The Chazin Lab

People

Walter Chazin, Ph.D.
WJC2Dr. 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.

Research Philosophy

My background in NMR and chemistry frames the way I think, but the deciding factor for choosing problems is not the approach, but rather the biology and biochemistry. This requires a “whatever it takes” attitude in terms of approaches and generates the many collaborations (technical, biological, medical) that is a hallmark of our research. While trained in protein NMR, I have evolved into having a broad-based vision of structural biology/molecular biophysics that involves the complementary application of structural approaches, including spectroscopy, scattering, crystallography and microscopy. 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.

Research Assistants

Kateryna Ogorodnik
KO
As the lab manager, I develop laboratory guidelines, manage the day-to-day operations of the lab, and generate protein for various projects.
 
 
 
 
 
Noel Maxwell
NM2RAGE and calprotectin are proteins that have been identified as key components of cellular signaling and bacterial pathogenesis, respectively. I generate these proteins and others for structural and functional analysis by our lab and the labs of our collaborators.
 
 
 
Keven Pereira
KPIntracellular trafficking of the HIV-1 virus, a potential target for therapeutic treatment, is still poorly understood. In collaboration with the lab of Xinhong Dong at Meharry Medical College, we are investigating the role of filamin, an actin cross-linking protein, in the transport and organization of the HIV capsid. To do so, I am using a variety of structural and biochemical techniques to probe the specific interactions of this protein.

Postdoctoral Fellows

Remy Le Meur, Ph.D.
RLM2DNA replication and repair are fundamental biological mechanisms requiring the concerted action of a variety of proteins regulated in time and space. Replication Protein A (RPA) is the major single-stranded DNA binding protein, which both protects the sensitive single-stranded DNA and  recruits replication and repair factors to the DNA. My current research in the Chazin lab focuses on understanding how RPA can regulate replication-associated Base Excision Repair (BER), especially through its interaction with NEIL1. I am also interested in studying the structure and function of RADX, a newly discovered RPA-related protein that is involved in genome stability.

Agnieszka Topolska-Wos, Ph.D.
ATWNucleotide-excision repair (NER), a biological mechanism for repairing DNA damage, is a potential target for developing more effective anticancer combination therapies. This incredibly complex process involves co-operation of more than 30 different proteins bound to a DNA damage site and maintains the integrity of our genome. Unfortunately, NER and its components are still not fully understood. My project is focused on unravelling the role of the XPA and RPA proteins in NER. To define the structural and molecular details of the XPA-RPA interaction, I am using an array of structural biology techniques in combination with molecular biology tools, such as confocal microscopy on patient-derived cell lines. This analysis will eventually be extended to other proteins in the NER machinery.

Natalia (Natasha) Kozlyuk, Ph.D.
NK2
The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor associated with the inflammatory response via signaling through the NF-κB pathway. Surplus of RAGE activation has been shown to induce symptoms associated with chronic inflammation in diseases such as diabetes, arthritis and Alzheimer’s
disease. My research project consists of using SAR by NMR and a fragment-based drug design approach to generate small molecule inhibitors that block RAGE-ligand interactions. This will allow us to further dissect the mechanism of RAGE activation-induced inflammation.

Graduate Students

Marilyn E. Holt
MEH2Molecular machines drive DNA replication, a tightly-coordinated process performed with 
extraordinary accuracy. Currently, I am using an array of spectroscopic and biophysical techniques to probe the structure and function of human DNA primase, the enzyme that initiates synthesis on single-stranded DNA. This research will allow us to better understand how replicative polymerases communicate and provide insight into the functional dynamics of this multidomain protein.

Lauren Salay
LS2The polymerase α-primase complex initiates synthesis of a new DNA strand during replication. The primase enzyme begins synthesis by polymerizing 7-12 ribonucleotides before pausing. This product is then transferred to the active site of polymerase α. I am using a variety of biophysical, structural, biochemical, and electrochemical techniques to probe the basis for this intramolecular transfer. This will provide a basis for understanding polymerase handoff during replication.

Undergraduate Students

Yongseok (Sam) Cho
Sam2Small angle X-ray scattering (SAXS) is a powerful method to define the structural dynamics of large proteins, such as protein complexes in solution and antibodies.  The use of SAXS to characterize antibody structures has yet to be established, and my goal is to demonstrate the applicability of this approach. To this end, I am working in collaboration with members of the Crowe lab to develop protocols for using SAXS to characterize the solution structural dynamics of humanized monoclonal antibodies related to the respiratory syncytial virus (RSV).

Research Track and Visiting Faculty

Christopher Johnson, Ph.D.
CNJResearch Instructor
Find him here on the VUMC website!

 

 


Huiqing Chen, Ph.D.

HC2Visiting Professor
Find her website here!

 

 

 


Alumni

Mikael Akke
Ileana Alers
Arun Kumar Alphonse Ignatius
Anindita Basu
Shibani Bhattacharya
Giuseppe Bifulco
Marivic Botuyan
Christopher G. Bunick
Chris Brosey
Goran Carlstrom
Benjamin Chagot
Marie-Eve Chagot
Daniel Chazin
Shiow-Meei Chen
Seth Chitayat
John Christodoulou
Orlando Crescenzi
Steve Damo
Brian Dattilo
Yoana Dimitrova
Torbjorn Drakenberg
Joshua Eggold
Aaron Ehlinger
Peggy Eis
Mark Ehrhardt
Patricia Fagan-Jones
Michael Feldkamp
Yue (Ryan) Gao
Nicholas P. George
Benjamin Gilston
Brad Girod
Judd Glasser
Luigi Gomez-Paloma
Denille Gonzales
Haitao Hu
Michael Hunter
Sophie Jouan
Sarvesh Kaushik
Randal R Ketchem
Johan Kordell
Young-Tae Lee
Michael Lubienski
Jens Chr. Madsen
Lena Mäler
Anders Malmendal
Sheryll Mangahas
Georges Mer
Siobhan Miick
Melanie Nelson
Kyle Nordquist
Mohiuddin Ovee
Kelly Perry
Jeroen Pikkemaat
Barbara Potts
Dalyir Pretto
Reid Putney
Antonio Randazzo
Michelle Roh
Jan Rydzewski
Mallika Sastry
Libbey Schwertman
Vikas Shah
Mike Shell
Nick Skelton
Jarrod Smith
Jonathan Sheehan
Sarah Soss
Michael Starling
Melissa Stauffer
Norie Sugitani
Jennifer Sun
Matthew Thompson
Sivaraha Vaithiyalingam
Craig Vander Kooi
Drew Vartia
Sudha Veeraraghavan
Christoph Weber
Brian Weiner
Kevin Weiss
Brian Wile
Christina Williams
Brian Wimberly
Rachel Wright