Cancer Biology Faculty

The Weber lab studies tumor suppressor and oncogene networks in cancer biology. The lab's current interests include the collaboration of the ARF and p53 tumor suppressors in preventing triple-negative breast cancer, design and fabrication of novel microfluidic devices to model lymphatics in breast cancer metastasis. Visit jasonweberlab.com to learn more!

Hematopoietic stem cells (HSCs) reside in the bone marrow and are defined by their capacity for lifetime maintenance of the blood and bone marrow, achieved through their differentiation into the myriad of cellular components, as well as their ability to generate additional stem cells via self-renewal. The mechanisms that instruct the fate of stem cells toward differentiation versus self-renewal are still relatively poorly understood. A number of transcription factors have been identified as critical for HSC maintenance and self-renewal; however, we have little insight into how these factors are orchestrated by epigenetic mechanisms to ensure blood homeostasis. The central theme of the Challen Lab’s research is understanding how epigenetic marks such as histone methylation and acetylation, DNA methylation, and 5-hydroxymethylation co-ordinately act to regulate normal HSC function and how these processes go awry in hematopoietic diseases such as leukemia and lymphoma. In order to explore these questions, we use various mouse genetic models to study the roles of genetic mutations of different components of the epigenetic machinery in cancers of the blood and bone marrow. Visit https://challen-lab.com/  to learn more!

The Adhikari Lab focuses on interrogating RAS oncoprotein signaling networks through the lens of interactomes in cancer, based on an innovative functional proteomics platform combining proximity labeling technology coupled to CRISPR/Cas9 screening.

The Chheda lab focuses on cancer stem cells, oncolytic viruses, and functional genomics of brain tumors. They are interested in identifying and characterizing the genetic and epigenetic events that induce cancer and maintain tumors.

The DeNardo lab aims to understand how immune responses shape and are shaped by tumor progression and anti-cancer therapy. We aim to exploit these weaknesses to improve patient outcomes by enhancing responses to conventional or immunotherapies. Visit denardolabwusm.org for more!

One major obstacle to successfully applying CAR T cells to all cancers is the difficulty in finding target molecules that are only expressed on the tumor cells, and not on critical normal tissues. Further, if not every tumor cell expresses the target molecule, the cancer will not be cured, as the negative cells that escape will eventually grow back. One major focus of the lab is identifying novel ways by which CAR cellular therapy can overcome the problem of antigen escape, to fully eliminate disseminated, heterogeneous cancer cells, by modifying other immune cells besides T-cells with CARs specific to those cells. Additional problems exist in solid tumors, including poor penetration of the tumor by CAR T cells, and inherent resistance of particular tumors to T cell killing. The mechanisms by which these occur, and methods to overcome them, are active areas of investigation within the laboratory.Radiation therapy is known to modulate the immune response in a variety of ways, but its effect on cellular therapy is poorly understood. An additional major focus in the laboratory is to examine the effect of low dose radiation therapy on the systemic and local tumor response to CAR T cell therapy, and develop CARs that function synergistically with radiation and other established treatment modalities. Visit deselmlab.wustl.edu for more!

Cancer develops through accumulation of DNA mutations and structural aberrations collectively known as genome instability. Genome damage in adult-onset malignancies can be traced to exogenous carcinogens or simply the process of aging. However, pediatric cancers do not arise as a result of aging or exogenous genotoxic agents. We are interested in the etiology of genome instability in pediatric cancers and the resulting genome-protective responses, also called DNA damage responses, that are activated. Our long-term goal is to identify predictors of mutagenesis and therapeutic vulnerabilities within DNA damage response pathways in order to develop new treatment options for children with cancer. Visit abbygreenlab.org for more!

Cancer patients experience intense stress related to diagnosis, recurrence fears, and therapy duration. This stress is associated with higher metastasis risk and poorer survival, highlighting the need to understand stress-driven metastasis mechanisms for effective therapies. Studies in mice reveal stress-induced effects on primary tumor growth, treatment resistance, and metastatic colonization. While stress can enhance cancer cell proliferation, migration, and seeding in distant tissues, the tissue being colonized is not a passive recipient of cancer cell. Instead, the tissue microenvironment must create a pro-metastatic niche supporting disseminated cancer cell growth. Hence, our lab asks this key question: Do stress-triggered host changes impact tumor growth and metastasis? Visit https://sites.wustl.edu/xueyanhelab/ for more!

The Herzog lab  is interested in how the tumor microenvironment (TME) impacts the progression and response to therapy in lung cancer. Recent advances in immune-based therapy have improved outcomes for many lung cancer patients. Yet, despite the observed benefit of immune checkpoint blockade in the locally advanced and metastatic setting, not all patients respond to these agents and most of those who initially respond, eventually progress underscoring the need for additional therapy options. Understanding why patients do not initially respond to therapy and/or the mechanisms by which they develop resistance to therapy is critical to offering our patients more effective treatment options and improving outcomes. 

Research in the Hirbe lab is focused on better understanding the biology of sarcomas, rare tumors of bone and soft tissue.  There are over 100 different types of sarcomas all with a different underlying biology.  We aim to utilize genomic information from patient sarcoma samples coupled with mouse models to better understand the development and progression of these cancers.  Based on identification of mutated DNA repair pathways in a number of sarcomas (MPNSTs, rhabdomyosarcomas, pleiomorphic sarcomas, and osteosarcomas), there is an ongoing project aimed at evaluation of therapies targeting this defect for treatment of bone and soft tissue sarcomas. We also have a special interest in better understanding the development and spread of a particular soft tissue sarcoma, the malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma that occurs at an increased frequency in patients with the Neurofibromatosis Type 1 (NF1) tumor predisposition syndrome. 

Our laboratory focuses on fundamental issues of DNA repair and how they relate to cancer initiation, progression, and therapy responses. Current projects are aimed at developing strategies to suppress cancer formation and to identify new drug targets for cancers that lack effective treatments, including those resistant to current therapies.We work on developing innovative drug delivery systems that improve the efficacy and safety of drugs. Our team of experts uses advanced materials and techniques to create delivery systems that can target specific cells or tissues, and release drugs over a longer period of time. Visit kraislab.com for more!

People rarely die from their primary tumor, rather it is the spread of their tumor to other organs (metastasis) that leads to death, and when that occurs there is a general lack of treatment options. Crosstalk between tumor cells and their associated cellular, physical, and chemical environment is now appreciated to be critical for tumor progression, metastasis, and response to therapy, yet the cellular and molecular basis for these tumor-environment communications is complex and not fully understood. Our lab is interested in understanding how cancers invade and spread throughout the body with the goal to identify and understand molecular pathways important for metastasis and then develop effective and selective ways to prevent the spread of cancer by targeting these pathways. To address this problem we employ aspects of biochemistry, cell biology, developmental biology, biophysics, genetics, and cell and in vivo imaging.

Although initiated by genetic mutation, the unchecked proliferation, aberrant differentiation, and altered motility of cancer cells depends upon the integrity and activation state of specific signal transduction pathways. Our laboratory is interested in understanding how alterations in these signaling pathways contribute to human cancer, and whether exploitation of that understanding can aid in the development of new diagnostics, prognostics and therapeutic intervention strategies. To this end, we employ a global “systems level” integrative discovery platform, one that has as a foundation mass spectrometry-based proteomic interaction networks. More specifically, through LC/MS/MS, we define the physical interaction network for a signaling pathway of oncogenic interest. By small molecule and functional genomic screening, we then annotate the human genome for functional contribution to the pathway of interest. Integration of these data with cancer-associated mutation data and cancer-associated gene expression data yields a powerful tool for oncogenic discovery—a cancer annotated physical/functional map for a specific signaling pathway of interest. The models and hypotheses produced though integrative screening are challenged through mechanistic studies employing cultured human cancer cells, zebrafish, mice and in vitro biochemical systems. Visit majorlab.wustl.edu for more!

Pereira’s research program in the Disease Imaging and Therapy Lab is focused on exploring tumor-targeted multimodal imaging techniques and the regulation of membrane receptors in tumors and their microenvironment. Her work addressing drug resistance at both basic and clinical levels is supported by the National Institutes of Health, Siteman Cancer Center and philanthropic organizations.

Our lab explores how RNA, the molecule that helps turn DNA into proteins, plays a role in how diseases like cancer grow and spread. We aim to better understand how RNA works in cancer, especially in cases where the disease becomes more aggressive, so we can find new ways to treat it. We do this in a welcoming, supportive environment that encourages curiosity and collaboration. Visit silvafisherlab.com for more!

Age is the most significant risk factor for cancer development. While it is clear that cell autonomous mutations are integral to the transformation process, it has become increasingly evident that changes in the surrounding, ostensibly normal stroma drive the transformation process and tumor progression. Indeed, stromal cells isolated from a tumor (but not normal tissue) can stimulate tumor formation and progression by altering the microenvironment in profound ways including directly modulating the local immune response and changing the tissue parenchyma.  Senescent (i.e. “aged”) fibroblasts function analogously by activating similar mechanisms including stabilizing mRNAs (collectively referred to as the senescence associated secretory pathway, SASP) via activation of the p38MAPK-MK2 pathway. The laboratory is utilizing it’s discovery of these pathways and novel models to understand how changes in the stromal compartment contribute to tumor progression.  Visit stewartlab.net for more!

The Verma lab is  intrigued with the conundrum that while DNA replication and repair are essential for viability, cancer cells with defects in these pathways evolve mechanisms to ensure rapid proliferation. Unravelling this mystery offers possibilities to understand mechanisms that lead to genomic instability and identify vulnerabilities that can catalyze the development of improved therapeutic regimens. Visit vermalab.org for more!

The main interest of our laboratory is the discovery and characterization of gene mutations in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with the long term goal of understanding the molecular mechanisms that control abnormal hematopoiesis. MDS results from the expansion of one or more dominant hematopoietic clones that contain initiating mutations, while transformation from MDS to AML occurs as these clones accumulate additional progression factors (including point mutations in genes and cytogenetic abnormalities).

The Watteberg lab is interested in myeloid cells, which are heterogenous cells of the innate immune system that are pliable and possess the capacity for both tumor-supporting and tumoricidal functions. Yet how to reprogram myeloid cells or use myeloid cell functions to control cancer remains ill-defined. By integrating multi-omics analyses of samples from patients with cancer, transgenic mouse modeling of cancer and functional genomics, the Wattenberg lab aims to (i) define strategies to leverage tumoricidal myeloid cell functions for cancer therapy, and (ii) identify tumor-intrinsic mechanisms of resistance to myeloid cell cytotoxic programs. In doing so, I hope to inform the design of novel clinical trials and ultimately improve outcomes for patients with cancer.

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