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      Jlenia Guarnerio Image

      Jlenia Guarnerio, Ph.D.

      Department of Genetics, Division of Discovery Science

      Present Title & Affiliation

      Primary Appointment

      Assistant Professor, Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas

      Dual/Joint/Adjunct Appointment

      Assistant Professor, Department of Genetics, MD Anderson Cancer Center, Houston, TX

      Research Interests

      Throughout my scientific career, I have focused my research on leukemia and sarcoma, and dissected some of the molecular mechanisms responsible for the pathogenesis of these tumors. Although very different in nature, development, and genetics, leukemia and sarcoma share a common element, the Mesenchymal Stem/Stromal Cells (MSCs). MSCs sustain normal hematopoietic stem cells and, in pathological conditions, provide a protective environment to leukemic cells in the bone marrow. In solid tumors, MSC become cancer-associated fibroblasts (CAFs) that promote tumor growth. From a different standpoint, MSCs and their progenitors are the cells of origin for sarcomas, which are aggressive and deadly mesenchymal tumors.

      My initial studies on MSCs facilitated three independent research areas:

      1. Developing immunocompetent sarcoma mouse models through mesenchymal cells engineering (Guarnerio et al., Cancer Discovery 2015).
      2. Characterizing how MSCs shape the microenvironment of solid tumors and leukemia (Guarnerio et al., Cell Stem Cells 2014, Guarnerio et al., Nature Communications 2018).
      3. Defining the contribution of circular RNAs (circRNAs) to leukemia and sarcoma (Guarnerio et al., Cell 2016, Guarnerio et al., Cell Research 2019).

      The Guarnerio lab is now building on my previous work, and more broadly speaking is committed to unraveling the intricate molecular mechanisms employed by tumor cells to shape a pro-tumorigenic tumor microenvironment (TME). To gain a comprehensive understanding of the TME and the interactions among the cells that compose it, we characterize both mouse and human tissues by employing leading-edge technologies such as single-cell RNA sequencing and spatial transcriptomics. Furthermore, we leverage functional genomics tools and immune-competent tumor mouse models to investigate specific molecular mechanisms in a functional context. Our research endeavors are firmly rooted in translational science, aiming to bridge the gap between fundamental discoveries and their practical applications in clinical settings. Ultimately, our overarching goal is to develop novel cancer therapies based on reprogramming tumor cells and the TME.


      Education & Training

      Degree-Granting Education

      2012University San Raffaele, Milan, IT, PhD
      2008University San Raffaele, Milan, IT, MS
      2006University San Raffaele, Milan, IT, Medical and Pharmaceutical Biotechnology, BS

      Postgraduate Training

      2012-2018Postdoctoral Fellow, Harvard Medical School BIDMC, Boston, MA

      Experience & Service

      Faculty Academic Appointments

      Adjunct Assistant Professor, Hematology and Oncology, UCLA, Los Angeles, CA, 2018 - 2024

      Assistant Professor, Biomedical Science, Radiation Oncology - Research, Cedars-Sinai Medical Center, Los Angeles, CA, 2018 - 2024

      Extramural Institutional Committee Activities

      Reviewer, GSBS Membership Committee, The University of Texas MD Anderson Cancer Center, 2026 - 2029

      Faculty Advisor, G&E PhD Program Retreat Committee, University of Texas MD Anderson Cancer Center, 2025 - 2025

      Faculty Advisor and Host, G&E PhD Program Rotation Talks, University of Texas MD Anderson Cancer Center, 2025

      Member, Academic Review Committee, University of Texas MD Anderson Cancer Center, 2025 - Present

      Member, Flow Cytometry Core Faculty Advisory Committee Meeting, Cedars-Sinai Medical Center, 2023 - 2024

      Member, Committee for Oversight of Training and Education, Cedars-Sinai Medical Center, 2021 - 2024

      Member, Radiation Safety Committee, Cedars-Sinai Medical Center, 2021 - 2024

      Honors & Awards

      2023Scholar Award, American Cancer Society
      2021Recognition Award, UCLA Clinical and Translational Science Institute (CTSI)
      2019Recognition Award, UCLA Clinical and Translational Science Institute (CTSI)
      2016Pathway to Independence Award (K99/R00), NIH/NCI
      2013Scientific Excellence in Medicine Award, American Italian Cancer Foundation (AICF)

      Professional Memberships

      Society for Immunotherapy of Cancer

      2026 - Present

      Sarcoma Foundation of America

      2019 - Present

      American Association of Cancer Research

      2014 - Present

      Selected Presentations & Talks

      Local Presentations

      1. 2026. New Insights into Molecular and Cellular Dynamics in the Sarcoma Microenvironment. Sarcoma Medical Oncology Lecture Series. Houston, Texas, US.
      2. 2026. New Insights into Molecular and Cellular Dynamics in the Sarcoma Microenvironment. Pediatrics Division. Houston, Texas, US.
      3. 2025. Role of circRNAs in the tumor microenvironment. Houston, Texas, US.
      4. 2024. Spotlight on cellular and molecular elements in the sarcoma microenvironment. Houston, Texas, US.
      5. 2023. Circular RNAs and mechanisms of immune exclusion in sarcoma. Houston, TX, US.
      6. 2023. Circular RNAs and mechanisms of immune exclusion in sarcoma. Houston, TX, US.

      National Presentations

      1. 2025. New insights into Molecular and Cellular Dynamics in the Sarcoma Microenvironment. Seattle, WA, US.
      2. 2024. Metabolic targeting of sarcoma associated fibroblasts: Therapeutic implications. Strategic Advances in Sarcoma Science (SASS). Bethesda, MD, US.
      3. 2023. Circular RNAs and mechanisms of immune exclusion in sarcoma. Boston, MA, US.
      4. 2023. New molecular and cellular components of the sarcoma microenvironment. Los Angeles, CA, US.
      5. 2022. Targeting sarcoma-TME interacting elements. Drug Discovery Focus Meeting. Los Angeles, CA, US.
      6. 2022. Comparative modeling of sarcoma microenvironment for the discovery of biomarkers and tumor vulnerabilities. Oncology Models Forum, Annual Meeting. Bethesda, MD, US.

      International Presentations

      1. 2024. New insights into Molecular and Cellular Dynamics in the Sarcoma Microenvironment. Milan, IT.
      2. 2019. Identifying the role of circular RNAs in tumorigenesis. Milan, IT.
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      Selected Publications

      Peer-Reviewed Articles

      1. Pareek S, Wright RD, Ballaro R, Xue C, Bartelli TF, Chandra V, Li L, Ortiz J, Lam T, Patel H, Lee J, Shrestha P, Savage H, Le Roux O, Liu H, Vallejo-Schmidt T, De Maleki R, Putluri V, Putluri N, Petrosino JF, Burks JK, Gomez JA, Guarnerio J, Katz MHG, Ngo-Huang A, Prakash LR, Parker NH, Petzel MQB, Tan L, Baydogan S, McAllister F, Schadler KL. Exercise modulates microbial metabolites and induces stromal remodeling in pancreatic cancer. Cancer Res, 2026. e-Pub 2026. PMID: 42623301.
      2. Silva TF, Concato-Lopes V, Bedier F, Newman L, Kitka D, Brown J, Victor B, Kim M, Vagner T, Grasso C, Sheyn D, You S, Freeman M, Sutterwala F, Goodridge H, Jefferies C, Candia PD, Guarnerio J, Di Vizio AD. Large oncosomes reprogram bone marrow mesenchymal stem cells to establish a pre-metastatic niche. Cancer Res. e-Pub 2026.
      3. Piras R, Xiao J, Fowler A, Ko EY, Guarnerio J. Mesothelial stress adaptation drives retroperitoneal sarcoma progression through the Enpp2–LPA signaling axis. Cell Res. e-Pub 2026.
      4. Xiao J, Ko EY, Smith A, Piras R, Fowler A, Ishaya K, Wang L, Wang B, Paulucci-Holthauzen A, Landers SM, Bhalla AD, Torres KE, Shamsutdinova D, Wani KM, Lazar AJ, Keung EZ, Somaiah N, Nassif Haddad EF, Guarnerio J. LPAR4 mediates adaptation to interferon-induced stress in soft tissue sarcoma. Science Advances. Sci Adv 12(24), 2026. e-Pub 2026. PMID: 42284392.
      5. Silva, TF, Hutchins, E, Zhao, W, Ciani, Y, Kim, M, Ko, EY, Mariscal, J, Qiu, Z, Bedier, F, Kittel, A, Zhou, B, Wang, Y, Hall, M, Galasso, F, Reiman, R, Freeman, MR, Parker, SJ, van Eyk, JE, Yang, W, Posadas, EM, Guarnerio, J, Nolan, J, Thery, C, Zijlstra, A, Stott, SL, You, S, Demichelis, F, Boutros, PC, Van Keuren-Jensen, K, Di Vizio, D. Extracellular vesicle heterogeneity through the lens of multiomics. Cell Reports Medicine 6(7), 2025. e-Pub 2025. PMID: 40482644.
      6. Xiao, J, Ishaya, K, Ko, EY, Fowler, A, Broz, MT, Guarnerio, J. Periostin Promotes Sarcoma Growth by Promoting Tumor-Associated Macrophage Migration and Differentiation. Cancer Research Communications 5(12):2224-2235, 2025. e-Pub 2025. PMID: 41448855.
      7. Broz MT, Ko EY, Ishaya K, Xiao J, De Simone M, Hoi XP, Piras R, Basia G, Tessaro FHG, Karlstaedt A, Orsulic S, Lund A, Chan KS, Guarnerio J. Metabolic targeting of cancer associated fibroblasts overcomes T-cell exclusion and chemoresistance in soft-tissue sarcomas. Nat Commun 15(1), 2024. e-Pub 2024. PMID: 38509063.
      8. Piras R, Ko EY, Barrett C, De Simone M, Lin X, Broz MT, Tessaro FHG, Castillo-Martin M, Cordon-Cardo C, Goodridge HS, Di Vizio D, Batish M, Lawrenson K, Chen YG, Keith Chan KS, Guarnerio J. circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment. Nat Commun 13(1), 2022. e-Pub 2022. PMID: 36433954.
      9. Tessaro FHG, Ko EY, De Simone M, Piras R, Broz MT, Goodridge HS, Balzer B, Shiao SL, Guarnerio J. Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity. Cell Reports 39(12), 2022. e-Pub 2022. PMID: 35732118.
      10. Nikolos F, Hayashi K, Hoi XP, Alonzo ME, Mo Q, Kasabyan A, Furuya H, Trepel J, Di Vizio D, Guarnerio J, Theodorescu D, Rosser C, Apolo A, Galsky M, Chan KS. Cell death-induced immunogenicity enhances chemotherapeutic response by converting immune-excluded into T-cell inflamed bladder cancer. Nat Commun 13(1), 2022. e-Pub 2022. PMID: 35347124.
      11. Koppula A, Abdelgawad A, Guarnerio J, Batish M, Parashar V. circFISH: A Novel Method for the Simultaneous Imaging of Linear and Circular RNAs. Cancers (Basel) 14(2), 2022. e-Pub 2022. PMID: 35053590.
      12. Chin A, Mariscal J, Kim M, Guerra G, Victor B, Qian C, Broseghini E, Posadas E, Freeman MR, Sharma S, Gandellini P, Zaffaroni N, You S, Chan KS, Guarnerio J, Fabbri M, Di Vizio D. miR-1227 targets SEC23A to regulate the shedding of large extracellular vesicles. Cancers (Basel), 2021. e-Pub 2021. PMID: 34831007.
      13. Shiao SL, Kershaw KM, Limon JJ, You S, Yoon J, Ko EY, Guarnerio J, Potdar AA, McGovern DPB, Bose S, Dar TB, Noe P, Lee J, Kubota Y, Maymi VI, Davis MJ, Henson RM, Choi RY, Yang W, Tang J, Gargus M, Prince AD, Zumsteg ZS, Underhill DM. Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy. Cancer Cell, 2021. e-Pub 2021. PMID: 34329585.
      14. Guarnerio J, Zhang Y, Cheloni G, Panella R, Katon JM, Simpson M, Matsumoto A, Papa A, Loretelli C, Petri A, Kauppinen S, Garbutt C, Nielsen GP, Deshpande V, Castillo-Martin M, Cordon-Cardo C, Dimitrios S, Clohessy JG, Batish M, Pandolfi PP. Intragenic antagonistic role for Zbtb7a protein and circRNA in tumorigenesis. Cell Res, 2019. e-Pub 2019. PMID: 31209250.
      15. Mugoni V, Panella R, Cheloni G, Chen M, Pozdnyakova O, Stroopinsky D, Guarnerio J, Monteleone E, Lee JD, Mendez L, Venugopal Menon A, Aster JC, Lane AA, Stone AM, Galinsky I, Zamora JC, Lo-Coco F, Bhasin MK, Avigan D, Longo L, Clohessy JG, Pandolfi PP. Vulnerabilities in mIDH2 AML confer sensitivity to APL-like targeted combination therapy. Cell Res, 2019. e-Pub 2019. PMID: 31024166.
      16. Guarnerio J, Mendez LM, Asada N, Menon AV, Fung J, Berry K, Frenette PS, Ito K, Pandolfi PP. A non-cell-autonomous role for PML in the maintenance of leukemia initiating cells from the niche. Nat Commun, 2018. e-Pub 2018. PMID: 29302031.
      17. German NJ, Yoon H, Yusuf RZ, Murphy JP, Finley LW, Laurent G, Haas W, Satterstrom FK, Guarnerio J, Zaganjor E, Santos D, Pandolfi PP, Beck AH, Gygi SP, Scadden DT, Jr KW, Haigis MC. PHD3 Loss in Cancer Enables Metabolic Reliance on Fatty Acid Oxidation via Deactivation of ACC2. Mol Cell, 2016. e-Pub 2016. PMID: 27635760.
      18. Guarnerio J, Bezzi M, Jeong JC, Paffenholz SV, Berry K, Naldini MM, Lo-Coco F, Tay Y, Beck AH, Pandolfi PP. Oncogenic role of aberrant fusion-circRNAs derived from cancer associated chromosomal translocations. Cell, 2016. e-Pub 2016. PMID: 27040497.
      19. Wei S, Kozono S, Kats L, Nechama M, Li W, Guarnerio J, Luo M, You MH, Yao Y, Kondo A, Hu H, Bozkurt G, Moerke NJ, Cao S, Reschke M, Chen CH, Rego EM, Lo-Coco F, Cantley LC, Lee TH, Wu H, Zhang Y, Pandolfi PP, Zhou XZ, Lu KP. Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer. Nat Med, 2015. e-Pub 2015. PMID: 25849135.
      20. Lunardi A, Varmeh S, Chen M, Taulli R, Guarnerio J, Ala U, Seitzer N, Ishikawa T, Carver BS, Hobbs RM, Quarantotti V, Ng C, Berger AH, Nardella C, Poliseno L, Montironi R, Castillo-Martin M, Cordon-Cardo C, Signoretti S, Pandolfi PP. Suppression of CHK1 by ETS Family Members Promotes DNA Damage Response Bypass and Tumorigenesis. Cancer Discov, 2015. e-Pub 2015. PMID: 25653093.
      21. Guarnerio J, Riccardi L, Taulli R, Maeda T, Wang G, Hobbs RM, Song MS, Sportoletti P, Bernardi R, Bronson RT, Castillo-Martin M, Cordon-Cardo C, Lunardi A, Pandolfi PP. A genetic platform to model sarcomagenesis from primary adult mesenchymal stem cells. Cancer Discov, 2015. e-Pub 2015. PMID: 25614485.
      22. Guarnerio J, Coltella N, Ala U, Tonon G, Pandolfi PP, Bernardi R. Bone Marrow endosteal mesenchymal progenitors depend on HIF factors for maintenance and regulation of hematopoiesis. Stem Cell Reports, 2014. e-Pub 2014. PMID: 24936467.
      23. Coltella N, Percio S, Valsecchi R, Cuttano R, Guarnerio J, Ponzoni M, Pandolfi PP, Melillo G, Pattini L, Bernardi R. HIF factors cooperate with PML-RARα to promote acute promyelocytic leukemia progression and relapse. EMBO Mol Med, 2014. e-Pub 2014. PMID: 24711541.
      24. Papa A, Wan L, Bonora M, Salmena L, Song MS, Hobbs RM, Lunardi A, Webster K, Ng C, Newton RH, Knoblauch N, Guarnerio J, Ito K, Turka LA, Beck AH, Pinton P, Bronson RT, Wei W, Pandolfi PP. Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. Cell, 2014. e-Pub 2014. PMID: 24766807.
      25. Schiering C, Guarnerio J, Basso V, Muzio L, Mondino A. Antigen-experienced CD4(+) T cells limit naïve T-cell priming in response to therapeutic vaccination in vivo. cancer research, 2010. e-Pub 2010. PMID: 20631073.
      26. Caserta S, Alessi P, Guarnerio J, Basso V, Mondino AA. Synthetic CD4 T cell- targeted Antigen-presenting cells elicit protective antitumor responses. Cancer Res, 2008. e-Pub 2008. PMID: 18413771.

      Review Articles

      1. Lunardi A, Guarnerio J, Wang G, Maeda T, Pandolfi PP. Role of LRF/Pokemon in lineage fate decisions. Blood, 2013. e-Pub 2013. PMID: 23396304.

      Abstracts

      1. Xiao JF, Ko E, Smith A, Piras R, Fowler A, Ishaya K, Guarnerio J. Stress adaptation defines therapeutic response to CDK4/6 inhibitors in sarcoma. AACR Annual Meeting.
      2. Kitka D, Sagini K, Victor B, Kim M, You S, Sutterwala F, Grasso C, Jefferies C, Guarnerio J, Candia PD, Cavassani K, Vagner T, Vizio DD. Heterogeneus Induction of Interferon Pathway in the Tumor Microenvironment by Different Populations of Cancer-Derived Extracellular Vesicles. ISEV 2022.
      3. Broz MT, DeSimone M, Ko E, Piras R, Guarnerio J. Uncovering transcriptional signatures of drug resistant tumor cells: mechanisms of therapeutic resistance and opportunities for combination therapies. AACR Tumor Immunology Meeting.
      4. Tessaro F, Ko E, Simone MD, Piras R, Broz M, Goodridge H, Balzer B, Shiao S, Guarnerio J. Single-cell RNA-seq analysis of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity. AACR Tumor Immunology Meeting.
      5. Xiao J, Broz M, Piras R, Ishaya K, Ko E, Guarnerio J. Profiling tumor microenvironment for therapeutic interventions to soft-tissue sarcoma. AACR annual meeting 2023.
      6. Piras R, Ko E, Simone MD, Tessaro F, Guarnerio J. Circular RNAs repress interferon responses in the sarcoma cells and promote tumor growth by forging a pro-tumorigenic immune-microenvironment. AACR annual meeting 2023.
      7. Nguyen AT, Dar TB, Viramontes J, Stevens S, Jang JK, Ko EY, Lu DJ, Chung EM, Zhang SC, Atkins KM, Kamrava M, Sandler HM, Guarnerio J, Knott S, Zumsteg ZS, Underhill DM, Shiao SL. Non-redundant mechanisms of immune-resistance to radiotherapy converge on innate immunity. AACR annual meeting 2024.
      8. Broz MT, Ko E, Xiao J, DeSimone M, Piras R, Ishaya K, Hoi XP, Guarnerio J. Glucose dependent CD73+ CAFs enforce a tumor metabolic barrier that promotes T cell exclusion. AACR annual meeting 2024.

      Letters to the Editor

      1. Bezzi M, Guarnerio J, Pandolfi PP. A circular twist on microRNA regulation. Cell Res, 2017.
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