Department: Chemical and Systems Biology

Administrative Associate to the Chair, Tobias Meyer of Chemical and Systems Biology Administrative Associate to the High Throughput Bioscience Center Financial Assistant to Jun Penano, DFA to the Department of Chemical and Systems Biology

Our lab uses chemical, biochemical, and cell biological methods to study protease function in human disease. Projects include: 1) Design and synthesis of novel chemical probes for each of the primary protease families. 2) Understanding the role of proteolysis in the life cycle of the human parasites, Plasmodium falciparum and Toxoplasma gondii. 3) Defining the specific functional roles of proteases during the process of tumorogenesis. 4) In vivo imaging of protease activity

Our laboratory combines synthetic chemistry and developmental biology to investigate the molecular events that regulate embryonic patterning, tissue regeneration, and tumorigenesis. We are currently using genetic and small-molecule approaches to study the molecular mechanisms of Hedgehog signaling, and we are developing chemical technologies to perturb and observe the genetic programs that underlie vertebrate development.

The use of genetic, biochemical and chemical approaches to understand the DNA damage-induced cell cycle checkpoints and the processes that contribute to maintenance of genomic stability.

Our focus is on building computational models of complex biological processes, and using them to guide an experimental program. Such an approach leads to a relatively rapid identification and validation of previously unknown components and interactions. Biological systems of interest include metabolic, regulatory and signaling networks as well as cell-cell interactions. Current research involves the dynamic behavior of NF-kappaB, an important family of transcription factors.

Developing new mass spectrometry-based experimental and computational tools that advance the field of proteomics, and applying them to a variety of important biomedical paradigms, including cancer, aging, and stem cell biology.

My lab has two main goals: to understand mitotic regulation and to understand the systems-level logic of simple signaling circuits. We often make use of Xenopus laevis oocytes, eggs, and cell-free extracts for both sorts of study. We also carry out single-cell fluorescence imaging studies on mammalian cell lines. Our experimental work is complemented by computational and theoretical studies aimed at identifying the design principles of regulatory circuits.

Structure, dynamics and function of proteins involved in transport and regulatory processes; high resolution nuclear magnetic resonance studies of conformational transitions and protein folding; study of the mechanism of action of the trp-repressor, ankyrin-domain proteins and the development of programs to calculate protein solution structure

Survival in changing environments requires the acquisition of new heritable traits. However, mechanisms that safeguard the fidelity of DNA replication often limit the source of such novelty to relatively modest changes in the genetic code. Thus, the acquisition of new forms and functions is thought to be driven by rare variants that occur at random, and are enriched during times of stress. We have begun to study an intriguing alternative hypothesis: that intrinsic links between protein folding ..

Mechanisms of Aging in C. elegans and humans.

Structure, function and physiology of adrenergic receptors.

We explore angiogenesis, cancer genomics, intestinal stem cells, and hepatic glucose metabolism. Angiogenesis projects include endothelial miRNA and GPCR ko mice, blood-brain barrier regulation, stroke therapeutics and anti-angiogenic cancer therapy. Intestinal stem cell projects use primary intestinal culture and mouse genetics to study injury-inducible vs homeostatic stem cells. We use primary organoid cultures of diverse tissues for oncogene functional screening and therapeutics discovery.

Stem cell based therapies for treatment of heart disease

CELLULAR INFORMATION PROCESSING The main problem in signal transduction is to understand how different receptor-stimuli specifically control diverse cell functions. We are using automated microscopy, live-cell fluorescent biosensors and perturbations of predicted signaling proteins to systematically dissect signaling networks. This allows us to identify signaling modules and to elucidate and ultimately model the flow of cellular information.

Beverly Mitchell's research relates to the development of new therapies for hematologic malignancies, including leukemias and myelodsyplastic syndromes. She is interested in preclinical proof of principle studies on mechanisms inducing cell death and on metabolic targets involving nucleic acid biosynthesis in malignant cells. She is also interested in the translation of these studies into clinical trials.