Jlenia Guarnerio, Ph.D.
Department of Genetics, Division of Division of Discovery Science
Present Title & Affiliation
Primary Appointment
Assistant Professor, Department of Genetics, Division of Discovery Science, 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:
- Developing immunocompetent sarcoma mouse models through mesenchymal cells engineering (Guarnerio et al., Cancer Discovery 2015).
- Characterizing how MSCs shape the microenvironment of solid tumors and leukemia (Guarnerio et al., Cell Stem Cells 2014, Guarnerio et al., Nature Communications 2018).
- 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
| 2012 | University San Raffaele, Milan, IT, PhD |
| 2008 | University San Raffaele, Milan, IT, MS |
| 2006 | University San Raffaele, Milan, IT, Medical and Pharmaceutical Biotechnology, BS |
Postgraduate Training
| 2012-2018 | Postgraduate Fellow, Harvard Medical School BIDMC, Boston, MA |
Experience & Service
Faculty Academic Appointments
Assistant Professor, Department of Radiation Oncology - Research, Cedars-Sinai Medical Center, Los Angeles, CA, 2018 - 2024
Adjunct Assistant Professor, Department of Hematology/Oncology, UCLA, Los Angeles, CA, 2018 - 2024
Intramural Institutional Committee Activities
Member, Academic Review Committee, MD Anderson Cancer Center, 2025 - Present
Extramural Institutional Committee Activities
Member, Flow Cytometry Core Faculty Advisory Committee Meeting, Cedars-Sinai Medical Center - UCLA, 2023 - 2024
Member, Committee for Oversight of Training and Education, Cedars-Sinai Medical Center - UCLA, 2021 - 2024
Member, Radiation Safety Committee, Cedars-Sinai Medical Center - UCLA, 2021 - 2024
Honors & Awards
| 2022 | Los Angeles ResearcHERS Speaker, American Cancer Society |
| 2019 - 2020 | UCLA CTSI Recognition Award |
| 2013 | Finalist for the ISSANF-Award |
| 2013 - 2015 | American Italian Cancer Foundation (AICF) Award |
| 2009 - 2012 | International PhD in Molecular Medicine fellowship, University San Raffaele |
Professional Memberships
Selected Presentations & Talks
Regional Presentations
- 2024. Spotlight on cellular and molecular elements in the sarcoma microenvironment. Invited. Houston, TX, US.
- 2023. Circular RNAs and mechanisms of immune exclusion in sarcoma. Invited. Houston, TX, US.
- 2023. Circular RNAs and mechanisms of immune exclusion in sarcoma. Invited. Houston, TX, US.
- 2023. New molecular and cellular components of the sarcoma microenvironment. Invited. Los Angeles, CA, US.
- 2022. Targeting sarcoma-TME interacting elements. Invited. Drug discovery focus meeting. Los Angeles, CA, US.
National Presentations
- 2025. New insights into Molecular and Cellular Dynamics in the Sarcoma Microenvironment. Invited. Seattle, WA, US.
- 2024. Metabolic targeting of sarcoma associated fibroblasts: Therapeutic implications. Conference. SASS24. Bethesda, MD, US.
- 2023. Circular RNAs and mechanisms of immune exclusion in sarcoma. Invited. Boston, MA, US.
- 2022. Single-cell RNA-seq analysis of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity. Poster. AACR Tumor Immunology Meeting. Boston, MA, US.
- 2022. Comparative modeling of sarcoma microenvironment for the discovery of biomarkers and tumor vulnerabilities. Conference. Oncology models forum, annual meeting. Bethesda, MD, US.
International Presentations
- 2024. Spotlight on circular RNAs and cellular interactions in the sarcoma microenvironment. Invited. Milan.
Grant & Contract Support
| Date: | 2025 - 2028 |
| Title: | Unveiling Glycolytic Cancer-Associated Fibroblasts as Barriers to T Cell Infiltration in Sarcoma |
| Funding Source: | CPRIT |
| Role: | PI |
| ID: | RP260042 CPRIT |
| Date: | 2025 - 2030 |
| Title: | Generation of Novel Immunocompetent Mouse Models of Dedifferentiated Liposarcoma |
| Funding Source: | NCI |
| Role: | PI |
| ID: | R01CA306978 |
| Date: | 2025 - 2023 |
| Title: | Overcoming T Cell Exclusion for Sarcoma: Molecular Mechanisms and Therapeutic Strategies |
| Funding Source: | NCI |
| Role: | PI |
| ID: | R01CA306978 |
| Date: | 2025 - 2026 |
| Title: | Comprehensive analysis of the LMS microenvironment using spatial profiling and mouse models |
| Funding Source: | University of Michigan |
| Role: | PI |
| ID: | LMS SPORE |
| Date: | 2025 - 2026 |
| Title: | Single Cell Multiomics of Primary Soft Tissue Sarcomas and Their Matched Metastases |
| Funding Source: | SSO |
| Role: | Co-I |
| ID: | SSO Clinical Investigator Award |
| Date: | 2025 - 2027 |
| Title: | Extracellular vesicle enclosed circular RNA and interferon responses in tumor host interactions |
| Funding Source: | NCI |
| Role: | PI |
| ID: | R21CA299812 |
| Date: | 2025 - 2029 |
| Title: | Regulation of cardiac metabolism during Leukemia |
| Funding Source: | NHLBI |
| Role: | Co-I |
| ID: | R01 HL177461 |
| Date: | 2025 - 2030 |
| Title: | Endogenous circular RNAs limit abemaciclib anti-tumor immune responses |
| Funding Source: | NCI |
| Role: | PI |
| ID: | R01CA295834-01 |
| Date: | 2025 - 2026 |
| Title: | Targeting glyCAFs and their mechanisms of action in pancreatic cancer |
| Funding Source: | MD Anderson Cancer Center |
| Role: | PI |
| ID: | IRG MD Anderson |
| Date: | 2024 - 2026 |
| Title: | Glut1+ cancer associated fibroblasts enforce a metabolic barrier to tumor T cell infiltration |
| Funding Source: | NCI |
| Role: | Mentor |
| ID: | F31CA284888 |
| Date: | 2023 - 2026 |
| Title: | Investigate extracellular matrix proteins’ local and systemic role in promoting soft tissue sarcoma |
| Funding Source: | DoD |
| Role: | PI |
| ID: | DoD PCRP CA2102690 |
| Date: | 2023 - 2027 |
| Title: | Characterize the contribution of circular RNAs to sarcoma progression and treatment response |
| Funding Source: | American Cancer Society |
| Role: | PI |
| ID: | RSG-23-1037040-01-RMC |
| Date: | 2023 - 2024 |
| Title: | Engineered iPSC-derived Tumor-Associated Macrophages (iTAM) for tumor therapy |
| Funding Source: | Cedars-Sinai Cancer Center |
| Role: | PI |
| ID: | Cancer Center and Regenerative Medicine department joined award |
| Date: | 2023 - 2025 |
| Title: | Regulation of Cardiac Metabolism in Leukemia |
| Funding Source: | Cedars-Sinai Cancer Center |
| Role: | Co-I |
| ID: | CSRI-IRP |
| Date: | 2022 - 2023 |
| Title: | Generate Ewing’s sarcoma immunocompetent mouse models for the discovery of novel druggable tumor vulnerabilities |
| Funding Source: | ALAN B. SLIFKA FOUNDATION |
| Role: | PI |
| Date: | 2022 - 2023 |
| Title: | Cardiovascular remodeling in Leukemia |
| Funding Source: | LEUKEMIA RESEARCH FOUNDATION |
| Role: | Co-I |
| ID: | LRF |
| Date: | 2021 - 2026 |
| Title: | Comparative modeling of sarcoma microenvironments for the discovery of biomarkers and tumor vulnerabilities |
| Funding Source: | NCI |
| Role: | PI |
| ID: | R01CA258265 |
| Date: | 2021 - 2023 |
| Title: | Investigating molecular and cellular mechanisms of sarcoma relapsing |
| Funding Source: | Cedars-Sinai Cancer Biology Program |
| Role: | PI |
| ID: | CS - Project accelleration award |
| Date: | 2020 - 2022 |
| Title: | Extracellular vesicles enclosed circular RNA in tumor-host interactions |
| Funding Source: | Cedars-Sinai Cancer Biology Program |
| Role: | PI |
| ID: | CS |
| Date: | 2020 - 2023 |
| Title: | Oncogenic Roles of circular RNAs in tumorigenesis |
| Funding Source: | MARGARET E. EARLY MEDICAL RESEARCH TRUST |
| Role: | PI |
| ID: | Margaret Early Award |
| Date: | 2020 - 2022 |
| Title: | Characterize new interactions between AML cells and the endosteal bone marrow niche |
| Funding Source: | MELAMED DISCOVERY FUND |
| Role: | PI |
| ID: | melamed award |
| Date: | 2019 - 2021 |
| Title: | Identifying novel therapeutic targets in circular RNAs that bolster the sarcoma-protective microenvironment |
| Funding Source: | TOWER CANCER RESEARCH FOUNDATION |
| Role: | PI |
| ID: | Tower Cancer Foundation |
| Date: | 2019 - 2020 |
| Title: | Switching the tumor immune microenvironment from “cold” to “hot” in UPS |
| Funding Source: | SARCOMA FOUNDATION OF AMERICA |
| Role: | PI |
| ID: | SFA grant |
| Date: | 2016 - 2021 |
| Title: | Investigation and functional characterization of new drivers of mesenchymal tumorigenesis |
| Funding Source: | NCI |
| Role: | PI |
| ID: | CA212200 |
Selected Publications
Peer-Reviewed Articles
- 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.
- F Silva T, Hutchins E, Zhao W, Ciani Y, Kim M, Ko E, Mariscal J, Qiu Z, Kittel A, Zhou B, Wang Y, Hall M, Galasso F, Reiman R, Freeman MR, Parker S, Eyk JV, Yang W, Posadas E, Guarnerio J, Nolan J, Théry C, Zijlstra A, Stott S, You S, Demichelis F, Boutros PC, Keuren-Jensen KV, Di Vizio AD. Extracellular Vesicles heterogeneity through the lens of multiomics. e-Pub 2025.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. PMID: 34831007.
- 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. PMID: 34329585.
- 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. PMID: 31209250.
- 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. PMID: 31024166.
- 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. PMID: 29302031.
- 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. PMID: 27635760.
- 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. PMID: 27040497.
- 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. PMID: 25849135.
- 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. PMID: 25653093.
- 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. PMID: 25614485.
- 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. PMID: 24936467.
- 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. PMID: 24711541.
- 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. PMID: 24766807.
- 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. PMID: 20631073.
- 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. PMID: 18413771.
Review Articles
- Lunardi A, Guarnerio J, Wang G, Maeda T, Pandolfi PP. Role of LRF/Pokemon in lineage fate decisions. Blood, 2013. PMID: 23396304.
Abstracts
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Letters to the Editor
- Bezzi M, Guarnerio J, Pandolfi PP. A circular twist on microRNA regulation. Cell Res, 2017.
Patient Reviews
CV information above last modified September 25, 2025