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PrintHerman O. Sintim
Assistant Professor
Personal Data
Education
- University College London, B.Sc 1999
- University of Oxford, PhD 2002
- University of Oxford, Post-Doctoral Fellow, 2002-2004 (with Timothy Donohoe)
- Stanford University, Post-Doctoral Fellow, 2004-2006 (with Eric Kool)
Professional Experience
- 2006 - Present: Assistant Professor, University of Maryland, College Park.
- 2004 - 2006: Research Associate in Chemical Biology, Stanford University.
- 2002 - 2004: Postdoctoral Researcher in Organic Chemistry, University of Oxford.
Research Interests
1) The chemical biology of bacterial communication, virulence factors production and biofilm formation (quorum sensing and c-di-GMP signaling in bacteria).
2) The discovery of new antibiotics with novel modes of action.
3) The catalytic cycle of total syntheses of complex bioactive molecules and the discovery of new reaction methodologies.
4) New DNA nanostructures and machines for biotechnological applications such as simple detection of pathogenic genes in clinical samples.
5) New microfluidic devices for sensing and the study of biological processes (collaborative project with NIST scientists).
Major Recognitions and Honors
- Camille Dreyfus Teacher-Scholar Award (2011)
- Allen Angerio Award for Excellence in Faculty Mentorship (2010)
- Kavli fellow (Indo-US Frontiers of science symposium, 2009)
NSF Career award (2008) - UMD Invention of the year finalist (2008)
- University of Maryland General Research Board Summer Research Award (2007)
- Roche’s top award, Switzerland (2002, Leading Chemists of the Next Decade Symposium),
- Pfizer UK PhD Prize (2001, First Prize Award)
- First Innocentive Awardee (2001, Ely Lilly): Profile featured in The Scientist, Volume 16 (1), page 60 (Seeking Scientific Riddle Solvers)
- ORS fellowship, (2000-2002, University of Oxford, 2000-2002)
- Pathfinder fellow, (University College London, 1996-1999)
Publications
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Understanding biology with chemistry
Research in the Sintim laboratory takes a multi-disciplinary approach to several biological problems. We use the tools of organic chemistry to develop chemical probes to study biology. Our broad interest lies in understanding signaling pathways that are involved in bacterial virulence production and biofilm formation using new chemical tools and novel molecular detection systems.
The three main projects in our laboratory are,
1) The catalytic cycle of novel reaction discovery and the total syntheses of natural products that have antibiotic properties.
We are currently developing concise approaches to many natural products that have been shown to have antibiotic properties. Platensimycin, a small molecule produced by Streptomyces platensis, has caused so much excitement in the antibiotic field because this molecule kills gram-positive bacteria by inhibiting FabF of the fatty acid synthesis pathway. Although the FabF target has been a subject of intense studies for more than two decades, it is only until recently that a potent inhibitor of this enzyme has been discovered. We have developed a concise methodology that permits an expeditious entry into the core structure of platensimycin (see: Jingxin Wang, Vincent Lee and Herman O. Sintim Chem. Eur. J., 2009, 15, 2747-2750).
We are also developing new C-H activation/insertion strategies that allow the construction of tertiary and quaternary centers found in several bioactive natural product targets.
2) Development of novel fluorophore reconstitution paradigms to follow sRNA processing in bacterial cells.
The last decade has witnessed an explosive growth in the development of probes that can detect nucleic acids in vitro. Such probes have found utility in medical diagnostics and the study of gene expression levels in both normal and disease-state cells. Extending these precedent background technologies to detect messenger and regulatory RNA in vivo has been challenging due to the complex environment of the cell. We are currently working on a novel nucleic acid detection platform that should lead to practical oligonucleotide detection probes that can be used to follow RNA processing in both bacterial and human cells and also find applicability in detecting pathogens in both clinical and environmental samples.
We have recently described a new enabling technology for the detection of DNA and RNA called Junction probes (ref: Junction Probes- Sequence Specific Detection of Nucleic Acids via Template Enhanced Hybridization Processes Shizuka Nakayama, Lei Yan and Herman O. Sintim*, J. Am. Chem. Soc., 2008, 130 (38), 12560-12561). Current work in our group is focused on a new generation junction probe technology and the adaptation of the junction probe concept for multi-analytes detection.
3) Understanding bacterial virulence and biofilm formation with chemical probes.
One of the key projects in our group is to use novel chemical probes to study key proteins that are involved in bacterial signaling that lead to virulence or biofilm formation. In the last few years, it has become evident that the dinucleotide, cyclic guanylic acid (c-di-GMP) and quorum sensing autoinducers play key roles in both the maintenance of bacterial biofilms and the expression of virulence genes in several bacteria of both clinical and industrial importance. Our broad aim is to provide an understanding of the structural features of c-di-GMP that confer specificity to c-di-GMP processing enzymes and to discover small molecules that inhibit bacterial cell-to-cell communication. Our laboratory has recently developed probably the most concise strategies that allow the expeditious syntheses of both c-di-GMP and the so-called universal quorum sensing molecule AI-2.
Research in the Sintim laboratory takes a multi-disciplinary approach to several biological problems. We use the tools of organic chemistry to develop chemical probes to study biology. Our broad interest lies in understanding signaling pathways that are involved in bacterial virulence production and biofilm formation using new chemical tools and novel molecular detection systems.
The three main projects in our laboratory are,
1) The catalytic cycle of novel reaction discovery and the total syntheses of natural products that have antibiotic properties.
We are currently developing concise approaches to many natural products that have been shown to have antibiotic properties. Platensimycin, a small molecule produced by Streptomyces platensis, has caused so much excitement in the antibiotic field because this molecule kills gram-positive bacteria by inhibiting FabF of the fatty acid synthesis pathway. Although the FabF target has been a subject of intense studies for more than two decades, it is only until recently that a potent inhibitor of this enzyme has been discovered. We have developed a concise methodology that permits an expeditious entry into the core structure of platensimycin (see: Jingxin Wang, Vincent Lee and Herman O. Sintim Chem. Eur. J., 2009, 15, 2747-2750).
We are also developing new C-H activation/insertion strategies that allow the construction of tertiary and quaternary centers found in several bioactive natural product targets.
2) Development of novel fluorophore reconstitution paradigms to follow sRNA processing in bacterial cells.
The last decade has witnessed an explosive growth in the development of probes that can detect nucleic acids in vitro. Such probes have found utility in medical diagnostics and the study of gene expression levels in both normal and disease-state cells. Extending these precedent background technologies to detect messenger and regulatory RNA in vivo has been challenging due to the complex environment of the cell. We are currently working on a novel nucleic acid detection platform that should lead to practical oligonucleotide detection probes that can be used to follow RNA processing in both bacterial and human cells and also find applicability in detecting pathogens in both clinical and environmental samples.
We have recently described a new enabling technology for the detection of DNA and RNA called Junction probes (ref: Junction Probes- Sequence Specific Detection of Nucleic Acids via Template Enhanced Hybridization Processes Shizuka Nakayama, Lei Yan and Herman O. Sintim*, J. Am. Chem. Soc., 2008, 130 (38), 12560-12561). Current work in our group is focused on a new generation junction probe technology and the adaptation of the junction probe concept for multi-analytes detection.
3) Understanding bacterial virulence and biofilm formation with chemical probes.
One of the key projects in our group is to use novel chemical probes to study key proteins that are involved in bacterial signaling that lead to virulence or biofilm formation. In the last few years, it has become evident that the dinucleotide, cyclic guanylic acid (c-di-GMP) and quorum sensing autoinducers play key roles in both the maintenance of bacterial biofilms and the expression of virulence genes in several bacteria of both clinical and industrial importance. Our broad aim is to provide an understanding of the structural features of c-di-GMP that confer specificity to c-di-GMP processing enzymes and to discover small molecules that inhibit bacterial cell-to-cell communication. Our laboratory has recently developed probably the most concise strategies that allow the expeditious syntheses of both c-di-GMP and the so-called universal quorum sensing molecule AI-2.
