecule STAT3 Inhibitors. J Med Chem; 64, 695 – 710.

Yue P, Lopez-Tapia F, Paladino D, Li Y, Chen C-H, Namanja AT, Hilliard T, Chen Y, Tius MA, Turkson J. (2016). Hydroxamic Acid and Benzoic Acid-Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes In Vitro and In Vivo. Cancer Res; 76, 652-663.

Asari A, Lam Y, Tius MA, Houk KJ. (2015). Origins of the Stereoselectivity in a Thiourea–Primary Amine-catalyzed Nazarov Cyclization. J Am Chem Soc; 137, 13191 – 13199.

Zhou Z, Tius MA. (2015). Synthesis of Each Enantiomer of Rocaglamide by Means of a Pd(0)-Catalyzed Nazarov-Type Cyclization. Angew Chem Int Ed; 54, 6037-6040.

Shimada N, Stewart C, Bow WF, Jolit A, Wong K, Zhou Z, Tius MA. (2012). Neutral Nazarov-Type Cyclization Catalyzed by Palladium(0). Angew Chem Int Ed; 51, 5727-5729.

Publication list via PubMed

Active Grants

M. Tius, Co-PI; J. Turkson, PI
NIH/NCI
5R01CA208851-02
“STAT3, G6PD and TrxR as underlying mechanisms for antitumor responses to hirsutinolides”
We propose to investigate Signal Transducer and Activator of Transcription (STAT3), thioredoxin reductase (TrxR)1 cytoplasmic isoform 3, and glucose-6-phosphate 1-dehydrogenase (G6PD) isoform a as the targeting mechanisms underlying the antitumor responses of GBM and triple-negative breast cancer to hirsutinolide compounds.
03/01/2017 - 02/28/2022