Translational Systems Immunology of Host-Microbiome Interactions

Case Western Reserve University School of Medicine

The Brubaker Lab takes a cross-cutting transdisciplinary approach to multiple disease applications of our core research areas. We believe that insights gleaned from addressing clinical need and elucidating disease mechanisms in one area will catalyze breakthroughs in others. Our lab has projects in the following disease areas which are constantly evolving through collaboration and emphasis varies over time.

Contact us for our current efforts.

People

Douglas Brubaker, Ph.D.

Assistant Professor, Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University School of Medicine

Dr. Brubaker obtained his Ph.D. in Systems Biology and Bioinformatics under the supervision of Dr. Mark R. Chance in the Center for Proteomics and Bioinformatics at Case Western Reserve University. As part of the March of Dimes Prematurity Research Center - Ohio Collaborative, his dissertation focussed on network and dynamical systems modeling of signaling networks in preterm birth.

Dr. Brubaker pursued postdoctoral studies with Dr. Douglas Lauffenburger in the Department of Biological Engineering at MIT where he developed computational methods to translate observations from animal models to humans. Dr. Brubaker started as an Assistant Professor in the Weldon School of Biomedical Engineering at Purdue University in Fall 2020.

The Brubaker Lab aims to understand the core mechanisms by which (i) host physiology is regulated by microbiomes and (ii) microbiome ecology and function are regulated by the host. We are a highly collaborative group with current efforts focused on Inflammatory Bowel Diseases, Musculoskeletal Pathologies, Type 2 Diabetes, and Bacterial Vaginosis.

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Publications

• Cross-Species Modeling Identifies Gene Signatures in Type 2 Diabetes Mouse Models Predictive of Inflammatory and Estrogen Signaling Pathways Associated with Alzheimer's Disease Outcomes in Humans, Ball, Brendan K.; Proctor, Elizabeth A.; Brubaker, Douglas K., Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 2025

• SYSTEMS MODELING OF GUT MICROBIOME REGULATION OF ESTROGEN RECEPTOR BETA SIGNALING IN ULCERATIVE COLITIS, Munoz-Briones, Javier; Trinh, Alan; Simpson, Abigail; Stingel, Rachel; Jena, Smrutiti; Doszpoly, Agnes; Urlu, Merve; Trapecar, Martin; Cross, Tzu-Wen; Brubaker, Douglas K, SYSTEMS MODELING OF HOST MICROBIOME INTERACTIONS IN INFLAMMATORY BOWEL DISEASES, 2024

• LATENT INTERACTING VARIABLE-EFFECTS (LIVE) MODELING OF GUT MICROBIOME MULTI-OMICS IN INFLAMMATORY BOWEL DISEASE, Munoz-Briones, Javier; Brubaker, Douglas K, SYSTEMS MODELING OF HOST MICROBIOME INTERACTIONS IN INFLAMMATORY BOWEL DISEASES, 2024

• Detailed survey of an in vitro intestinal epithelium model by single-cell transcriptomics, Ran, Ran; Muñoz Briones, Javier; Jena, Smrutiti; Anderson, Nicole L.; Olson, Matthew R.; Green, Leopold N.; Brubaker, Douglas K., iScience, 2024

• Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer's disease-associated metabolites, Ball, Brendan K.; Kuhn, Madison K.; Fleeman Bechtel, Rebecca M.; Proctor, Elizabeth A.; Brubaker, Douglas K., Scientific Reports, 2024

• Diagnostic and Therapeutic Microbial Circuit with Application to Intestinal Inflammation, Merk, Liana N.; Shur, Andrey S.; Jena, Smrutiti; Munoz, Javier; Brubaker, Douglas K.; Murray, Richard M.; Green, Leopold N., ACS synthetic biology, 2024

• Computational Microbiome Pharmacology Analysis Elucidates the Anti-Cancer Potential of Vaginal Microbes and Metabolites, Lawore, Damilola C.; Jena, Smrutiti; Berard, Alicia R.; Birse, Kenzie; Lamont, Alana; Mackelprang, Romel D.; Noel-Romas, Laura; Perner, Michelle; Hou, Xuanlin; Irungu, Elizabeth; Mugo, Nelly; Knodel, Samantha; Muwonge, Timothy R.; Katabira, Elly; Hughes, Sean M.; Levy, Claire; Calienes, Fernanda L.; Hladik, Florian; Lingappa, Jairam R.; Burgener, Adam D.; Green, Leopold N.; Brubaker, Douglas K., bioRxiv: The Preprint Server for Biology, 2024

• Cross-disease modeling of peripheral blood identifies biomarkers of type 2 diabetes predictive of Alzheimer's disease, Ball, Brendan K.; Hyun Park, Jee; Proctor, Elizabeth A.; Brubaker, Douglas K., bioRxiv: The Preprint Server for Biology, 2024

• Systematic analysis of human colorectal cancer scRNA-seq revealed limited pro-tumoral IL-17 production potential in gamma delta T cells, Ran, Ran; Trapecar, Martin; Brubaker, Douglas K., Neoplasia (New York, N.Y.), 2024

• Association Between Intestinal Changes and Systemic Cytokines in Mouse Dysbiosis Models, Jeffries, Alison; Villarreal, Cameron; Brubaker, Douglas; Chan, Deva, Proceedings of IMPRS, 2023

• Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling, Berard, Alicia R.; Brubaker, Douglas K.; Birse, Kenzie; Lamont, Alana; Mackelprang, Romel D.; Noël-Romas, Laura; Perner, Michelle; Hou, Xuanlin; Irungu, Elizabeth; Mugo, Nelly; Knodel, Samantha; Muwonge, Timothy R.; Katabira, Elly; Hughes, Sean M.; Levy, Claire; Calienes, Fernanda L.; Lauffenburger, Douglas A.; Baeten, Jared M.; Celum, Connie; Hladik, Florian; Lingappa, Jairam; Burgener, Adam D., Cell Reports, 2023

• TRANS-OMIC KNOWLEDGE TRANSFER MODELING INFERS GUT MICROBIOME BIOMARKERS OF ANTI-TNF RESISTANCE IN ULCERATIVE COLITIS, Trinh, Alan; Ran, Ran; Brubaker, Douglas K., Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 2023

• Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer's disease-associated metabolites, Ball, Brendan K.; Kuhn, Madison K.; Fleeman, Rebecca M.; Proctor, Elizabeth A.; Brubaker, Douglas K., bioRxiv: The Preprint Server for Biology, 2023

• Enhanced annotation of CD45RA to distinguish T cell subsets in single-cell RNA-seq via machine learning, Ran, Ran; Brubaker, Douglas K., Bioinformatics Advances, 2023

• Latent Interacting Variable-Effects Modeling of Gut Microbiome Multi-Omics in Inflammatory Bowel Disease, Munoz, Javier. E.; Brubaker, Douglas. K., , 2022

• Method Development Involving Modeling Bacterial Metabolite Regulation of Vaginal Epithelial Cell Signaling in Bacterial Vaginosis, Trinh, Alan; Brubaker, Douglas, , 2022

• Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes, Pendyala, Meghana; Woods, Paige S.; Brubaker, Douglas K.; Blaber, Elizabeth A.; Schmidt, Tannin A.; Chan, Deva D., PloS One, 2022

• Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation, Suarez-Lopez, Lucia; Shui, Bing; Brubaker, Douglas K.; Hill, Marza; Bergendorf, Alexander; Changelian, Paul S.; Laguna, Aisha; Starchenko, Alina; Lauffenburger, Douglas A.; Haigis, Kevin M., iScience, 2021

• Computational Interspecies Translation Between Alzheimer's Disease Mouse Models and Human Subjects Identifies Innate Immune Complement, TYROBP, and TAM Receptor Agonist Signatures, Distinct From Influences of Aging, Lee, Meelim J.; Wang, Chuangqi; Carroll, Molly J.; Brubaker, Douglas K.; Hyman, Bradley T.; Lauffenburger, Douglas A., Frontiers in Neuroscience, 2021

• Cell surface integrin α5ß1 clustering negatively regulates receptor tyrosine kinase signaling in colorectal cancer cells via glycogen synthase kinase 3, Starchenko, Alina; Graves-Deal, Ramona; Brubaker, Douglas; Li, Cunxi; Yang, Yuping; Singh, Bhuminder; Coffey, Robert J.; Lauffenburger, Douglas A., Integrative Biology: Quantitative Biosciences from Nano to Macro, 2021

• Translating preclinical models to humans, Brubaker, Douglas K.; Lauffenburger, Douglas A., Science (New York, N.Y.), 2020

• Clostridioides difficile-Associated Antibiotics Alter Human Mucosal Barrier Functions by Microbiome-Independent Mechanisms, Kester, Jemila C.; Brubaker, Douglas K.; Velazquez, Jason; Wright, Charles; Lauffenburger, Douglas A.; Griffith, Linda G., Antimicrobial Agents and Chemotherapy, 2020

• An interspecies translation model implicates integrin signaling in infliximab-resistant inflammatory bowel disease, Brubaker, Douglas K.; Kumar, Manu P.; Chiswick, Evan L.; Gregg, Cecil; Starchenko, Alina; Vega, Paige N.; Southard-Smith, Austin N.; Simmons, Alan J.; Scoville, Elizabeth A.; Coburn, Lori A.; Wilson, Keith T.; Lau, Ken S.; Lauffenburger, Douglas A., Science Signaling, 2020

• Coagulopathy signature precedes and predicts severity of end-organ heat stroke pathology in a mouse model, Proctor, Elizabeth A.; Dineen, Shauna M.; Van Nostrand, Stephen C.; Kuhn, Madison K.; Barrett, Christopher D.; Brubaker, Douglas K.; Yaffe, Michael B.; Lauffenburger, Douglas A.; Leon, Lisa R., Journal of thrombosis and haemostasis: JTH, 2020

• Tissue-Specific Oncogenic Activity of KRASA146T, Poulin, Emily J.; Bera, Asim K.; Lu, Jia; Lin, Yi-Jang; Strasser, Samantha Dale; Paulo, Joao A.; Huang, Tannie Q.; Morales, Carolina; Yan, Wei; Cook, Joshua; Nowak, Jonathan A.; Brubaker, Douglas K.; Joughin, Brian A.; Johnson, Christian W.; DeStefanis, Rebecca A.; Ghazi, Phaedra C.; Gondi, Sudershan; Wales, Thomas E.; Iacob, Roxana E.; Bogdanova, Lana; Gierut, Jessica J.; Li, Yina; Engen, John R.; Perez-Mancera, Pedro A.; Braun, Benjamin S.; Gygi, Steven P.; Lauffenburger, Douglas A.; Westover, Kenneth D.; Haigis, Kevin M., Cancer Discovery, 2019

• Proteogenomic Network Analysis of Context-Specific KRAS Signaling in Mouse-to-Human Cross-Species Translation, Brubaker, Douglas K.; Paulo, Joao A.; Sheth, Shikha; Poulin, Emily J.; Popow, Olesja; Joughin, Brian A.; Strasser, Samantha Dale; Starchenko, Alina; Gygi, Steven P.; Lauffenburger, Douglas A.; Haigis, Kevin M., Cell Systems, 2019

• Substrate-based kinase activity inference identifies MK2 as driver of colitis, Strasser, Samantha Dale; Ghazi, Phaedra C.; Starchenko, Alina; Boukhali, Myriam; Edwards, Amanda; Suarez-Lopez, Lucia; Lyons, Jesse; Changelian, Paul S.; Monahan, Joseph B.; Jacobsen, Jon; Brubaker, Douglas K.; Joughin, Brian A.; Yaffe, Michael B.; Haas, Wilhelm; Lauffenburger, Douglas A.; Haigis, Kevin M., Integrative Biology: Quantitative Biosciences from Nano to Macro, 2019

• Computational translation of genomic responses from experimental model systems to humans, Brubaker, Douglas K.; Proctor, Elizabeth A.; Haigis, Kevin M.; Lauffenburger, Douglas A., PLoS computational biology, 2019

• Integrated microRNA and mRNA network analysis of the human myometrial transcriptome in the transition from quiescence to labor, Ackerman, William E.; Buhimschi, Irina A.; Brubaker, Douglas; Maxwell, Sean; Rood, Kara M.; Chance, Mark R.; Jing, Hongwu; Mesiano, Sam; Buhimschi, Catalin S., Biology of Reproduction, 2018

• Integrated in vivo multiomics analysis identifies p21-activated kinase signaling as a driver of colitis, Lyons, Jesse; Brubaker, Douglas K.; Ghazi, Phaedra C.; Baldwin, Katherine R.; Edwards, Amanda; Boukhali, Myriam; Strasser, Samantha Dale; Suarez-Lopez, Lucia; Lin, Yi-Jang; Yajnik, Vijay; Kissil, Joseph L.; Haas, Wilhelm; Lauffenburger, Douglas A.; Haigis, Kevin M., Science Signaling, 2018

• FREQUENT SUBGRAPH MINING OF PERSONALIZED SIGNALING PATHWAY NETWORKS GROUPS PATIENTS WITH FREQUENTLY DYSREGULATED DISEASE PATHWAYS AND PREDICTS PROGNOSIS, Durmaz, Arda; Henderson, Tim A. D.; Brubaker, Douglas; Bebek, Gurkan, Pacific Symposium on Biocomputing, 2017

• Computational Investigation of Biological Networks and Progesterone Signaling Dynamics in Preterm Birth, Brubaker, Douglas K.; Barnholtz-Sloan, Jill; Mesiano, Sam; Barbaro, Alethea, , 2016

• A dynamical systems model of progesterone receptor interactions with inflammation in human parturition, Brubaker, Douglas; Barbaro, Alethea; R Chance, Mark; Mesiano, Sam, BMC systems biology, 2016

• Finding lost genes in GWAS via integrative-omics analysis reveals novel sub-networks associated with preterm birth, Brubaker, Douglas; Liu, Yu; Wang, Junye; Tan, Huiqing; Zhang, Ge; Jacobsson, Bo; Muglia, Louis; Mesiano, Sam; Chance, Mark R., Human Molecular Genetics, 2016

• Drug Intervention Response Predictions with PARADIGM (DIRPP) identifies drug resistant cancer cell lines and pathway mechanisms of resistance, Brubaker, Douglas; Difeo, Analisa; Chen, Yanwen; Pearl, Taylor; Zhai, Kaide; Bebek, Gurkan; Chance, Mark; Barnholtz-Sloan, Jill, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 2014

Contact

Biomedical Research Building 420
2109 Adelbert Road
Cleveland, OH 44106

[email protected]