Kristen E. Pauken, Ph.D.
Department of Immunology, Division of Discovery Science
About Dr. Kristen E. Pauken
Dr. Pauken received her Bachelor's of Science in Microbiology in 2007 from Colorado State University, where she studied how sand fly saliva impacted innate immunity to parasitic infection in the lab of Dr. Richard Titus. She then went on to receive her Ph.D. at the University of Minnesota in 2013 in the lab of Dr. Brian Fife, studying PD-1-mediated regulation of autoreactive CD4 + T cells during Type 1 Diabetes. Following completion of her Ph.D., Dr. Pauken moved to the University of Pennsylvania, examining how PD-1 blockade impacted exhausted CD8 + T cells in the lab of Dr. E. John Wherry. Here, Dr. Pauken made the seminal observation that T cell exhaustion represents its own unique cell state, fundamentally different at the epigenetic level than functional effector or memory cells that develop during acute infection. Importantly, PD-1 inhibitors were not capable of reprogramming this inflexible epigenetic state; rather, these inhibitors temporarily boosted effector activity of genes that were confined to the open chromatin landscape within exhausted T cells. In 2016, Dr. Pauken then went on to study in the lab of Dr. Arlene Sharpe at Harvard Medical School, where she focused on mechanisms of PD-1-mediated regulation of CD8 + T cells in cancer. In Dr. Sharpe’s lab, Dr. Pauken developed significant expertise in single cell RNA seq, and developed a method using single cell sequencing of the T cell receptor (TCR) to track T cell clones of interest based on having a shared TCR sequence between tissue types or treatment groups.
Present Title & Affiliation
Primary Appointment
Assistant Professor, Department of Immunology, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
Dr. Pauken is combining her passion for exhaustion and tolerance, interrogating the mechanisms by which the immune system regulates the balance between protective immunity and immune-driven pathologies. Using mouse models of cancer and autoimmunity, the main goal of her lab is to better understand how PD-1 inhibitors regulate both protective and pathogenic CD8 + T cell responses. Dr. Pauken's long term goal is to develop novel strategies to uncouple the protective effects of immunotherapy from the toxic side effects.
Education & Training
Degree-Granting Education
| 2013 | University of Minnesota, Minneapolis, MN, USA, PHD, Immunology |
| 2007 | Colorado State University, Fort Collins, CO, USA, BS, Microbiology |
Postgraduate Training
| 2016-2022 | Postdoctoral Training, Immunology, cancer immunotherapy, Harvard Medical School, Boston, MA |
| 2013-2016 | Postdoctoral Training, Immunology, chronic infection, University of Pennsylvania, Philadelphia, PA |
Selected Publications
Peer-Reviewed Articles
- Collier JL, Pauken KE, Lee CAA, Patterson DG, Markson SC, Conway TS, Fung ME, France JA, Mucciarone KN, Lian CG, Murphy GF, Sharpe AH. Single-cell profiling reveals unique features of diabetogenic T cells in anti-PD-1-induced type 1 diabetes mice. J Exp Med 220(10), 2023. e-Pub 2023. PMID: 37432393.
- Alvarez-Breckenridge C, Markson SC, Stocking JH, Nayyar N, Lastrapes M, Strickland MR, Kim AE, de Sauvage M, Dahal A, Larson JM, Mora JL, Navia AW, Klein RH, Kuter BM, Gill CM, Bertalan M, Shaw B, Kaplan A, Subramanian M, Jain A, Kumar S, Danish H, White M, Shahid O, Pauken KE, Miller BC, Frederick DT, Hebert C, Shaw M, Martinez-Lage M, Frosch M, Wang N, Gerstner E, Nahed BV, Curry WT, Carter B, Cahill DP, Boland GM, Izar B, Davies MA, Sharpe AH, Suvà ML, Sullivan RJ, Brastianos PK, Carter SL. Microenvironmental Landscape of Human Melanoma Brain Metastases in Response to Immune Checkpoint Inhibition. Cancer Immunol Res 10(8):996-1012, 2022. PMID: 35706413.
- Lagattuta KA, Kang JB, Nathan A, Pauken KE, Jonsson AH, Rao DA, Sharpe AH, Ishigaki K, Raychaudhuri S. Repertoire analyses reveal T cell antigen receptor sequence features that influence T cell fate. Nat Immunol 23(3):446-457, 2022. e-Pub 2022. PMID: 35177831.
- Schenkel JM, Herbst RH, Canner D, Li A, Hillman M, Shanahan SL, Gibbons G, Smith OC, Kim JY, Westcott P, Hwang WL, Freed-Pastor WA, Eng G, Cuoco MS, Rogers P, Park JK, Burger ML, Rozenblatt-Rosen O, Cong L, Pauken KE, Regev A, Jacks T. Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes. Immunity 54(10):2338-2353.e6, 2021. e-Pub 2021. PMID: 34534439.
- Pauken KE, Shahid O, Lagattuta KA, Mahuron KM, Luber JM, Lowe MM, Huang L, Delaney C, Long JM, Fung ME, Newcomer K, Tsai KK, Chow M, Guinn S, Kuchroo JR, Burke KP, Schenkel JM, Rosenblum MD, Daud AI, Sharpe AH, Singer M. Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment. J Exp Med 218(4), 2021. PMID: 33651880.
- Lo JA, Kawakubo M, Juneja VR, Su MY, Erlich TH, LaFleur MW, Kemeny LV, Rashid M, Malehmir M, Rabi SA, Raghavan R, Allouche J, Kasumova G, Frederick DT, Pauken KE, Weng QY, Pereira da Silva M, Xu Y, van der Sande AAJ, Silkworth W, Roider E, Browne EP, Lieb DJ, Wang B, Garraway LA, Wu CJ, Flaherty KT, Brinckerhoff CE, Mullins DW, Adams DJ, Hacohen N, Hoang MP, Boland GM, Freeman GJ, Sharpe AH, Manstein D, Fisher DE. Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses. Sci Transl Med 13(581), 2021. PMID: 33597266.
- Johnnidis JB, Muroyama Y, Ngiow SF, Chen Z, Manne S, Cai Z, Song S, Platt JM, Schenkel JM, Abdel-Hakeem M, Beltra JC, Greenplate AR, Ali MA, Nzingha K, Giles JR, Harly C, Attanasio J, Pauken KE, Bengsch B, Paley MA, Tomov VT, Kurachi M, Vignali DAA, Sharpe AH, Reiner SL, Bhandoola A, Johnson FB, Wherry EJ. Inhibitory signaling sustains a distinct early memory CD8+ T cell precursor that is resistant to DNA damage. Sci Immunol 6(55), 2021. PMID: 33452106.
- Chen IX, Newcomer K, Pauken KE, Juneja VR, Naxerova K, Wu MW, Pinter M, Sen DR, Singer M, Sharpe AH, Jain RK. A bilateral tumor model identifies transcriptional programs associated with patient response to immune checkpoint blockade. Proc Natl Acad Sci U S A 117(38):23684-23694, 2020. e-Pub 2020. PMID: 32907939.
- Pauken KE, Godec J, Odorizzi PM, Brown KE, Yates KB, Ngiow SF, Burke KP, Maleri S, Grande SM, Francisco LM, Ali MA, Imam S, Freeman GJ, Haining WN, Wherry EJ, Sharpe AH. The PD-1 Pathway Regulates Development and Function of Memory CD8+ T Cells following Respiratory Viral Infection. Cell Rep 31(13):107827, 2020. PMID: 32610128.
- Osum KC, Burrack AL, Martinov T, Sahli NL, Mitchell JS, Tucker CG, Pauken KE, Papas K, Appakalai B, Spanier JA, Fife BT. Interferon-gamma drives programmed death-ligand 1 expression on islet β cells to limit T cell function during autoimmune diabetes. Sci Rep 8(1):8295, 2018. e-Pub 2018. PMID: 29844327.
- Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, Harmon S, Giles JR, Wenz B, Adamow M, Kuk D, Panageas KS, Carrera C, Wong P, Quagliarello F, Wubbenhorst B, D'Andrea K, Pauken KE, Herati RS, Staupe RP, Schenkel JM, McGettigan S, Kothari S, George SM, Vonderheide RH, Amaravadi RK, Karakousis GC, Schuchter LM, Xu X, Nathanson KL, Wolchok JD, Gangadhar TC, Wherry EJ. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature 545(7652):60-65, 2017. e-Pub 2017. PMID: 28397821.
- Benci JL, Xu B, Qiu Y, Wu TJ, Dada H, Twyman-Saint Victor C, Cucolo L, Lee DSM, Pauken KE, Huang AC, Gangadhar TC, Amaravadi RK, Schuchter LM, Feldman MD, Ishwaran H, Vonderheide RH, Maity A, Wherry EJ, Minn AJ. Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade. Cell 167(6):1540-1554.e12, 2016. PMID: 27912061.
- Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, Khan O, Drake AM, Chen Z, Sen DR, Kurachi M, Barnitz RA, Bartman C, Bengsch B, Huang AC, Schenkel JM, Vahedi G, Haining WN, Berger SL, Wherry EJ. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science 354(6316):1160-1165, 2016. e-Pub 2016. PMID: 27789795.
- Bengsch B, Johnson AL, Kurachi M, Odorizzi PM, Pauken KE, Attanasio J, Stelekati E, McLane LM, Paley MA, Delgoffe GM, Wherry EJ. Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8(+) T Cell Exhaustion. Immunity 45(2):358-73, 2016. e-Pub 2016. PMID: 27496729.
- Manlove LS, Schenkel JM, Manlove KR, Pauken KE, Williams RT, Vezys V, Farrar MA. Heterologous Vaccination and Checkpoint Blockade Synergize To Induce Antileukemia Immunity. J Immunol 196(11):4793-804, 2016. e-Pub 2016. PMID: 27183622.
- Schenkel JM, Fraser KA, Casey KA, Beura LK, Pauken KE, Vezys V, Masopust D. IL-15-Independent Maintenance of Tissue-Resident and Boosted Effector Memory CD8 T Cells. J Immunol 196(9):3920-6, 2016. e-Pub 2016. PMID: 27001957.
- Kalekar LA, Schmiel SE, Nandiwada SL, Lam WY, Barsness LO, Zhang N, Stritesky GL, Malhotra D, Pauken KE, Linehan JL, O'Sullivan MG, Fife BT, Hogquist KA, Jenkins MK, Mueller DL. CD4(+) T cell anergy prevents autoimmunity and generates regulatory T cell precursors. Nat Immunol 17(3):304-14, 2016. e-Pub 2016. PMID: 26829766.
- Martinov T, Spanier JA, Pauken KE, Fife BT. PD-1 pathway-mediated regulation of islet-specific CD4+ T cell subsets in autoimmune diabetes. Immunoendocrinology (Houst) 3, 2016. PMID: 27656680.
- Gupta PK, Godec J, Wolski D, Adland E, Yates K, Pauken KE, Cosgrove C, Ledderose C, Junger WG, Robson SC, Wherry EJ, Alter G, Goulder PJ, Klenerman P, Sharpe AH, Lauer GM, Haining WN. CD39 Expression Identifies Terminally Exhausted CD8+ T Cells. PLoS Pathog 11(10):e1005177, 2015. e-Pub 2015. PMID: 26485519.
- Manlove LS, Berquam-Vrieze KE, Pauken KE, Williams RT, Jenkins MK, Farrar MA. Adaptive Immunity to Leukemia Is Inhibited by Cross-Reactive Induced Regulatory T Cells. J Immunol 195(8):4028-37, 2015. e-Pub 2015. PMID: 26378075.
- Odorizzi PM, Pauken KE, Paley MA, Sharpe A, Wherry EJ. Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells. J Exp Med 212(7):1125-37, 2015. e-Pub 2015. PMID: 26034050.
- Pauken KE, Nelson CE, Martinov T, Spanier JA, Heffernan JR, Sahli NL, Quarnstrom CF, Osum KC, Schenkel JM, Jenkins MK, Blazar BR, Vezys V, Fife BT. Cutting edge: identification of autoreactive CD4+ and CD8+ T cell subsets resistant to PD-1 pathway blockade. J Immunol 194(8):3551-3555, 2015. e-Pub 2015. PMID: 25769925.
- Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520(7547):373-7, 2015. e-Pub 2015. PMID: 25754329.
- Schenkel JM, Fraser KA, Beura LK, Pauken KE, Vezys V, Masopust D. T cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science 346(6205):98-101, 2014. e-Pub 2014. PMID: 25170049.
- Pauken KE, Linehan JL, Spanier JA, Sahli NL, Kalekar LA, Binstadt BA, Moon JJ, Mueller DL, Jenkins MK, Fife BT. Cutting edge: type 1 diabetes occurs despite robust anergy among endogenous insulin-specific CD4 T cells in NOD mice. J Immunol 191(10):4913-7, 2013. e-Pub 2013. PMID: 24123682.
- Pauken KE, Jenkins MK, Azuma M, Fife BT. PD-1, but not PD-L1, expressed by islet-reactive CD4+ T cells suppresses infiltration of the pancreas during type 1 diabetes. Diabetes 62(8):2859-69, 2013. e-Pub 2013. PMID: 23545706.
- Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q, Azuma M, Krummel MF, Bluestone JA. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol 10(11):1185-92, 2009. e-Pub 2009. PMID: 19783989.
- Wheat WH, Pauken KE, Morris RV, Titus RG. Lutzomyia longipalpis salivary peptide maxadilan alters murine dendritic cell expression of CD80/86, CCR7, and cytokine secretion and reprograms dendritic cell-mediated cytokine release from cultures containing allogeneic T cells. J Immunol 180(12):8286-98, 2008. PMID: 18523295.
Invited Articles
- Fife BT, Pauken KE. The role of the PD-1 pathway in autoimmunity and peripheral tolerance. Ann N Y Acad Sci 1217:45-59, 2011. PMID: 21276005.
Patient Reviews
CV information above last modified April 01, 2024