Andrew James Martins, PhD
Assistant Professor
Research & Publications
Biography
Research Summary
The Martins lab focuses on understanding human immunology through the lens of systems biology. We aim to enable a deeper analysis of clinical samples by adapting single cell -omics technologies to be feasible across studies with variable sample types, sizes, and with large sample numbers. We expect that assessment of individual cell states across a wide range of clinical studies will lead to 1) comprehensive catalogues of cell states and their association with healthy or diseased donor/patient outcomes 2) new therapeutic interventions that target cell subset specific phenotypes to fine-tune immune behavior 3) insights into the role of cell state heterogeneity (the variability in cell states in a population of cells) to immune responses. In addition, we seek to add new methods to assess and mechanistically interrogate single cell behaviors in human samples through dynamic imaging assays and tissue-mimicking culture conditions. Lab projects typically will combine wet bench and computational components and involve collaboration between lab members and with other labs. Examples of available projects:
- Modification of existing single cell analysis methods to be cheaper and more scalable, to enable application to a wider range of clinical studies.
- Utilizing existing single cell data to generate refined, interpretable cell subset specific gene sets
- In vitro modeling of immune responses and dynamic cell phenotype tracking with in-culture microscopy
Coauthors
Research Interests
Immunity, Innate; Systems Biology; Gene Regulatory Networks; Single-Cell Analysis
Public Health Interests
Bioinformatics; Genetics, Genomics, Epigenetics; Immunology; Infectious Diseases; Maternal & Child Health; Vaccines
Selected Publications
- Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccinede Assis F, Hoehn K, Zhang X, Kardava L, Smith C, Merhebi O, Buckner C, Trihemasava K, Wang W, Seamon C, Chen V, Schaughency P, Cheung F, Martins A, Chiang C, Li Y, Tsang J, Chun T, Kleinstein S, Moir S. Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine. Cell Reports 2023, 42: 112780. PMID: 37440409, PMCID: PMC10529190, DOI: 10.1016/j.celrep.2023.112780.
- Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19Sparks R, Lau W, Liu C, Han K, Vrindten K, Sun G, Cox M, Andrews S, Bansal N, Failla L, Manischewitz J, Grubbs G, King L, Koroleva G, Leimenstoll S, Snow L, Chen J, Tang J, Mukherjee A, Sellers B, Apps R, McDermott A, Martins A, Bloch E, Golding H, Khurana S, Tsang J. Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19. Nature 2023, 614: 752-761. PMID: 36599369, PMCID: PMC10481789, DOI: 10.1038/s41586-022-05670-5.
- Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of childrenXu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, Oguz C, Chen J, Liu C, Tang J, Grubbs G, Stein S, Ramelli S, Kabat J, Behzadpour H, Karkanitsa M, Spathies J, Kalish H, Kardava L, Kirby M, Cheung F, Preite S, Duncker P, Kitakule M, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, McGuire P, Pittaluga S, Germain R, Apps R, Schwartz D, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P, Manthiram K. Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children. Nature Immunology 2022, 24: 186-199. PMID: 36536106, DOI: 10.1038/s41590-022-01367-z.
- Normalizing and denoising protein expression data from droplet-based single cell profilingMulè M, Martins A, Tsang J. Normalizing and denoising protein expression data from droplet-based single cell profiling. Nature Communications 2022, 13: 2099. PMID: 35440536, PMCID: PMC9018908, DOI: 10.1038/s41467-022-29356-8.
- 540 Baseline mTOR transcriptional signatures in CD8 T cells are associated with immune-related adverse events but not anti-tumor responses in patients receiving immune checkpoint inhibitorsZhao C, Mule M, Martins A, Fernandez I, Donahue R, Chen J, Schlom J, Gulley J, Mammen A, Tsang J, Rajan A. 540 Baseline mTOR transcriptional signatures in CD8 T cells are associated with immune-related adverse events but not anti-tumor responses in patients receiving immune checkpoint inhibitors. Journal For ImmunoTherapy Of Cancer 2021, 9: a570-a570. DOI: 10.1136/jitc-2021-sitc2021.540.
- Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potentialRogers D, Sood A, Wang H, van Beek J, Rademaker T, Artusa P, Schneider C, Shen C, Wong D, Bhagrath A, Lebel M, Condotta S, Richer M, Martins A, Tsang J, Barreiro L, François P, Langlais D, Melichar H, Textor J, Mandl J. Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential. Cell Reports 2021, 37: 110064. PMID: 34852223, DOI: 10.1016/j.celrep.2021.110064.
- Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19Liu C, Martins AJ, Lau WW, Rachmaninoff N, Chen J, Imberti L, Mostaghimi D, Fink DL, Burbelo PD, Dobbs K, Delmonte OM, Bansal N, Failla L, Sottini A, Quiros-Roldan E, Lee Han K, Sellers BA, Cheung F, Sparks R, Chun TW, Moir S, Lionakis MS, , Rossi C, Su H, Kuhns D, Cohen J, Notarangelo L, Tsang J, , Abers M, Apps R, Bosticardo M, Milanez-Almeida P, Mulè M, Shaw E, Zhang Y, , Castelli F, Muiesan M, Tomasoni G, Scolari F, Tucci A. Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19. Cell 2021, 184: 1836-1857.e22. PMID: 33713619, PMCID: PMC7874909, DOI: 10.1016/j.cell.2021.02.018.
- Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cellsBaharom F, Ramirez-Valdez RA, Tobin KKS, Yamane H, Dutertre CA, Khalilnezhad A, Reynoso GV, Coble VL, Lynn GM, Mulè MP, Martins AJ, Finnigan JP, Zhang XM, Hamerman JA, Bhardwaj N, Tsang JS, Hickman HD, Ginhoux F, Ishizuka AS, Seder RA. Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells. Nature Immunology 2020, 22: 41-52. PMID: 33139915, PMCID: PMC7746638, DOI: 10.1038/s41590-020-00810-3.
- Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupusKotliarov Y, Sparks R, Martins A, Mulè M, Lu Y, Goswami M, Kardava L, Banchereau R, Pascual V, Biancotto A, Chen J, Schwartzberg P, Bansal N, Liu C, Cheung F, Moir S, Tsang J. Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus. Nature Medicine 2020, 26: 618-629. PMID: 32094927, PMCID: PMC8392163, DOI: 10.1038/s41591-020-0769-8.
- Cancer prognosis with shallow tumor RNA sequencingMilanez-Almeida P, Martins A, Germain R, Tsang J. Cancer prognosis with shallow tumor RNA sequencing. Nature Medicine 2020, 26: 188-192. PMID: 32042193, DOI: 10.1038/s41591-019-0729-3.
- Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid CellsZhong C, Zheng M, Cui K, Martins A, Hu G, Li D, Tessarollo L, Kozlov S, Keller J, Tsang J, Zhao K, Zhu J. Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells. Immunity 2019, 52: 83-95.e4. PMID: 31882362, PMCID: PMC6962539, DOI: 10.1016/j.immuni.2019.12.001.
- Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturationAustin JW, Buckner CM, Kardava L, Wang W, Zhang X, Melson VA, Swanson RG, Martins AJ, Zhou JQ, Hoehn KB, Fisk JN, Dimopoulos Y, Chassiakos A, O'Dell S, Smelkinson MG, Seamon CA, Kwan RW, Sneller MC, Pittaluga S, Doria-Rose NA, McDermott A, Li Y, Chun TW, Kleinstein SH, Tsang JS, Petrovas C, Moir S. Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation. Science Translational Medicine 2019, 11 PMID: 31776286, PMCID: PMC7479651, DOI: 10.1126/scitranslmed.aax0904.
- IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responsesGottschalk R, Dorrington M, Dutta B, Krauss K, Martins A, Uderhardt S, Chan W, Tsang J, Torabi-Parizi P, Fraser I, Germain R. IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses. ELife 2019, 8: e46836. PMID: 31385572, PMCID: PMC6684266, DOI: 10.7554/elife.46836.
- Resident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory DamageUderhardt S, Martins A, Tsang J, Lämmermann T, Germain R. Resident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage. Cell 2019, 177: 541-555.e17. PMID: 30955887, PMCID: PMC6474841, DOI: 10.1016/j.cell.2019.02.028.
- Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolismMao K, Baptista A, Tamoutounour S, Zhuang L, Bouladoux N, Martins A, Huang Y, Gerner M, Belkaid Y, Germain R. Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature 2018, 554: 255-259. PMID: 29364878, DOI: 10.1038/nature25437.
- Transcriptional Response of Respiratory Epithelium to Nontuberculous MycobacteriaMatsuyama M, Martins A, Shallom S, Kamenyeva O, Kashyap A, Sampaio E, Kabat J, Olivier K, Zelazny A, Tsang J, Holland S. Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria. American Journal Of Respiratory Cell And Molecular Biology 2017, 58: 241-252. PMID: 28915071, PMCID: PMC5806000, DOI: 10.1165/rcmb.2017-0218oc.
- Sequential activity of innate and adaptive lymphocytes supports non-inflammatory gut microbial commensalismMao K, Baptista A, Bouladoux N, Martins A, Tamoutounour S, Davis J, Huang Y, Gerner M, Belkaid Y, Germain R. Sequential activity of innate and adaptive lymphocytes supports non-inflammatory gut microbial commensalism. The Journal Of Immunology 2017, 198: 200.14-200.14. DOI: 10.4049/jimmunol.198.supp.200.14.
- Induced negative regulation decodes PAMP quality and quantity to generate bacteria-specific inflammatory responsesGottschalk R, Dutta B, Krauss K, Dorrington M, Martins A, Uderhardt S, Tsang J, Torabi-Parizi P, Fraser I, Germain R. Induced negative regulation decodes PAMP quality and quantity to generate bacteria-specific inflammatory responses. The Journal Of Immunology 2017, 198: 222.26-222.26. DOI: 10.4049/jimmunol.198.supp.222.26.
- Combining gene expression data from inflamed tissue and machine learning for blood biomarker discoveryMilanez-Almeida P, Martins A, Narayanan M, Torabi-Parizi P, Franco L, Tsang J, Germain R. Combining gene expression data from inflamed tissue and machine learning for blood biomarker discovery. The Journal Of Immunology 2017, 198: 81.7-81.7. DOI: 10.4049/jimmunol.198.supp.81.7.
- Environment Tunes Propagation of Cell-to-Cell Variation in the Human Macrophage Gene NetworkMartins A, Narayanan M, Prüstel T, Fixsen B, Park K, Gottschalk R, Lu Y, Andrews-Pfannkoch C, Lau W, Wendelsdorf K, Tsang J. Environment Tunes Propagation of Cell-to-Cell Variation in the Human Macrophage Gene Network. Cell Systems 2017, 4: 379-392.e12. PMID: 28365150, PMCID: PMC8392141, DOI: 10.1016/j.cels.2017.03.002.
- Robust Inference of Cell-to-Cell Expression Variations from Single- and K-Cell ProfilingNarayanan M, Martins A, Tsang J. Robust Inference of Cell-to-Cell Expression Variations from Single- and K-Cell Profiling. PLOS Computational Biology 2016, 12: e1005016. PMID: 27438699, PMCID: PMC4954693, DOI: 10.1371/journal.pcbi.1005016.
- Distinct NF-κB and MAPK Activation Thresholds Uncouple Steady-State Microbe Sensing from Anti-pathogen Inflammatory ResponsesGottschalk R, Martins A, Angermann B, Dutta B, Ng C, Uderhardt S, Tsang J, Fraser I, Meier-Schellersheim M, Germain R. Distinct NF-κB and MAPK Activation Thresholds Uncouple Steady-State Microbe Sensing from Anti-pathogen Inflammatory Responses. Cell Systems 2016, 2: 378-390. PMID: 27237739, PMCID: PMC4919147, DOI: 10.1016/j.cels.2016.04.016.
- Protective role of G-CSF in dextran sulfate sodium-induced acute colitis through generating gut-homing macrophagesMeshkibaf S, Martins A, Henry G, Kim S. Protective role of G-CSF in dextran sulfate sodium-induced acute colitis through generating gut-homing macrophages. Cytokine 2015, 78: 69-78. PMID: 26687628, DOI: 10.1016/j.cyto.2015.11.025.
- Random yet deterministic: convergent immunoglobulin responses to influenzaMartins A, Tsang J. Random yet deterministic: convergent immunoglobulin responses to influenza. Trends In Microbiology 2014, 22: 488-489. PMID: 25179798, PMCID: PMC4961090, DOI: 10.1016/j.tim.2014.07.005.
- Recent progress using systems biology approaches to better understand molecular mechanisms of immunityGottschalk R, Martins A, Sjoelund V, Angermann B, Lin B, Germain R. Recent progress using systems biology approaches to better understand molecular mechanisms of immunity. Seminars In Immunology 2012, 25: 201-208. PMID: 23238271, PMCID: PMC3834012, DOI: 10.1016/j.smim.2012.11.002.
- The anti‐inflammatory role of granulocyte colony‐stimulating factor in macrophage–dendritic cell crosstalk after Lactobacillus rhamnosus GR‐1 exposureMartins A, Spanton S, Sheikh H, Kim S. The anti‐inflammatory role of granulocyte colony‐stimulating factor in macrophage–dendritic cell crosstalk after Lactobacillus rhamnosus GR‐1 exposure. Journal Of Leukocyte Biology 2011, 89: 907-915. PMID: 21385950, DOI: 10.1189/jlb.0810445.
- Lactobacillus rhamnosus GR-1-Induced IL-10 Production in Human Placental Trophoblast Cells Involves Activation of JAK/STAT and MAPK PathwaysYeganegi M, Leung C, Martins A, Kim S, Reid G, Challis J, Bocking A. Lactobacillus rhamnosus GR-1-Induced IL-10 Production in Human Placental Trophoblast Cells Involves Activation of JAK/STAT and MAPK Pathways. Reproductive Sciences 2010, 17: 1043-1051. PMID: 20858906, DOI: 10.1177/1933719110377237.
- Lactobacillus rhamnosus GR-1 Stimulates Colony-Stimulating Factor 3 (Granulocyte) (CSF3) Output in Placental Trophoblast Cells in a Fetal Sex-Dependent Manner1Yeganegi M, Leung C, Martins A, Kim S, Reid G, Challis J, Bocking A. Lactobacillus rhamnosus GR-1 Stimulates Colony-Stimulating Factor 3 (Granulocyte) (CSF3) Output in Placental Trophoblast Cells in a Fetal Sex-Dependent Manner1. Biology Of Reproduction 2010, 84: 18-25. PMID: 20811016, PMCID: PMC4480822, DOI: 10.1095/biolreprod.110.085167.
- The multifaceted effects of granulocyte colony‐stimulating factor in immunomodulation and potential roles in intestinal immune homeostasisMartins A, Han J, Kim S. The multifaceted effects of granulocyte colony‐stimulating factor in immunomodulation and potential roles in intestinal immune homeostasis. IUBMB Life 2010, 62: 611-617. PMID: 20681025, PMCID: PMC2916186, DOI: 10.1002/iub.361.
- Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm laborYeganegi M, Watson C, Martins A, Kim S, Reid G, Challis J, Bocking A. Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor. American Journal Of Obstetrics And Gynecology 2009, 200: 532.e1-532.e8. PMID: 19285652, DOI: 10.1016/j.ajog.2008.12.032.
- Reduced expression of basal and probiotic‐inducible G‐CSF in intestinal mononuclear cells is associated with inflammatory bowel diseaseMartins A, Colquhoun P, Reid G, Kim S. Reduced expression of basal and probiotic‐inducible G‐CSF in intestinal mononuclear cells is associated with inflammatory bowel disease. Inflammatory Bowel Diseases 2008, 15: 515-525. PMID: 19058228, DOI: 10.1002/ibd.20808.
- Cathepsin B Is Involved in the Trafficking of TNF-α-Containing Vesicles to the Plasma Membrane in MacrophagesHa S, Martins A, Khazaie K, Han J, Chan B, Kim S. Cathepsin B Is Involved in the Trafficking of TNF-α-Containing Vesicles to the Plasma Membrane in Macrophages. The Journal Of Immunology 2008, 181: 690-697. PMID: 18566436, DOI: 10.4049/jimmunol.181.1.690.
- G‐CSF‐mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus‐induced suppression of TNF production in macrophagesKim S, Sheikh H, Ha S, Martins A, Reid G. G‐CSF‐mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus‐induced suppression of TNF production in macrophages. Cellular Microbiology 2006, 8: 1958-1971. PMID: 16889627, DOI: 10.1111/j.1462-5822.2006.00763.x.