Melanie Rutkowski

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Primary Appointment

Associate Professor, Microbiology, Immunology, and Cancer Biology

Education

  • PhD, Molecular Biology, Montana State University

Research Disciplines

Cancer Biology, Immunology, Microbiology, Translational Science

Research Interests

Influence of commensal microbes on immune homeostasis, anti-tumor immunity, and metastasis

Research Description

Humans are colonized with trillions of microorganisms, collectively termed the microbiota. Aside from providing a first line of defense to invading pathogens or aiding in digestion and metabolism, commensal microbes are indispensable for the development of systemic inflammatory immune responses. The question is whether these microorganisms can directly influence diseases associated with systemic inflammation, such as cancer. Recently, we have shown that commensal microbes modulate systemic tumor-promoting inflammation by facilitating crosstalk between the immune system and a tumor developing outside of the intestines (Rutkowski et al. Cancer Cell, 2015). This was due, in part, to TLR5-mediated differences within the composition of commensal microbes in addition to tumor-induced inflammation.
We are currently interested in extending these studies further, so that we can understand how crosstalk between the commensal microbiome and immune system influence tumor initiation, growth, and metastatic dissemination. Our lab is interested in two major areas:
1) How do commensal microbes influence tumor growth and metastasis?
Tumor initiation, growth, and metastatic dissemination are dynamic processes that are influenced by local and systemic factors, including changes to commensal microbes. We have developed a breast cancer model where we can deliberately perturb the commensal ecosystem to attenuate metastatic disease, allowing the characterization of cellular and molecular factors within the tumor microenvironment that facilitate early dissemination and metastatic spread of breast tumor cells. Other projects are focused towards the identification of commensal-modulated immune or metabolic factors that impact tumor progression and metastatic disease in both ovarian and breast cancer, using transgenic mice and in vivo Crispr/Cas9 genome editing. The overarching goal for these projects is to leverage our discoveries towards the development of strategies that enhance anti-tumor immune responses or that alleviate immune-suppressive inflammation.
2) How do tumors influence the immune homeostasis at barrier surfaces?
We are also interested in understanding in how extraintestinal tumors influence the immune homeostasis at mucosal surfaces, with a focus upon characterizing innate immune changes. Projects include defining a role for exosomes in modulating the systemic immune environment and developing strategies that synergize with using checkpoint inhibitor therapy for the treatment of advanced hormone receptor+ breast cancer and for ovarian cancer. We are also characterizing how changes within the composition of commensal microbes might provide early biomarkers for developing tumors or for advanced metastatic disease and whether changes occurring at mucosal surfaces can predict responsiveness to immunotherapy. By combining mouse models with analysis of human specimens, our goal is to re-engineer the systemic immune environment of individuals with cancer through the restoration of commensal homeostasis to enhance treatment of metastatic disease.
The Rutkowski lab is accepting graduate students from the BIMS and MSTP programs.
http://bims.virginia.edu/
https://mstp.med.virginia.edu/

Training

  • Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences
  • Biotechnology Training Grant
  • Cancer Research Training in Molecular Biology
  • Interdisciplinary Training Program in Immunology

Selected Publications

2022

Feng, T. -Y., Azar, F. N., Dreger, S. A., Rosean, C. B., McGinty, M. T., Putelo, A. M., . . . Rutkowski, M. R. (2022). Reciprocal Interactions Between the Gut Microbiome and Mammary Tissue Mast Cells Promote Metastatic Dissemination of HR plus Breast Tumors. CANCER IMMUNOLOGY RESEARCH, 10(11), 1309-1325. doi:10.1158/2326-6066.CIR-21-1120

Harris, A. R., Esparza, S., Azimi, M. S., Cornelison, R., Azar, F. N., Llaneza, D. C., . . . Munson, J. M. (2022). Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy. FRONTIERS IN ONCOLOGY, 12. doi:10.3389/fonc.2022.801764

2021

McKee, A. M., Kirkup, B. M., Madgwick, M., Fowler, W. J., Price, C. A., Dreger, S. A., . . . Robinson, S. D. (2021). Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth. ISCIENCE, 24(9). doi:10.1016/j.isci.2021.103012

Melssen, M. M., Lindsay, R. S., Stasiak, K., Rodriguez, A. B., Briegel, A. M., Cyranowski, S., . . . Engelhard, V. H. (2021). Differential Expression of CD49a and CD49b Determines Localization and Function of Tumor-Infiltrating CD8(+) T Cells. CANCER IMMUNOLOGY RESEARCH, 9(5), 583-597. doi:10.1158/2326-6066.CIR-20-0427

2020

Bishop, R. C., Boretto, M., Rutkowski, M. R., Vankelecom, H., & Derre, I. (2020). Murine Endometrial Organoids to ModelChlamydiaInfection. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 10. doi:10.3389/fcimb.2020.00416

2019

Martinez, L. M., Robila, V., Clark, N. M., Du, W., Idowu, M. O., Rutkowski, M. R., & Bos, P. D. (2019). Regulatory T Cells Control the Switch From in situ to Invasive Breast Cancer. FRONTIERS IN IMMUNOLOGY, 10. doi:10.3389/fimmu.2019.01942

Rosean, C. B., Bostic, R. R., Ferey, J. C. M., Feng, T. -Y., Azar, F. N., Tung, K. S., . . . Rutkowski, M. R. (2019). Preexisting Commensal Dysbiosis Is a Host-Intrinsic Regulator of Tissue Inflammation and Tumor Cell Dissemination in Hormone Receptor-Positive Breast Cancer. CANCER RESEARCH, 79(14), 3662-3675. doi:10.1158/0008-5472.CAN-18-3464

Rosean, C. B., Feng, T. -Y., Azar, F. N., & Rutkowski, M. R. (2019). Impact of the microbiome on cancer progression and response to anti-cancer therapies. IMMUNOTHERAPY OF CANCER, 143, 255-294. doi:10.1016/bs.acr.2019.03.005

2018

Song, M., Sandoval, T. A., Chae, C. -S., Chopra, S., Tan, C., Rutkowski, M. R., . . . Cubillos-Ruiz, J. R. (2018). IRE1 alpha-XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity. NATURE, 562(7727), 423-+. doi:10.1038/s41586-018-0597-x

Perales-Puchalt, A., Perez-Sanz, J., Payne, K. K., Svoronos, N., Allegrezza, M. J., Chaurio, R. A., . . . Conejo-Garcia, J. R. (2018). Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy. JOURNAL OF LEUKOCYTE BIOLOGY, 103(5), 799-805. doi:10.1002/JLB.5HI1117-446RR

2017

Rosean, C. M. B., & Rutkowski, M. R. (2017). The influence of the commensal microbiota on distal tumor-promoting inflammation. SEMINARS IN IMMUNOLOGY, 32(C), 62-73. doi:10.1016/j.smim.2017.06.002

Svoronos, N., Perales-Puchalt, A., Allegrezza, M. J., Rutkowski, M. R., Payne, K. K., Tesone, A. J., . . . Conejo-Garcia, J. R. (2017). Tumor Cell-Independent Estrogen Signaling Drives Disease Progression through Mobilization of Myeloid-Derived Suppressor Cells. CANCER DISCOVERY, 7(1), 72-85. doi:10.1158/2159-8290.CD-16-0502

Perales-Puchalt, A., Svoronos, N., Rutkowski, M. R., Allegrezza, M. J., Tesone, A. J., Payne, K. K., . . . Conejo-Garcia, J. R. (2017). Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target. CLINICAL CANCER RESEARCH, 23(2), 441-453. doi:10.1158/1078-0432.CCR-16-0492

2016

Allegrezza, M. J., Rutkowski, M. R., Stephen, T. L., Svoronos, N., Perales-Puchalt, A., Nguyen, J. M., . . . Conejo-Garcia, J. R. (2016). Trametinib Drives T-cell-Dependent Control of KRAS-Mutated Tumors by Inhibiting Pathological Myelopoiesis. CANCER RESEARCH, 76(21), 6253-6265. doi:10.1158/0008-5472.CAN-16-1308

Sheen, M. R., Marotti, J. D., Allegrezza, M. J., Rutkowski, M., Conejo-Garcia, J. R., & Fiering, S. (2016). Constitutively activated PI3K accelerates tumor initiation and modifies histopathology of breast cancer. ONCOGENESIS, 5. doi:10.1038/oncsis.2016.65

Zhu, H., Bengsch, F., Svoronos, N., Rutkowski, M. R., Bitler, B. G., Allegrezza, M. J., . . . Zhang, R. (2016). BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression. CELL REPORTS, 16(11), 2829-2837. doi:10.1016/j.celrep.2016.08.032

Conejo-Garcia, J. R., Rutkowski, M. R., & Cubillos-Ruiz, J. R. (2016). State-of-the-art of regulatory dendritic cells in cancer. PHARMACOLOGY & THERAPEUTICS, 164, 97-104. doi:10.1016/j.pharmthera.2016.04.003

Allegrezza, M. J., Rutkowski, M. R., Stephen, T. L., Svoronos, N., Tesone, A. J., Perales-Puchalt, A., . . . Conejo-Garcia, J. R. (2016). IL15 Agonists Overcome the Immunosuppressive Effects of MEK Inhibitors. CANCER RESEARCH, 76(9), 2561-2572. doi:10.1158/0008-5472.CAN-15-2808

Tesone, A. J., Rutkowski, M. R., Brencicova, E., Svoronos, N., Perales-Puchalt, A., Stephen, T. L., . . . Conejo-Garcia, J. R. (2016). Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells. CELL REPORTS, 14(7), 1774-1786. doi:10.1016/j.celrep.2016.01.056

2015

Conejo-Garcia, J. R., & Rutkowski, M. R. (2015). Small but Mighty: Selected Commensal Bacterial Species Determine the Effectiveness of Anti-cancer Immunotherapies. IMMUNITY, 43(6), 1037-1039. doi:10.1016/j.immuni.2015.11.014

Cubillos-Ruiz, J. R., Silberman, P. C., Rutkowski, M. R., Chopra, S., Perales-Puchalt, A., Song, M., . . . Glimcher, L. H. (2015). ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis. CELL, 161(7), 1527-1538. doi:10.1016/j.cell.2015.05.025

Rutkowski, M. R., Stephen, T. L., Svoronos, N., Allegrezza, M. J., Tesone, A. J., Perales-Puchalt, A., . . . Conejo-Garcia, J. R. (2015). Microbially Driven TLR5-Dependent Signaling Governs Distal Malignant Progression through Tumor-Promoting Inflammation. CANCER CELL, 27(1), 27-40. doi:10.1016/j.ccell.2014.11.009

Rutkowski, M. R., & Conejo-Garcia, J. R. (2015). Size does not matter: commensal microorganisms forge tumor-promoting inflammation and anti-tumor immunity.. Oncoscience, 2(3), 239-246. doi:10.18632/oncoscience.145

Rutkowski, M. R., Svoronos, N., Perales-Puchalt, A., & Conejo-Garcia, J. R. (2015). The Tumor Macroenvironment: Cancer-Promoting Networks Beyond Tumor Beds. IMMUNOTHERAPY OF CANCER, 128, 235-262. doi:10.1016/bs.acr.2015.04.011

Rutkowski, M. R., & Conejo-Garcia, J. R. (2015). TLR5 signaling, commensal microbiota and systemic tumor promoting inflammation: the three parcae of malignant progression. ONCOIMMUNOLOGY, 4(8). doi:10.1080/2162402X.2015.1021542

2014

Rutkowski, M. R., Allegrezza, M. J., Svoronos, N., Tesone, A. J., Stephen, T. L., Perales-Puchalt, A., . . . Conejo-Garcia, J. R. (2014). Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (92). doi:10.3791/51171

Stephen, T. L., Rutkowski, M. R., Allegrezza, M. J., Perales-Puchalt, A., Tesone, A. J., Svoronos, N., . . . Conejo-Garcia, J. R. (2014). Transforming Growth Factor beta-Mediated Suppression of Antitumor T Cells Requires FoxP1 Transcription Factor Expression. IMMUNITY, 41(3), 427-439. doi:10.1016/j.immuni.2014.08.012

Rutkowski, M. R., Allegrezza, M. J., Svoronos, N., Tesone, A. J., Stephen, T. L., Perales-Puchalt, A., . . . Conejo-Garcia, J. R. (2014). Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (85). doi:10.3791/51171

2013

Baird, J. R., Fox, B. A., Sanders, K. L., Lizotte, P. H., Cubillos-Ruiz, J. R., Scarlett, U. K., . . . Bzik, D. J. (2013). Avirulent Toxoplasma gondii Generates Therapeutic Antitumor Immunity by Reversing Immunosuppression in the Ovarian Cancer Microenvironment. CANCER RESEARCH, 73(13), 3842-3851. doi:10.1158/0008-5472.CAN-12-1974

Cubillos-Ruiz, J. R., Rutkowski, M. R., Tchou, J., & Conejo-Garcia, J. R. (2013). Reprogramming immune responses via microRNA modulation. . microRNA diagnostics and therapeutics, 1(1), 2013-0001. doi:10.2478/micrnat-2013-0001

2012

Hampton, T. H., Ballok, A. E., Bomberger, J. M., Rutkowski, M. R., Barnaby, R., Coutermarsh, B., . . . Stanton, B. A. (2012). Does the Delta F508-CFTR mutation induce a proinflammatory response in human airway epithelial cells?. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 303(6), L509-L518. doi:10.1152/ajplung.00226.2011

Cubillos-Ruiz, J. R., Baird, J. R., Tesone, A. J., Rutkowski, M. R., Scarlett, U. K., Camposeco-Jacobs, A. L., . . . Conejo-Garcia, J. R. (2012). Reprogramming Tumor-Associated Dendritic Cells In Vivo Using miRNA Mimetics Triggers Protective Immunity against Ovarian Cancer. CANCER RESEARCH, 72(7), 1683-1693. doi:10.1158/0008-5472.CAN-11-3160

Scarlett, U. K., Rutkowski, M. R., Rauwerdink, A. M., Fields, J., Escovar-Fadul, X., Baird, J., . . . Conejo-Garcia, J. R. (2012). Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. JOURNAL OF EXPERIMENTAL MEDICINE, 209(3), 495-506. doi:10.1084/jem.20111413

Rutkowski, M. R., Stephen, T. L., & Conejo-Garcia, J. R. (2012). Anti-tumor immunity: Myeloid leukocytes control the immune landscape. CELLULAR IMMUNOLOGY, 278(1-2), 21-26. doi:10.1016/j.cellimm.2012.06.014

2011

Rutkowski, M. R., Stevens, C. A., & Green, W. R. (2011). Impaired memory CD8 T cell responses against an immunodominant retroviral cryptic epitope. VIROLOGY, 412(2), 256-268. doi:10.1016/j.virol.2010.11.013

2010

Cubillos-Ruiz, J. R., Martinez, D., Scarlett, U. K., Rutkowski, M. R., Nesbeth, Y. C., Camposeco-Jacobs, A. L., & Conejo-Garcia, J. R. (2010). cd277 is a Negative Co-stimulatory Molecule Universally Expressed by Ovarian Cancer Microenvironmental Cells. ONCOTARGET, 1(5), 329-338. doi:10.18632/oncotarget.165

Nesbeth, Y. C., Martinez, D. G., Toraya, S., Scarlett, U. K., Cubillos-Ruiz, J. R., Rutkowski, M. R., & Conejo-Garcia, J. R. (2010). CD4(+) T Cells Elicit Host Immune Responses to MHC Class II- Ovarian Cancer through CCL5 Secretion and CD40-Mediated Licensing of Dendritic Cells. JOURNAL OF IMMUNOLOGY, 184(10), 5654-5662. doi:10.4049/jimmunol.0903247

Pittet, L. A., Hall-Stoodley, L., Rutkowski, M. R., & Harmsen, A. G. (2010). Influenza Virus Infection Decreases Tracheal Mucociliary Velocity and Clearance of Streptococcus pneumoniae. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 42(4), 450-460. doi:10.1165/rcmb.2007-0417OC

Cubillos-Ruiz, J. R., Rutkowski, M., & Conejo-Garcia, J. R. (2010). Blocking ovarian cancer progression by targeting tumor microenvironmental leukocytes. CELL CYCLE, 9(2), 260-268. doi:10.4161/cc.9.2.10430