Current trainees and their projects.
Coronaviruses (CoVs) are widely distributed amongst several species and exhibit great potential for crossing species barriers. There are no clinically available antivirals or vaccines available at present against these infections, demonstrating the need for new antivirals broadly effective against CoVs. GS-5734 is a nucleoside analog prodrug that shows strong antiviral activity against several viruses, including Respiratory Syncytial Virus (RSV), Ebola virus, and CoVs. However, the mechanism of action of this antiviral in CoVs remains unknown. These studies will focus on finding the mechanism of action of GS-5734 and to also look at analogs to GS-5734. These studies will help with future antiviral drug design.
Sarah Arcos is a graduate student in the department of Biochemistry and is mentored by Dr. Manuel Ascano. Her project involves the study of post-transcriptional gene regulation in innate immunity. Sarah is currently working on characterizing the role of RNA-binding proteins during innate immune activation, particularly proteins that specifically recognize and bind to N6-methyladenosine (m6A) modified RNA. The methylation of RNAs at the N6 position of adenosines is a highly conserved chemical modification found in viral genomes to higher eukaryotes, and is thought to play a regulatory role by affecting RNA stability or translation. She will be using a photochemical biology approach developed in the lab to characterize the effector proteins that directly associate with m6A-RNAs. In addition, Sarah is developing a functional screen to identify RNA-binding proteins that are necessary for robust innate immune activation in response to nucleic acid-induced stress. The screen will be performed using novel small molecule antagonists that directly inhibit the pattern recognition receptor cGAS, the primary intracellular sensor of cytoplasmic dsDNA.
Monique Bennett is a graduate student in the department of Pathology, Microbiology and Immunology at Vanderbilt and is co-mentored by Dr. James E. Crowe, Jr and Dr. Eric Skaar. Her project involves the isolation and characterization of S. aureus human monoclonal antibodies. These antibodies are specific to a unique set of metal receptors and will be used to highlight the importance of metal acquisition in S. aureus growth, metabolism, signaling and virulence.
Samuel D Dooyema,
Sam is a student in the Microbe-Host Interactions graduate program in the department of Pathology, Microbiology, and Immunology. He is mentored by Dr. Richard Peek and is studying the pathogen Helicobacter pylori. Specifically, how H. pylori can use a previously ascribed virulence constituent, the cag TFSS, to suppress inflammation, and potentially induce TLR9-mediated epithelial responses with carcinogenic potential, providing fresh insights into how H. pylori can both persist and induce disease in human hosts. Of interest, in intestinal epithelial cells, TLR9 mediates distinct responses that are either pro- or anti-inflammatory, depending on which cell surface domains are activated. Therefore, we will investigate the response to H. pylori or known TLR9 chemical ligands based upon route of activation. Also, in a collaboration with Dr. Manuel Ascano at Vanderbilt in Biochemistry, we hope to further define at a molecular level the innate DNA sensing components required for TLR9 activation such as STING and c-GAS.
Michael P Doyle
Michael is a graduate student in the department of Pathology, Microbiology, and Immunology, and is mentored by Dr. James E. Crowe, Jr. The focus of his work involves the isolation and characterization of monoclonal antibodies from survivors of flavivirus infection. Defining the novel epitopes recognized by these antibodies will assist in rationally designing vaccines against these viruses.
Eric is a member of the Townsend lab, a synthetic organic chemistry lab interested in the synthesis of carbohydrate natural products and other molecules of biological interest. Eric is currently working toward the synthesis and chemical derivatization of a depsipeptide natural product that has shown activity against Staphylococcus aureus quorum sensing.
Amyn Murji is a graduate student at Vanderbilt University in the department of Pathology, Microbiology and Immunology. He is mentored by Dr. Ivelin Georgiev and is currently working on a project that focuses on the design of effective vaccines and antibody therapeutics against viruses of biomedical importance. One aspect of Amyn’s work relates to the application of chemical biology and structural bioinformatics principles to the design of immunogens capable of eliciting protective antibody responses against target antigens. In addition, Amyn also intends to work on engineering antibodies with improved antigen affinity and neutralization potency. He hopes his efforts will culminate in the development of a clinical product candidate that will contribute to the improvement of human health.
Kelsey Pilewski is a graduate student in the department of Pathology, Microbiology and Immunology and a member of Dr. Ivelin Georgiev's laboratory. Kelsey's project relates to the application of a variety of computational and experimental approaches to gain a better understanding of the antibody response to infection and vaccination against antigens of biomedical significance. In particular, Kelsey aims to use rational design of protein immunogens to study the antibody response against notoriously immune system-evading pathogens, such as Mycobacterium tuberculosis, as results from these studies have the ability to inform new immunization strategies, as well as to provide further insight into the basic immunology of infection.
Staphylococcus aureus is a widespread human pathogen, capable of infecting nearly every organ in the human body. S. aureus is particularly adept at colonizing the bone to cause osteomyelitis. In order for the bacterium to thrive in this infection environment, a diverse array of genetic programs must be in place to accommodate this lifestyle. Using the unbiased, genome wide approach TnSeq, we identified the two-component system SrrAB as a bacterial factor essential for inducing invasive osteomyelitis. SrrAB is known to regulate the aerobic/anaerobic shift, mediate resistance to oxidative stress, and modulate toxin production. My thesis project is to determine the regulatory role of SrrA under aerobic and hypoxic conditions and identify the exact metabolic pathways that SrrA controls during osteomyelitis.
Jade Williams is a graduate student in the Chemistry Department at Vanderbilt University. She is mentored by Dr. Gary Sulikowski and her project focuses on the development of efficient and concise syntheses of naturally occurring microbial metabolites in order to enable their biological study. Jade is currently working toward the synthesis of two siderophores, which are only naturally accessible in small quantities. A convenient synthetic route to these siderophores would provide ample material for use as chemical tools in the study of metal acquisition and homeostasis in select bacteria.