Research Program Members
Molecular signaling mechanisms that orchestrate daily rhythms in our brain and how their dysregulation contributes to various neurological and psychiatric diseases. We are particularly interested in the role of mammalian target of rapamycin (mTOR) signaling and mechanisms that control mRNA translation in the circadian clock.
Genetic mechanisms that control gene expression with a focus on post-transcriptional gene regulation mediated by specific regulatory factors including RNA-binding proteins, RNA degrading enzymes, and long non-coding RNAs. These regulators control expression of cancer genes and affect cell proliferation, genome stability, and other cancer-related processes.
Clinical and translational research in gynecologic, hepato-biliary and gastrointestinal disease including cancer using immunohistochemical techniques; antibodies and biomarkers as prognosticators of how a tumor may progress and respond to treatment
Oncology, clinical pharmacology of anti-cancer agents; cell culture models to evaluate administration schedules for anti-cancer agents with the goal of optimizing chemotherapy administration through assessment of drug pharmacokinetics in human subjects
Molecular abnormalities in lung cancer and mesothelioma, focusing primarily on cell cycle regulator genes and their loss of function in cancer; detection of micrometastatic disease in lung cancer and the acquired molecular abnormalities in micrometastases.
Establishing a clinical and research registry for patients at high risk for hereditary cancer and use of a family cancer screening tool for individual risk assessment. Optimizing preoperative imaging of rectal cancer using magnetic resonance imaging (MRI); using magnetic resonance spectroscopy to identify residual rectal cancer following neoadjuvant therapy.
Cell and molecular biology of HIV and HTLV; antiviral drug discovery and development; antiviral drug resistance; HIV genetic variation, evolution and population genetics; viral quasispecies; virus assembly; evolution of emerging viruses
Use of recombinant retroviral and lentiviral vectors for gene transfer into hematopoietic stem cells to treat cancer and inherited disorders; introduction of drug-resistance genes into normal hematopoietic cells to protect against toxic side effects of cancer chemotherapy; use of adeno-associated virus for treatment of storage diseases and as a vector for gene transfer into the central nervous system for treatment of neurological disorders; adaptation of a novel vertebrate transposon Sleeping Beauty to viral and non-viral delivery systems for gene therapy.
Genetic origins of the development and progression of childhood cancers including sarcomas, leukemia, and brain tumors; utilizing novel technologies to more accurately model cancer to test new treatments and validate mechanisms of disease development and progression such as Transcription Activator-Like Effector Nucleases and the CRISPR/Cas9 system.
Stem cells and non-melanoma skin cancer
Dependence of leukemic cells on oncogenic signaling. Using a model of AML driven by Mll/AF9 and NRAS, we integrate signaling data with gene expression data to study the signals critical for leukemia maintenance and how to pharmacologically inhibit these signals for therapeutic effect.
Genetics of multiple myeloma; role of specific mutations (RAS, Rb, and p530 in the biology of myeloma; therapeutic responses and changes in gene expression profiles; utilization of single nucleotide polymorphism (SNP) analysis to identify genetic associations with myeloma risk and response to therapy
Computational analysis of high-throughput cancer genomics data, as it relates to high-throughput data mining and modeling, heterogeneous genomics data integration, comparative genomics, integrating copy number variation, gene expression profiling, sequence somatic mutations and proteomic data, and novel methods development.
Chronic obstructive pulmonary disease (COPD); identification of biomarkers of chronic allograft rejection and causal pathways in COPD leading to lung cancer; co-director of Lung Volume Reduction Surgery Program and participant in NIH COPD Clinical Research Network
Cancer gene therapy with Adenovirus Vector; conditionally replicative adenovirus for the treatment of cancer; non-invasive in vivo molecular imaging; gene therapy of gastrointestinal diseases, cancers of pancreas, esophagus, prostate, breast, and multiple myeloma