Haitao (Mark) Ji
Assistant Professor of Chemistry
B.S. Second Military Medical University, China
Ph.D. Second Military Medical University, China
Mark Ji's Email: markji@chem.utah.edu
Mark Ji's Lab Page
Mark Ji's PubMed Literature Search
Research
Our laboratory is a place where chemistry meets biology. We mainly focus on structure-based design and synthesis of “smart” small molecules that can modulate cellular signaling pathways with an emphasis on protein-protein interactions and target specificity. Technique cores in our laboratory are fragment-based screening and de novo design, the design and synthesis of versatile fragment building blocks from natural products, and construction of fragment libraries to explore isozyme selectivity. Our goal is to use multidisciplinary and innovative approaches to tackle fundamental problems associated with human diseases, and the translation of the fundamental scientific findings into biomedical and biotechnological applications.
Specific areas of interest include: (1) Fragment-based design of novel small-molecules to selectively disrupt key interactions in the Wnt/beta-catenin signaling pathway; (2) Development of new organic chemistry-oriented techniques to differentiate drug target cytochrome P450s from drug-metabolizing P450s, and the design and synthesis of selective inhibitors for drug target P450s; (3) Incorporation of natural product building blocks into peptides to mimic their biological functions. 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.
In our laboratory, researchers in the field of chemistry, biology and biochemistry work together closely to develop new methods/approaches for structure-based inhibitor discovery, design and synthesize novel bioactive compounds, and elucidate illness-causing mechanisms at molecular level. A graduate or postdoctoral student in our group expect to receive training in structure-based inhibitor design, synthetic organic chemistry, computer modeling, medicinal chemistry, and molecular and cell biology.
References
1. Zhang M, Huang Z, Yu B, Ji H (2012) New homogeneous high-throughput assays for inhibitors of β-catenin/Tcf protein-protein interactions. Anal Biochem, 424(1): 57-63
2. Ji H, Jing Q, Huang J, Silverman, RB (2012) Acid-facilitated debenzylation of N-Boc, N-benzyl double protected 2-aminopyridinomethyl pyrrolidine derivatives. Tetrahedron, 68(5): 1359-1366
3. Ji H, Delker SL, Li H, Martásek P, Roman LJ, Poulos TL, Silverman RB (2010) Exploration of the active site of neuronal nitric oxide synthase by the design and synthesis of pyrrolidinomethyl 2-aminopyridine derivatives. J Med Chem, 53(21):7804-7824
4. Delker SL, Ji H, Li H, Jamal J, Fang J, Xue F, Silverman RB, Poulos TL (2010) 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, 132(15):5437−5442
5. Ji H, Tan S, Igarashi J, Li H, Derrick M, Martásek P, Roman LJ, Vásquez-Vivar J, Poulos TL, Silverman RB (2009) Selective neuronal nitric oxide synthase inhibitors and the prevention of cerebral palsy. Ann Neurol, 65(2):209−217
6. Ji H, Li H, Martásek P, Roman LJ, Poulos TL, Silverman RB (2009) Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping. J Med Chem, 52(3):779−797
7. Ji H, Stanton BZ, Igarashi J, Li H, Martásek P, Roman LJ, Poulos TL, Silverman RB (2008) 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, 130(12):3900−3914
8. Ji H, Gómez-Vidal JA, Martásek P, Roman LJ, Silverman RB (2006) Conformationally restricted dipeptide amides as potent and selective neuronal nitric oxide synthase inhibitors. J Med Chem, 49(21):6254−6263
9. Ji H, Li H, Flinspach M, Poulos TL, Silverman RB (2003) Computer modeling of selective regions in the active site of nitric oxide synthases: implication for the design of isoform-selective inhibitors. J Med Chem, 46(26):5700−5711
10. Ji H, Zhang W, Zhang M, Kudo M, Aoyama Y, Yoshida Y, Sheng C, Song Y, Yang S, Zhou Y, Lü J, Zhu J (2003) Structure-based de novo design, synthesis and biological evaluation of nonazole inhibitors specific for lanosterol 14α-demethylase of fungi. J Med Chem, 46(4):474−485
11. Ji H, Zhang W, Zhou Y, Zhang M, Zhu J, Song Y, Lü J, Zhu J (2000) A three-dimensional model of lanosterol 14alpha-demethylase of Candida albicans and its interaction with azole antifungals. J Med Chem, 43(13):2493−2505
Updated 4/18/2012
