Personal Statement
I am a cell biologist with a long-standing interest in learning about cell-intrinsic host defenses against infectious disease.
Key Publications
Journal Article
Saha, B, Salemi, M, Williams, G, L Oh, S, Paffett, M, L Phinney, B, Mandell, Michael, 2022 Interactomic analysis reveals a homeostatic role for the HIV restriction factor TRIM5? in mitophagy. Cell reports, vol. 39, Issue 6, 110797
Journal Article
Saha, B, Chisholm, D, Kell, A, M Mandell, Michael, 2020 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5?. PLoS pathogens, vol. 16, Issue 10, e1009017
Journal Article
Kehl, S, R Soos, B, A Saha, B, Choi, S, W Herren, A, W Johansen, T, Mandell, Michael, 2019 TAK1 converts Sequestosome 1/p62 from an autophagy receptor to a signaling platform. EMBO reports, vol. 20, Issue 9, e46238
Journal Article
Mandell, Michael, Jain, A, Kumar, S, Castleman, M, J Anwar, T, Eskelinen, E, L Johansen, T, Prekeris, R, Deretic, V, 2016 TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation. Journal of cell science, vol. 129, Issue 19, 3562-3573
Journal Article
Mandell, Michael, Jain, A, Arko-Mensah, J, Chauhan, S, Kimura, T, Dinkins, C, Silvestri, G, Münch, J, Kirchhoff, F, Simonsen, A, Wei, Y, Levine, B, Johansen, T, Deretic, V, 2014 TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition. Developmental cell, vol. 30, Issue 4, 394-409
Languages
- English
- Spanish
Courses Taught
Dr. Mandell is a co-block chair for the "Microbiology and Immunology" course that is part of the first-year medical school curriculum.
He has also taught in the following courses at UNM School of Medicine: Infectious Disease (medical school, year 2); Molecular Virology (BSGP); and Immunopathogenesis (BSGP).
Research and Scholarship
The goal of the Mandell laboratory is to understand how cells coordinate responses to intracellular threats with a focus on retroviral infection. In particular, we study members of the TRIM family of proteins. There are more than 70 TRIMs in the human genome, many of which function to protect cells from viral infection. As antiviral molecules, TRIMs can both directly interfere with viral life cycles and can function as key regulators of innate immunity. Our studies revealed a novel, yet highly conserved, action of TRIMs in another cytoprotective pathway: autophagy. Autophagy is a degradative pathway responsible for the removal of unnecessary and/or potentially dangerous cytoplasmic contents including viruses. Autophagy also has emerging roles in controlling innate immunity. We have shown that TRIMs can control when the cell ‘turns on’ autophagy and can also determine which cellular components are selectively targeted for autophagic removal. Thus, TRIM proteins are positioned as the ‘ringleaders’ of cellular antiviral and innate immune functions. We are working to uncover how TRIMs coordinate these actions.
Our current studies are focused on the HIV-1 restriction factor TRIM5. We have shown that TRIM5 biochemically interacts with multiple components of the autophagy machinery and assembles them into functional complexes. We recently connected these autophagy-related functions of TRIM5 to its actions in antiviral defense. We found that TRIM5 leverages the autophagy machinery to promote antiviral signaling and the establishment of a broadly antiviral state. In this setting, we identified a novel role for the autophagy machinery in scaffolding the assembly of active TRIM5 signaling structures which is in contrast the typical degradative actions of the autophagy pathway.
We are using cell biological, immunological, and proteomic approaches to understand the mechanisms underlying how autophagy contributes to TRIM5’s actions in transducing antiviral signaling. We anticipate that these experiments will advance our understanding of how cells respond to viral infection and reveal novel functions of TRIM5 while also enabling an improved understanding of how autophagy works in mammalian cells.
A list of Dr. Mandell's publications can be found at this link:
http://www.ncbi.nlm.nih.gov/sites/myncbi/1bqFzVvi-8oAm/bibliography/40998872/public/?sort=date&direction=ascending