Haitao (Mark) Ji

 

 

Mark Ji 2015





ORGANIC & BIOORGANIC CHEMISTRY

  Assistant Professor
   B.S., Second Military Medical University, China, 1994
   Ph.D., Second Military Medical University, China, 1999
   Postdoctoral fellow, Northwestern University, 2002-2006

 

Phone: (801) 581-6747

Office: 4428 HEB-S

Email: markji@chem.utah.edu

Research Group

Biological Chemistry Program

Activities & Awards

  • I. M. Rosenzweig Young Investigator Award by the Pulmonary Fibrosis Foundation, 2012

Research Interests

We mainly focus on structure-based design and synthesis of small molecules that can modulate cellular signaling pathways with an emphasis on protein-protein interactions and target specificity. Technique cores in our laboratory are stucture-based de novo design and fragment-based screening, and the development of fragment libraries to explore inhibitor selectivity for protein-protein interactions.

Specific areas of interest include: (1) Development of new chemistry-oriented techniques to design highly selective small-molecule inhibitors for protein–protein interactions; (2) Development of rational approaches for small-molecule allosteric inhibition of protein–protein interactions; (3) Incorporation of natural product building blocks into peptides for the regulation of protein–protein interactions. Our long-term goal of this study is the systematic data mining of natural product building blocks and the study of their ability as versatile building blocks for fragment-based inhibitor design; (4) Discovery of novel small-molecule inhibitors for the downstream effectors of the canonical Wnt/beta-catenin signaling pathway. We take multidisciplinary approaches toward achieving these research goals including synthetic organic chemistry, computer modeling, molecular and cell biology.

Selected Publications

  • Wisniewski, J. A.; Yin, J.; Tesucher, K. B.; Zhang, M.; Ji, H. Structure-based design of 1,4-dibenzoylpiperazines as β-catenin/B-cell lymphoma 9 protein–protein interaction inhibitors. ACS Med. Chem. Lett.  2016, ASAP. DOI: 10.1021/acsmedchemlett.5b00284.
  • Zhang, Y.; Teuscher, K. B.; Ji, H. Direct α-heteroarylation of amides (α to nitrogen) and ethers through a benzaldehyde-mediated photoredox reaction. Chem. Sci.  2016, 7 (3), 2111-2118
  • Hoggard, L. R.; Zhang, Y.; Zhang, M.; Panic, V.; Wisniewski, J. A.; Ji, H. Rational design of selective small-molecule inhibitors for β-catenin/B-cell lymphoma 9 protein–protein interactions. J. Am. Chem. Soc.  2015, 137 (38), 12249–12260.

  • Catrow, J. L.; Zhang, Y.; Zhang, M.; Ji, H. Discovery of selective small-molecule inhibitors for the β-catenine/T-cell factor protein-protein interaction though the optimization of the acyl hydrazone moiety. J. Med. Chem.  2015, 58 (11), 4678-4692.

  • Zhang, M.; Wisniewski, J. A.; Ji, H. AlphaScreen selectivity asssay for β-catenine/B-cell lymphoma 9 inhibitors. Anal. Biochem.  2015, 469, 43-53.

  • Huang, Z.; Zhang, M.; Burton, S. D.; Katsakhyan, L. N.; Ji, H. Targeting the Tcf4 G13ANDE17 binding site to selectively disrupt β-catenin/T-cell factor protein–protein interactions. ACS Chem. Biol.  2014, 9 (1), 193–201.       

  • Zhang, M.; Catrow, J. L.; Ji, H. High-throughput selectivity assays for small-molecule inhibitors of β-catenin/T-cell factor protein–protein interactions. ACS Med. Chem. Lett.  2013, (2), 306-311.

  • Yu, B.; Huang, Z.; Dillard, D. R.; Ji, H. Rational design of small-molecule beta-catenin/T-cell factor inhibitors by bioisostere replacement. ACS Chem. Biol.  2013, (3), 524-529.

  • Zhang, M.; Huang, Z.; Yu, B.; Ji, H. New homogeneous high-throughput assays for inhibitors of β-catenin/Tcf protein-protein interactions. Anal. Biochem.  2012, 424 (1), 57-63.

  • Huang, H.; Ji, H.; Li, H.; Jing, Q.; Labby, K. J.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Selective monocationic inhibitors of neuronal nitric oxide synthase. Binding mode insights from molecular dynamics simulations. J. Am. Chem. Soc.  2012, 134 (28), 11559-11572.

  • Ji, H.; Delker, S. L.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Exploration of the active site of neuronal nitric oxide synthase by the design and synthesis of pyrrolidinomethyl 2-aminopyridine derivatives. J. Med. Chem.  2010, 53(21), 7804-7824.

  • Delker, S. L.; Ji, H.; Li, H.; Jamal, J.; Fang, J.; Xue, F.; Silverman, R. B.; Poulos, T. L. Unexpected binding modes of nitric oxide synthase inhibitors effective in the prevention of a cerebral palsy phenotype in an animal model. J. Am. Chem. Soc.  2010, 132 (15), 5437-5442.

  • Ji, H.; Tan, S.; Igarashi, J.; Li, H.; Derrick, M.; Martásek, P.; Roman, L. J.; Vásquez-Vivar, J.; Poulos, T. L.; Silverman, R. B. Selective neuronal nitric oxide synthase inhibitors and the prevention of cerebral palsy. Ann. Neurol.  2009, 65 (2), 209-217.

  • Ji, H.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping. J. Med. Chem.  2009, 52 (3), 779-797.

  • Ji, H.; Stanton, B. Z.; Igarashi, J.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors. J. Am. Chem. Soc.  2008, 130 (12), 3900-3914.

  • Ji, H.; Gómez-Vidal, J. A.; Martásek, P.; Roman, L. J.; Silverman, R. B. Conformationally restricted dipeptide amides as potent and selective neuronal nitric oxide synthase inhibitors. J. Med. Chem.  2006, 49 (21), 6254-6263.

  • Ji, H.; Li, H.; Flinspach, M.; Poulos, T. L.; Silverman, R. B. Computer modeling of selective regions in the active site of nitric oxide synthases: implication for the design of isoform-selective inhibitors. J. Med. Chem.  2003, 46 (26), 5700-5711.

  • Ji, H.; Zhang, W.; Zhang, M.; Kudo, M.; Aoyama, Y.; Yoshida, Y.; Sheng, C.; Song, Y.; Yang, S.; Zhou, Y.; Lü, J.; Zhu, J. Structure-based de novo design, synthesis and biological evaluation of nonazole inhibitors specific for lanosterol 14alpha-demethylase of fungi. J. Med. Chem.  2003, 46 (4), 474-485.

  • Ji, H.; Zhang, W.; Zhou, Y.; Zhang, M.; Zhu, J.; Song, Y.; Lü, J.; Zhu J. A three-dimensional model of lanosterol 14a-demethylase of Candida albicans and its interaction with azole antifungals. J. Med. Chem.  2000, 43 (13), 2493-2505.