The In-vivo Cellular and Molecular Imaging Center conducts multidisciplinary research on cellular and molecular imaging related to cancer. We provide resources, such as consultation on biostatistics and bioinformatics and optical imaging and probe development, to understand and effectively treat cancer. Our molecular oncology experts consult on preclinical studies, use of human tissues, interpretation of data and molecular characterization of cells and tumor tissue.

Dr. Dispenza’s laboratory focuses on allergies and IgE-mediated allergic reactions including anaphylaxis.  Overall goals of the lab include understanding the mechanisms driving anaphylaxis severity and phenotypes, discovering new biomarkers for the accurate diagnosis of anaphylaxis, and developing novel strategies for the prevention of IgE-mediated reactions.  One major project focuses on the prevention of anaphylaxis, for which there are no known reliable preventative therapies.  They found that small molecule inhibitors of the enzyme Bruton’s tyrosine kinase (BTK), which is a key component of the IgE signaling pathway, completely suppress IgE-mediated human mast cell and basophil activation and significantly protect against death from severe anaphylaxis in humanized mice.  Further, in an investigator-initiated clinical trial, they demonstrated in an investigator-initiated trial that treatment with just 2 days of the oral BTK inhibitor acalabrutinib completely prevents clinical reactivity from eating peanut in the majority of peanut-allergic adults and markedly increases the tolerance level of the remainder.  These exciting data suggest that a long sought-after preventative therapy for anaphylaxis may finally be within reach.

The Taverna Laboratory studies histone marks, such as lysine methylation and acetylation, and how they contribute to an epigenetic/histone code that dictates chromatin-templated functions like transcriptional activation and gene silencing. Our lab uses biochemistry and cell biology in a variety of model organisms to explore connections between gene regulation and proteins that write and read histone marks, many of which have clear links to human diseases like leukemia and other cancers. We also investigate links between small RNAs and histone marks involved in gene silencing.

The Sean Leng Lab studies the biology of healthy aging. Specific projects focus on chronic inflammation in late-life decline; immunosenescence and its relationship to the basic biological and physiological changes related to aging and frailty in the human immune system; and T-cell repertoire analysis.

The Richard J. Jones Lab studies normal and cancerous stem cells in order to make clinical improvements in areas such as blood and marrow transplantation (BMT). We discovered one of the most common stem-cell markers, Aldefluor, which identifies cells based on their expression of aldehyde dehydrogenase 1 (ALDH1), and have used this marker to detect and characterize normal stem cells and cancer stem cells from many hematologic malignancies. We also developed post-transplant cyclophosphamide and effective related haploidentical BMT.

Human induced pluripotent stem cells (hiPSCs) provide unprecedented opportunities for cell replacement approaches, disease modeling and drug discovery in a patient-specific manner. The Gabsang Lee Lab focuses on the neural crest lineage and skeletal muscle tissue, in terms of their fate-determination processes as well as relevant genetic disorders. Previously, we studied a human genetic disorder (familial dysautonomia, or FD) with hiPSCs and found that FD-specific neural crest cells have low levels of genes needed to make autonomous neurons--the ones needed for the ""fight-or-flight"" response. In an effort to discover novel drugs, we performed high-throughput screening with a compound library using FD patient-derived neural crest cells. We recently established a direct conversion methodology, turning patient fibroblasts into ""induced neural crest (iNC)"" that also exhibit disease-related phenotypes, just as the FD-hiPSC-derived neural crest. We're extending our research to the neural crest's neighboring cells, somite. Using multiple genetic reporter systems, we identified sufficient cues for directing hiPSCs into somite stage, followed by skeletal muscle lineages. This novel approach can straightforwardly apply to muscular dystrophies, resulting in expandable myoblasts in a patient-specific manner.

Current projects include: The evaluation of mechanisms of immune tolerance to cancer in mouse models of breast and pancreatic cancer. We have characterized the HER-2/neu transgenic mouse model of spontaneous mammary tumors. This model demonstrates immune tolerance to the HER-2/neu gene product. This model is being used to better understand the mechanisms of tolerance to tumor. In addition, this model is being used to develop vaccine strategies that can overcome this tolerance and induce immunity potent enough to prevent and treat naturally developing tumors. More recently, we are using a genetic model of pancreatic cancer developed to understand the early inflammatory changes that promote cancer development. The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach developed in our laboratory. Human tumor specific T cells from vaccinated patients are used to identify immune relevant antigens that are chosen based on an initial genomic screen of overexpressed gene products. Several candidate targets have been identified and the prevelence of vaccine induced immunity has been assessed . This rapid screen to identify relevant antigenic targets will allow us to begin to dissect the mechanisms of tumor immunity induction and downregulation at the molecular level in cancer patients. More recently, we are using proteomics to identify proteins involved in pancreatic cancer development. We recently identified Annexin A2 as a molecule involved in metastases. The analysis of antitumor immune responses in patients enrolled on vaccine studies. The focus is on breast and pancreatic cancers. We are atttempting to identify in vitro correlates of in vivo antitumor immunity induced by vaccine strategies developed in the laboratory and currently under study in the clinics.