Kathryn Miller-Jensen, PhD
Research & Publications
Biography
News
Extensive Research Description
Dr. Miller-Jensen's research program focuses on a quantitative, systems biology approach to studying changes in intracellular signaling, particularly after viral infection. Her laboratory has a significant focus on HIV infection and viral latency, which is a very important indirect human carcinogen. In addition, they have several ongoing efforts that are relevant to other aspects of cancer research. First, they use experimental models of latent HIV infection to study the dynamics and heterogeneity of transcriptional activation in different chromatin environments (see Miller- Jensen et al., Integrative Biology, 2012). The primary application of this work is to design therapeutic strategies to activate and treat latent HIV, which could have a dramatic impact on cancer incidence in this population. The findings are also useful for understanding chromatin-mediated heterogeneity in cancer (see Miller-Jensen et al, Trends in Biotechnology, 2011). Dr. Jensen also has an NCI U01 contract grant in collaboration with Prof. Rong Fan in the Dept. of Biomedical Engineering at Yale to develop a micro-chip device to detect cytokine and phosphorylation signatures in single cells. They will apply this technology to measure heterogeneity in cancer cell lines and primary tumor samples, as well as following viral infection. Finally, the Miller-Jensen Lab is collaborating with Prof. Paul Turner of Yale Ecology and Evolutionary Biology to study how strains of vesicular stomatitis virus (VSV) that were evolved on different host cell lines differentially activate the cellular innate immune response in different cell lines. They are particularly interested in the response of cancer cell lines with impaired innate immune signaling, and plan to build predictive models of signaling and apoptosis analogous to previous work Dr. Miller-Jensen published on adenoviral vector-mediated apoptosis in cancer cell lines (see Miller-Jensen et al, Nature, 2007). One potential application of this work is to design more effective VSV-based oncolytic vectors.
Specialized terms: Systems biology, signal transduction, virus-host interactions
Coauthors
Research Interests
Biomedical Engineering
Selected Publications
- Single-Cell Analysis Reveals a Subset of High IL-12p40-Secreting Dendritic Cells within Mouse Bone Marrow-Derived Macrophages Differentiated with M-CSF.Bridges K, Pizzurro G, Khunte M, Chen M, Salvador Rocha E, Alexander A, Bass V, Kellman L, Baskaran J, Miller-Jensen K. Single-Cell Analysis Reveals a Subset of High IL-12p40-Secreting Dendritic Cells within Mouse Bone Marrow-Derived Macrophages Differentiated with M-CSF. The Journal Of Immunology 2024, 212: 1357-1365. PMID: 38416039, DOI: 10.4049/jimmunol.2300431.
- Apoptosis recognition receptors regulate skin tissue repair in miceJustynski O, Bridges K, Krause W, Forni M, Phan Q, Sandoval-Schaefer T, Carter K, King D, Hsia H, Gazes M, Vyce S, Driskell R, Miller-Jensen K, Horsley V. Apoptosis recognition receptors regulate skin tissue repair in mice. ELife 2023, 12: e86269. PMID: 38127424, PMCID: PMC10735221, DOI: 10.7554/elife.86269.
- A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily betterDjureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.
- Reframing macrophage diversity with network motifsPizzurro G, Miller-Jensen K. Reframing macrophage diversity with network motifs. Trends In Immunology 2023, 44: 965-970. PMID: 37949786, PMCID: PMC11057955, DOI: 10.1016/j.it.2023.10.009.
- Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.
- Functionally and Metabolically Divergent Melanoma-Associated Macrophages Originate from Common Bone-Marrow PrecursorsPizzurro G, Bridges K, Jiang X, Vidyarthi A, Miller-Jensen K, Colegio O. Functionally and Metabolically Divergent Melanoma-Associated Macrophages Originate from Common Bone-Marrow Precursors. Cancers 2023, 15: 3330. PMID: 37444440, PMCID: PMC10341323, DOI: 10.3390/cancers15133330.
- Abstract 3287: A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily betterDjureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. Abstract 3287: A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Cancer Research 2023, 83: 3287-3287. DOI: 10.1158/1538-7445.am2023-3287.
- Langerhans cells are essential components of the angiogenic niche during murine skin repairWasko R, Bridges K, Pannone R, Sidhu I, Xing Y, Naik S, Miller-Jensen K, Horsley V. Langerhans cells are essential components of the angiogenic niche during murine skin repair. Developmental Cell 2022, 57: 2699-2713.e5. PMID: 36493773, PMCID: PMC10848275, DOI: 10.1016/j.devcel.2022.11.012.
- Abstract B48: CD40-agonist treatment can prime the inflammatory response of macrophages and reverse checkpoint inhibitor resistance in melanomaPizzurro G, Bridges K, Kaech S, Bosenberg M, Miller-Jensen K. Abstract B48: CD40-agonist treatment can prime the inflammatory response of macrophages and reverse checkpoint inhibitor resistance in melanoma. Cancer Immunology Research 2022, 10: b48-b48. DOI: 10.1158/2326-6074.tumimm22-b48.
- A transcriptional cycling model recapitulates chromatin-dependent features of noisy inducible transcriptionBullock ME, Moreno-Martinez N, Miller-Jensen K. A transcriptional cycling model recapitulates chromatin-dependent features of noisy inducible transcription. PLOS Computational Biology 2022, 18: e1010152. PMID: 36084132, PMCID: PMC9491597, DOI: 10.1371/journal.pcbi.1010152.
- Mapping and Validation of scRNA-Seq-Derived Cell-Cell Communication Networks in the Tumor MicroenvironmentBridges K, Miller-Jensen K. Mapping and Validation of scRNA-Seq-Derived Cell-Cell Communication Networks in the Tumor Microenvironment. Frontiers In Immunology 2022, 13: 885267. PMID: 35572582, PMCID: PMC9096838, DOI: 10.3389/fimmu.2022.885267.
- 3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting PhenotypePizzurro GA, Liu C, Bridges K, Alexander AF, Huang A, Baskaran JP, Ramseier J, Bosenberg MW, Mak M, Miller-Jensen K. 3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype. Cancers 2021, 13: 4579. PMID: 34572807, PMCID: PMC8471848, DOI: 10.3390/cancers13184579.
- Single-cell secretion analysis reveals a dual role for IL-10 in restraining and resolving the TLR4-induced inflammatory responseAlexander AF, Kelsey I, Forbes H, Miller-Jensen K. Single-cell secretion analysis reveals a dual role for IL-10 in restraining and resolving the TLR4-induced inflammatory response. Cell Reports 2021, 36: 109728. PMID: 34551303, PMCID: PMC8995750, DOI: 10.1016/j.celrep.2021.109728.
- TNF stimulation primarily modulates transcriptional burst size of NF‐κB‐regulated genesBass VL, Wong VC, Bullock ME, Gaudet S, Miller‐Jensen K. TNF stimulation primarily modulates transcriptional burst size of NF‐κB‐regulated genes. Molecular Systems Biology 2021, 17: e10127. PMID: 34288498, PMCID: PMC8290835, DOI: 10.15252/msb.202010127.
- 624 Langerhans cells promote revascularization and repair during skin wound healingWasko R, Xing Y, Sidhu I, Bridges K, Miller-Jensen K, Naik S, Horsley V. 624 Langerhans cells promote revascularization and repair during skin wound healing. Journal Of Investigative Dermatology 2021, 141: s108. DOI: 10.1016/j.jid.2021.02.653.
- Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cellsMuñoz-Rojas AR, Kelsey I, Pappalardo JL, Chen M, Miller-Jensen K. Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells. Nature Communications 2021, 12: 301. PMID: 33436596, PMCID: PMC7804107, DOI: 10.1038/s41467-020-20540-2.
- Microfluidic platform enables live-cell imaging of signaling and transcription combined with multiplexed secretion measurements in the same single cellsRamji R, Alexander AF, Muñoz-Rojas AR, Kellman LN, Miller-Jensen K. Microfluidic platform enables live-cell imaging of signaling and transcription combined with multiplexed secretion measurements in the same single cells. Integrative Biology 2019, 11: 142-153. PMID: 31242304, PMCID: PMC8672722, DOI: 10.1093/intbio/zyz013.
- Fold-Change Detection of NF-κB at Target Genes with Different Transcript OutputsWong VC, Mathew S, Ramji R, Gaudet S, Miller-Jensen K. Fold-Change Detection of NF-κB at Target Genes with Different Transcript Outputs. Biophysical Journal 2019, 116: 709-724. PMID: 30704857, PMCID: PMC6382958, DOI: 10.1016/j.bpj.2019.01.011.
- Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repairShook BA, Wasko RR, Rivera-Gonzalez GC, Salazar-Gatzimas E, López-Giráldez F, Dash BC, Muñoz-Rojas AR, Aultman KD, Zwick RK, Lei V, Arbiser JL, Miller-Jensen K, Clark DA, Hsia HC, Horsley V. Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair. Science 2018, 362 PMID: 30467144, PMCID: PMC6684198, DOI: 10.1126/science.aar2971.
- Using data to guide model constructionMiller-Jensen K, Arnold K. Using data to guide model construction. 2018, 51-70. DOI: 10.1201/9781315119847-4.
- Advancing systems immunology through data-driven statistical analysisFong LE, Muñoz-Rojas AR, Miller-Jensen K. Advancing systems immunology through data-driven statistical analysis. Current Opinion In Biotechnology 2018, 52: 109-115. PMID: 29656236, PMCID: PMC6294467, DOI: 10.1016/j.copbio.2018.03.009.
- Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunityPerry CJ, Muñoz-Rojas AR, Meeth KM, Kellman LN, Amezquita RA, Thakral D, Du VY, Wang JX, Damsky W, Kuhlmann AL, Sher JW, Bosenberg M, Miller-Jensen K, Kaech SM. Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity. Journal Of Experimental Medicine 2018, 215: 877-893. PMID: 29436395, PMCID: PMC5839759, DOI: 10.1084/jem.20171435.
- NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional NoiseWong VC, Bass VL, Bullock ME, Chavali AK, Lee REC, Mothes W, Gaudet S, Miller-Jensen K. NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise. Cell Reports 2018, 22: 585-599. PMID: 29346759, PMCID: PMC5812697, DOI: 10.1016/j.celrep.2017.12.080.
- Systems analysis of latent HIV reversal reveals altered stress kinase signaling and increased cell death in infected T cellsFong LE, Sulistijo ES, Miller-Jensen K. Systems analysis of latent HIV reversal reveals altered stress kinase signaling and increased cell death in infected T cells. Scientific Reports 2017, 7: 16179. PMID: 29170390, PMCID: PMC5701066, DOI: 10.1038/s41598-017-15532-0.
- Tumor Necrosis Factor-α and IL-17A Activation Induces Pericyte-Mediated Basement Membrane Remodeling in Human Neutrophilic DermatosesLauridsen HM, Pellowe AS, Ramanathan A, Liu R, Miller-Jensen K, McNiff JM, Pober JS, Gonzalez AL. Tumor Necrosis Factor-α and IL-17A Activation Induces Pericyte-Mediated Basement Membrane Remodeling in Human Neutrophilic Dermatoses. American Journal Of Pathology 2017, 187: 1893-1906. PMID: 28609645, PMCID: PMC5530916, DOI: 10.1016/j.ajpath.2017.04.008.
- Distinct Signaling Thresholds Distinguish Friend from FoeMiller-Jensen K. Distinct Signaling Thresholds Distinguish Friend from Foe. Cell Systems 2016, 2: 360-361. PMID: 27336965, DOI: 10.1016/j.cels.2016.06.003.
- Redefining Signaling Pathways with an Expanding Single-Cell ToolboxGaudet S, Miller-Jensen K. Redefining Signaling Pathways with an Expanding Single-Cell Toolbox. Trends In Biotechnology 2016, 34: 458-469. PMID: 26968612, PMCID: PMC4958913, DOI: 10.1016/j.tibtech.2016.02.009.
- Generalized selection to overcome innate immunity selects for host breadth in an RNA virusWasik BR, Muñoz‐Rojas A, Okamoto KW, Miller‐Jensen K, Turner PE. Generalized selection to overcome innate immunity selects for host breadth in an RNA virus. Evolution 2016, 70: 270-281. PMID: 26882316, DOI: 10.1111/evo.12845.
- High-Throughput Secretomic Analysis of Single Cells to Assess Functional Cellular HeterogeneityMiller-Jensen K, Fan R. High-Throughput Secretomic Analysis of Single Cells to Assess Functional Cellular Heterogeneity. 2016, 41-54. DOI: 10.1142/9789814678735_0004.
- Distinct promoter activation mechanisms modulate noise-driven HIV gene expressionChavali AK, Wong VC, Miller-Jensen K. Distinct promoter activation mechanisms modulate noise-driven HIV gene expression. Scientific Reports 2015, 5: 17661. PMID: 26666681, PMCID: PMC4678399, DOI: 10.1038/srep17661.
- A passive-flow microfluidic device for imaging latent HIV activation dynamics in single T cellsRamji R, Wong VC, Chavali AK, Gearhart LM, Miller-Jensen K. A passive-flow microfluidic device for imaging latent HIV activation dynamics in single T cells. Integrative Biology 2015, 7: 998-1010. PMID: 26138068, PMCID: PMC4558391, DOI: 10.1039/c5ib00094g.
- Analysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulationXue Q, Lu Y, Eisele MR, Sulistijo ES, Khan N, Fan R, Miller-Jensen K. Analysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulation. Science Signaling 2015, 8: ra59. PMID: 26082435, PMCID: PMC5735825, DOI: 10.1126/scisignal.aaa2155.
- Assessing Host Immune Response to Dengue Virus Infection at Single‐Cell ResolutionSulistijo E, Miller‐Jensen K. Assessing Host Immune Response to Dengue Virus Infection at Single‐Cell Resolution. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.571.26.
- Highly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligandsLu Y, Xue Q, Eisele MR, Sulistijo ES, Brower K, Han L, Amir el-AD, Pe'er D, Miller-Jensen K, Fan R. Highly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligands. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e607-e615. PMID: 25646488, PMCID: PMC4343126, DOI: 10.1073/pnas.1416756112.
- “Pop-slide” patterning: rapid fabrication of microstructured PDMS gasket slides for biological applicationsRamji R, Khan NT, Muñoz-Rojas A, Miller-Jensen K. “Pop-slide” patterning: rapid fabrication of microstructured PDMS gasket slides for biological applications. RSC Advances 2015, 5: 66294-66300. PMID: 26949529, PMCID: PMC4772973, DOI: 10.1039/c5ra09056c.
- Quantitative Evaluation and Optimization of Co-drugging to Improve Anti-HIV Latency TherapyWong VC, Fong LE, Adams NM, Xue Q, Dey SS, Miller-Jensen K. Quantitative Evaluation and Optimization of Co-drugging to Improve Anti-HIV Latency Therapy. Cellular And Molecular Bioengineering 2014, 7: 320-333. PMID: 26191086, PMCID: PMC4501041, DOI: 10.1007/s12195-014-0336-9.
- Genetic Selection for Context-Dependent Stochastic Phenotypes: Sp1 and TATA Mutations Increase Phenotypic Noise in HIV-1 Gene ExpressionMiller-Jensen K, Skupsky R, Shah PS, Arkin AP, Schaffer DV. Genetic Selection for Context-Dependent Stochastic Phenotypes: Sp1 and TATA Mutations Increase Phenotypic Noise in HIV-1 Gene Expression. PLOS Computational Biology 2013, 9: e1003135. PMID: 23874178, PMCID: PMC3708878, DOI: 10.1371/journal.pcbi.1003135.
- High-Throughput Secretomic Analysis of Single Cells to Assess Functional Cellular HeterogeneityLu Y, Chen JJ, Mu L, Xue Q, Wu Y, Wu PH, Li J, Vortmeyer AO, Miller-Jensen K, Wirtz D, Fan R. High-Throughput Secretomic Analysis of Single Cells to Assess Functional Cellular Heterogeneity. Analytical Chemistry 2013, 85: 2548-2556. PMID: 23339603, PMCID: PMC3589817, DOI: 10.1021/ac400082e.
- Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expressionMiller-Jensen K, Dey SS, Pham N, Foley JE, Arkin AP, Schaffer DV. Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression. Integrative Biology 2012, 4: 661-671. PMID: 22555315, PMCID: PMC3362694, DOI: 10.1039/c2ib20009k.
- Systems biology of virus-host signaling network interactionsXue Q, Miller-Jensen K. Systems biology of virus-host signaling network interactions. BMB Reports 2012, 45: 213-220. PMID: 22531130, DOI: 10.5483/bmbrep.2012.45.4.213.
- Varying virulence: epigenetic control of expression noise and disease processesMiller-Jensen K, Dey SS, Schaffer DV, Arkin AP. Varying virulence: epigenetic control of expression noise and disease processes. Trends In Biotechnology 2011, 29: 517-525. PMID: 21700350, DOI: 10.1016/j.tibtech.2011.05.004.
- Control of Stochastic Gene Expression by Host Factors at the HIV PromoterBurnett JC, Miller-Jensen K, Shah PS, Arkin AP, Schaffer DV. Control of Stochastic Gene Expression by Host Factors at the HIV Promoter. PLOS Pathogens 2009, 5: e1000260. PMID: 19132086, PMCID: PMC2607019, DOI: 10.1371/journal.ppat.1000260.
- Common effector processing mediates cell-specific responses to stimuliMiller-Jensen K, Janes KA, Brugge JS, Lauffenburger DA. Common effector processing mediates cell-specific responses to stimuli. Nature 2007, 448: 604-608. PMID: 17637676, DOI: 10.1038/nature06001.
- Adenoviral vector saturates Akt pro-survival signaling and blocks insulin-mediated rescue of tumor-necrosis-factor-induced apoptosisMiller-Jensen K, Janes KA, Wong YL, Griffith LG, Lauffenburger DA. Adenoviral vector saturates Akt pro-survival signaling and blocks insulin-mediated rescue of tumor-necrosis-factor-induced apoptosis. Journal Of Cell Science 2006, 119: 3788-3798. PMID: 16940353, DOI: 10.1242/jcs.03102.