Amanda C. Poholek, PhD
- Director, Health Sciences Sequencing Core and Assistant Professor of Pediatrics and Immunology
- Scholar, Richard King Mellon Foundation Institute for Pediatric Research
Poholek received her PhD in Cell Biology from Yale University in 2009, where she worked with Dr. Joe Craft on the role of Bcl6 in the differentiation and function of T follicular helper (TFH) cells to drive humoral immunity in autoimmunity. Her work was fundamental in demonstrating that the transcriptional repressor Bcl6 was a master regulator of TFH cells, the subset of T cells necessary for antibody generation. To build on her understanding of transcription factors and their regulation of T cell differentiation, Poholek joined Dr. John O’Shea’s lab at the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) to study how the STAT family of transcription factors impact the epigenome to drive T cell differentiation and function. Here, she described important regulators of Bcl6 and Blimp-1, another transcriptional repressor that is important for effector T cell function.
Poholek began her own lab at the University of Pittsburgh in the Department of Pediatrics in 2015. Her research focuses on understanding how immune cells integrate signals encountered in the environment to drive functional outcomes at the molecular and epigenetic level in both health and disease. While the basic mechanisms of immune cell differentiation have been defined, the role that transcription factors play in shaping the epigenetic landscape during differentiation remains unclear. Specific projects are focused on the role of Blimp-1 in allergic asthma, and the role of metabolism in shaping the epigenome of T cells during differentiation and function. She is also the Director of the Health Sciences Sequencing Core at UPMC Children’s Hospital of Pittsburgh.
Professional and Scientific Society Memberships
- American Association for the Advancement of Science, 2017-Present
- American Association of Immunologists, 2015-Present
- American Association of Immunologists, Trainee Member, 2009-2015
Education & Training
- BS, Biological Sciences, Fordham University, 2002
- PhD, Cell Biology, Yale University, 2009
- Postdoctoral Fellow, National Institutes of Health/National Institute of Allergy and Infectious Diseases, 2009-2011
- Postdoctoral Fellow, National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, 2012-2015
He K, Hettinga A, Kale SL, Hu S, Xie MM, Dent AL, Ray A, Poholek AC. Blimp-1 is essential for allergen-induced asthma and Th2 cell development in the lung. The Journal of Experimental Medicine. In Press. 2020.
Ren Q, Gliozzi ML, Rittenhouse NL, Edmunds LR, Rbaibi Y, Locker JD, Poholek AC, Jurczak MJ, Baty CJ, Weisz OA. Shear stress and oxygen availability drive differential changes in opossum kidney proximal tubule cell metabolism and enocytosis. Traffic. Jun;20(6):448-459. 2019.
Sawant DW, Yano H, Chikina M, Zhang Q, Liao M, Liu C, Sun Z, Sun T, Tabib T, Pennathur A, Luketich JD, Lafyatis R, Chen W, Poholek AC, Bruno TC, Workman CJ, Vignali DAA. Adaptive plasticity of IL10+ and IL35+ regulatory T cells cooperatively promote intratumoral T cell exhaustion. Nature Immunology.Jun;20(6)724-735. 2019.
Majumder S, Amatya N, Revu S, Jawale CV, Wu D, Rittenhouse N, Menk A, Kupul S, Du F, Raphael I, Bhattacharjee A, Siebenlist U, Hand TW, Delgoffe GM, Poholek AC, Gaffen SL, Biswas PS, McGeachy MJ. IL-17 metabolically reprograms activated fibroblastic reticular cells for proliferation and survival. Nature Immunology. May;20(5):534-545. 2019.
Revu S, Wu j, Henkel M, Rittenhouse N, Menk A, Delgoffe GM, Poholek AC, McGeachy MJ. IL-23 and IL-1b drive human Th17 cell differentiation and metabolic reprogramming in the absence of CD28 costimulation. Cell Reports. Mar 6;22(10):2642-2653. 2018.
Simpson-Abelson MR, Hernandez-Mir G, Childs EE, Cruz JA, Poholek AC, Chattopadhyay A, Gaffen SL, McGeachy M. CCAAT/Enhancer-binding protein β promotes pathogenesis of EAE. Cytokine. Apr;92:24-32. 2017.
Poholek AC*, Jankovic D, Villarino A, Villarino A, Petermanm F, Shouval DS, Snapper SB, Kaech SM, Brooks SR, Vahedi G, Sher A, Kanno Y, O’Shea JJ*. IL-10 induces a STAT3-dependent autoreguatory loop in Th2 cells that promotes Blimp-1- restriction of cell expansion via antagonism of STAT5 target genes. Science Immunology. Nov. 11;1(5). 2016. *Corresponding authors
Weinstein JS, Bertino, SA, Hernandez SG, Poholek AC, Teplitzky TB, Nowyhed HN, Craft J. B cells in T follicular helper cell development and function: separable roles in delivery of ICOS ligand and antigen. The Journal of Immunology. Apr 1;192(7):3116-79. 2014.
Nakayamada S*, Poholek AC*#, Lu KT, Takahashi H, Hirahara K, Kato, M, Iwata S, Cannons JL, Schwartzberg PL, Vahedi G, Sun H, Kanno Y, O’Shea JJ. Type I Interferon induces binding of STAT1 to Bcl6: Divergent Roles of STAT-family transcription factors in the TFH cell genetic program. The Journal of Immunology. Mar 1;192(5):2156-66. 2014. *Equal Contribution. #Corresponding author.
Sciume G, Hirahara K, Takahasi H, Laurence A, Villarino AV, Singleton KL, Spencer SP, Wilhelm C, Poholek AC, Vahedi G, Kanno Y, Belkaid Y, O’Shea JJ. Distinct Requirements for T-bet in Gut Lymphoid Cells. The Journal of Experimental Medicine. Dec 17;209(13):2331-8. 2012.
Academic and Research Interests
Dr. Poholek's research focuses on understanding how immune cells integrate signals encountered in the environment to drive functional outcomes at the molecular and epigenetic level in both health and disease. While the basic mechanisms of immune cell differentiation have been defined, the role that transcription factors and metabolism play in shaping the epigenetic landscape during differentiation remains unclear.
NIH R01, Regulation of T cell activation and exhaustion by Tim-3 (Co-I, 7% effort, PI: Kane), 2018-2022.
NIH R01, Proximal tubule endocytosis in normal and nephrotic kidneys (Co-I, 8% effort, PI: Weisz), 2019-2024.
NIH R01, Molecular Mechanisms of IL-17 dependent autoimmune signaling (Co-I, 4% effort, PI: Gaffen), 2019-2024.
NIH R01, DNA damage signaling to dormant origins of replication (Co-I, 5% effort, PI: Bakkenist), 2019-2024.
NIH R01, IL-17 regulates LN stromal cell metabolism and function (Co-I, 5% effort, PI: McGeachy), 2020-2023.
Mark Foundation Emerging Leader Award, Improving cancer immunotherapy through metabolic modulation (Co-I, 5% effort, PI: Delgoffe), 2020-2022.