Dr. Mahan received his B.S./M.S. degrees in biochemistry/genetics from the University of California, Davis, his Ph.D. in genetics at the University of Utah, and conducted postdoctoral research in microbial pathogenesis at Harvard Medical School before joining the faculty at UCSB. Honored by AAAS for the top paper published in Science for his co-development of In Vivo Expression Technology (IVET) that measured bacterial gene expression during infection, Mahan was a recipient of the Beckman Young Investigator Award, American Cancer Society Junior Faculty Research Award, and the UCSB Faculty Distinguished Teaching Award. During the pandemic, he received a commendation from the Journal of the American Medical Association for development of a COVID diagnostic that was in the top 5% of all research outputs ever tracked. He was also co-founder and Director of Remedyne Corporation, a biotech company in Santa Barbara, California. 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.
Our research is focused on the molecular mechanisms underlying microbial pathogenesis and the host responses that drive infection, compromise immunity, and trigger microbial sepsis. Our applied goal is to translate this research into front-line therapies (vaccines, antibiotics, diagnostics). From our discoveries of host/pathogen interactions, we developed a cross-protective vaccine that protects livestock against many Salmonella strains simultaneously. In response to the COVID pandemic, we developed a new cell phone app that transformed a smartphone into a rapid, accurate and low-cost diagnostic for COVID and the flu. By mimicking environmental conditions in the body, we developed an antimicrobial susceptibility test (AST) revealing that existing antibiotics can cure multidrug-resistant infections, and, thus the "antibiotic toolbox" may be much more useful than previously thought. Additionally, by screening a new class of chemical compounds that interact with the bacterial membrane, we identified a broad-spectrum antibiotic that kills every pathogen tested and does not evoke bacterial resistance. These compounds are being developed as a new versatile therapy for bacterial pathogens that are resistant to all existing antibiotics.
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. [see Commentary, Nat. Med., 29, 1583 (2023)].
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. [see Commentary, Nat. Med., 29, 1583 (2023)].
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.
Haslund-Gourley, B.S., P.V. Aziz, D.M. Heithoff, D. Restagno, J.C. Fried, M-B. Ilse, H. Bäeumges, M.J. Mahan, and T. Lübke, J.D. Marth. (2022). Establishment of blood glycosidase activities and their excursions in the pathogenesis and prognosis of sepsis. Proc. Natl. Acad. Sci. Nexus, 1, pgac113.
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. [see Commentary, eBioMedicine, 37:11-12].
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. [see Commentary, eBioMedicine, 22:26-27].
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.