Areas of Research Interest

Our research is part of the Department of Chemistry and Biochemistry at the University of Maryland, Baltimore County. We are also part of the Metallotherapeutics Research Center based out of the University of Maryland School of Pharmacy. 

There are three current research areas in the lab: 

1) The mechanism and regulation of post-translational arginylation

2) Pathogenic ferrous iron uptake and delivery

3) Bacterial ferrous iron sensing and generation

Iron is an essential element for virtually every living organism and has been adopted to serve in major biological processes such as nitrogen fixation, methane oxidation, hydrogen production, aerobic cellular respiration, oxygen transport, DNA biosynthesis, and even gene regulation. However, iron-based life represents a double-edged sword, as Fe(II) is bioavailable but highly reactive, whereas Fe(III) is intractable but fairly chemically inert. Every organism that utilizes iron employs biological pathways to obtain this element from the environment, to regulate its bioavailable concentration, and to sequester its excess. In order to establish infection in humans, pathogenic bacteria have evolved several responses to manage iron acquisition and utilization. The ability to acquire and utilize iron aids in the proliferation of numerous infectious bacteria. One important route for the uptake of Fe(II) for bacteria is via the ferrous iron uptake (Feo) system However, the mechanism of iron uptake through this pathway is poorly understood by comparison to Fe(III) and heme uptake pathways. In an era of increasing antibacterial resistance, understanding and targeting the routes of bacterial nutrient uptake are crucial to stem bacterial virulence. We are using a multifaceted approach to understand the structure and function of proteins involved in bacterial Fe(II) uptake.

This research project aims to understand how pathogenic bacteria acquire ferrous iron, with the goal of targeting this system for novel antibiotic developments.

There is an emerging connection between Feo and additional membrane-bound proteins that function more broadly in bacterial Fe(II) homeostasis through: 1) sensing Fe(II) as part of a mechanism to control biofilm formation in antibiotic-resistant pathogens and 2) using Fe(III)-siderophores to supply Fe(II) to the Feo system for hyper iron accumulation in select bacteria. For example, studies have identified a two-component signal transduction system, BqsR-BqsS, that regulates biofilm formation and quorum sensing in Pseudomonas aeruginosa through the sensing of periplasmic Fe(II), and these proteins appear to be conserved in many bacteria. Moreover, there is an increasing consensus that a family of small membrane proteins known as membrane ferric reductases (mFRs) contribute to the Fe(II) pool in bacteria through the reductive dissociation of iron from Fe(III)-siderophores, which could explain why the Feo system is expressed even under O2-replete conditions. We hypothesize that mFRs are heme b-containing proteins of the enigmatic cytb561 family that couple Fe(III) reduction to Feo-mediated Fe(II) transport in bacteria. Using structural, biochemical, and biophysical methods coupled with in vivo approaches, we are working to uncover the complex interplay of these membrane proteins in maintaining Fe(II) homeostasis in both pathogenic prokaryotes as well as magnetotactic bacteria that are capable of synthesizing complex iron nanoparticles.

This research project aims to understand how pathogenic bacteria acquire sense and generate ferrous iron, with the goal of targeting this system for attenuating bacterial virulence and for new material developments aided by hyper iron accumulating bacteria.