Martha S. Jordan, PhD

Research Associate Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania

Associate Vice Chair for Education
Department of Pathology and Laboratory Medicine

Contact InformationPerelman School of Medicine at the University of Pennsylvania
Department of Pathology and Laboratory Medicine
Biomedical Research Building II/III, Room 507
421 Curie Boulevard
Philadelphia, PA 19104
Tel: 215-746-5546

Specialty Division

Cancer and Immunobiology

Research Expertise

Research Interests: T cell signaling and the regulation of T cell differentiation

Research Summary:
T cells integrate multiple signals from their environment, and the culmination of these signals direct how CD4 and CD8 T cells differentiate. My lab uses a variety of in vivo model systems to understand how distinct pathways and proteins regulate T cell fates. Some active areas of investigation include the following:

• T cell activation leads to transient changes in the activation states of many proteins and enzymes, but it also results in heritable changes at the epigenetic level. DNA methylation is a common epigenetic modification that is regulated via both active and passive mechanisms. TET2 is a methylcytosine dioxgenase involved in the active demethylation of DNA and is frequently mutated in a specific class of T cell lymphomas. Our lab has shown that TET2 regulates the development of memory CD8+ T cells as well as CD4+ T cell differentiation. We are currently investigating the underlying mechanisms by which TET2 and other DNA methylation modifying enzymes regulate T cell differentiation.

• When T cells are continually exposed antigen, as in the setting of chronic viral infection or cancer, they can become “exhausted.” Exhausted T cells (Tex) are characterized by high expression of inhibitory receptors and loss of robust effector function. How T cell signaling pathways regulate the differentiation of Tex cells during chronic antigen exposure is not fully known. To bridge this gap in knowledge, we are exploring the role of signaling proteins, including NFkB family members, in the establishment and persistence of CD8 T cell exhaustion. In collaboration with Dr. Warren Pear’s lab, we have identified the pseudokinase, Trib1, as a negative regulator of T cell activation and have defined a role for this scaffolding protein in regulating Tex cell differentiation. Future work aims to define the molecular mechanism underlying these findings as well as further defining how Trib1 regulates T cell differentiation in other settings.

• Exposure to chronic antigen stimulation also impacts CD4 T cell differentiation and function. Using similar approaches previously used to defining CD8 T cell exhaustion, we are currently investigating the molecular mechanisms that contribute to CD4 T cell exhaustion.

Itmat Expertise

T cell differentiation and function; T cell exhaustion; T cell signal transduction


BS (Biology), University of Richmond, 1994
PhD (Immunology), University of Pennsylvania, 2000

Postgraduate Training

Postdoctoral Fellow, University of Pennsylvania, 2000-04

Awards and Honors

Baker-William and Mary Award, Virginia Academy of Science, 1992
May L. Keller Academic Scholarship, University of Richmond, 1993
Phi Beta Kappa, University of Richmond, 1994
Monica Shander Award, 1999
Saul Winegrad Award, University of Pennsylvania, 2001
Young Investigator Award, Midwinter Conference of Immunologist, 2013
Simon Flexner Award for Graduate Student Education, University of Pennsylvania, 2023

Memberships and Professional Organizations

Institute for Immunology and Immune Health (I3H; fka Institute for Immunology), Penn Medicine, 2012-present
Institute for Translational Medicine and Therapeutics (ITMAT), Perelman School of Medicine at the University of Pennsylvania, 2013-present
Immunology Graduate Group (IGG), University of Pennsylvania, 2009-present
--- Preliminary Examiner, 2014-present
--- Thesis Committee, Chair, 2014-present
--- Student Affairs Committee, 2016-present
--- IGG Rotation Talk & Preliminary Exam Committee, Co-Chair, 2021-present
Parker Institute for Cancer Immunotherapy, 2016-present
American Association of Immunologists, 2021-23

Selected Publications

The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR+ CD8+ effector state, and its deletion improves checkpoint blockade

McClory SE, Bardhan O, Rome KS, Giles JR, Baxter AE, Xu L, Gimotty PA, Faryabi RB, Wherry EJ, Pear WS, Jordan MS. Cell Rep 42(8):112905, Aug 2023. doi: 10.1016/j.celrep.2023.112905. Epub 2023 Jul 31. PMID: 37527035; PMCID: PMC10540077.

The SWI/SNF chromatin remodeling complexes BAF and PBAF differentially regulate epigenetic transitions in exhausted CD8+ T cells

Baxter AE, Huang H, Giles JR, Chen Z, Wu JE, Drury S, Dalton K, Park SL, Torres L, Simone BW, Klapholz M, Ngiow SF, Freilich E, Manne S, Alcalde V, Ekshyyan V, Berger SL, Shi J, Jordan MS, Wherry EJ. Immunity 56(6):1320-1340.e10, June 2023. doi: 10.1016/j.immuni.2023.05.008. PMID: 37315535.

MicroRNA-29a attenuates CD8 T cell exhaustion and induces memory-like CD8 T cells during chronic infection

Stelekati E, Cai Z, Manne S, Chen Z, Beltra JC, Buchness LA, Leng X, Ristin S, Nzingha K, Ekshyyan V, Niavi C, Abdel-Hakeem MS, Ali MA, Drury S, Lau CW, Gao Z, Ban Y, Zhou SK, Ansel KM, Kurachi M, Jordan MS, Villarino AV, Ngiow SF, Wherry EJ. Proc Natl Acad Sci U S A 119(17):e2106083119, Apr 2022. doi: 10.1073/pnas.2106083119. Epub 2022 Apr 21. PMID: 35446623; PMCID: PMC9169946.

The interferon-stimulated gene RIPK1 regulates cancer cell intrinsic and extrinsic resistance to immune checkpoint blockade

Cucolo L, Chen Q, Qiu J, Yu Y, Klapholz M, Budinich KA, Zhang Z, Shao Y, Brodsky IE, Jordan MS, Gilliland DG, Zhang NR, Shi J, Minn AJ. Immunity 55(4):671-685.e10, Apr 2022. doi: 10.1016/j.immuni.2022.03.007. PMID: 35417675. 

CD28 Regulates Metabolic Fitness for Long-Lived Plasma Cell Survival

Utley A, Chavel C, Lightman S, Holling GA, Cooper J, Peng P, Liu W, Barwick BG, Gavile CM, Maguire O, Murray-Dupuis M, Rozanski C, Jordan MS, Kambayashi T, Olejniczak SH, Boise LH, Lee KP. Cell Rep 31(12):107815, Jun 2020. doi: 10.1016/j.celrep.2020.107815. PMID: 32579940; PMCID: PMC7405645.

Trib1 regulates T cell differentiation during chronic infection by restraining the effector program

Rome KS, Stein SJ, Kurachi M, Petrovic J, Schwartz GW, Mack EA, Uljon S, Wu WW, DeHart AG, McClory SE, Xu L, Gimotty PA, Blacklow SC, Faryabi RB, Wherry EJ, Jordan MS, Pear WS. J Exp Med 217(5):e20190888, May 2020. doi: 10.1084/jem.20190888. PMID: 32150623; PMCID: PMC7201917.

Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells

Fraietta JA, Nobles CL, Sammons MA, Lundh S, Carty SA, Reich TJ, Cogdill AP, Morrissette JJD, DeNizio JE, Reddy S, Hwang Y, Gohil M, Kulikovskaya I, Nazimuddin F, Gupta M, Chen F, Everett JK, Alexander KA, Lin-Shiao E, Gee MH, Liu X, Young RM, Ambrose D, Wang Y, Xu J, Jordan MS, Marcucci KT, Levine BL, Garcia KC, Zhao Y, Kalos M, Porter DL, Kohli RM, Lacey SF, Berger SL, Bushman FD, June CH, Melenhorst JJ. Nature 558(7709):307-312, Jun 2018. doi: 10.1038/s41586-018-0178-z. Epub 2018 May 30. PMID: 29849141; PMCID: PMC6320248.

The Loss of TET2 Promotes CD8+ T Cell Memory Differentiation

Carty SA, Gohil M, Banks LB, Cotton RM, Johnson ME, Stelekati E, Wells AD, Wherry EJ, Koretzky GA, Jordan MS. J Immunol 200(1):82-91, Jan 2018. doi: 10.4049/jimmunol.1700559. Epub 2017 Nov 17. PMID: 29150566; PMCID: PMC5736442.

mTORC2 regulates multiple aspects of NKT-cell development and function

Sklarz T, Guan P, Gohil M, Cotton RM, Ge MQ, Haczku A, Das R, Jordan MS. Eur J Immunol 47(3):516-526, Mar 2017. doi: 10.1002/eji.201646343. Epub 2017 Jan 27. PMID: 28078715; PMCID: PMC5656007.

Regulatory T cells require TCR signaling for their suppressive function

Schmidt AM, Lu W, Sindhava VJ, Huang Y, Burkhardt JK, Yang E, Riese MJ, Maltzman JS, Jordan MS, Kambayashi T. J Immunol 194(9):4362-70, May 2015. doi: 10.4049/jimmunol.1402384. Epub 2015 Mar 27. PMID: 25821220; PMCID: PMC4402269.

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