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Adam D. Sylvester Lab
Research in the Adam D. Sylvester Lab primarily focuses on the way in which humans and primates move through the environment, with the aim of reconstructing the locomotor repertoire of extinct hominins and other primates. We use a quantitative approach that involves the statistical analysis of three-dimensional biological shapes, specifically musculoskeletal structures, and then link the anatomy to function and function to locomotor behavior.
The goal of research in the Beer Lab is to understand how gene regulatory information is encoded in genomic DNA sequence. Our work uses functional genomics DNase-seq, ChIP-seq, RNA-seq, and chromatin state data to computationally identify combinations of transcription factor binding sites that operate to define the activity of cell-type specific enhancers. We are currently focused on improving SVM methodology by including more general sequence features and constraints predicting the impact of SNPs on enhancer activity (delta-SVM) and GWAS association for specific diseases, experimentally assessing the predicted impact of regulatory element mutation in mammalian cells, systematically determining regulatory element logic from ENCODE human and mouse data, and using this sequence based regulatory code to assess common modes of regulatory element evolution and variation.
The Berger Lab's research is focused on understanding how multi-subunit assemblies use ATP for overcoming topological challenges within the chromosome and controlling the flow of genetic information. A long-term goal is to develop mechanistic models that explain in atomic level detail how macromolecular machines transduce chemical energy into force and motion, and to determine how cells exploit and control these complexes and their activities for initiating DNA replication, shaping chromosome superstructure and executing myriad other essential nucleic-acid transactions.
Our principal approaches include a blend of structural (X-ray crystallography, single-particle EM, SAXS) and solution biochemical methods to define the architecture, function, evolution and regulation of biological complexes. We also have extensive interests in mechanistic enzymology and the study of small-molecule inhibitors of therapeutic potential, the development of chemical approaches to trapping weak protein/p...rotein and protein/nucleic acid interactions, and in using microfluidics and single-molecule approaches for biochemical investigations of protein dynamics. view more
The Linda Smith-Resar Lab primarily investigates hematologic malignancy and molecular mechanisms that lead to cancer as well as sickle cell anemia. Recent studies suggest that education is an important and effective component of a patient blood management program and that computerized provider order entry algorithms may serve to maintain compliance with evidence-based transfusion guidelines. Another recent study indicated that colonic epithelial cells undergo metabolic reprogramming during their evolution to colorectal cancer, and the distinct metabolites could serve as diagnostic tools or potential targets in therapy or primary prevention.
Michael Wolfgang Laboratory
The Wolfgang Laboratory is interested in understanding the metabolic properties of neurons and glia at a mechanistic level in situ. Some of the most interesting, enigmatic and understudied cells in metabolic biochemistry are those of the nervous system. Defects in these pathways can lead to devastating neurological disease. Conversely, altering the metabolic properties of the nervous system can have surprisingly beneficial effects on the progression of some diseases. However, the mechanisms of these interactions are largely unknown.
We use biochemical and molecular genetic techniques to study the molecular mechanisms that the nervous system uses to sense and respond to metabolic cues. We seek to understand the neurometabolic regulation of behavior and physiology in obesity, diabetes and neurological disease.
Current areas of study include deconstructing neurometabolic pathways to understand the biochemistry of the nervous system and how these metabolic pathways impact animal beh...avior and physiology, metabolic heterogeneity and the evolution of metabolic adaptation. view less
Molecular Oncology Laboratory
Our Molecular Oncology lab seeks to understand the genomic wiring of response and resistance to immunotherapy through integrative genomic, transcriptomic, single-cell and liquid biopsy analyses of tumor and immune evolution. Through comprehensive exome-wide sequence and genome-wide structural genomic analyses we have discovered that tumor cells evade immune surveillance by elimination of immunogenic mutations and associated neoantigens through chromosomal deletions. Additionally, we have developed non-invasive molecular platforms that incorporate ultra-sensitive measurements of circulating cell-free tumor DNA (ctDNA) to assess clonal dynamics during immunotherapy. These approaches have revealed distinct dynamic ctDNA and T cell repertoire patterns of clinical response and resistance that are superior to radiographic response assessments. Our work has provided the foundation for a molecular response-adaptive clinical trial, where therapeutic decisions are made not based on imaging but b...ased on molecular responses derived from liquid biopsies. Overall, our group focuses on studying the temporal and spatial order of the metastatic and immune cascade under the selective pressure of immune checkpoint blockade with the ultimate goal to translate this knowledge into “next-generation” clinical trials and change the way oncologists select patients for immunotherapy. view more
Our scientists pursue out-of-the-box approaches at the very edge of knowledge to:
1) Elucidate the molecular/cellular/physiological landscapes of ovarian and uterine cancers.
2) Understand the earliest events in their development and mechanisms of tumor evolution/dormancy and drug resistance.
3) Deliver promises for better prevention, detection and treatment to women who have diseases or are at an increased risk to have these cancers.
Tamara O'Connor Lab
The O'Connor Lab studies the molecular basis of infectious disease using Legionella pneumophila pathogenesis as a model system.
We are looking at the network of molecular interactions acting at the host-pathogen interface. Specifically, we use L. pneumophila pathogenesis to examine the numerous mechanisms by which an intracellular bacterial pathogen can establish infection, how it exploits host cell machinery to accomplish this, and how individual proteins and their component pathways coordinately contribute to disease.
We are also studying the role of environmental hosts in the evolution of human pathogens. Using genetics and functional genomics, we compare and contrast the repertoires of virulence proteins required for growth in a broad assortment of hosts, how the network of molecular interactions differs between hosts, and the mechanisms by which L. pneumophila copes with this variation.