This is an accordion element with a series of buttons that open and close related content panels.
Paul Ahlquist
We are studying the novel, RNA-based pathways and virus-host interactions underlying replication, gene expression and evolution by positive-strand RNA viruses, the largest class of viruses. Positive strand RNA viruses include many important human pathogens such as hepatitis C virus, which chronically infects nearly 3% of the world population, causing progressive liver damage and liver cancer, and the new SARS coronavirus. We are also studying selected replication processes of a reverse-transcribing virus, hepatitis B virus, which is also a major human tumor virus. Our studies integrate molecular genetics, genomics, biochemistry and cell biology to address fundamental questions in virus replication and virus-cell interactions.
To learn more
Caroline Alexander
We are studying aspects of mammary gland biology and neoplasia using transgenic mouse models. Particularly, we have found that Wnt signaling dysregulates mammary stem cells, and that this precedes the formation of differentiated, bilineal tumors. Wnt signaling is highly oncogenic to mammalian epithelia, and indeed comprises one of the main sources of human tumor initiation identified to date. Our hypothesis is that the transforming potential of Wnt signaling is unique to stem/progenitor cells.
To Learn More
Ricahrd Anderson
The goals of the Anderson lab’s research are to understand the biological roles of cell signaling and the underlying mechanisms by which receptors, cell stresses and second messengers modulate specific cellular processes. The research is currently focused in two broad general areas.
To Learn More
Lisa Arendt
Obesity is a world-wide problem, and two-thirds of the population in the United States is currently considered to be either overweight or obese. Obesity increases the risk for multiple different types of cancer. In particular, obesity significantly increases the risk for postmenopausal breast cancer. Obesity also enhances other risk factors, such as in women with a family history of breast cancer. Postmenopausal women are most commonly diagnosed with breast tumors that have a marker called estrogen receptor alpha (ERa). However in women with a higher body mass index, these ERa positive tumors are larger at the time of diagnosis and are more clinically aggressive. Both pre- and postmenopausal women who develop breast cancer also have an increased incidence of triple negative breast tumors. These tumors, which lack the markers ERa, progesterone receptor, and Her-2, are more difficult to treat clinically. Obese women also have an increased risk for the development of metastases and a shorter time before tumors may recur.
To Learn More
Jon Audhya
Dysregulated cell proliferation underlies all forms of oncogenesis. In particular, chromosomal aberrations sometimes enable a subpopulation of cells to grow in an uncontrolled fashion, leading to tumor formation. Such defects are often associated with changes in cellular signal transduction pathways, such as the Ras-Raf-MEK-ERK kinase cascade, which promotes cell survival and growth. Notably, upregulated ERK activity has been implicated in numerous malignancies, including papillary thyroid carcinoma, pancreatic cancer, colorectal cancer, melanoma, and lung cancer. During the course of their studies, members of the Audhya laboratory demonstrated that two oncogenic fusion proteins, TFG-NTRK1 and TFG-ALK, created by distinct chromosomal translocation events, localize to subdomains of the endoplasmic reticulum (sites of COPII vesicle formation) and dramatically upregulate ERK activity. Using phosphoproteomic approaches, they are mapping downstream effectors of TFG-NTRK1 and TFG-ALK that simultaneously drive cell transformation and regulate vesicle secretion. By altering membrane transport in the early secretory pathway, TFG fusion proteins may modulate cargo export, potentially enhancing the secretion of growth factors that help to sustain a rich tumor microenvironment.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
David Beebe
Dr. Beebe continues to lead a large research effort consisting of 30-40 researchers. His research spans many fields including microfluidics, cell biology, cancer biology, global health, and diagnostics. While originally trained in engineering, he completed a 5 year “re-training” in cell biology via an NIH K25 award which transitioned his lab to more biology and medically focused work. Additionally, his retraining was cancer focused, and he now co-leads the Tumor Microenvironment Program within the University of Wisconsin Carbone Cancer Center (UWCCC). The Beebe laboratory is now focused on an integrated research process that works to match unmet biological and clinical needs with appropriate technology development and adaptation. Via multiple collaborations they are developing and applying micro-scale technologies to study and diagnose a range of cancers (e.g., prostate, lung, kidney, multiple myeloma). The laboratory’s emphasis is increasingly on clinical diagnosis through the analysis of patient samples (e.g., blood, tissue).
To Learn More
Alexander Birbrair
Our lab is committed to understand the mechanisms of impairment and failure of biological systems under pathological conditions, focusing on tissue stem cells, vasculature and the peripheral nervous system present in different tissues microenvironments, with emphasis on preventing or reversing these deleterious processes. We are interested in studying mechanisms that lead to cell behavior changes during development, throughout life and disease. Understanding how these mechanisms are affected in cancer will help develop targets for novel therapies. For this, we take advantage of state-of-the-art technologies, including two-photon and confocal microscopy, in vivo lineage-tracing methods, FACS-sorting, single-cell RNA sequencing, organ, tissue and cell transplantation, neural circuitry analysis, and sophisticated Cre/loxP techniques in combination with cancer mouse models. Thus, our ultimate goal is to identify novel potential cellular and molecular targets for cancer therapy.
To Learn More
Christopher Bradfield
Our laboratory is interested in a family of transcriptional regulators known as PAS proteins. Members of this emerging family of proteins control a number of processes, including xenobiotic metabolism (Ah-receptor and Arnt), circadian rhythms (Per), angiogenesis (HIF1a and Arnt), and neurogenesis (Sim). The model system that is currently emphasized is the signal transduction pathway mediated by Ah-receptor/Arnt heterodimeric complex. These helix-loop-helix-PAS proteins regulate the induction of a number of xenobiotic metabolizing enzymes that occur in response to exposure to a variety of polycyclic aromatic environmental pollutants. In addition, the Ah-receptor mediates a second battery of genes responsible for a number of “toxic effects” of dioxins, such as epithelial hyperplasia, immunosuppression, teratogenesis, and tumor promotion.
To Learn More
Emery Bresnick
We use multidisciplinary approaches to understand stem/progenitor cell function, blood cell development, and vascular biology. Such approaches include genomics, proteomics, chemical genetics, embryonic stem cell differentiation, computational analysis, and traditional methodologies.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
Christian Capitini
Dr. Capitini leads an NIH-supported laboratory focusing on development of cell-based therapies, including NK cells and CAR T cells, for the treatment of childhood cancers like neuroblastoma and osteosarcoma. The laboratory also manufactures alternatively activated macrophages for complications of hematopoietic stem cell transplant, like graft-versus-host-disease and acute radiation syndrome. In the clinic, Dr. Capitini was a site Principal Investigator for the first multi-center CAR T cell trial, which led to FDA approval of tisagenlecleucel (Kymriah) for the treatment of recurrent/refractory B cell leukemia in children. He remains a site PI for trials testing Kymriah as upfront therapy for high risk B cell leukemias and for treatment of relapsed non-Hodgkin lymphoma.
To Learn More
Jane Churpek
The Churpek lab is focused on defining the contribution of rare genetic variation to risk of blood disorders and cancer and how environmental factors interact with inherited genetic variation to contribute to penetrance and/or progression from the at risk state to overt disease. Specific projects include defining new rare genetic variants that cause inherited bone marrow failure and inherited blood cancer syndromes in families clustering these disorders; comparing acquired tumor genomic signatures across subjects with and without inherited mutations to identify differences in pathogenesis; and testing functional consequences of specific inherited variants in both in vitro and in vivo model systems to determine mechanism.
To Learn More
Pippa Cosper
The Cosper laboratory aims to study how chromosomal instability (CIN), an ongoing rate of chromosome missegregation events over the course of multiple cell divisions, which is very common in cancer, affects sensitivity to radiation therapy. Cosper has a particular interest in viral-driven cancers as many of these viruses can themselves induce CIN. For example, Human Papilloma Virus (HPV) is implicated in over 95% of cervical cancers and is now recognized as the main etiologic agent in oropharyngeal carcinoma (OPC). HPV16 induces specific types of CIN, thus we are interested in comparing the types and extents of CIN between different HPV genotypes as well as using these biological characteristics to our advantage to promote radiation induced cell death. The Cosper lab is also studying how CIN and oncogenic viruses affect the innate and adaptive immune responses in the context of radiation therapy. The ultimate goal is to be able to tailor radiation therapy to the biology of each patient’s tumor to decrease unnecessary side effects and improve patient outcomes.
Vincent Cryns
The Cryns lab focuses on understanding how tumors adapt to and survive metabolic stress caused by their rapid growth. They are particularly interested in translating these insights into improved biomarkers and therapies. The Cryns laboratory group is widely recognized for identifying the molecular chaperone aB-crystallin as a novel anti-apoptotic protein that inhibits caspase-3 activation and for linking aB-crystallin to triple-negative breast cancer (TNBC). They have also developed unique mouse models of metastatic TNBC and demonstrated that aB-crystallin plays a key role in brain metastasis, a devastating complication with few treatment options.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
Dustin Deming
My laboratory is investigating kinase modulation of cellular signaling pathways driven by oncogenic mutant proteins. To screen combinations of targeted agents in the setting of specific genetic alterations, novel mouse models of colorectal cancer including tumors driven by a constitutively active PI3K [Cancer Research, 2012; PLoSOne, 2013; Oncogene, 2013]. In addition to my laboratory research, I have also been active in early phase clinical trials. I have developed the concepts and chaired NCI/CTEP sponsored phase I clinical trials including AZD6244 in combination with cetuximab for KRAS mutant colorectal cancer [ASCO Annual Meeting, 2012] and ABT-888 in combination with capecitabine and oxaliplatin for BRCA mutant tumors and gastrointestinal cancers.
To Learn More
Huy Dinh
Cancer is a heterogeneous disease that complicates its study and therefore treatment. Immunotherapy has revolutionized cancer treatment but many patients still are faced with little or no clinical benefit with the same treatment. Recent high-dimensional technologies have allowed us the ability to understand the tumor ecosystem and its impact on treatment response. We are motivated by the question of how the tumor microenvironment changes upon cancer progress, before and after treatment. We follow a systems biology approach, using high-dimensional data from multi-omics genome-wide (genomics and epigenomics) and single-cell assays, data mining, and bioinformatics. We develop and employ computational biology methods to mine publicly available data and in-house generated data for the specific questions we ask.
David Evans
Dr. Evan’s research program is directed toward understanding host-pathogen interactions for human and simian immunodeficiency viruses. Current areas of investigation include mechanisms of lentiviral resistance to tetherin/BST-2, the role of killer-cell immunoglobulin-like receptor (KIR) and MHC class I interactions in regulating natural killer (NK) cell responses, and antibody-dependent cell-mediated cytotoxicity (ADCC) as a mechanism of protective immunity. Recent studies from the Evan’s lab have contributed to understanding the role of antibody-dependent cell-mediated cytotoxicity (ADCC) in immunodeficiency virus infection. Together the lab has developed an assay for measuring the ability of antibodies to direct the killing of HIV-1- and SIV-infected cells expressing native conformations of the viral envelope glycoprotein (Alpert et al. J. Virol. 2012).
To Learn More
Anne Griep
We are interested in understanding the role of cellular tumor suppressor genes in normal development and cancer. To this end we have focused on determining the molecular pathways that regulate a cell’s switch from proliferation to differentiation in various epithelial tissues of the mouse eye. Through our studies, we have contributed towards the understanding that the retinoblastoma susceptibility protein (pRB), which when mutated leads to retinoblastoma and other cancers, and its family members along with multiple growth factor signaling pathways are coordinately involved in regulating the developmental processes in the eye. Proper cell adhesion and polarity also are believed to be vital to the growth and differentiation of epithelial tissues and to maintaining their long-term integrity. In Drosophila melanogaster and Caenorhabditis elegans members of the PDZ (PSD95/Dlg/ZO-1) family regulate cell adhesion, polarity and proliferation. A major emphasis in the lab is to understand if, and how, the mouse homologs of dlg and scrib contribute to mammalian development. Finally, due to one approach used in the lab, we also are learning new properties that certain oncoproteins from human papillomaviruses (HPV) possess in vivo and how these novel activities may contribute to HPV-associated cancer. We use a variety of genetic, molecular, cell biological and embryological techniques and transgenic and knockout mice.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
Rich Halberg
Colorectal cancer is the second leading cause of cancer death in the United States. These cancers, like most cancers, are often heterogeneous with abnormal cells within a single tumor varying in several distinguishable properties including differentiation state, proliferation rate, and metastatic potential. Dr. Halberg’s research focuses on identifying sources of intratumoral heterogeneity and determining how such heterogeneity impacts prevention and treatment in the clinic.
To Learn More
Paul Harari
The overall theme of my clinical and laboratory research is to improve treatment outcome for patients with head and neck cancer (HNC). Areas of particular research emphasis include the interaction of molecular growth inhibitors combined with radiation and the use of conformal radiation treatment techniques to limit normal tissue toxicity. I serve as PI for a recently funded SPORE Grant in HNC at the University of Wisconsin and direct one scientific project as well as the Administrative Core within the SPORE Grant. I have served as PI for NIH R29 and R01 laboratory research grants investigating HNC response and resistance mechanisms in combination with radiation. I have been an active RTOG HNC Committee member for more than 20 years (now NRG) and serve as PI or co-PI for a series of national and international HNC clinical trials.
To Learn More
Gaelen Hess
With the emerging appreciation of precision medicine, the link of genetic and epigenetic perturbations to their phenotypes is vital. With the advent of CRISPR-mediated genome editing and high-throughput sequencing, we can both systematically perturb the genome and quantitatively measure their phenotypic effects. In the Hess lab, we are interested in both the development and application of these and other functional genomics technologies to address critical biological questions and improve human health. Using these cutting-edge genomics tools, we focus on three areas: (1) investigating mechanisms of drug resistance and response, (2) regulation of mammalian DNA repair, and (3) studying effectors secreted by bacterial pathogens.
Anna Huttenlocher
Dr. Huttenlocher studies the basic molecular mechanisms that regulate cell migration and is interested in the implications of these mechanisms to human disease. Her laboratory has pioneered approaches to visualize and manipulate cell motility and innate immunity in zebrafish. Her work centers on understanding mechanisms that regulate the invasiveness of cancer cells using both human cell lines in vitro and cancer models in zebrafish. Her laboratory is also probing the role of the innate immune system in cancer progression using zebrafish models of melanoma and hepatocellular carcinoma
To Learn More
David Jarrard
David Frazier Jarrard, MD, is a tenured Professor of Urology and an Associate Director at the UW Carbone Cancer Center. He trained at the University of Chicago and Johns Hopkins. His laboratory studies clinically relevant epigenetic factors underlying cancer development and progression is part of the campus-wide Epigenetics consortium. They were the first to identify that altered genomic imprinting with aging occurs and this increases the risk of prostate cancer development. Alterations in CTCF, an insulator protein, underlies these epigenetic alterations and links diet and oxidative stress to cancer progression. This epigenetic field effect arises in the histologically normal prostate tissue of men with prostate cancer and serves as a clinical diagnostic marker for the presence of prostate cancer.
To Learn More
Eric Johannsen
Our research focuses on the molecular biology of Epstein-Barr virus (EBV) nuclear proteins, their role in the virus lifecycle and the pathogenesis of EBV associated malignancies. Herpesviruses infect their hosts for life and EBV precisely manipulates growth and survival signaling pathways of B lymphocytes, resulting in their immortalization. Understanding the mechanisms that EBV has evolved to exploit infected cells is an important basis for therapy of EBV associated diseases and offers a unique vantage from which to view and understand complex cellular pathways.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
Rob Kalejta
Our lab focuses on determining the mechanisms of human cytomegalovirus (HCMV) replication and pathogenesis, and also uses the virus as a tool to probe the pathways that lead to cell cycle progression and oncogenesis. We are interested in HCMV because it is a ubiquitous and medically relevant virus that causes severe disease in immunocompromised patients, is the leading viral cause of birth defects, and impacts upon the etiology and/or progression of cardiovascular disease and cancer. As an obligate intracellular parasite, HCMV relies upon its host cell for its replication. Thus, to promote its own survival, HCMV has evolved ways to commandeer cellular pathways such as cell cycle progression, transcriptional silencing, and protein degradation.
To Learn More
Shannon Kenney
Dr. Kenney’s research effort has been focused upon understanding the molecular regulation and pathogenesis of the human herpesvirus, Epstein-Barr virus (EBV). Her work in EBV spans a broad range of topics, including viral gene regulation, the effects of the virus on the host immune response, and the development of novel, EBV-targeted therapies for EBV-positive tumors. She has extensively studied the mechanisms by which both EBV immediate-early proteins, BZLF1 and BRLF1, activate the lytic form of viral infection. Her group discovered that BZLF1 preferentially binds to, and transcriptionally activates, the methylated form of its downstream target promoter, suggesting a unique and unexpected mechanism by which EBV overcomes the inhibitory effect of viral genome methylation. Her group has also shown how the two EBV immediate-early proteins alter the host cell environment in multiple different ways, including usurping control of the host cell cycle, activating a variety of signal transduction pathways, inhibiting p53 function, dispersing PML nuclear bodies, and attenuating the host innate immune response. Dr. Kenney is now translating the results of these basic molecular studies into the development of new, EBV-targeted therapies for EBV-positive tumors. Her group is also developing a new small animal model to study EBV pathogenesis in vivo.
To Learn More
Randy Kimple
My research laboratory is focused on understanding why cancers don’t always respond to treatment. We use patient-derived xenografts—patient tumor samples grown in animals—to test radiation, chemotherapy and combinations of therapies to understand which characteristics of a patient’s tumor may predict response to treatment. The goal of this work is to enable more personalized treatment and to find ways to combine different treatment methods to decrease treatment side effects without reducing cure rates.
To Learn More
Pamela Kreeger
The Kreeger lab utilizes systems biology and tissue engineering to analyze cellular behavior in a variety of biological contexts. We utilize an iterative approach, where we develop model culture systems that allow us to study a disease in a controlled environment, use high-throughput experimental methods to gather information about the cellular signaling network and cellular responses, and employ computational models to interpret the data. Ultimately, our models will be utilized to identify new drug targets, match patients to the most effective drugs, and identify methods to direct cellular behavior.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
Paul Lambert
Our lab’s research is focused on understanding the role of human papillomavirus (HPV) in cancer. HPVs cause 5% of all human cancers. These include cervical cancer, other anogenital cancers and a growing proportion of head and neck cancers. Through the use of genetically engineered mice (GEM) we have developed models for HPV-associated cervical, anal and head/neck carcinogenesis, defined the individual roles of viral oncogenes in carcinogenesis in these organs, identified the mechanisms of action by which these oncogenes contribute to carcinogenesis, defined their temporal role in carcinogenesis, and defined the roles of estrogen and its receptor in cervical carcinogenesis and the utility of estrogen receptor antagonists in treating and preventing cervical cancer. Major current directions in the lab that make continued use of the GEM models include understanding the interplay between viral oncogenes and cellular signaling and DNA damage response pathways in causing cancer, and the influences of viral genes on epigenetic regulation and epithelial stem cell biology.
To Learn More
Jessica Lang
My scientific mission is to leverage genomics and epigenetics in ovarian cancer (OvCa) models to produce translational and impactful science building on my research in somatic mutations in chromatin remodeling factors and epigenetic dysfunction through the following research goals: 1) Understand dynamics of epigenetic features following chemotherapy treatment and resistance; 2) Identify potential therapies for treatment that exploit epigenomic features; 3) Integrate epigenomic features with somatic cancer mutations towards a more comprehensive OvCa picture. I will approach these research goals using human cell lines and tumor tissue to identify shared and necessary OvCa enhancers, validated by innovative functional epigenomics approaches and preclinical models. I will also continue my history of scientific collaborations and clinical partnerships to support my research and ensure clinical translation of findings.
Joshua Lang
The Lang laboratory has two focus areas with the overarching goal of improving clinical outcomes of prostate cancer: translational biomarkers and epigenetic mechanisms of immune evasion. Dr. Lang’s early studies identified mechanisms by which epigenetic modifying agents could improve immune recognition of tumor cells (3, 7, 10). His laboratory discovered a panel of neoantigens, known as Cancer-Testis Antigens that can be induced in a broad range of prostate cancer cell lines. To evaluate the translational relevance of these findings, they developed an ex vivo drug culture model to treat primary human prostate cancer biopsies with different epigenetic drugs followed by molecular analysis of mechanisms of response and resistance. These agents can also improve antigen presentation on tumor cells that may target one of the primary mechanisms of resistance to immune-based therapies.
To Learn More
Peter Lewis
My research program is rooted in the idea that chromatin, the physiologically relevant form of eukaryotic genomes, contains an indexing system, sometimes referred to as a “histone or epigenetic code”, that represents a fundamental regulatory mechanism that operates outside of the DNA sequence itself. Covalent modifications to DNA and histones – the proteins that package our genome – are implicated in the epigenetic regulation of gene expression and the stable maintenance of cell type-specific gene expression patterns and cellular identity.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
Kinjal Majumder
Parvovirinae are small DNA viruses that are pathogenic in most animals, made up of small linear single-stranded DNA genome, and rely extensively on host nuclear factors, particularly the DNA Damage Response (DDR) machinery that usually protects us from cancer. Upon infection, the parvovirus minute virus of mice (MVM) localizes to cellular sites of DDR to jumpstart its replication in host cells. As it replicates in the host cell nucleus, it continues to induce additional DNA damage through various means, which also serve as sites of viral replication, thereby enabling the virus to amplify in the host nuclear environment. We seek to elucidate the molecular mechanisms by which MVM localizes to cellular DDR sites, induce additional DNA damage and generate chromosomal aberrations. We have developed systems to study where viral genomes localize using genomics and single-cell imaging, inducible DNA damage systems to investigate the cause-effect relationship between the virus and cellular DDR, and have optimized methods to study how viral infection causes chromosomal aberrations. The findings from our work are applicable to understand the biology of small DNA viruses such as HPV and HBV, which are oncogenic, and for gene therapy applications which use modified AAV parvoviruses.
To Learn More
Paul Marker
Research in the Marker laboratory is focused on understanding the biology of the prostate gland at the molecular level. Interest in understanding the biology of the prostate is driven both by the fascinating nature of the developmental processes that function during organogenesis of the prostate and by the high incidence in humans of prostatic diseases including prostatic adenocarcinoma and benign prostatic hyperplasia. The Marker lab is particularly interested in the role of intercellular communication between epithelial and mesenchymal/stromal cells during the progression of prostate cancer. Current projects in this area include a series of studies to investigate PDE4D and cAMP signaling in prostate cancer. This project is based on a genetic screen for novel prostate cancer genes.
To Learn More
Daniel R. Matson
Disorders of the blood and bone marrow are of great public health significance. During development and in the adult bone marrow, a relatively small number of critical transcription factors promote complex and diverse cellular processes to bring about faithful and timely hematopoiesis. The mechanisms by which these factors interface with chromatin to modulate gene expression, and the partner factors that are critical for this function, are the primary research focus of the Matson Laboratory.
Douglas McNeel
Dr. McNeel is a genitourinary medical oncologist with a laboratory and clinical research program focused on prostate cancer immunology. The goal of these efforts is to develop effective anti-tumor vaccines as treatments for prostate cancer, and Dr. McNeel has been focused on this area for nearly 20 years. His initial studies sought to identify immunologically recognized antigens as potential targets for vaccines using blood from patients with prostate cancer, prostatitis, or patients treated with various immune-modulating agents. More recent efforts have focused on three specific antigens (prostatic acid phosphatase (PAP), the ligand-binding domain of the androgen receptor (AR LBD), and synovial sarcoma X breakpoint 2 (SSX2)), characterizing these as tumor antigens, evaluating anti-tumor genetic vaccines targeting these antigens in appropriate rodent models, and translating these findings to early phase human clinical trials. Dr. McNeel and his laboratory have specifically focused on plasmid DNA genetic vaccines as a means of antigen delivery, methods to increase the immunogenicity of DNA vaccines, and understanding the mechanisms of tumor resistance to anti-tumor immunization. This research is translational in nature, taking results from the laboratory to clinical testing, and back again to the laboratory, and has been continuously supported by federal funding from NIH and/or DOD. In the context of this research, Dr. McNeel has trained over 40 post-doctoral fellows, graduate students, and undergraduate students in laboratory research. To date, they have conducted (or are conducting) six separate clinical trials using DNA vaccines developed in the McNeel laboratory. Dr. McNeel has also been principal investigator for over 20 investigator-initiated clinical trials, primarily focused on immune-based treatment approaches. As a physician-scientist with research experience in the laboratory and clinic, and focused on the development and evaluation of new cancer therapies, Dr. McNeel previously served as co-leader of the Experimental Therapeutics Program of the UW Carbone Cancer Center (UWCCC) from 2007 to 2015, and currently serves as UWCCC Director of Solid Tumor Immunology Research.
To Learn More
Kavi Mehta
The Mehta lab focuses on understanding the replication stress response and the mutagenic consequences of DNA-strand specific obstacles. Our goal is to provide a new context for understanding how endogenous (byproducts of metabolism and ribonucleotides) and exogenous/environmental (chemicals, genotoxins, and viruses) stresses mutagenize DNA and how repair mechanisms maintain faithful replication.
To Learn More
Shigeki Miyamoto
Over the last two decades, the Miyamoto lab has pursued a variety of research interests centered around cell signaling and asked “what happens when cells are no longer able to communicate effectively?” Most of the current research is focused on understanding the NF-κB signaling pathway as a model. Our lab, and others, have shown that NF-κB is key in promoting cell survival (anti-apoptotic), normal immune system development, stress response, early embryonic development, cell adhesion, and tumor metastasis.
To Learn More
Zachary Morris
In the Morris Lab, we are focused on using preclinical and translational research approaches to study the mechanisms whereby radiation may impact the anti-tumor response to immunotherapies. Our primary objective is to determine whether and how radiation may optimally be employed to simultaneously modulate the tumor immune microenvironment and to increase the susceptibility of tumor cells to immune response. We seek to test these approaches in early phase clinical studies where they may be further refined with the ultimate aim of improving survival and achieving cures in patients with metastatic cancers.
To Learn More
Deane Mosher
My laboratory has been a leader in characterization of structure and function of molecules of blood plasma, platelets, and extracellular matrix. We are best known for studies of fibronectin, thrombospondins, and vitronectin and participate in collaborative studies that utilize the reagents and expertise that we have developed over the years.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
Xuan Pan
It is of critical importance that the rates of hematopoietic stem cell (HSC) differentiation and self-renewal are carefully regulated and kept in balance, because severe disease states arise when this balance is disrupted. Unfortunately, the mechanisms that maintain this balance are poorly understood, and this lack of understanding represents a major roadblock to research progress, while also severely restricting the clinical potential of HSC-based therapeutic interventions. Our group identified PcG protein YY1 as an essential regulator of HSC self-renewal and differentiation in mice. Hematopoietic Stem Cell (HSC) quiescence is regulated by both intrinsic and extrinsic signals. Cell-cycle regulators, transcription factors, as well as epigenetic modifications, have been identified as intrinsic regulators of HSC cell-cycle progression. However, correlations of epigenetic signatures are often not highly instructive, and the mechanistic implication of epigenetic signatures in HSC self-renewal is incompletely understood. We have generated a conditional mouse knockout of YY1 in HSCs and showed that YY1 knockout decreases HSC long-term repopulating activity and ectopic YY1 expression expands HSCs. YY1-deficiency deregulates the genetic network that regulates HSC proliferation and impaired stem cell factor/c-Kit signaling, and interferes with establishment of quiescence in HSCs. These results reveal how a ubiquitously-expressed epigenetic repressor regulates lineage-specific functions and plays a critical role during hematopoiesis in adult mice. Our group currently is focusing on assessing the structure-function relationships in YY1 and dissecting the underlying mechanisms that control chromosome structural change at the Kit locus.
To Learn More
Suzanne Ponik
My group is interested in understanding the molecular mechanisms underlying breast cancer risk due to breast density. Patients with mammographically dense breast tissue have a four to six-fold increased risk of developing breast carcinomas. In fact, 1/3 of all breast cancer cases are attributed to breast density, making it one of the greatest risk factors for carcinoma. Increased breast density is associated with a significant increase in the deposition of extracellular matrix (ECM) components, most notably the protein, collagen. We have developed in vitro and in vivo model systems to understand why increased breast density results in an increased risk for developing breast carcinoma. Additionally, our group uses multiphoton microscopy and intravital imaging approaches to characterize the collagen structure surrounding tumors so that we can better understand the physical relationship between cells and the collagen fibers found in breast tissue.
We are particularly interested in molecular signaling events related to cell interactions with the ECM. During oncogenic transformation, normal interactions with the ECM are profoundly altered, resulting in cells that lose their polarization and differentiation, lose anchorage dependent growth control, and acquire a migratory, invasive phenotype. Further, we have identified an overall increase in inflammatory signals in tumors that arise in a collagen dense microenvironment. Together, these data demonstrate that collagen density creates an invasive, inflammatory tumor microenvironment leading to enhanced disease progression. We are interested in understanding how physical changes in the ECM determine cell phenotype and signaling related to the recruitment, differentiation and polarization of cells in the tumor microenvironment.
To Learn More
Matt Reynolds
My laboratory focuses on developing innovative tools for investigating and combating human diseases. Our primary area of research is evaluating the virologic and immunologic mechanisms that control AIDS virus replication. We developed a novel model for establishing latent simian immunodeficiency virus (SIV) reservoirs of precise sizes by infusing defined numbers of in vitro generated latently infected cells into SIV-naive rhesus macaques. With this model, we are investigating how latent reservoir size affects an individual’s ability to control virus replication after stopping antiretroviral drug treatment.
To learn more
Will Ricke
Dr. Ricke’s laboratory focuses on the tumor microenviroment as related to hormone action and stromal-epithelial interactions in prostate diseases including prostate cancer. He discovered that steroid hormone action is critical in the stroma rather than epithelia for malignant transformation and metastasis in prostate cancer, and, that targeting stromal receptors with therapies are the primary mode of therapy. Currently, the Ricke lab is investigating the role of hormones on collagen changes/metrics in gene expression, collagen fiber density and alignment. Changes in collagens appear to be correlated with aggressive of prostate disease.
To Learn More
Lixin Rui
The major research interest in Dr. Rui’s laboratory is the mechanisms of the JAK-STAT signaling pathway in lymphomagenesis. The goal of his research is to discover effective molecular targets in this pathway for therapeutic, diagnostic and prognostic development of human lymphoma. His research team employs a multidisciplinary approach, using biochemistry, RNA interference, next-generation sequencing (including ChIP-seq and RNA-seq), and systems biology methods, to identify JAK1 target genes in this lymphoma and to investigate crosstalk between JAK1 and other signaling pathways, such as NF-kB. Dr. Rui has collaborated with Dr. Shigeki Miyamoto in this area for the past four years, yielding three co-authored publications in Experimental Cell Research, Oncogene, and Molecular Cancer Research.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
Linda Schuler
Prolactin exposure has been epidemiologically linked to elevated risk for aggressive ERα+ breast cancer. Anti-estrogen resistant metastatic ERα+ cancers account for the majority of breast cancer deaths. The Schuler laboratory uses preclinical models to examine the role of prolactin in the developing pathology of metastatic ERα+ breast cancer, and its crosstalk with estrogen, growth factors, and properties of the extracellular matrix in tumor behavior and therapeutic responsiveness. Using the NRL-PRL transgenic mouse, which elevates prolactin locally in the mammary gland, they have shown that prolactin can powerfully influence the epithelial hierarchy and transcriptional regulatory programs in the absence of estrogen and progesterone, resulting in increased progenitor/stem cell populations. Prolactin can also temper the actions of ovarian steroids, opposing steroid-driven luminal maturation. Together, these actions begin to explain its role in development of breast cancer. The ERα+ cancers that develop in the NRL-PRL mouse can be serially transplanted to syngeneic recipients, providing a model to examine cancer stem cells and responses to anti-estrogens and other adjuvant therapies. Recent investigations have revealed that anti-estrogens can raise cancer stem cell activity in the absence of effects on growth, and that primary tumors and lung metastases display activation of different signaling pathways and responses to therapies. These studies are illuminating the biology of luminal B cancers, and will facilitate development of prevention and treatment strategies.
To Learn More
Nathan Sherer
Retroviruses cause a variety of cancers and immunodeficiencies throughout the animal kingdom. Our group is interested in the cell biology underlying the assembly and spread of the human immunodeficiency virus type 1 (HIV-1), the etiological agent causing the acquired immunodeficiency syndrome (AIDS), as well as oncoretroviruses such as the murine leukaemia virus (MLV). Like all viruses, retroviruses have evolved to hijack specific features of their cellular hosts in ways that favor efficient viral replication. Understanding virus-host interactions can inform the development of novel antiviral strategies, and, in general, retroviruses provide great tools for probing questions of cellular function and immunity.
To Learn More
Melissa Skala
Dr. Skala’s lab develops biomedical optical imaging technologies for cancer research, cell therapy, and immunology. Current projects focus on tumor immunology and immunotherapy, cell-level metabolic heterogeneity, and cell-cell interactions. Collaborative projects leverage these unique photonics-based tools for clinical problems, including quality control in T cell and stem cell therapies, designing personalized treatment plans for cancer patients, and discovering new therapies for a range of diseases. Projects are highly diverse and range from translational research to hypothesis-driven questions to algorithm / instrumentation development.
Megan Spurgeon
Tumor viruses cause at least 15% of human cancers worldwide. The Spurgeon Lab studies two different small DNA tumor viruses: Merkel cell polyomavirus (MCPyV) and human papillomaviruses (HPVs). Merkel cell polyomavirus (MCPyV) is the most recently discovered human tumor virus and causes Merkel cell carcinoma (MCC), a neuroendocrine cancer of the skin. Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and cause cancers at various anatomical sites including the anogenital tract and oral cavity in both women and men. Our research investigates the virus-host interactions that contribute to the pathogenesis and oncogenic potential of MCPyV and HPV and seeks to elucidate the mechanisms by which their viral proteins cause disease and cancer. To do so, the Spurgeon Lab specializes in the development and application of novel preclinical models of small DNA tumor virus action. Our research interests intersect with several scientific disciplines, including virology, cancer biology, dermatology, and cell/molecular biology.
Bill Sugden
We work with Epstein-Barr Virus (EBV) because it causes several different cancers in people. EBV is a herpesvirus that causes the common, benign infectious mononucleosis, as well as lymphomas such as Burkitt’s Lymphoma, most B-cell lymphomas in immunocompromised hosts, and carcinomas such as nasopharyngeal carcinoma. We study EBV both to understand its contributions to these diseases molecularly and to develop rational means to treat them.
To Learn More
Aussie Suzuki
Our lab focuses on discovering the molecular mechanisms underlying force production, mitotic checkpoint control, and error correction in accurate cell division, with a focus on the role of the highly conserved Ndc80 complex and the kinetochore structural integirty. We recently developed a FRET (fluorescent resonance energy transfer)-based Ndc80 tension biosensor, which allows us to measure cellular tension using light microscopy. Using this tension biosensor, we will elucidate the mechanisms of how kinetochores generate and transmit force for accurate chromosome segregation. Tension at kinetochores may be important for the kinetochore deformation, which is thought to be critical for mitotic checkpoint control. We will investigate the kinetochore structural changes by super-resolution microscopy, electron microscopy, and ExM (expansion microscopy). In addition, we are committed to understanding how the loss of centromere/kinetochore integrity causes carcinogenesis and cancer progression. We recently found that the CENP-H/I complex, which is a member of core-kinetochore proteins, is overexpressed in primary colon cancer and its expression levels inversely depends on the stage of cancer progression. We are investigating the functions of CENP-H/I complex in cancer. In order to reveal centromere/kinetochore functions, our lab uses advanced light and electron microscopy techniques. They include quantitative confocal microscopy to measure cellular protein copy number, light-sheet microscopy for high spatial/temporal live cell imaging, various super-resolution microscopy (SIM/STORM/STED) for nm-scale analysis, FRET-based tension biosensor, FRAP/TIRF system for cellular protein dynamics, and immuno-electron microscopy.
To Learn More
This is an accordion element with a series of buttons that open and close related content panels.
Owen Tamplin
In the Tamplin lab, we study the basic biology of hematopoietic stem cells (HSCs) and their microenvironment. These stem cells are clinically important as a curative treatment for many blood cancers and diseases. A better understanding of HSCs and their supportive niche will help us improve these treatments and thereby patient survival.
We are investigating the intercellular crosstalk between a stem cell and its surrounding niche cells. The means of communication can be paracrine signals, direct contact, or transfer of cellular material. Our overall research goal is to understand mechanistically how different signals are translated into HSC fate decisions.
We use complementary mouse and zebrafish model organisms. The zebrafish is the only vertebrate genetic model that allows high-resolution live imaging of endogenous cellular behaviors. We can harness the strengths of the zebrafish model to develop and test unique hypotheses that could not be acquired using any other system. We then use the mouse model to test translation of our findings to a mammalian system.
To Learn More
Randal Tibbetts
Current work in our lab is aimed at understanding how diverse growth-inhibitory signals, including DNA damage, cell-cell contact and growth factor depletion down regulate gene expression through the CREB pathway and how defects in this regulation contribute to tumorigenesis. A second related project is deciphering how alternative splicing influences DNA damage repair and tumor suppression using cellular and in vivo (mouse) models. Finally, our laboratory has developed several Drosophila melanogaster (fruit fly) models for the motor neuron disease amyotrophic lateral sclerosis. We are using these models to probe genetic mechanisms of neurodegeneration. We actively collaborate with both basic science and clinical colleagues within and outside the UW campus on each of these projects. I also teach material related to cell growth and DNA damage repair for several on-campus graduate programs, serve on both NINDS and NCI grant review panels and have served as editor and ad hoc reviewer for the Journal of Biological Chemistry, Nature, the EMBO Journal and other journals.
To Learn More
Beth Weaver
The goal of Dr. Weaver’s research is to determine the consequences of mitotic defects on tumor initiation, progression and response to chemotherapy. Defects during mitosis result in the production of daughter cells with an abnormal number of chromosomes, a condition known as aneuploidy. Aneuploidy is a hallmark of tumor cells, which has led to the hypothesis that aneuploidy promotes tumors. The Weaver laboratory has found in animal models and cell culture that aneuploidy can both promote and suppress tumors, depending on the rate of chromosome missegregation. Low rates of chromosome missegregation are weakly tumor promoting, while high rates of chromosome missegregation lead to cell death and tumor suppression due to the loss of one or more essential chromosomes. Recently, they have also shown that high rates of chromosome missegregation suppress tumor growth and progression, rather than tumor initiation. These results suggested the hypothesis that inducing high rates of chromosome missegregation could be a useful strategy for tumor therapy. Indeed, the Weaver laboratory has recently shown that paclitaxel (TaxolTM), a cornerstone of chemotherapy for the last 30 years, causes chromosome missegregation on multipolar spindles in breast cancers. Future experiments will utilize cell culture, mouse models and clinical studies to leverage our fundamental knowledge of mitosis to improve treatment outcomes for cancer patients.
To Learn More
Deric Wheeler
My laboratory is focused on understanding mechanisms of resistance to molecular targeting agents directed against receptor tyrosine kinases. Specifically, we center our work on cancers of the head and neck and breast. We use molecular biology, proteomics, mouse modeling, including patient derived xenografts, and human tissues to understand how tumors that are initially responsive to therapy become resistant over time. The overall goal of this research is to identify these mechanisms of resistance and to target specific pathways to increase the efficacy of molecular targeting agents. Ultimately, our goal is to take basic science discoveries in the lab and translate them to the clinic.
To Learn More
Yongna Xing
My lab is interested in elucidation of signaling pathways related to cancer using multi-disciplinary biophysics and biochemical approaches, including structural biology and proteomics, in combination with cell biology. We focus on signaling pathways that affect cancer cell metabolism and cancer cell genome integrity.
To Learn More
Wei Xu
My laboratory is focused on the transcriptional regulation of estrogen receptor (ER) signaling pathways by nuclear receptor co-factors. We identified a natural plant product that significantly decreased ERa but increased ERb stability. Via distinct mechanism from the existing agents for endocrine therapy, this compound also significantly promoted degradation of mutant ERa that is found in ~25% of patients with metastatic ERa-positive breast cancers. Biological functions of these estrogenic compounds have been investigated in cell-based and breast cancer mouse models. The bioactive derivatives may be developed as novel agents for treating metastatic, endocrine-resistant breast cancers caused by ERa mutations. Furthermore, we investigated the crosstalk between ERa pathways and other growth factors (e.g., HER2) and kinase networks, as these mechanisms account for the intrinsic or acquired endocrine resistance.
To Learn More
Jing Zhang
The research program in my lab focuses on cell signaling, in particular Ras signaling, in hematopoiesis and leukemogenesis. We generated and characterized multiple genetically engineered mouse models for oncogenic Ras-driven blood cancers, including juvenile monocytic leukemia, chronic myelomonocytic leukemia and its transformation to acute myeloid leukemia, multiple myeloma, and early T cell precursor acute lymphoblastic leukemia.
To Learn More
Shuang George Zhao
In the Zhao Lab, we focus on developing novel clinical biomarkers that predict response and resistance to specific therapies in prostate cancer and other malignancies. These biomarkers can be used to better select which patients derive a benefit from treatment, which patients do not and can be spared potential toxicity, as well as monitor for emergence of resistance. We seek to use advanced sequencing and computational technologies to better personalize the care of cancer patients.