Herman Sintim

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

1) Cyclic dinucleotide signaling in bacteria and immune cells: we use chemical probes, as well as global proteomics, to identify signaling pathways and key proteins that are involved in cyclic dinucleotide (Cdn) signaling. Inhibitors of Cdn signaling have the potential to be used as anti-cancer and anti-inflammatory agents.

2) Bacterial quorum sensing: Bacteria communicate with each other via small diffusible signal molecules (autoinducers). We are interested in developing novel inhibitors of quorum sensing as anti-virulence and anti-biofilm agents.

3) Inhibitors of protein kinases (examples are: FLT3, ABL1, ROCK1/2, LRRK2, RET, CDKs): There are over 500 protein kinases in mammalian cells and these are involved in diverse processes. Protein kinases are targets for several disease states (such as cancer, Parkinson's, Alzheimer's and inflammatory diseases). Many cancers are driven by mutated kinases. We are developing orally bioactive protein kinase inhibitors against FLT3 (AML), ABL1(CML), RET(NSCLC), LRRK2 (potentially Parkinson's) and ROCK1/2 (metastatic cancer, glaucoma and stroke).

4) Novel antibacterial and anti-biofilm agents: We are developing novel compounds that are active against methicillin-resistant Staphylococcus aureus, MRSA. We are particularly interested in small molecules (MW<500) that are able to clear MRSA from host cells, such as macrophages.

Selected Publications:

Evidence of link between quorum sensing and sugar metabolism in Escherichia coli revealed via cocrystal structures of LsrK and HPr. Ha JH, Hauk P, Cho K, Eo Y, Ma X, Stephens K, Cha S, Jeong M, Suh JY, Sintim HO, Bentley WE, Ryu KS. Sci Adv. 2018, 1;4(6):eaar7063.

Proteomic analysis of RAW macrophages treated with cGAMP or c-di-GMP reveals differentially activated cellular pathways. Sooreshjani MA, Gursoy UK, Aryal UK and Sintim HO. RSC Adv., 2018, 8, 36840-3685.

N-(1,3,4-oxadiazol-2-yl)benzamide analogs, bacteriostatic agents against methicillin- and vancomycin-resistant bacteria. Opoku-Temeng C, Naclerio GA, Mohammad H, Dayal N, Abutaleb NS, Seleem MN, Sintim HO. Eur J Med Chem. 2018,15;155:797-805.

Tetrahydro-3H-pyrazolo[4,3-a]phenanthridine-based CDK inhibitor. Clement Opoku-Temeng, Neetu Dayal, Delmis E. Hernandez, N. Naganna and Herman O. Sintim Chem. Commun. 2018, 54, 4521-4524.

Inhibition of Innate Immune Cytosolic Surveillance by a M. tuberculosis Phosphodiesterase. Ruchi Jain Dey, Bappaditya Dey, Yue Zheng, Laurene S. Cheung, Jie Zhou, David Sayre, Pankaj Kumar, Haidan Guo, Herman O. Sintim, William R. Bishai Nature Chem. Biol. 2017, 13, 210-217.

Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover. Mona W. Orr, Gregory P. Donaldson, Geoffrey B. Severin, Jingxin Wang, Herman O. Sintim, Christopher M. Walters and Vincent T. Lee. Proc. Natl. Acad. Sci. USA, 2015, 112(36): E5048-E5057.