Diana C.F. Monteiro, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 538, Room 205
- Frederick, MD 21702
- 301-846-6282
- diana.monteiro@nih.gov
RESEARCH SUMMARY
I am a protein crystallographer focused on molecular mechanisms and protein dynamics. My group develops and employs new methods to obtain high-resolution structures of medically-relevant proteins, including room-temperature, serial and time-resolved crystallography. We also determine protein-ligand structures to link to medicinal chemistry efforts, both with pre-determined binders and through high-throughput small molecule screening.
Areas of Expertise
Diana C.F. Monteiro, Ph.D.
Research
Visualizing protein dynamics and determining dynamic-activity relationships
Protein dynamics underpin protein function, from structural changes associated with signal transduction to those associated with enzyme catalysis and allosteric regulation. Determining dynamic-function relationships can open avenues to novel drug discovery pathways. Our team performs high-throughput crystallographic studies to allow for the mapping of dynamic and druggable protein sites and room-temperature and time-resolved crystallography to visualize structural transitions in operando.
Protein mechanisms and medicinal chemistry
By obtaining high-resolution structures of protein-ligand complexes, we can open avenues for further compound development and drug design. My laboratory has both a biochemistry/structural biology section as well as a synthetic chemistry section. The two areas work together to iterate quickly between compounds and protein-ligand structures.
Methods development
All of our projects use synergistic approaches, employing organic chemistry and biophysics tools. We collaborate with scientists at X-ray radiation facilities (i.e., NSLSII and PETRAIII) in a bottom-up approach, harnessing the most cutting-edge synchrotron hardware available. We employ a robust crystallization approach, starting with crystallization screening at the National Crystallization Center and optimization in-house using robotics. We make use of frequent beamtime at synchrotrons to ensure rapid feedback on crystal quality and diffraction. Our approaches include the generation of large, ordered macrocrystals for both cryo- and room-temperature crystallography as well as batch microcrystallization for serial crystallography experiments.
Our current protein targets include oncogenic fusion proteins and metalloproteins, and further protein-ligand structural projects span a variety of targets through collaborative projects.
Publications
Using photocaging for fast time- resolved structural biology studies
3D-MiXD: 3D-printed X-ray-compatible microfluidic devices for rapid, low-consumption serial synchrotron crystallography data collection in flow
Photocage-initiated time-resolved solution X-ray scattering investigation of protein dimerization
X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease
Homogeneous batch micro-crystallization of proteins from ammonium sulfate
Biography
Diana C.F. Monteiro, Ph.D.
Diana Monteiro earned her Bachelor’s and Master’s degrees in Medicinal Chemistry from the University of Leeds (U.K.). She was awarded a Wellcome Trust Ph.D. Studentship with the Astbury Center for Structural Biology (School of Cellular and Molecular Biology, University of Leeds), where she pivoted her studies from chemistry to protein crystallography. As a Louise Johnson Fellow with the Center for Ultrafast Imaging at the University of Hamburg (Germany), she expanded further into methods development for room-temperature and time-resolved crystallography, working with both synchrotrons and X-ray free-electron lasers, and developing microfluidics for sample delivery to X-ray beams. In 2019, she joined the Hauptman-Woodward Medical Research Institute in Buffalo, NY, first as a postdoctoral researcher, and then progressing to an assistant investigator position. In Buffalo, she set up and oversaw the operation of an organic chemistry laboratory which worked synergistically with her structural biology research. Now as a Stadtman Investigator with the Center for Structural Biology, Dr. Monteiro's group works at the interface of structural biology and medicinal chemistry, addressing protein crystallography challenges.
Job Vacancies
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Team
News
The first annual Monteiro Lab BBQ was a success! We ate and chatted, played spike ball (thanks Kailin!) and took a very sweaty group photo afterwards.
Moya spent her summer with us and 10 weeks flew by! She learned everything from expressing and purifying a protein, to collecting diffraction data and solving a structure! She presented her poster at our Summer Student symposium and although her crystals did not cooperate (looked beautiful under the microscope, diffracted supper poorly) we learned a lot along the way. Thank you for being part of our team! We will miss you!
It's summer 2024 and the lab has been operational for a few months. I'm delighted to introduce you all to our team: Ian, Brent, Kailin, Sean, Hande and Moya! We strive to keep a supportive and enjoyable work environment in the lab, while working hard on our science. Look at these smiles!