Salamango, Dan, Ph.D.

Research

Our lab is broadly interested in host-pathogen interactions between cellular proteins and viral pathogens. We utilize traditional and “new age” molecular virology approaches (i.e., deep mutational scanning and whole genome CRISPR/Cas9 screening) to study viral protein localization, function, and interactions with host-cell processes to uncover novel mechanisms that facilitate virus replication. In addition, we are also interested in virus-associated disease pathologies, such as virus-induced neuropathy, and elucidating the underlying molecular mechanisms. Finally, as we uncover and explore cellular pathways manipulated by viral pathogens, we also investigate knowledge-gaps associated with how these pathways function in general biology. Some example projects are outlined below:

1. Understanding the functional consequences of HIV-1 Vif-induced remodeling of the cellular phosphoproteome

The canonical role of the HIV-1 Vif accessory protein is to counteract the enzymatic activity of host APOBEC3 antiviral restriction factors. Vif achieves this by hijacking a host E3-ubiquitin ligase complex to target the APOBEC3s for proteasomal degradation before they can “attack” the HIV- genome. Interestingly, Vif also induces global phosphoproteome remodeling by antagonizing a major host cell phosphatase (PP2A). However, the virologic and metabolic outcomes of this activity are not well understood.

2. Deciphering assembly mechanisms of protein phosphatase holoenzymes

Reversible protein phosphorylation at serine, threonine, or tyrosine residues is one of the most common mechanisms of protein regulation and is carried out by a tightly regulated network of kinases and phosphatases. While roughly 400 serine/threonine kinases have been identified in the human genome, only about 40 serine/threonine protein phosphatases have been discovered. How the limited number of phosphatases counterbalances the activity of abundant kinases arises from their dynamic and modular nature. Under steady-state conditions, most serine/threonine phosphatases exist as inactive monomers or dimers that require the docking of a regulatory subunit to become enzymatically active. Regulatory subunits can be one of several dozen structurally and functionally distinct proteins that recognize discrete subsets of cellular proteins, which gives rise the dynamic regulatory capacity of phosphatase complexes. When this process becomes dysregulated, it leads to numerous human diseases, including cancer and neurological disorders. Are questions are 1) what are the molecular mechanisms that dictate which regulatory subunit docs to the inactive enzyme, 2) how do regulatory subunits recognize and discriminate between cellular targets, and 3) can we comprehensively define substrate interactomes for discrete protein phosphatase complexes?

3. Determining the role of phosphorylation, and de-phosphorylation, in regulating IAV protein functions

Almost all IAV proteins become phosphorylated at multiple different amino acid residues during the course of an infection. For some of these events, phosphorylation has been linked to regulation of subcellular localization, protein oligomerization, counteraction of innate immune responses, and binding to viral RNAs. However, the functional role for many of these phosphorylation events has yet to be characterized. Importantly, virtually nothing is known about the role of cellular phosphatases in regulating the dynamic nature of these phosphorylation events. We are interested in 1) determining the roles of cellular phosphatases in regulating IAV biology, and 2) ascribing functions to phosphorylation events that have yet to be characterized.

4. Elucidating the molecular mechanisms that underly HIV-associated neurocognitive disease

HIV-associated neurocognitive disorder (HAND) persists in over half of HIV+ patients despite effective antiretroviral therapies (ART). Current therapeutics have curbed the most severe forms of disease and have shifted neuropathology from a rapidly progressing encephalitis to a prolonged neurodegenerative disease with hallmarks that include astrogliosis and microgliosis. However, the molecular mechanisms driving HAND onset and severity are still poorly understood. Infected astrocytes and microglia are thought to serve as brain-resident HIV reservoirs that drive chronic neuroinflammation and oxidative tissue damage due to the persistent expression of viral proteins. Our lab has evidence that multiple HIV accessory proteins independently block host DNA damage repair responses and induce DNA damage/DNA strand breaks. We hypothesize that this activity exacerbates neuroinflammation and potentially leads to brain cell death in patients.

For a list of complete publications: https://pubmed.ncbi.nlm.nih.gov/?term=salamango+d

Awards & Accomplishments

• 2021  Selected to mBio Junior Editorial Board
• 2019  K99/R00 Cancer Transition Award, NIAID
• 2015  Best Postdoctoral Talk, BMBB Dept., University of Missouri
• 2011  Dr. C. Gherke Jr. Memorial Teaching Scholarship, University of Missouri
• 2010  Sigma Xi Senior Research Award, Hope College
• 2007  NCAA Division III MIAA Football Champion, Hope College
• 2006  NCAA Division III MIAA Football Champion, Hope College

R01 AI189230 (Salamango, PI)     2025 – 2030
National Institutes of Health/NIAID
Impact of Vpr-induced epigenetic remodeling on HIV persistence
Total Direct Amount: $2,161,420

Lab Members

Publications

37) Saladino N, Leavitt EL, Wong HT, Ji J, Ebrahimi D, and Salamango DJ. HIV-1 Vpr drives epigenetic remodeling to enhance virus transcription and latency reactivation (2025). In process.
36) Luperchio AM, and Salamango DJ. Defining the protein phosphatase 2A (PP2A) subcomplexes that regulate FoxO transcription factor localization (2025). Cells. 14: 342
35) Saladino N and Salamango DJ. Wielding a double-edged sword: Viruses exploit host DNA repair to facilitate replication while bypassing immune activation (2024). Frontiers in Virology. 4: 1410258
34)  Salamango DJ. Finally neutralizing the threat? Progress towards SARS-CoV-2 vaccines that elicit enhanced neutralizing antibody responses (2024). mBio. e0006724 (invited commentary)
33)  Wong H, Luperchio AM, Riley S, and Salamango DJ. Inhibition of ATM-directed antiviral responses by HIV-1 Vif (2023). PLoS Pathog. 19: e1011634
32)  Conde JN, Himmler G, Mladinich M, Setoh YX, Schutt W, Saladino N, Gorbunova E, Salamango DJ, Kim HK, and Mackow E. Establishment of a CPER reverse genetics system for Powassan virus defines attenuating NS1 glycosylation sites and an infectious NS1-GFP11 reporter virus (2023). mBio. e0138823
31)  Luperchio AM, Jonsson SR, and Salamango DJ. Evolutionary conservation of PP2A antagonism and G2/M cell cycle arrest in maedi-visna virus Vif (2022). Viruses. 14: 1701
30) Wong H, Cheung V, and Salamango DJ. Decoupling SARS-CoV-2 ORF6 localization and interferon antagonism (2022). J Cell Sci. 136: jcs.259666

Featured article in “News Medical Life Sciences” (December 2021)

29) Rieffer AE, Chen Yanjun, Salamango DJ, Moraes SN, and Harris RS. APOBEC Reporter Systems for Evaluating dinucleotide Editing Levels (ARSENEL) of Cytosine Base Editors (2023). CRISPR J. 6: 430-446
28) McCann JL, Cristini A, Law EK, Lee YS, Tellier M, Carpenter MA, Beghe C, Kim JJ, Jarvis MC, Stefanovska B, Temiz NA, Bergstrom EN, Salamango DJ, Brown MR, Murphy S, Alexandrov LB, Miller KM, Gromak N, and Harris RS. APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer (2023). Nature Genetics. 55: 1721-34
27)  Auerbach A, Becker JT, Moraes SN, Moghadasi SA, Duda J, Salamango DJ, and Harris RS. Ancestral APOBEC3B Nuclear Localization is Maintained in Humans and Apes and Altered in Most other Old World Primate Species (2022). mSphere. 7: e0045122
26)  Alvarez-Gonzalez J, Yasgar A, Maul RW, Rieffer AE, Crawford DJ, Salamango DJ, Dorsuren D, Zakharov A, Jansen D, Rai G, Marugan J, Simeonov A, Harris RS, Kohli R, and Gearhart PJ. Small molecular inhibitors of activation-induced deaminase decrease class switch recombination in B cells (2021). ACS Pharmacology and Translational Science. 4: 1214-1226
25)  Salamango DJ§ and Harris RS§. Demystifying Cell Cycle Arrest by HIV-1 Vif (2021). (§ Co-corresponding authors). Trends in Microbiol. 29: 381-84
24)  Salamango DJ§ and Harris RS§. Dual functionality of HIV-1 Vif in APOBEC3 counteraction and cell cycle arrest (2021). (§ Co-corresponding authors). Frontiers in Microbiol. 11: 622012
23)  Salamango DJ§, McCann JL, Demir O, Becker JT, Wang J, Lingappa J, Brown WL, Amaro RE, and Harris RS§. Functional and Structural Insights into a Vif/PPP2R5 Complex Elucidated by Patient HIV-1 Isolates and Computational Modeling (2020). J Virol. 94: e00631-20. (§ Co-corresponding authors).
22)  Bhatt V*, Shi Ke*, Salamango DJ*, Moeller NH, Pandey K, Bera S, Kurniawan F, Orellana K, Zhang W, Grandgenett DP, Harris RS, Sundborger-Lunna AC, and Aihara H. Structural basis of host protein hijacking in human T-cell leukemia virus integration (2020). (* Equal Contribution). Nat. Commun. 11: 3121.
21)  McCann JL, Salamango DJ, Law EK, Brown WL, and Harris RS. MagnEdit—A Real-Time System for Reporting Endogenous APOBEC3 Editing Activity in Living Cells (2020). Life Science Alliance. 24: e201900606.
20)  Salamango D§, Ikeda T, Moghadasi SA, Wang J, McCann J, Serebrenik A, Ebrahimi D, Jarvis M, Brown W, and Harris R§. HIV-1 Vif Triggers Cell Cycle Arrest by Degrading Cellular PPP2R5 Phospho-Regulators (2019). Cell Reports. 29:1057-1065. (§ Co-corresponding authors).
19)  Wang J, Ke Shi, Becker J, Lauer K, Salamango D, Aihara H, Shaban N, and Harris R. The Role of RNA in HIV-1 Vif-Mediated Degradation of Human APOBEC3H (2019). J Mol. Biol. 431: 5019-31
18)  Serebrenik A, Starrett G, Leenen S, Shaban N, Brown W, Carpenter M, Salamango D, and Harris R. The deaminase APOBEC3B triggers the death of cells lacking uracil DNA glycosylase (2019). Proc. Nat. Acad. Sci. 116: 22158-63
17) McCann J, Klein M, Leland E, Brown W, Salamango D§, and Harris R§. The Cytosine Deaminase APOBEC3B Disrupts Cell Cycle Regulation Through Interaction with CDK4 (2019). J Biol. Chem. 294: 12099-111. (§ Co-corresponding authors).
16)  Ikeda T, Molan A, Jarvis M, Salamango DJ, Brown W, and Harris R. HIV-1 Restriction by APOBEC3G in the Myeloid Cell Line THP-1 (2019). J Gen. Virol. 100: 1140-52.
15)  St. Martin A, Salamango DJ, Shaban N, Brown W, and Harris R. A Panel of eGFP Reporters for Single-base Editing by APOBEC-Cas9 Editosome Complexes (2019). Sci. Rep. 9: 497.
14) Ebrahimi D, Richards C, Carpenter M, Wang J, Ikeda T, Cheng A, Becker J, McCann J, Shaban N, Salamango DJ, Starrett G, Lingappa J, Yong J, Brown W, and Harris R. Genetic and Mechanistic Basis for APOBEC3H Alternative Splicing, Differential Retrovirus Restriction, and Counteraction by HIV-1 Protease (2018). Nat. Commun. 9: 4137.
13)  Salamango DJ§, Becker JT, McCann JL, Cheng AZ, Demir O, Amaro RE, Brown WL, Shaban NM, and Harris RS§. APOBEC3H Subcellular Localization Determinants Define Zipcode for Targeting HIV-1 Restriction (2018). Mol. Cell Biol. 38: e00356-18 (§ Co-corresponding authors).
12)  Salamango DJ, McCann JM, Demir O, Brown W, Amaro R, and Harris RS. Nuclear Import of APOBEC3B Requires Two Distinct N-Terminal Domain Surfaces (2018). J Mol. Biol. 430: 2695-2708.
11)  St. Martin A*, Salamango D*, Shaban N, Brown WL, Donati F, Munagala U, Conticello S, and Harris R. A Novel Fluorescent Reporter for Quantification of APOBEC-Cas9 Base Editing in Living Cells (2018). (* Equal Contribution) Nucleic Acids Res. 46: e84.
10)  Shaban NM, Shi K, Lauer K, Carpenter MA, Richards CM, Salamango DJ, Wang J, Lopresti MW, Banarjee S, Levin-Klein R, Brown WL, Aihara H, and Harris RS (2018). The Antiviral and Cancer Genomic DNA Deaminase APOBEC3H is Regulated by a RNA-Mediated Dimerization Mechanism. Mol. Cell. 69: 75-86.
9)  Shi K, Carpenter MA, Banerjee S, Shaban NM, Kurahashi K, Salamango DJ, McCann JL, Starrett GJ, Duffy J, Harki DA, Harris RS, and Aihara H. Structural Basis for Targeted DNA Cytosine Deamination and Mutagenesis by APOBEC3A and APOBEC3B (2017). Nat. Struct. Mol. Biol. 24: 131-9.

• Featured article in “News & Views” (February 2017)

8) Collins C, LaMontagne E, Clarke A, Bond L, Salamango D, Cornish P, Peck S, and Heese A. Arabidopsis clathrin adapter EPSIN1 modulated plasma membrane abundance of Flagellin Sensing 2 (FLS2) for effective immune responses (2020). Plant Phys. 182: 1762-75
7) Jeong Y, Deghlas S, Kahveci A, Salamango DJ, Gentry ZB, Brown M, Pearsall S, and Phillips C. Soluble Activating Receptor IIB Decoy Receptor Differentially Impacts Murine Osteogenesis Imperfecta Muscle Function (2018). Muscle and Nerve. 57: 294-304.
6) Kunkler B, Salamango D, Lewis S, Ploch C, Dean S, Hledin M, Marquez G, Madden J, Debruine Z, Schnell A, Short M, and Hledin M. CUL5 is Required for Thalidomide-Dependent Inhibition of Cellular Proliferation (2018). PLoS One. 13: e0196760.
5) Salamango DJ, Alam KK, Burke DH, and Johnson MC. In Vivo Analysis of Infectivity, Fusogenicity, and Incorporation of a Mutagenic Viral Glycoprotein Library Reveals Determinants for Viral Incorporation (2016). J Virol. 90: 6502-14

• Featured as “Spotlight Selection” article (June 2016)

4) Salamango DJ and Johnson MC. Characterizing the Murine Leukemia Virus Envelope Glycoprotein Membrane-Spanning Domain for its Roles in Interface Alignment and Fusogenicity (2015). J Virol. 89: 12492-500.
3) Jeong Y, Carleton SM, Gentry BA, Yao X, Ferreira JA, Salamango DJ, Weis M, Oestreich AK, Williams AM, McCray MG, Eyre DR, Brown M, Wang Y, and Phillips CL. Hindlimb Skeletal Muscle Function and Skeletal Quality and Strength in +/G610C Mice with and without Weight-Bearing Exercise (2015). J Bone and Mineral Res. 30: 1874-86.
2) Smith JM*, Salamango DJ*, Leslie ME, Collins CA, and Heese A. Sensitivity to FLG22 is Modulated by Ligand-Induced Degradation and De Novo Synthesis of the Endogenous Flagellin-Receptor FLAGELLIN-SENSING2 (2014). (* Equal Contribution) Plant Physiol. 164: 440-54.
1) Salamango DJ*, Evans DA*, Baluyot MF*, Furlong JN, and Johnson MC. Recombination Can Lead to Spurious Results in Retroviral Transduction with Dually Fluorescent Reporter Genes (2013). (* Equal Contribution) J Virol. 24: 13900-3