Program Leaders
Allergy, Asthma and Other Inflammatory Diseases
De'Broski R. Herbert, Ph.D.
Associate Professor, Pathobiology, University of Pennsylvania School of Veterinary Medicine
Through the study of parasitic helminths and protozoa, my group has made important contributions towards understanding mechanisms controlling development of alternatively activated macrophages and Type 2 inflammation within the respiratory and gastrointestinal tract.
Jorge Henao-Mejia, M.D., Ph.D.
Associate Professor of Pathology and Laboratory Medicine
The overarching goal of Henao-Mejia Lab is to use novel mouse genetic tools to define the molecular mechanisms of chronic inflammatory disorders. Since it's beginning in May of 2014, we have used the revolutionary CRISPR/Cas9 system to rapidly generate novel genetic tools that allow us to precisely establish the molecular mechanisms involved in the development of chronic inflammatory conditions. In particular, we have used this technology to interrogate the role of non-coding RNAs (lncRNAs, miRNAs) transcribed from regions of the genome associated with the development of inflammatory pathologies.
Autoimmunity
Edward Behrens, M.D.
Joseph Hollander Associate Professor in Pediatric Rheumatology
The Behrens Laboratory is mainly focused on the understanding the pathogenesis of Cytokine Storm Syndrome, a common pathologic endpoint of a heterogeneous group of initiating diseases. There are a number of specific current projects that are active in the lab. The following is a list of some representative long-term projects:
1) The role of IL-33/ST2 in Familial Hemophagocytic Lymphohistiocytosis (FHL)
2) The role of Interferon gamma (IFNg) in FHL
3) The role of the microbiome in cytokine storm
4) The role of Heme-oxygenase 1 (HO1) in cytokine storm
5) Hematopoiesis during inflammation
Terri Laufer, M.D.
Associate Professor of Medicine
Major histocomatibility complex (MHC) class II molecules are required for the normal development in the thymus of CD4+ T cells and function to present peptide antigens to those CD4 cells in the periphery. Our current studies are directed toward understanding the peptide specificity, function, and pathologic potential of these autoreactive T cells:
1) Examination of a series of K14-derived autoreactive T hybridomas demonstrates that the autoreactive population of CD4 cells is polyclonal; however, we are beginning to identify the individual peptides responsible for stimulating the autoreactive response.
2) Development of autoimmunity: Adoptive transfer systems are being utilized to tease apart the T cell and target-organ abnormalities that must be present to initiate an autoimmune disease.
3) Requirement for MHC class II in other antigen presenting populations.
Cancer Immunology
Ivan Maillard, M.D., Ph.D.
Professor of Medicine and Vice Chair for Research, Division of Hematology-Oncology
My laboratory investigates the regulation of normal and malignant hematopoiesis, bone marrow transplantation and T cell alloimmunity. A central focus of our studies is the role of Notch signaling in T cell development, differentiation and function. Using mouse models of bone marrow transplantation, we discovered essential functions for Notch receptors and ligands in graft-versus-host disease with a high fundamental and translational impact. We are also interested to understand the role of Trithorax family epigenetic regulators in hematopoiesis and leukemia.
Marco Ruella, M.D.
Assistant Professor of Medicine
Dr. Ruella's laboratory focuses on the mechanisms of relapse after chimeric antigen receptor T cell (CART) immunotherapies with the goal of rationally design innovative combined immunotherapies for relapsing/refractory leukemia and lymphoma.
Innate and Adaptive Immunity to Pathogens
Michael R. Betts, Ph.D.
Associate Professor of Microbiology
My laboratory studies human T lymphocyte function in order to understand the role of these cells in controlling or eliminating viral pathogens and providing protection from infection. Our primary interest is in determining how and if the human CD8+ T cell response to HIV controls viral replication. The current direction within the lab is to determine the underlying mechanisms that control the cell fate and functional characteristics of HIV-specific T and B cells in the context of HIV infection and disease progression.
Sunny Shin, Ph.D.
Associate Professor of Microbiology
My lab is interested in uncovering innate immune mechanisms used by the host to defend itself against bacterial pathogens and how bacterial pathogens evade host immunity to cause disease.We utilize the intracellular bacterial pathogen Legionella pneumophila, causative agent of the severe pneumonia Legionnaires' disease, as our primary model. Legionella has evolved numerous mechanisms for modulating eukaryotic processes in order to survive and replicate within host cells. The ease with which Legionella can be genetically manipulated provides a powerful system for dissecting immune responses to bacteria that differ in defined virulence properties and for elucidating mechanisms of bacterial pathogenesis.
Systems Immunology and Genomics
Golnaz Vahedi, PhD
Assistant Professor of Genetics
The overarching goal of the hybrid wet and dry Vahedi laboratory is to exploit the epigenome in addition to mouse and human genetics to understand how T cell identity is established. Why the epigenome? Information encoded in DNA is interpreted, modified, and propagated as chromatin. The diversity of inputs encountered by immune cells demands a matching capacity for transcriptional outcomes provided by the combinatorial and dynamic nature of epigenetic processes. Advances in genome editing and genome-wide analyses have revealed unprecedented complexity of chromatin pathways involved in the immune response, offering explanations to long-standing questions and presenting new challenges.
Transplantation Immunology
Matthew Levine, M.D., Ph.D.
Associate Professor of Surgery
My research interests focus on topics of translational immunology and epigenetics as applies to transplantation with a specific focus on the modulation of ischemia reperfusion injury and drug toxicity by intervention in the histone deacetylase (HDAC)/nuclear corerpressor complex axis as well as interventions involving sex hormones. Via collaboration with Wayne Hancock, we have co-investigated regulatory T cell biology in the setting of vascularized composite allotransplantation, solid organ transplantation and scenarios of malignancy with a focus on hepatocellular carcinoma (HCC).
Andrew Wells, Ph.D.
Associate Professor of Pathology and Laboratory Medicine
My laboratory studies how T lymphocyte activation, differentiation, and tolerance are regulated by components of the cyclin-dependent kinase (CDK) cascade like CDK2 and p27KIP1, and by transcription factors like FOXP3 and IKAROS in cooperation with epigenetic factors like DNMT3A. We have over 15 years of experience in cellular immunology, cell biology, and molecular biology research, including mouse models, in vivo and in vitro lymphocyte function, biochemistry, transcriptional biology and epigenetics. More recently, we have incorporated ‘next generation’ approaches like ATAC-seq, ChIP-seq and methyl-DIP-seq to study transcription factor binding, chromatin remodeling, and DNA methylation genome-wide, and three-dimensional chromosome conformation capture (3C)-based techniques like 4C-seq and Capture C to study long-range interactions between enhancers and promoters.