DYNAMITE

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Project leads

  • Dr. Cesar Arias (Houston Methodist)
  • Dr. Tor Savidge (Texas Childrens)
  • Dr. Sam Shelburne (MD Anderson)

Summary

Antimicrobial resistance (AMR) in community and hospital-associated pathogens has been named one of the most pressing public health priorities by the United Nations. Among the most relevant multidrug-resistant (MDR) bacteria, vancomycin-resistant enterococci (VRE), extended spectrum ?-lactamase producing/carbapenem-resistant Enterobacteriaceae (ESBL-E/CRE) and Clostridiodes difficile are considered high priority inasmuch as these organisms commonly infect severely ill and immunocompromised patients, and there is a paucity of therapeutic options to treat infections caused by these bacteria. For each of these key pathogens, the intestines are the site of initial colonization and, under the influence of broad- spectrum antimicrobial therapies, these organisms can ?dominate? the gastrointestinal tract increasing the risk of clinical disease. Importantly, it is becoming progressively clear that colonization of the intestines by either VRE, ESBL-E/CRE, or C. difficile is markedly associated with subsequent colonization by other members of this group, but whether pathogen-to-pathogen signaling plays a role is not known. Further, data generated from microbiome-based studies to date has not allowed for clinically impactful interventions due to the imprecise identification of high-risk patients and it is currently unclear why only a subset of patients, under apparently similar conditions, develop colonization/disease. Our overarching hypothesis is that patient susceptibility to gut-derived nosocomial colonization and subsequent infection is critically dependent on functional microbiota- pathogen interactions that can be detected via a holistic combination of pathogen, host, and commensal microbiota analyses. The DYNAMITE program (Dynamics of Colonization and Infection by Multidrug-Resistant Pathogens in Immunocompromised and Critically Ill Patients) seeks to fill these important gaps in knowledge. Indeed, we have identified keystone microbiota features that are broadly protective against gut-derived pathogens via previously unappreciated antimicrobial mechanisms suggesting that lack of such organisms may be a critical factor in determining pathogen colonization and infection.

The aims of the program are:

  1. Dissect the main microbial, clinical and antimicrobial resistance determinants that impact colonization and infection by VRE, ESBL-E/CRE and C. difficile
  2. Evaluate the role of the commensal microbiota in VRE, ESBL-E/CRE and C. difficile colonization
  3. Define the functional aspects of keystone microbiota and mechanisms of protection against colonization/infection.
Advait Balaji
Advait Balaji
PhD student

Advait (4th year PhD student) obtained a dual degree, B.E Computer Science and MS Biological Sciences from BITS, Pilani in India. During his undergraduate degree, he received the Khorana Scholarship (2016) from the Indo-US Science and Technology Forum and also a thesis fellowship (2017-18) to work at Icahn School of Medicine, Mount Sinai, NY. At Mount Sinai, he worked on creating a Sub-cellular process-based ontology that predicts whole cell function using Natural Language Processing. His research interests are at the intersection of genomic data science and designing efficient algorithms to analyze genomic data.

Bryce Kille
Bryce Kille
PhD student

Bryce (1st year PhD student) received his MS in Bioinformatics and BS in Computer Science + Chemistry from the University of Illinois at Urbana-Champaign. As an undergraduate, he worked at Dow Agrosciences in both the computational biology and cheminformatics groups. His projects included developing software for phylogeny analysis and creating models for compound activity prediction. During his Master’s program, Bryce worked in a biochemistry lab developing software for genome mining as well as a on research project for creating bit-wise algorithms for the C++ STL. One of his main interests is casting biological and chemical problems into theoretical computer science questions.

Dr. Mike Nute
Dr. Mike Nute
Postdoctoral Scientist

Mike (Postdoctoral Scientist) received his Ph.D. in Statistics in 2019 from the University of Illinois at Urbana-Champaign where he was advised by Dr. Tandy Warnow in the Department of Computer Science and worked on algorithms related to multiple sequence alignment and phylogenetic tree estimation, in particular applying these methods to studying microbial communities. He was co-advised by Dr. Rebecca Stumpf in the Department of Anthropology where he and other lab members developed novel methods to compare the microbiomes of human and non-human primates. His research interest is in discovering a new applications for our understanding of microbial communities.

Todd J. Treangen
Todd J. Treangen
Assistant Professor of Computer Science

My research interests include algorithms and data structures for efficient analysis of microbial genomes and metagenomes

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