Amanda Poholek, PhD
Campus: 4401 Penn Ave.
Office: Rangos Research Center Rm. 8129
Pittsburgh, PA 15224
- BS, Biological Sciences, 2002, Fordham University
- PhD, Cell Biology, 2009, Yale University
- Post-doctoral Fellowship, NIAMS, NIH; Dr. John J. O'Shea
- Assistant Professor, Department of Pediatrics
- Assistant Professor, Department of Immunology
- Director, Health Sciences Sequencing Core at UPMC Children's Hospital of Pittsburgh
Immune cells, such as T cells, play a critical role in establishing and maintaining whole organism health, while aberrant immune cell function underlies a host of diseases ranging from immunodeficiency to autoimmunity. As a model system for cellular differentiation, immune cells have the unique property of both maintaining homeostasis and responding to environmental or pathogenic insult.
Using NextGen sequencing technologies, the Poholek lab seeks to understand how tissue-specific environments control T cell differentiation and function at the transcriptomic and epigenomic level to understand the greater impact of immune cell regulation on health and disease.
Areas of Focus:
Context-dependent Function of the Transcriptional Repressor, Blimp-1
Transcription factors play a critical role in modulating the transcriptome and epigenome of cells. Blimp-1 is a BTB-POZ Zinc finger transcription factor expressed by many cell types, including T and B cells. In T cells, we have identified context-dependent functions of Blimp-1 controlling T cell differentiation and effector function and are exploring the molecular regulation and function of Blimp-1 as a model transcription factor that controls immune cells in health in disease. Our research on Blimp-1 seeks to answer the following questions:
1) How is Blimp-1 regulated in a cell-type specific manner?
2) What is the molecular function of Blimp-1 in vivo in various immunological contexts?
ur studies have uncovered novel genomic elements controlling the expression of Blimp-1 and the tissue-specific functions of Blimp-1 that control autoimmunity while also promoting responses to allergens. Using genetic mouse models and NextGen sequencing technologies, we are, at the molecular level, exploring how this important transcription factor shapes T cell differentiation and function at homeostasis and in the face of contextual environmental changes.
Epigenetic Landscape of T Cell Exhaustion in the Tumor
In collaboration with Greg Delgoffe, PhD, at the UPMC Hillman Cancer Center, we are exploring the epigenetics of T cells in murine tumors using a new low-cell number ChIP-seq assay (CUT & RUN) developed by Steve Henikoff at the Fred Hutch Cancer Institute. As T cells enter a tumor’s microenviroment, they experience a unique combination of signals that promote a state of T cell dysfunction (also called exhaustion). Our lab is working to understand the transcriptomic and epigenomic landscape of T cell exhaustion in a tumor in order to understand the signals that drive exhaustion and identify novel therapeutic targets for immunotherapy.
Metabolic and Epigenomic Intersection Controlling T Cell Activation and Differentiation
T cells are unique in that they can rapidly shift their metabolism after activation as well as undergo rapid cell division. The cellular mechanics that underlie these changes are unique to T cells and are in the early stages of being understood. Our lab is using NextGen Sequencing technologies to modulate the environmental signals and metabolic requirements that T cells experience after activation to determine the intersection of these inputs on the epigenetic landscape. Our goal is to understand how shifts in metabolites or environmental signals impact T cell differentiation and function from the initiation of T cell activation at the chromatin level in order to understand the plasticity and heterogeneity that exists in the T cell compartment in vivo.
Allergen-induced Airway Inflammation and Th2 Cell Development Requires Blimp-1
He K, Hettinga A, Kale S, Xie M, AL D, Ray A, Poholek AC
2019 Sep 12 (Preprint)
IL-10 Induces a STAT3-dependent Autoregulatory Loop in Th2 Cells That Promotes Blimp-1 Restriction of Cell Expansion via Antagonism of STAT5 Target Genes
Poholek AC, Jankovic D, Villarino AV, Petermann F, Hettinga A, Shouval DS, Snapper SB, Kaech SM, Brooks SR, Vahedi G, Sher A, Kanno Y, O'Shea JJ
2016 Nov 11
Transcriptional and Epigenetic Networks of Helper T Cells and Innate Lymphoid Cells
Shih HY, Sciume G, Poholek AC, Vahedi G, Hirahara K, Villarino A, Bonelli M, Bosselut R, Kanno Y, Muljo S, O’Shea JJ
2014 Aug 14
Type I Interferon Induces Binding of STAT1 to Bcl6: Divergent Roles of STAT-family transcription factors in the TFH Cell Genetic Program
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
The Journal of Immunology
2014 Mar 1
Helper T Cell Identity and Evolution of Differential Transcriptomes and Epigenomes
Vahedi G*, Poholek AC*, Hand TW, Laurence A, Kanno Y, O’Shea JJ, Hirahara K
2013 Feb 13
In Vivo Regulation of Bcl6 and T Follicular Helper Cell Development
Poholek AC, Hansen K, Hernandez S, Eto D, Chandele A, Weinstein JS, Dong X, Odegard J, Kaech SM, Dent AL, Crotty S, Craft J
The Journal of Immunology
2010 Jul 1
Bcl6 and Blimp-1 are Reciprocal and Antagonist Regulators of T Follicular Helper Cell Differentiation
Johnston R*, Poholek AC*, DiToro D, Yusuf I, Eto D, Barnett B, Dent A, Craft J, Crotty S
2009 Aug 2
- Transcription Factors
- Chromatin regulation
- T cell differentiation and effector function
- NextGen sequencing
Angela Hettinga - Technician
Kun He, PhD - Postdoctoral Fellow
Rhodes Ford - PMI Graduate Student
Elizabeth Schmitz - Undergraduate Student - Bioinformatics
Shivani Pandya - Undergraduate Student - Bioinformatics
David Tempestini - Undergraduate Student - Bioinformatics