CHRISTENSEN LAB
Dr. Christensen's laboratory aims to uncover the roles of cell profiles and epigenetic alterations in the development and progression of cancer that lead to the development of clinically useful tools. The Christensen group uses molecular epidemiology and computational approaches to further develop and apply methods for DNA-based cell typing (methylation cytometry). We have developed methylation cytometry methods for blood immune profiling and for tumor microenvironment cell typing. Our group also has contributed DNA methylation analysis methods for clustering, and inter-platform data integration, as well as deep learning approaches. Our group aims to identify methylation alterations along the cancer continuum from preinvasive to invasive disease, as well as in association with patient outcomes including response to immunotherapy.
COLE LAB
Dr. Cole's laboratory was among the first to describe the chromosomal translocation between Myc and the immunoglobulin locus in 1982, and they have studied various aspects of Myc function ever since. The oncogenic activity of transcription factors depends on protein domains associated with transcriptional activation, which provides an avenue to study both cancer biology and the mechanisms of gene regulation. A major contribution of the lab was the discovery of the link between Myc and E2F and TRRAP-containing histone acetyltransferase complexes, which is currently the dominant model for the mechanism of Myc transactivation. Beyond studies of Myc cofactors, the Cole lab has launched a high throughput screen for Myc inhibitors based on a novel assay for Myc binding to TRRAP. The goal is to discover a novel anti-cancer drug that would be extremely useful against the 70% of cancers with Myc over-expression.
FIERING LAB
Dr. Fiering's laboratory is primarily focused on in situ vaccination to generate therapeutic anti-tumor immunity. The immune system recognizes cancers, and many are eliminated before they are clinically recognized. Cancer can be considered to be a failure of the immune system and it is now becoming clear that this immune failure is often due to active immunosuppression generated by the tumor. One approach to cancer therapy is finding ways to stimulate the immune system to seek out and destroy tumor cells much like it seeks out and destroys infectious organisms. Our lab is currently focused on developing novel approaches to boosting anti-tumor immunity by injection of immune stimulatory reagents directly into recognized tumors, an approach termed “ in situ vaccination”. The goal is to overcome the local immunosuppression, get an effective local antitumor immune response and generate a systemic antitumor immune response to fight metastatic disease. All vaccines include an antigen to be recognized by the immune system and an adjuvant to stimulate the response against the antigen. For in situ vaccination the tumor carries all relevant antigens and injection of adjuvant into the tumor supports recognition of both tumor-associated and neoantigens expressed by the tumor. There are many options to how in situ vaccination can be performed and we explore the options in mice as well as working with dogs with spontaneous tumors and studying the local and systemic immune response involved. The goal is to develop clinically useful in situ vaccination approaches.
GAUR LAB
Dr. Gaur's laboratory research can be broadly divided into the following three areas:
Basic Research: Understanding the critical contribution of microRNAs and their targets to various pathologies of the nervous system.
Translational Research: Running clinical trials to establish the role of microRNAs as diagnostic and prognostic biomarkers and therapeutic agents in gliomas as well as biomarkers of treatment efficacy and toxicity in glioma patients.
Biomedical Engineering: Developing innovative, in vivo wireless, nano scale devices for early detection of disease as well as regulated and targeted drug delivery.
GERBER LAB
Research in the Dr. Gerber's laboratory uses a combination of cell biology, biochemistry and mass spectrometry-based proteomics approaches to understand cell signaling in the cell cycle, in particular in cell division. Some of the essential effectors of cell division are oncogenes when overexpressed or dysregulated in cancer; we seek to better understand how cancer cells co-opt essential signaling pathways for survival, in the hopes of developing new therapeutic strategies.
HUANG LAB
Dr. Huang's laboratory research interests: T lymphocytes are a critical component of the adaptive immune system and provide specific protection against pathogens and cancer cells. Defects in T cell activation or migration lead to primary immunodeficiency diseases, characterized by increased susceptibility to viral and bacterial infections. However, T cell hyperactivity can result in autoimmune attack of one’s own tissue. The quality and magnitude of a T cell response are controlled by positive and negative cues from the microenvironment. We investigate how T cells appropriately and inappropriately translate activation and migration cues during a) thymocyte development, b) CD4 T cell differentiation, and c) tumor immune responses.
KETTENBACH LAB
Dr. Kettenbach's laboratory focuses on uncovering novel roles of phosphatases in cellular signaling networks in normal tissues and in cancer. The lab uses a mass spectrometry-based approach to study phosphatase signaling on a system-wide level in cells, and reconstitute individual components in vitro to confirm, specify and validate them.
LEACH LAB
Dr. Leach's laboratory has a long track record of research productivity in the field of pancreatic cancer biology and is known for establishing important links between pancreatic development and pancreatic cancer using both mouse and zebrafish model systems. Past accomplishments include the initial discovery of abnormal Notch pathway activation as an important driver of pancreatic tumorigenesis, creation of the first zebrafish model of pancreatic cancer, a detailed mapping of a unique immune neoepitope landscape associated with long term survival and the discovery of altered mRNA splicing as a key driver of this disease. Current studies focus on the generation of transcriptional and epigenetic heterogeneity during pancreatic cancer spread and the role of arsenic in promoting epigenetic reprogramming of immune cells in the tumor microenvironment.
MALANEY LAB
Dr. Malaney's laboratory focuses on:
The Role of RNA-Binding Protein Mutations in Health and Disease.
Increased accessibility to whole exome sequencing has helped identify RBP mutations in cancer and neurodevelopmental diseases. The Malaney Lab is specifically focused on mutations in a family of RBPs called hnRNPs (heterogenous nuclear ribonucleoproteins) and their contribution to malignancy and neurodevelopmental disease. We use a suite of biochemical, molecular biology and mouse modeling techniques to understand the function of hnRNP proteins in normal homeostasis and how these homeostatic pathways are disrupted in a disease context. The overall goal in the lab is to unravel the mechanistic basis of the pathogenicity of hnRNP mutations to identify therapeutic vulnerabilities.
MCKENNA LAB
About research in Dr. McKenna's laboratory: My lab is interested in how cells grow and divide to form complex structures, such as the transformation from the zygote to an adult human or from a transformed cell into a tumor mass. To study these processes, we develop technologies to trace the pattern of cell divisions that recovers the lineage of each cell. This information can be combined with other measures of cell state such as single-cell transcriptomic data to develop a rich picture of how choices are made in development, and how this process is dysregulated in diseases such as cancer.
MIERKE LAB
About research in the Dr. Mierke's laboratory: The major thrust of my research is the structural characterization of peptides and proteins with the ultimate goal of therapeutic design. We make extensive use of experimental (high resolution NMR, fluorescence, circular dichroism) and theoretical (molecular dynamics, modeling, screening) approaches in our examination of peptide/receptor targets. We are currently designing molecules that inhibit the formation of the IKK complex, by disrupting the association of the IKKa/IKKb kinases with IKKg (also known as NEMO). These molecules should be specific for the canonical NF-kB signaling pathway. Another project targets the formation of the DISC complex important in the regulation of apoptosis, with particular efforts placed on blocking the recruitment of cFLIP to the DISC, shown to be pro-survival leading to resistance to a number of chemotherapies. A final project involves the use of a novel NMR technique to screen for direct inhibitors of the small GTPase Rac1, a mediator of cellular proliferation, adhesion, migration and cell death, whose overexpression and mutant forms promote or drive tumorigenesis.
PIOLI LAB
Dr. Pioli's laboratory is focused on identifying the molecular mechanisms that regulate macrophage activation in the context of both autoimmunity and cancer. Taking advantage of macrophage plasticity, we then use this information to determine how macrophage activation can be altered for maximal therapeutic benefit.
POINTER LAB
Dr. Pointer's laboratory focuses on translational and preclinical approaches to overcome radiation resistance and toxicity. Between half and two thirds of patients will receive radiation therapy during their cancer treatment. While radiation therapy is curative in many cases, radiation can paradoxically cause tumor resistance and can also cause harm. The Pointer lab is interested in understanding the mechanisms behind radiation resistance and developing ways to overcome this resistance, as well as ways to improve patient quality of life after radiation therapy.
ROSATO LAB
Tissue resident memory T cells (T RM ) combine the exquisite specificity of adaptive immunity, with rapid frontline antiviral functions conventionally executed by innate immune cells.
Dr. Rosato's laboratory is interested in understanding the function and regulation of T RM in distinct tissue environments to be able to contextualize their role in cancer, infection and autoimmunity.
SALAS LAB
Dr. Salas' laboratory is studying cell heterogeneity in cancer and human diseases using epigenetics and single-cell omic technologies.
Using bioinformatics tools to investigate how cell heterogeneity impacts human health and disease, with an emphasis on how genetic, environmental, and lifestyle factors model the human epigenome and therefore cell plasticity. The Salas’ lab studies how some key epigenetic mechanisms (DNA methylation, DNA hydroxymethylation, and miRNA alterations) affect gene expression and cancer outcomes, including how the immune cells are altered in this disease. Other research interests include biomarker development, chronic inflammation, and human disease, and how exposures during fetal life alter newborn and childhood outcomes.
SAMKOE LAB
Research in Dr. Samkoe's laboratory focuses on translational applications of quantitative molecular imaging to biomedical engineering and systems biology.
Protein quantification in living systems is an important part of diagnosing, understanding, and treating disease, especially cancer. Yet the majority of protein quantification techniques are developed for tissue that has been removed from the living system - such as pathology tissue samples, and cell culture. Molecular fluorescence imaging allows microscopic information from proteins, or molecules, to visualized over a wide range of resolutions - allowing for a systems approach to understanding protein expression and function within a living system. One of the lab's main focus is using a fluorescence imaging methodology called "paired-agent imaging" to quantify protein concentrations in living systems for applications in oncology. Quantification of cell surface receptors is being used to differentiate between cancerous tissue and normal tissue for surgical guidance in head and neck cancers. Intracellular cell signaling proteins can be quantified using novel fluorescent small molecule inhibitors to study drug-target availability, occupancy, and downstream response to understand tumor response heterogeneity and therapeutic resistance. In addition, our lab is involved in the translation of fluorescent molecular imaging agents for clinical use through the FDA's exploratory Investigational New Drug pathway.
WANG LAB
Current research in Dr. Wang's laboratory is focused on understanding the role of chromatin remodeling SWI/SNF complex (mutated in 25% human cancers) in tumor development. We combine multiple cutting-edge technologies such as TurboID, Genome editing (dTAG), CUT&RUN, ATAC-seq, scRNA/ATAC, and Hi-ChIP to 1) identify novel interacting proteins, 2) map their genomic targets, 3) assess chromatin accessibilities and higher order chromatin interactions, to understand how SWI/SNF targeting to chromatin is tightly regulated and how dysregulation of such process is contributing to tumorigenesis.
ZHAO LAB
Dr. Zhao's laboratory focuses on studying the genetic etiology of human diseases, in particular, cancer. We develop computational methods and tools to analyze large-scale genomic datasets, aiming to translate data into biological insights. Specific areas of interest include modeling of mutation selection in cancer, integration of multiple types of genomic datasets for disease gene discovery, genotype-phenotype association analysis, etc .
