Michael E. Selsted, MD, PhD

Dr. Selsted is a board certified pathologist, physician scientist, and administrator. His academic career includes appointments as Professor (1989-2009) and Chair of Pathology at UC Irvine School of Medicine (2000 – 2009) and Professor and Chair of Pathology in the Keck School of Medicine (2009 – 2024). Dr. Selsted leads a multidisciplinary research program focused on mammalian host defense, innate immunity, and inflammation. This focus led to the discovery and characterization of α-, β-, and θ-defensins, microbicidal and immunomodulatory peptides expressed in myeloid and epithelial cells of vertebrates. These investigations, continuously funded by NIH since 1986, have resulted in more than 50 US and foreign patents, as well as clinical translation of a θ-defensin for treatment of rheumatoid arthritis. Ongoing studies seek to elucidate the immunoregulatory mechanisms of these peptides, design and application of novel analogs, and application of θ-defensin-inspired macrocyclic peptides in models of autoimmune diseases, cancer, and infections caused by MDR bacterial and fungal pathogens.

• An ADAM10 Exosite Inhibitor Is Efficacious in an In Vivo Collagen-Induced Arthritis Model. Pharmaceuticals (Basel). 2024 Jan 09; 17(1).. View in PubMed
• Inhibition of miR-146a Expression and Regulation of Endotoxin Tolerance by Rhesus Theta-Defensin-1. Mediators Inflamm. 2023; 2023:8387330.. View in PubMed
• Preclinical Pharmacokinetics and Safety of Intravenous RTD-1. Antimicrob Agents Chemother. 2022 03 15; 66(3):e0212521.. View in PubMed
• A host-directed macrocyclic peptide therapeutic for MDR gram negative bacterial infections. Sci Rep. 2021 12 06; 11(1):23447.. View in PubMed
• Anti-Inflammatory Effects of RTD-1 in a Murine Model of Chronic Pseudomonas aeruginosa Lung Infection: Inhibition of NF-κB, Inflammasome Gene Expression, and Pro-IL-1β Biosynthesis. Antibiotics (Basel). 2021 Aug 26; 10(9).. View in PubMed
• Host Defense Peptides as Templates for Antifungal Drug Development. J Fungi (Basel). 2020 Oct 23; 6(4).. View in PubMed
• RTD-1 therapeutically normalizes synovial gene signatures in rat autoimmune arthritis and suppresses proinflammatory mediators in RA synovial fibroblasts. Physiol Genomics. 2019 12 01; 51(12):657-667.. View in PubMed
• Rhesus Theta Defensin 1 Promotes Long Term Survival in Systemic Candidiasis by Host Directed Mechanisms. Sci Rep. 2019 11 15; 9(1):16905.. View in PubMed
• Essential role of IFN-γ in T cell-associated intestinal inflammation. JCI Insight. 2018 09 20; 3(18).. View in PubMed
• Fungicidal Potency and Mechanisms of θ-Defensins against Multidrug-Resistant Candida Species. Antimicrob Agents Chemother. 2018 06; 62(6).. View in PubMed
• Rhesus θ-Defensin-1 Attenuates Endotoxin-induced Acute Lung Injury by Inhibiting Proinflammatory Cytokines and Neutrophil Recruitment. Am J Respir Cell Mol Biol. 2018 03; 58(3):310-319.. View in PubMed
• Macrocyclic θ-defensins suppress tumor necrosis factor-α (TNF-α) shedding by inhibition of TNF-α-converting enzyme. J Biol Chem. 2018 02 23; 293(8):2725-2734.. View in PubMed
• Efficacy of Rhesus Theta-Defensin-1 in Experimental Models of Pseudomonas aeruginosa Lung Infection and Inflammation. Antimicrob Agents Chemother. 2017 08; 61(8).. View in PubMed
• Suppression and resolution of autoimmune arthritis by rhesus θ-defensin-1, an immunomodulatory macrocyclic peptide. PLoS One. 2017; 12(11):e0187868.. View in PubMed
• Rhesus θ-defensin-1 (RTD-1) exhibits in vitro and in vivo activity against cystic fibrosis strains of Pseudomonas aeruginosa. J Antimicrob Chemother. 2016 Jan; 71(1):181-8.. View in PubMed
• Rhesus macaque θ-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-κB and MAPK pathways. J Leukoc Biol. 2015 Dec; 98(6):1061-70.. View in PubMed
• θ-Defensin RTD-1 improves insulin action and normalizes plasma glucose and FFA levels in diet-induced obese rats. Am J Physiol Endocrinol Metab. 2015 Jul 15; 309(2):E154-60.. View in PubMed
• Microbicidal effects of α- and θ-defensins against antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Innate Immun. 2015 Jan; 21(1):17-29.. View in PubMed
• Hydrophobic determinants of α-defensin bactericidal activity. Infect Immun. 2014 Jun; 82(6):2195-202.. View in PubMed
• Differential Susceptibility of Bacteria to Mouse Paneth Cell α-Defensins under Anaerobic Conditions. Antibiotics (Basel). 2014; 3(4):493-508.. View in PubMed
• Killing of staphylococci by θ-defensins involves membrane impairment and activation of autolytic enzymes. Antibiotics (Basel). 2014; 3(4):617-31.. View in PubMed
• Immunology. HD6 defensin nanonets. Science. 2012 Jul 27; 337(6093):420-1.. View in PubMed
• Alternative luminal activation mechanisms for paneth cell α-defensins. J Biol Chem. 2012 Mar 30; 287(14):11205-12.. View in PubMed
• RTD-1mimic containing γPNA scaffold exhibits broad-spectrum antibacterial activities. J Am Chem Soc. 2012 Mar 07; 134(9):4041-4.. View in PubMed
• Rhesus macaque theta defensins suppress inflammatory cytokines and enhance survival in mouse models of bacteremic sepsis. PLoS One. 2012; 7(12):e51337.. View in PubMed
• High fidelity processing and activation of the human α-defensin HNP1 precursor by neutrophil elastase and proteinase 3. PLoS One. 2012; 7(3):e32469.. View in PubMed
• Cycloquest: identification of cyclopeptides via database search of their mass spectra against genome databases. J Proteome Res. 2011 Oct 07; 10(10):4505-12.. View in PubMed
• Criterion for amino acid composition of defensins and antimicrobial peptides based on geometry of membrane destabilization. J Am Chem Soc. 2011 May 04; 133(17):6720-7.. View in PubMed
• Rhesus macaque θ-defensin isoforms: expression, antimicrobial activities, and demonstration of a prominent role in neutrophil granule microbicidal activities. J Leukoc Biol. 2011 Feb; 89(2):283-90.. View in PubMed
• Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms. PLoS One. 2010 Mar 17; 5(3):e9737.. View in PubMed
• Rhesus theta-defensin prevents death in a mouse model of severe acute respiratory syndrome coronavirus pulmonary disease. J Virol. 2009 Nov; 83(21):11385-90.. View in PubMed
• SDF2L1, a component of the endoplasmic reticulum chaperone complex, differentially interacts with {alpha}-, {beta}-, and {theta}-defensin propeptides. J Biol Chem. 2009 Feb 27; 284(9):5602-9.. View in PubMed
• The cell-penetrating peptide, Pep-1, has activity against intracellular chlamydial growth but not extracellular forms of Chlamydia trachomatis. J Antimicrob Chemother. 2009 Jan; 63(1):115-23.. View in PubMed
• Synthesis, structure, and activities of an oral mucosal alpha-defensin from rhesus macaque. J Biol Chem. 2008 Dec 19; 283(51):35869-77.. View in PubMed
• Isolation, synthesis, and antimicrobial activities of naturally occurring theta-defensin isoforms from baboon leukocytes. Infect Immun. 2008 Dec; 76(12):5883-91.. View in PubMed
• Microbicidal properties and cytocidal selectivity of rhesus macaque theta defensins. Antimicrob Agents Chemother. 2008 Mar; 52(3):944-53.. View in PubMed
• Bovine peptidoglycan recognition protein-S: antimicrobial activity, localization, secretion, and binding properties. J Immunol. 2006 Jan 15; 176(2):1154-62.. View in PubMed
• Paneth cell alpha-defensins from rhesus macaque small intestine. Infect Immun. 2004 Mar; 72(3):1470-8.. View in PubMed
• alpha-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors. AIDS. 2003 Sep 26; 17(14):F23-32.. View in PubMed
• Isolation, characterization, and antimicrobial properties of bovine oligosaccharide-binding protein. A microbicidal granule protein of eosinophils and neutrophils. J Biol Chem. 2002 May 31; 277(22):19658-64.. View in PubMed
• Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells. Am J Physiol Gastrointest Liver Physiol. 2002 May; 282(5):G757-65.. View in PubMed
• Homodimeric theta-defensins from rhesus macaque leukocytes: isolation, synthesis, antimicrobial activities, and bacterial binding properties of the cyclic peptides. J Biol Chem. 2002 Feb 01; 277(5):3079-84.. View in PubMed

• Camarero Palao, Julio
• Schaal, Justin
• Tongaonkar, Prasad
• Beringer, Paul
• Klausner, Jeffrey