Jennifer Tran

Program: Immunology

Current advisor: Todd A. Fehniger, MD, PhD

Undergraduate university: University of Michigan-Ann Arbor, 2015

Enrollment year: 2019

Research summary
Molecular mechanisms of cytokine-induced memory-like NK cell differentiation

Natural killer (NK) cells are innate lymphoid cells that are crucial for host defense from viral infections and tumor cells. The ability of NK cells to recognize and kill malignant cells provides a strong premise to advance them as a cellular therapy in the clinical setting. While NK cell-based therapies are being explored in clinical trials, issues with persistence and in vivo functionality have been identified as limitations to their clinical application. Our lab pioneered cytokine-induced memory-like (ML) NK cells that are generated after brief activation with IL-12, IL-15, and IL-18. This overcomes many of the shortcomings of conventional NK cells as a cellular therapy. ML NK cells exhibited enhanced functionality, cytotoxicity, and persistence in a phase I clinical trial for acute myeloid leukemia (AML), with many patients achieving complete remissions from this novel intervention. Despite the translational advancement, there is little known about the underlying mechanisms of ML programming in NK cells. Clarifying the molecular programs that drive the ML phenotype will have broad implications for optimizing NK cells as a cellular-based therapy for hematological malignancies.

Graduate publications
Marin ND, Becker-Hapak M, Song WM, Alayo QA, Marsala L, Sonnek N, Berrien-Elliott MM, Foster M, Foltz JA, Tran J, Wong P, Cubitt CC, Pence P, Hwang K, Zhou AY, Jacobs MT, Schappe T, Russler-Germain DA, Fields RC, Ciorba MA, Fehniger TA. 2024 Memory-like differentiation enhances NK cell responses against colorectal cancer. Oncoimmunology, 13(1):2348254. PMCID: PMC11086027

Cubitt CC, Wong P, Dorando HK, Foltz JA, Tran J, Marsala L, Marin ND, Foster M, Schappe T, Fatima H, Becker-Hapak M, Zhou AY, Hwang K, Jacobs MT, Russler-Germain DA, Mace EM, Berrien-Elliott MM, Payton JE, Fehniger TA. 2024 Induced CD8α identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation. J Clin Invest, 134(15):e173602. PMCID: PMC11291271

Foltz JA, Tran J, Wong P, Fan C, Schmidt E, Fisk B, Becker-Hapak M, Russler-Germain DA, Johnson J, Marin ND, Cubitt CC, Pence P, Rueve J, Pureti S, Hwang K, Gao F, Zhou AY, Foster M, Schappe T, Marsala L, Berrien-Elliott MM, Cashen AF, Bednarski JJ, Fertig E, Griffith OL, Griffith M, Wang T, Petti AA, Fehniger TA. 2024 Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional regulation. Sci Immunol, 9(96):eadk4893. PMCID:

Shrestha N, Chaturvedi P, Zhu X, Dee MJ, George V, Janney C, Egan JO, Liu B, Foster M, Marsala L, Wong P, Cubitt CC, Foltz JA, Tran J, Schappe T, Hsiao K, Leclerc GM, You L, Echeverri C, Spanoudis C, Carvalho A, Kanakaraj L, Gilkes C, Encalada N, Kong L, Wang M, Fang B, Wang Z, Jiao JA, Muniz GJ, Jeng EK, Valdivieso N, Li L, Deth R, Berrien-Elliott MM, Fehniger TA, Rhode PR, Wong HC. 2023 Immunotherapeutic approach to reduce senescent cells and alleviate senescence-associated secretory phenotype in mice. Aging Cell, 22(5):e13806. PMCID: PMC10186597

Wong P, Foltz JA, Chang L, Neal CC, Yao T, Cubitt CC, Tran J, Kersting-Schadek S, Palakurty SX, Jaeger N, Russler-Germain DA, Marin ND, Gang M, Wagner JA, Zhou AY, Jacobs MT, Foster M, Schappe T, Marsala L, McClain E, Pence P, Becker-Hapak M, Fisk B, Petti AA, Griffith OL, Griffith M, Berrien-Elliott MM, Fehniger TA. 2023 T-BET and EOMES sustain mature human NK cell identity and anti-tumor function. J Clin Invest, 133(13)::e162530. PMCID: PMC10313375

Jacobs MT, Wong P, Zhou AY, Becker-Hapak M, Marin ND, Marsala L, Foster M, Foltz JA, Cubitt CC, Tran J, Russler-Germain DA, Neal C, Kersting-Schadek S, Chang L, Schappe T, Pence P, McClain E, Zevallos JP, Rich JT, Paniello RC, Jackson RS, Pipkorn P, Adkins DR, DeSelm CJ, Berrien-Elliott MM, Puram SV, Fehniger TA. 2023 Memory-like differentiation, tumor targeting monoclonal antibodies, and chimeric antigen receptors enhance natural killer cell responses to head and neck cancer. Clin Cancer Res, 29(20):4196-208. PMCID: PMC10796148

Cook ME, Bradstreet TR, Webber AM, Kim J, Santeford A, Harris KM, Murphy MK, Tran J, Abdalla NM, Schwarzkopf EA, Greco SC, Halabi CM, Apte RS, Blackshear PJ, Edelson BT. 2022 The ZFP36 family of RNA binding proteins regulates homeostatic and autoreactive T cell responses. Sci Immunol, 7(76):eabo0981. PMCID: PMC9832469

Berrien-Elliott MM, Foltz JA, Russler-Germain DA, Neal CC, Tran J, Gang M, Wong P, Fisk B, Cubitt CC, Marin ND, Zhou AY, Jacobs MT, Foster M, Schappe T, McClain E, Kersting-Schadek S, Desai S, Pence P, Becker-Hapak M, Eisele J, Mosior M, Marsala L, Griffith OL, Griffith M, Khan SM, Spencer DH, DiPersio JF, Romee R, Uy GL, Abboud CN, Ghobadi A, Westervelt P, Stockerl-Goldstein K, Schroeder MA, Wan F, Lie WR, Soon-Shiong P, Petti AA, Cashen AF, Fehniger TA. 2022 Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. Sci Transl Med, 14(633):eabm1375. PMCID: PMC9210521

Marin ND, Krasnick BA, Becker-Hapak M, Conant L, Goedegebuure SP, Berrien-Elliott MM, Robbins KJ, Foltz JA, Foster M, Wong P, Cubitt CC, Tran J, Wetzel CB, Jacobs M, Zhou A, Russler-Germain D, Marsala L, Schappe T, Fields RC, Fehniger TA. 2021 Memory-like differentiation enhances NK cell responses to melanoma. Clin Cancer Res, 27(17):4859-69. PMCID: PMC8416927

Becker-Hapak MK, Shrestha N, McClain E, Dee MJ, Chaturvedi P, Leclerc GM, Marsala LI, Foster M, Schappe T, Tran J, Desai S, Neal CC, Pence P, Wong P, Wagner JA, Russler-Germain D, Zhu X, Spanoudis CM, Gallo VL, Echeverri CA, Ramirez LL, You L, Egan JO, Rhode PR, Jiao JA, Muniz GJ, Jeng EK, Prendes CA, Sullivan RP, Berrien-Elliott MM, Wong HC, Fehniger TA. 2021 A Fusion Protein Complex that Combines IL-12, IL-15, and IL-18 Signaling to Induce Memory-Like NK Cells for Cancer Immunotherapy. Cancer Immunol Res, 9(9):1071-87. PMCID: PMC8416787

Gang M, Marin ND, Wong P, Neal CC, Marsala L, Foster M, Schappe T, Meng W, Tran J, Schaettler M, Davila ML, Gao F, Cashen AF, Bartlett NL, Mehta-Shah N, Kahl B, Kim M, Cooper ML, DiPersio JF, Berrien-Elliott MM, Fehniger TA. 2020 CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas. Blood, 136(20):2308-2318. PMCID: PMC7702478