- Lab Members
I joined the Wherry Lab in February of 2022 as a research specialist. I provide research assistance in developing projects related to reinvigoration of T cell exhaustion in chronic infection, with a particular focus on PD-1 pathway. I also assist our lab manager with routine lab tasks to ensure the laboratory operates smoothly.
Among many other molecules, CD8 T cells responding to viral infection upregulate the C-C chemokines RANTES and Mip-1α. It is not clear what functional capacities do these chemotactic cytokines confer on CD8 T cells. Using the mouse influenza infection model and adoptive transfer of CD8s expressing or lacking RANTES and Mip-1a we are attempting to elucidate the possible role/roles they play in CD8 T cell function.. Our preliminary data suggest that CD8 T cells are probably using these molecules to exert some command over the accumulation of a population/populations of myeloid cells, that appear to be involved in the regulatory circuits of the lung during CD8-driven immune response to influenza infection.
Immune checkpoint blockade has shown promising results in cancer therapeutics but has also been associated with a variety of immune related adverse events and iatrogenic autoimmunity. My goal is to study the immune dysregulation that follows checkpoint inhibition and eventually results in loss of self-tolerance using both human and murine samples.
The development of immunotherapies, such as PD-1 blockade, have revolutionized cancer treatment. These therapies work by reinvigorating exhausted T cells, but only a minority of patients experience a clinical benefit. I joined the Wherry and Jordan labs in March 2018 to study the epigenetic factors that mediate development of exhausted T cells, using cutting edge CRISPR, RNA-seq and ATAC-seq approaches. My goal is to understand how these epigenetic factors might be manipulated to promote better clinical responses to immunotherapy.
I am interested in combining big data analytics, deep phenotyping of clinical cohorts, and biological experiments to better understand drivers of disease, with the goal of translating new insights into improved therapeutic and diagnostic strategies. Currently, I am focused on 1) the role of interferon pathway signatures in immuno-oncology and viral infection and 2) technology development to enhance our analysis of biological context.
It is now well-established that exhausted CD8 T cells do not behave as a single homogenous population. During a chronic viral infection, a unique progenitor/progeny dynamic is rapidly set up to ensure continuous control of viremia. My current project aims to elucidate critical mechanisms involved in the development and lineage commitment of different subsets of exhausted CD8 T cells. My second interest is to identify relevant immunotherapeutic agents capable of synergizing with immune checkpoint blockade to further improve and prolonged the beneficial effect of such treatment in patients with cancer.
I joined the Wherry Lab in September of 2021. I am currently investigating the role of PD-1 signaling in human T:B interactions using high-dimensional flow cytometry and single-cell sequencing approaches.
Shin Foong obtained his PhD from the University of Melbourne in 2013 where he studied a number of immune suppressive pathways in cancer. He then joined the Wherry lab in Spring 2016, and has been working on projects to gain better understanding of the interactions between multiple immune receptors in regulating T cell exhaustion.
I am using NGS techniques, RNA-seq and ATAC-seq, to investigate the state of exhaustion in tumor infiltrating lymphocytes and determine whether immune checkpoint blockade leads to cellular reprogramming.
Rishi is a medical student at the University of Pennsylvania. In the lab, he studies vaccine immunology and is currently investigating antibody and memory B cell responses to SARS-CoV-2 vaccines.
I joined the Wherry and Berger labs in Feb 2019. My role is to provide bioinformatics and computational supports to the team and collaborators, including: Developing, implementing, and maintaining pipelines for processing NGS data in high-performance computing environment; Applying general statistical, machine learning and other advanced methods and algorithms for analyzing large scale biomedical data.
I'm a second-year student in the cancer biology PhD program. I'm interested in the epigenetic determinants underlying fate commitment to T cell exhaustion. Ultimately, I hope to leverage this understanding to improve CD8 functionality in cancer and chronic infections.
Hidradenitis Suppurativa is an inflammatory skin disease that causes non-healing painful nodules, abscesses, and draining sinus tracts. I am interested in understanding the immunologic mechanisms of this disease using highly multiplexed imaging and sequencing platforms with the goal of improving treatment options for patients.
I am interested in the epigenetic mechanisms governing T cell fate decisions and responses to viral infection. To that end, my work focuses on understanding the role of chromatin-modulating proteins in regulating immune function by leveraging high through-put techniques, engineered microfluidic devices, and mouse models.
In 2020, I joined the labs of E. John Wherry, PhD and Andy Minn, MD PhD as a graduate student in the Cell and Molecular Biology group (CAMB). My research primarily focuses on the contribution of pattern recognition receptor (PRR) signaling to CD8 T cell phenotypes during viral infection and cancers.
Medical Oncology Fellow
I am an oncology fellow at the University of Pennsylvania with clinical interests in neuro-oncology. I am pursuing a post-doc within the Wherry Lab to learn a variety of molecular and immune-profiling techniques. I am interested in applying these technologies to study the biology of primary brain tumors and mechanisms of response to immunotherapy in the context of early phase clinical trials. I hope our findings will help potentiate new therapeutic insights for these patients.
Clinical Research Coordinator
Oliva Kuthuru is a Clinical Research Coordinator at the Wherry Lab at Perelman School of Medicine. She primarily coordinates the lab’s clinical trials investigating and understanding the immune response to annual flu vaccines in the presence of immunotherapies. She is also currently involved in establishing clinical trials and data management with the Allen Institute. Prior to working at Penn, she gained experience working in a fast-paced clinical research setting and coordinating more than 10 clinical trials for the Department of Neurology at Thomas Jefferson University.
I joined Wherry Lab in 2015, my primary role has been to analyze, integrate and deduce mechanistic insights from various epigenetic & transcriptional profiling data of immune cell subsets.
I have worked on adapting Next Generation Sequencing analysis approaches to create flexible, modular workflows by using/integrating various software packages and algorithms.
Also developed and maintained web tools to host, visualize and analyze various sequencing data generated in the lab and from external sources.
I study various determinants in human blood or tissue that can dictate the response to immunotherapies in human cancers.
I am in charge of overseeing the work activities and personnel of the lab. I am responsible for allocating budgets, ordering supplies, and maintaining safety standards - amongst other things - to ensure the laboratory runs smoothly and efficiently.
Yuki has been dissecting the unique interaction between the immune system and DNA damage and repair response (DDR) to understand how that interaction impacts the immune cell biology and patient therapeutic response, continuing from her PhD work in the radio-immuno-oncology field. Yuki developed the high-dimensional DDR-Immune profiling platform that enables simultaneous analysis of DDR and T cell biology in single cell resolution in human T cells. Yuki applied that DDR-Immune platform and found unique patterns of DDR in human T cell subsets, and also found DDR-Immune signatures that can distinguish clinical response to immunotherapy. She has also been working on studies and immune profiling of cancers, radiation therapies, vaccination, Lynch syndrome and BRCA-mutated patients, as well as working on mouse viral infection and tumor models for memory/exhausted T cell biology.
I have worked in cancer genomics for over a decade, integrating experimental and computational approaches to uncover the basis of tumorogenesis, tumor progression, and relapse. I joined the Wherry lab in 2019 where I am validating in situ multiplexed imaging methods to investigate immune response and immunopathology in clinical tissues. As part of the Human Tumor Atlas Network (HTAN), I am integrating imaging data with single-cell RNA-seq and ATAC-seq to longitudinally and comprehensively profile the tumor immune microenvironment of high-grade gliomas, as a basis for rational immunotherapy design in the diagnostic and relapsed settings.
I joined the Wherry lab as a post-doc in 2021 and study the human immune response following SARS-CoV-2 vaccination and infection. I am also interested in the immune response to infection and vaccination in other settings, as well as human tumor immunotherapy.
I joined the Wherry lab as a post-doc in 2021. I am investigating factors controlling exhausted and memory CD8+ T cell differentiation in non-lymphoid and peripheral tissues during chronic infection and cancer, with the goal of leveraging this information to design novel immunotherapies.
I am trying to define the T cell epitopes for Human Norovirus by conducting peptide library screens on peripheral blood and intestinal samples. My other project involves deep immune phenotyping of T cell subsets from intestinal mucosa of IBD patients.
I am a graduate student in the Genomics and Computational Biology (GCB) Graduate Group. Under the co-mentorship of Dr. John Wherry and Dr. Marylyn Ritchie, I am developing computational immunology methods for single-cell data. Outside of science, I play Ultimate Frisbee, love cooking, and can usually be found exploring the outdoors.
I’m interested in the dynamical regulation of T cell exhaustion in cancer progression, especially the epigenetic role in this process. My goal is to apply single-cell omics and various CRISPR based tools to primary and engineered human immune cells to identify the functional elements and the key regulatory factors in effector and exhausted T cells.
I am a graduate student in the Immunology Graduate Group (IGG). For my thesis project, I’ve developed an in vitro model of CD8 T cell exhaustion and I am currently applying this model to uncovering novel transcriptional networks that control T cell exhaustion and fate differentiation. I was recently named a Parker Institute for Cancer Immunotherapy Scholar.
I am an undergraduate studying Biochemistry at the University of Pennsylvania. I joined the lab with interests in human cancer therapeutics and I am working on projects that evaluate various immunotherapies currently being given to patients. My hope is that the immune-profiling techniques I learn in the lab will allow me to give biological rationale for differential responses in treatment, and ultimately I hope to build upon current knowledge of cancer immunotherapies to improve outcomes for patients.
Past Lab Members
Cécile is a former PostDoc in the Wherry lab. She worked on samples from COVID patients, as well as PDAC, glioblastoma, lymphoma, and CART cancer patients with a translational approach. She is a Parker Bridge Scholar now in the independent phase as a Senior Scientist in the U932 (Amigorena) at Institut Curie, Paris, France, and the Deputy Director of the Clinical Immunology Laboratory at Institut Curie. Her team (T Cell Inspection, TCI) studies T cell biology in human health and disease. Her focus is on CMV and TE latent infections, COVID19, CAR T cells profiling, as well as thymic, lung and glioblastoma tumors. Cécile is an active collaborator of the Wherrylab, the University of Pennsylvania, and the Parker Institute for Cancer Immunotherapy (PICI).
My project is to examine the effect of different immunotherapy agents in humanized mice.
Checkpoint inhibitors that target the PD-1 inhibitory pathway reverse T cell exhaustion and reinvigorate anti-cancer T cells to become functional again, thus enabling the patient’s immune system to mount effective anti-tumor responses. However, sometimes anti-cancer T cells cannot be reinvigorated by checkpoint blockade alone. My project aims to identify other mechanisms that could rescue anti-cancer T cell responses and help them to recover and overcome exhaustion. My work will potentially identify novel approaches for new immunotherapies that can boost the ability of the immune system to fight highly resistant cancers.
I test antibodies and small molecule inhibitors in a chronic infection model for two different, but related purposes. First, investigating possible synergy between the PD1/PDL1 axis and other inhibitory or costimulatory pathways. Second, improving functionality of previously exhausted CD8 T-Cells.
I’m interested in the regulation of immune responses in infection, autoimmunity and cancer with a focus on the mechanisms driving T cell exhaustion. My research uses systems immunology approaches with a particular emphasis on mass cytometry for the comprehensive profiling and algorithmic data mining of immune cells in human disease. Further, I’m investigating the role of the regulation of immunometabolism in T cell exhaustion using the LCMV model system.
My research mainly focus on the regulatory function of microRNAs in CD8 T cell exhaustion. I’m also involved in the project about identifying key transcription regulators in CD8 T cell anti-viral response by in vivo CRISPR screening.
This is Zeyu Chen, a third year graduate student in the Cell and Molecular Biology (CAMB) Program. I am interesting in understanding T cell responses during acute and chronic diseases. My current main focus is modeling memory and exhausted T cell development in vivo using single cell gene expression profiling and Retroviral-CRISPR technologies. Besides, I am also working on how non-coding RNAs play important roles during memory formation and T cell exhaustion.
My main hobby is cooking and I have some secret recipes to "just share" in the Wherry Lab~
Assisting in Clinical trials and sample management.
I am working with Sarah Henrickson to investigate the role of T-cell dysfunction, inflammation and immunometabolism in pediatric inflammatory diseases.
I obtained my PhD from Vanderbilt University in 2018 where I studied systems immune monitoring in melanoma patients undergoing therapy. I joined the Wherry lab in early 2019 where my project focuses on dissecting the role of non-coding regions of the genome to better understand and control the exhaustion fate commitment in T cells.
Follicular helper CD4 T cells provide vital help for antibody responses. We have been studying repertoire dynamics of circulating T follicular helper CD4 cells following influenza vaccination in adults to understand the specific effects of aging and inflammation on this critical player in vaccine-mediated responses.
We study the mechanism of immunotherapies such as anti-PD1 and its effect on CD8 T cell exhaustion and re-invigoration in cancer patients. We then correlate the immune changes with clinical outcomes of patients to understand the determinants of response and non-response to immunotherapy. We have recently identified that the balance between re-invigoration of CD8 T cells and overall tumor burden may dictate clinical response to anti-PD1 therapy in melanoma patients using deep immune profiling of peripheral blood T cells (Nature 2017).
Mechanisms that grant cell-type-specific regulation of gene transcription allow for heterogenous function of cells due to differential expression of genes. These gene regulatory programs are established through cell-type-specific binding of transcription factors. However, while the architecture of the chromatin environment in the cell typically dictates the binding of transcription factors and impacts gene expression, we have identified transcription factors that instead govern the architecture of the chromatin environment in the development and differentiation of T cells. I am interested in determining the mechanisms that allow these transcription factors to modify the existing chromatin to establish cell-type-specific regulation of genes. We use genome-wide, next-generation sequencing methods such as ATAC-seq, single cell ATAC-seq, ChIP-seq, HiChIP, and RNA-seq to uncover these principles. In the future, we hope to use these mechanisms to reverse terminal cell programs and revitalize antigen-specific T cell responses.
Stress and the passage of time age the immune system like any other organ, and consequent immunosenescence impairs a panoply of functions that are critical for survival, including microbial defense and tumor immunosurveillance. Given their requirements for extensive and extremely rapid replication, T cells are particularly sensitive to immunosenescence. How pathogen-specific T cells manage genome integrity to forestall immunosenescence is the subject of my research.
Since I joined to the Wherry lab in 2011, I have been studying transcriptional control of CD8 T cell differentiation. Particularly, I’m interested in role of BATF and IRF4 as cardinal transcription factors in various phases of CD8 T cell response. We have already revealed that BATF serves as an essential differentiation checkpoint in transition from naïve to effector CD8 T cells, and BATF and IRF4 co-bind to genome of activated CD8 T cells [link]. Based on these findings, we are currently testing the hypothesis that BATF and IRF4 work as pioneering transcription factors in CD8 T cell differentiation. Role of these transcription factors in T cell exhaustion is also being studied.
Key words: CD8 T cell, BATF, IRF4, pioneer transcription factor, exhaustion
My research focuses on the regulation of the t-box transcription factors, T-bet and Eomesodermin, during CD8 T-cell exhaustion. Specifically, I am interested in understanding how these factors play different roles in memory cells compared to exhausted cells both through their own regulation by other cellular factors as well as through the downstream genes that they target.
We are studying the human CD4 T cell response after influenza vaccination, specifically in the T follicular helper (Tfh) cells. A subset of Tfh, circulating Tfh, can be found in the peripheral blood and may give us a way to get a glimpse of what is happening in the lymphoid tissue. I am also interested in studying the expression of activation induced markers for identifying antigen-specific cells.
The first question that I engage myself with is investigating the role of microRNAs in regulating CD8+ T cell function during acute and chronic viral infections. In addition, Ι am interested in the effect of ion flow upon T cell function.
I will be exploring how miR-29a regulates antiviral CD8+ T-cell responses in chronic infection.
I studied Architecture and had been working as a house designer in Daiwa House Co., one of the largest homebuilder company in Japan. Since joined the lab in 2011, I’ve been working as a research technician. Taking advantage of designer knowledge, I’ve also made several scientific concept figures for the lab. Representative works can be seen at here or here.
I am working with Laura Vella and Sarah Henrickson on a variety of topics ranging from HIV to pediatric inflammatory diseases with a particular focus on T cell immunology.
I am interested in the role of PD-1 and other inhibitor pathways in the regulation of primary and memory CD8 response to acute infections, specifically influenza. I am also interested in translational studies about the effect of PD-1 blockade on both acute and chronic pulmonary infections in patients in the ICU and those with underlying pulmonary disease.
I am a fourth year graduate student in the Immunology Graduate Group (IGG). My research focuses on immune dysfunction during chronic infection with a particular focus on B cell and CD4 T cell responses. I use the LCMV mouse model of chronic infection to look at cellular and molecular differences within LCMV-specific B cell response and how those differences can be exploited in a therapeutic setting such as immunotherapy or vaccination.
Works on human immunology and chronic infection, with a focus on T follicular helper cells and HIV.
"The role of microRNAs in regulating CD8 T cell differentiation during acute and chronic viral infections."
Attending Physician with the Division of Allergy at Children's Hospital of Philadelphia
Sarah works on T cell dysfunction in pediatric disease. She has two main projects, one investigating the immunometabolic alterations when asthmatic patients are also obese. The second focuses on novel immunodeficiency discovery in severe cutaneous viral infections.