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Evan Weber, PhD
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Assistant Professor of Pediatrics (Oncology)
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Assistant Professor, University of Pennsylvania, Perelman School of Medicine, Department of Pediatrics, Division of Oncology
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Member, Abramson Cancer Center, University of Pennsylvania
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Member, Center for Cellular Immunotherapies, University of Pennsylvania
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Member, Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia
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Member, Center for Childhood Cancer Research, Children's Hospital of Philadelphia
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Member, Institute for Immunology, University of Pennsylvania
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Principal Investigator, Cell and Gene Therapy Collaborative, Children's Hospital of Philadelphia
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Department: Pediatrics
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Graduate Group Affiliations
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- Cell and Molecular Biology 6a
- Pharmacology 5c
- Immunology e
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Contact information
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Children's Hospital of Philadelphia
38 Colket Translational Research Building, Rm 10018
39 3501 Civic Center Blvd
Philadelphia, PA 19104
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38 Colket Translational Research Building, Rm 10018
39 3501 Civic Center Blvd
Philadelphia, PA 19104
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Office: 267-425-5589
45 Lab: www.theweberlab.org
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Email:
weberew@chop.edu
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weberew@chop.edu
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Education:
21 7 BS 27 (Program in the Environment) c
5b University of Michigan College of Literature, Science and the Arts, 2008.
21 8 PhD 17 (Immunology) c
4c Northwestern University Feinberg School of Medicine, 2016.
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Permanent link21 7 BS 27 (Program in the Environment) c
5b University of Michigan College of Literature, Science and the Arts, 2008.
21 8 PhD 17 (Immunology) c
4c Northwestern University Feinberg School of Medicine, 2016.
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Description of Research Expertise
627 A major factor limiting the efficacy of chimeric antigen receptor (CAR) T cell therapy is T cell exhaustion, wherein chronic CAR signaling via antigen-independent CAR aggregation or high tumor burden drives global transcriptional and epigenetic alterations, overexpression of immune inhibitory receptors (ex. PD-1), and diminished anti-tumor function. My postdoctoral research demonstrated that transient cessation of CAR signaling, or “rest”, in exhausted CAR-T cells via enforced oscillations in CAR surface expression or pharmacologic inhibition of CAR signaling (Weber et al., Blood Adv, 2019) restores anti-tumor functionality through epigenetic remodeling (Weber et al., Science, 2021). This work is foundational to my independent research program centered around endowing human CAR-T cells with exhaustion resistance and improved durability. Utilizing an array of pharmacologic, gene-editing, and bioengineering approaches, my lab will identify and modulate transcriptional and epigenetic pathways that redirect human T cells towards more therapeutic cell states. Multi-omics analyses on experimental and patient CAR-T cells will enable us to link epigenetic features (ex. global or site-specific histone modifications) to cell phenotype, function, and patient outcomes, thereby informing our T cell engineering efforts. Collectively, our work will uncover molecular programs that drive human CAR-T cell dysfunction, identify targets for therapeutic intervention, and inform universal strategies that improve CAR-T cell efficacy in cancer patients.e 29
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107 Geoffrey T Rouin, Robert Hapke, Steven Pastore, Sixiang Yu, Junwei Shi, Evan Weber: Defining Epigenetic Mechanisms of Human CAR T Cell Exhaustion and Reversal Advance Therapies London 2025.
22c Doan A.*, Mueller K.P.*, Chen A.*, Rouin G.T., Chen Y., Daniel B., Lattin J., Markovska M., Mozarsky B., Arias-Umana J., Hapke R., Jung I.Y., Wang A., Xu P., Klysz D., Zuern G., Bashti M., Quinn P.J., Zhuang M., Sandor K., Zhang W., Chen G., Ryu F., Logun M., Hall J., Tan K., Grupp S.A., McClory S., Lareau C., Fraietta J.A., Sotillo E., Satpathy A.T., Mackall C.L.# and Weber E.W.# : FOXO1 is a master regulator of CAR T memory programming Nature 629(8010): 211–218, April 2024.
121 Geoffrey T Rouin, Robert Hapke, Steven Pastore, Sixiang Yu, Junwei Shi, Evan Weber: Defining Epigenetic Mechanisms of Human CAR T Cell Exhaustion and Reversal. Society for Immunotherapy of Cancer Annual Meeting 2024.
161 Jose Arias-Umana, Oishi Bardhan, Martina Markovska, Yingshi Chen, Jeremy Grenier, Gabrielle Zuern, Robert Hapke, Geoffery Rouin, Katherine Mueller, Evan Weber: Defining the role of TCF1 in CAR T cell memory and persistence. Society for Immunotherapy of Cancer Annual Meeting 2024.
154 Hou Y., Zak J., Shi Y., Pratumchai I., Dinner B., Wang W., Qin K., Weber E.W., Teijaro J.R., Wu P: Suppression by Tazemetostat during In Vitro Expansion Maintains T-Cell stemness and Improves Adoptive T-Cell Therapy. Cancer Immunology Research Dec 11; OF1-OF19, 2024.
2ff Dimitri A.J.*, Baxter A.E.*, Chen G.M.*, Hopkins C.R., Rouin G.T., Huang H., Kong W., Holliday C.H., Wiebking V., Bartoszek R., Drury S., Dalton K., Koucky O.M., Chen Z., Giles J.R., Dils A.T., Jung I.Y., O’Connor R., Collins S., Everett J.K., Amses K., Sherrill-Mix S., Chandra A., Goldman N., Vahedi G., Jadlowsky J.K., Young R.M., Melenhorst J.J., Maude S.L., Levine B.L., Frey N.V., Berger S.L., Grupp S.A., Porter D.L., Herbst F., Porteus M.H., Carty S.A., Bushman F.D., Weber E.W., Wherry E.J., Jordan M.S.#, Fraietta J.A#: Tet2 regulates early and late transitions in exhausted CD8+ T cell differentiation and limits CAR T cell function. Science Advances Nov 13; 10(46):eadp9371, 2024.
175 Larmarche C., Ward-Hartstonge K., Mi T., Lin D.T.S., Huang Q., Brown A., Edwards K., Novakovsky G.E., Qi C.N., Kobor M.S., Zebley C.C., Weber E.W., Mackall C.L., Levings M.K. : Tonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion. PNAS 120(14): e2219086120, April 2023.
1a7 Tousley A.M., Rotiroti M.C., Labanieh L., Rysavy L.W., Kim W.J., Lareau C., Sotillo E., Weber E.W., Rietberg S.P., Dalton G.N., Yin Y., Klysz D., Xu P., de la Serna E.L., Dunn A.R., Satpathy A.T., Mackall C.L., Majzner R.G. : Coopting T cell proximal signaling molecules enables Boolean logic-gated CAR T control. Nature 615(7952): 507-516, Mar 2023.
188 Yingqin Hou, Jaroslav Zak, Yujie Shi, Isaraphorn Pratumchai, Brandon Dinner, Wenjian Wang, Ke Qin, Evan Weber, John R. Teijaro, Peng Wu: Transient EZH2 suppression by Tazemetostat during in vitro expansion maintains T cell stemness and improves adoptive T cell therapy. bioRxiv Page: doi: 10.1101, Feb 2023 Notes: epub.
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Selected Publications
1c6 Robert Hapke, Aditya Bharti, Canjing Zhang, Yue Shao, Jose Arias-Umana, Yingshi Chen, Martina Markovska, Stephen Pastor, Junior Hall, Geoffery Rouin, Gabrielle Zuern, Jeremy Grenier, Junwei Shi, Andy Minn, and Evan Weber: In vivo CRISPR screens identify novel regulators of CAR T cell persistence in solid tumors. SITC Spring Scientific on Cellular Therapies for Solid Tumors 2025.107 Geoffrey T Rouin, Robert Hapke, Steven Pastore, Sixiang Yu, Junwei Shi, Evan Weber: Defining Epigenetic Mechanisms of Human CAR T Cell Exhaustion and Reversal Advance Therapies London 2025.
22c Doan A.*, Mueller K.P.*, Chen A.*, Rouin G.T., Chen Y., Daniel B., Lattin J., Markovska M., Mozarsky B., Arias-Umana J., Hapke R., Jung I.Y., Wang A., Xu P., Klysz D., Zuern G., Bashti M., Quinn P.J., Zhuang M., Sandor K., Zhang W., Chen G., Ryu F., Logun M., Hall J., Tan K., Grupp S.A., McClory S., Lareau C., Fraietta J.A., Sotillo E., Satpathy A.T., Mackall C.L.# and Weber E.W.# : FOXO1 is a master regulator of CAR T memory programming Nature 629(8010): 211–218, April 2024.
121 Geoffrey T Rouin, Robert Hapke, Steven Pastore, Sixiang Yu, Junwei Shi, Evan Weber: Defining Epigenetic Mechanisms of Human CAR T Cell Exhaustion and Reversal. Society for Immunotherapy of Cancer Annual Meeting 2024.
161 Jose Arias-Umana, Oishi Bardhan, Martina Markovska, Yingshi Chen, Jeremy Grenier, Gabrielle Zuern, Robert Hapke, Geoffery Rouin, Katherine Mueller, Evan Weber: Defining the role of TCF1 in CAR T cell memory and persistence. Society for Immunotherapy of Cancer Annual Meeting 2024.
154 Hou Y., Zak J., Shi Y., Pratumchai I., Dinner B., Wang W., Qin K., Weber E.W., Teijaro J.R., Wu P: Suppression by Tazemetostat during In Vitro Expansion Maintains T-Cell stemness and Improves Adoptive T-Cell Therapy. Cancer Immunology Research Dec 11; OF1-OF19, 2024.
2ff Dimitri A.J.*, Baxter A.E.*, Chen G.M.*, Hopkins C.R., Rouin G.T., Huang H., Kong W., Holliday C.H., Wiebking V., Bartoszek R., Drury S., Dalton K., Koucky O.M., Chen Z., Giles J.R., Dils A.T., Jung I.Y., O’Connor R., Collins S., Everett J.K., Amses K., Sherrill-Mix S., Chandra A., Goldman N., Vahedi G., Jadlowsky J.K., Young R.M., Melenhorst J.J., Maude S.L., Levine B.L., Frey N.V., Berger S.L., Grupp S.A., Porter D.L., Herbst F., Porteus M.H., Carty S.A., Bushman F.D., Weber E.W., Wherry E.J., Jordan M.S.#, Fraietta J.A#: Tet2 regulates early and late transitions in exhausted CD8+ T cell differentiation and limits CAR T cell function. Science Advances Nov 13; 10(46):eadp9371, 2024.
175 Larmarche C., Ward-Hartstonge K., Mi T., Lin D.T.S., Huang Q., Brown A., Edwards K., Novakovsky G.E., Qi C.N., Kobor M.S., Zebley C.C., Weber E.W., Mackall C.L., Levings M.K. : Tonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion. PNAS 120(14): e2219086120, April 2023.
1a7 Tousley A.M., Rotiroti M.C., Labanieh L., Rysavy L.W., Kim W.J., Lareau C., Sotillo E., Weber E.W., Rietberg S.P., Dalton G.N., Yin Y., Klysz D., Xu P., de la Serna E.L., Dunn A.R., Satpathy A.T., Mackall C.L., Majzner R.G. : Coopting T cell proximal signaling molecules enables Boolean logic-gated CAR T control. Nature 615(7952): 507-516, Mar 2023.
188 Yingqin Hou, Jaroslav Zak, Yujie Shi, Isaraphorn Pratumchai, Brandon Dinner, Wenjian Wang, Ke Qin, Evan Weber, John R. Teijaro, Peng Wu: Transient EZH2 suppression by Tazemetostat during in vitro expansion maintains T cell stemness and improves adoptive T cell therapy. bioRxiv Page: doi: 10.1101, Feb 2023 Notes: epub.
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