Michael Mahan

Biography

Dr. Mahan received his B.S./M.S. degrees in biochemistry/genetics from the University of California, Davis, and his Ph.D. in genetics from the University of Utah. He conducted postdoctoral research in bacterial pathogenesis at Harvard Medical School before joining the faculty at UCSB. Mahan was honored by AAAS with the Newcomb-Cleveland Prize for the top paper published in Science for pioneering the development of In Vivo Expression Technology (IVET), enabling the assessment of bacterial gene expression during infection. Mahan was a recipient of the Beckman Young Investigator Award; American Cancer Society Junior Faculty Research Award; UCSB Faculty Distinguished Teaching Award; and a JAMA commendation for a smartphone-based COVID diagnostic that was in the top 5% of research outputs ever tracked. Mahan was co-founder and Director of Remedyne Corporation, a biotech company in Santa Barbara, CA (vaccines, antimicrobials). His students have received international recognition and awards, including the AAAS Young Investigator Prize for the top Ph.D. dissertation in Molecular Biology in North America.

Research

Dr. Mahan’s research is focused on the molecular mechanisms underlying bacterial pathogenesis and developing practical solutions to combat infectious agents. He co-developed In Vivo Expression Technology (IVET), a genetic tool for discovering bacterial genes expressed during infection. His laboratory discovered an essential role for DNA adenine methylation (Dam) in bacterial virulence. Dam-deficient mutants aberrantly express multiple bacterial antigens, enabling the development of novel live vaccines. They also co-discovered a general mechanism of secreted glycoprotein aging and turnover that modulates sepsis pathogenesis and disease outcome. This host-protective mechanism is disrupted by Gram-negative pathogens that accelerate aging and clearance of host anti-inflammatory enzymes that drive LPS detoxification, thereby increasing inflammation and mortality. Additionally, recurrent subtherapeutic Salmonella infections led to the development of colitis, potentially linking food poisoning to intestinal bowel disease via reduced LPS detoxification in the gut. In response to the COVID-19 pandemic, Mahan’s laboratory developed a smartphone-based pathogen detection system that brings state-of-the-art diagnostics within reach of smartphone users. To address the escalating threat of antibiotic resistance, they developed a novel antimicrobial susceptibility test that identified several effective antibiotics rejected by standard testing, and may improve the way antibiotics are developed, tested, and prescribed. Further, they identified a broad-spectrum antibiotic (conjugated oligoelectrolyte) that cured otherwise untreatable infections and is being developed as a new versatile therapy for multi-drug resistant infections.

Related Organizations

• UCSB-MIT-Caltech Institute for Collaborative Biotechnologies (ICB)
• Biomolecular Science and Engineering (BMSE)

Selected Publications

Heithoff, D.M. S.P. Mahan, L. Barnes V, S.A. Leyn, C.X. George, J.E. Zlamal, J. Limwongyut, G.C. Bazan, J.C. Fried, L.N. Fitzgibbons, C.E. Samuel, A.L. Osterman, D.A. Low, and M.J. Mahan. (2023). A broad-spectrum antibiotic that does not evoke bacterial resistance. eBioMedicine, 89, e104461.

Heithoff, D.M., L. Barnes V, S.P. Mahan, J.C. Fried, L.N. Fitzgibbons, J.K. House, and M.J. Mahan (2023). Reevaluation of FDA-approved antibiotics with increased diagnostic accuracy for assessment of antimicrobial resistance. Cell Rep. Med., 4, e101023.

Heithoff, D.M., L. Barnes V, S.P. Mahan, G.N. Fox, K.E. Arn, S.J. Ettinger, A.M. Bishop, L.N. Fitzgibbons, J.C. Fried, D.A. Low, C.E. Samuel, and M.J. Mahan. (2022). Assessment of a smartphone-based loop-mediated isothermal amplification assay for detection of SARS-CoV-2 and influenza viruses. JAMA Netw. Open, 5, e2145669.

Heithoff, D.M., G. Pimienta, S.P. Mahan, W.H. Yang, D.T. Le, J.K. House, J.D. Marth, J.W. Smith, and M.J. Mahan. (2022). Coagulation factor protein abundance in the pre-septic state predicts coagulopathic activities that arise during late-stage murine sepsis. eBioMedicine, 78, e103965.

Yang, W.H, J.S. Westman, D.M. Heithoff, M. Speradino, J.W. Cho, M.J. Mahan, and J.D. Marth (2021). Neu3 neuraminidase induction linked to intestinal inflammation and colitis in a model of recurrent human food poisoning. Proc. Natl. Acad. Sci. USA, 118, e2100937118.

Pimienta G., D.M. Heithoff, A. Rosa-Campos, M. Tran., J.D. Esko, M.J. Mahan, J.D. Marth, and J.W. Smith (2019). Plasma proteome signature of sepsis: a functionally connected protein network. Proteomics, 19:e1800389.

Yang, W.H, D.M. Heithoff, P. Aziz, B. Haslund-Gourley, J.S. Westman, S. Narisawa, A.B. Pinkerton, J.L. Millan, V. Nizet, M.J. Mahan, and J.D. Marth. (2018). Accelerated aging and clearance of host anti-inflammatory enzymes by discrete pathogens fuels sepsis. Cell Host Microbe, 24:500–513.

Barnes, L.V., D.M. Heithoff, S.P. Mahan, G.N. Fox, A. Zambrano, J. Choe, L.N. Fitzgibbons, J.D. Marth, J.C. Fried, H.T. Soh, and M.J. Mahan. (2018). Smartphone-based pathogen diagnosis in urinary sepsis patients. eBioMedicine, 36, 73-82.

Yang, W.H., D.M. Heithoff, P. Aziz, M. Speradino, V. Nizet, M.J. Mahan, and J.D. Marth. (2017). Recurrent infection progressively disables host protection against intestinal inflammation. Science, 358, eaao5610.

Ersoy, S.C., D.M. Heithoff, L. Barnes V, G.K. Tripp, J.K. House, J.D. Marth, J.W. Smith, and M.J. Mahan. (2017). Correcting a fundamental flaw in the paradigm for antimicrobial susceptibility testing.  eBioMedicine, 20:173-181.

Kubicek-Sutherland, J.Z., D.M. Heithoff, S.C. Ersoy, W.R. Shimp, J.K. House, J.D. Marth, J.W. Smith, and M.J. Mahan. (2015). Host-dependent induction of transient antibiotic resistance: a prelude to treatment failure. eBioMedicine, 2:1169–1178.

Yang, W.H., P.V. Aziz, D.M. Heithoff, M.J. Mahan, J.W. Smith and J.D. Marth. (2015). An intrinsic mechanism of secreted protein aging and turnover. Proc. Natl. Acad. Sci. USA, 112, 13657-13662.

Link to publications available via PubMed: 

https://pubmed.ncbi.nlm.nih.gov/?term=Mahan%2C+MJ&sort=pubdate