|Walter Chazin, Ph.D.|
Dr. Chazin received a B.Sc. in chemistry from McGill University in 1975 and a Ph.D. in chemistry from Concordia University in Montreal in 1983. He was a postdoctoral fellow in the lab of Kurt Wüthrich at the E.T.H. in Switzerland (2002 Nobel laureate in Chemistry). After 13 years on faculty in the Department of Molecular Biology at the Scripps Research Institute, he moved to Vanderbilt in 1999 where he holds the Chancellor’s Chair in Medicine as Professor in the Departments of Biochemistry and Chemistry, and serves as Director of the Center for Structural Biology and the Molecular Biophysics Training Program. He has mentored ~100 graduate students and postdocs and ~30 undergraduate students in his 29 years as an independent investigator. He has published over 200 peer reviewed papers and 50 book chapters and reviews, and serves on a number of advisory committees and editorial boards. His honors include American Cancer Society Junior Faculty and Faculty Research Awards, serving as a National Academy of Science International Travel Fellow and NAS Teaching Fellow, Regents Visiting Professor at the University of Naples in Italy, and appointments as a Fellow of the American Association for the Advancement of Science and Fellow of the Biophysical Society.
This means that although we focus on the medicine and biology, our problems sometimes require developing unique solutions. NMR remains the core approach, used mostly as a tool for characterization of structural interfaces and dynamics. X-ray crystallography is the method of choice for structure determination. Scattering provides the unique ability to study complex proteins and protein complexes, and we are rapidly adapting to the ‘electron microscopy revolution’ for these systems. With powerful structural information in hand, we are equipped to tackle in vitro and cell-based biochemistry and provide critical insights into the fundamental biology and medicine that drives our research.
|XPA is a scaffolding and DNA-binding protein that plays an essential role in nucleotide excision repair. I express and purify this protein and other genome replication and repair proteins for our lab.
|I work as a research assistant in the collaboration with Bayer pharmaceutical company to produce protein used for drug design. I also work on the production of proteins such as various constructs of Replication Protein A, as well as sRAGE for our lab and other collaborators.
Rachel Service, Ph.D.
|I have a varied research background that encompasses a wide array of proteins including, but not limited to, photosynthetic membrane, amyloid, designer proteins, and DNA replication. Currently I aim to identify structure/dynamic properties of the DNA polymerase α-primase complex responsible for the initiation of replication through creation of an RNA primer and the burgeoning DNA strand using a host of biophysical assays. I also pull double-duty in managing the Chazin lab.
Swati Balakrishnan, Ph.D.
|The regulation of stalled replication forks during the process of DNA replication is an essential component of genome maintenance. Replication forks may be stalled, often transiently, due to a variety of stressors. Replication re-start is regulated by a host of proteins including Rad51, RPA, SMARCAL1 and BRCA2. RadX is a recently discovered ssDNA binding protein that acts as a Rad51 antagonist at replication forks. My current work looks at the changes in the Rad51-DNA filament by electron microscopy in the presence of RadX, and the interaction of RadX with RPA subunits by NMR spectroscopy, as a precursor to the elucidation of a high-resolution structure of RadX in complex with binding partners.
Alexandra Blee, Ph.D.
|More than 1,000 somatic mutations have been reported in nucleotide excision repair (NER) genes by The Cancer Genome Atlas, but the functional consequences of the vast majority are unknown. NER activity is also inversely correlated with tumor sensitivity to cisplatin chemotherapy. I use a combination of computational, cell-based, and structural techniques to identify and characterize mutations in NER that lead to repair defects and sensitize cells to cisplatin.
Anais Naretto, Ph.D.
|My main project involves a collaboration with the Bayer pharmaceutical company to develop new drugs. I also assist with crystallography on the polymerase α-primase project.
Randika (Randy) Perera, Ph.D.
|Calprotectin consists of two S100 calcium-binding proteins (S100A8 and S100A9) and shows affinities for divalent cations. Calprotectin has two metal-binding sites, S1 and S2. The S2 binds only Zn and Cu as opposed to S1, which has an affinity for Mn, Zn, Cu, and Ni. Extracellular calprotectin manifests potent growth inhibitory activity against microorganisms by sequestering zinc. I am focused on engineering calprotectin variants with a high affinity to Zn by employing biophysical and structural biology techniques.
Areetha D’Souza, Ph.D.
|Nucleotide excision repair (NER) is an essential DNA repair pathway responsible for the removal of bulky DNA lesions and it functions through the concerted assembly and action of more than 20 proteins at the site of damage. My project focuses on understanding the scaffolding role of two proteins in the NER pathway -XPA and RPA using integrative structural biology techniques.Email: Areetha.firstname.lastname@example.org|
|Calprotectin (CP) is an S100 protein that plays a role in the inflammatory response by acting as a ligand for the receptor for advanced glycation end-products (RAGE) and Toll-like receptor 4 (TLR-4). Activation of these receptors leads to upregulation of inflammatory cytokines, chemokines, and CP through the NF-κB pathway. As CP is secreted from the cell it serves as a ligand for these receptors creating a positive feedback loop. In the case of people with irritable bowel disease (IBD) these pathways are stimulated which leads to damage of the gastrointestinal tract and disease symptoms. The goal of my work is to block the interaction of CP with these inflammatory receptors by developing high affinity inhibitors of CP.
John (Johnny) Cordoba
|The coordinated interaction of many proteins is required to faithfully replicate DNA. The synthesis of new DNA is initiated on unwound DNA by the polymerase α-primase complex, an enzyme complex unique in its ability to synthesize nucleotides de novo on a bare template. However, it is unclear how exactly pol α-primase gains access to single-stranded DNA that is tightly bound by RPA. I aim to elucidate the interaction of RPA and primase using biochemical and biophysical techniques in order to more fully understand how hand-off of the single-stranded template from RPA to primase occurs in the context of the greater replisome.
|XPA is a NER protein that serves as an essential scaffold for the NER complex. Mutation of the interface between XPA and one of its binding partners RPA severely impairs NER, making this interaction a prime target for inhibitor development. My work focuses on developing an XPA inhibitor using the approach termed fragment-based drug discovery. I am an undergraduate student majoring in Biochemistry and Medicine, Health, and Society. In my free time, I like hiking, reading, and baking.|