Biochemistry and Molecular Biology Directory
Role of the actin cytoskeleton in neuronal growth and regeneration, pathfinding, and in neurodegenerative diseases, especially Alzheimer disease. Signal transduction mechanisms controlling actin filament dynamics and cell behavior.
Our research focuses on understanding how accurate chromosome segregation is achieved in mitosis. We are analyzing the molecular architecture of the kinetochore-microtubule interface in vertebrate cells and studying how proteins and protein complexes at this interface drive and regulate chromosome movements.
The goal of this laboratory is to understand the molecular basis of human diseases that affect the biogenesis of melanosomes, platelet granules and other lysosome-related organelles as well as the endocytic pathway.
Our research is focused on elucidating the structure/function relationships of the chromatin fiber. My laboratory has pioneered the use of recombinant chromatin model systems to yield unique information about the condensed structures of chromatin fibers, and the architectural proteins that modulate these structures in solution.
Our laboratory has been recognized for elucidating the structures and structural gymnastics associated with the functions of nucleic acids. More recently, we have pioneered the use of biomolecular halogen bonds to control the structures of proteins and nucleic acids for bioengineering and rational drug design applications. To attack these problems, we apply X-ray crystallography, computational biology, biochemistry, and bioinformatics approaches.
I currently teach Principles of Biochemistry BC351, Comprehensive Biochemistry Laboratory BC404 and mentor biochemistry students for their Thesis BC499. I also serve on the Undergraduate Affairs Committee and advise biochemistry students.
My research centers on infusing active learning approaches in teaching cell biology and biochemistry and developing and testing ways of engaging students in the course concepts and big ideas through undergraduate research experiences and application to socio-scientific issues.
The research in our lab is focused on how various molecules conspire to coordinate the transport and delivery of cellular cargoes to their appropriate destinations. We pay particularly close attention to various classes of molecular motors -- nano-sized ATP-powered machines -- and how they are regulated to perform their myriad functions throughout the life of a cell.
My lab is interested in how mRNA transcripts are regulated at the single-cell and sub-cellular levels in developing embryos. We use a combination of experimental and computational approaches in the animal model C. elegans to examine the mechanisms and consequences of mRNA regulation.
During the last several years, the human T-cell leukemia virus type I (HTLV-I) has become increasingly recognized as an important cause for public health concern throughout the world. HTLV-I is the causative agent of a variety of clinical diseases, including an aggressive and fatal cancer called adult T-cell leukemia, and a neurological disorder that is clinically very similar to multiple sclerosis. A large body of evidence suggests that the clinical manifestations of HTLV-I infection occur as a consequence of a virally-encoded protein called Tax. My laboratory focuses on defining the intracellular consequences of Tax expression in the infected human cell, with emphasis on the Tax-dependent events that lead to malignant transformation.
The picornaviruses are a family of small positive sense single stranded RNA viruses that cause a wide range of diseases in humans and animals. These include the rhinoviruses that cause the common cold and poliovirus, the prototypical member of this family. We are interested in understanding the molecular details of picornaviral replication and are using structural biology and biophysical techniques to determine the structure of viral proteins and study their interactions.
I have dual appointments in two departments 1) Biochemistry and Molecular Biology and 2) Microbiology, Immunology, and Pathology. In the courses I teach, I share my passion for science and strive to instill principles of scientific integrity, collegiality, professionalism and the drive required to succeed. In LIFE 212, students learn the basic scientific skills of data collection and interpretation, critical thinking, and technical writing, all while learning the experimental methods and technology that are commonly used in cell and molecular biology research labs.
Numerous diseases including Alzheimer's disease, Parkinson's disease and transmissible spongiform encephalopathies are associated with protein misfolding into ordered aggregates, called amyloid fibrils. We are using yeast prions as a model system for examining the causes and consequences of amyloid fibril formation.
Members of the Archaea often thrive in unique, harsh and ever-changing biological niches. These changing environments necessitate precise and timely regulation of gene expression. Our laboratory focuses on the regulation of transcription, from a global perspective to a detailed structure-function analysis of the archaeal transcription apparatus. We apply combined biochemical and genetic methods to investigate not only transcription, but mechanisms of DNA replication, repair and recombination and energy-production strategies in hyperthermophliic archaea.
The replisome is a multiprotein machine that orchestrates duplication of the genome—including the epigenome—with strikingly high accuracy despite a constant barrage of obstacles. These challenges to replication pose risks for mutagenesis and replication fork collapse. My lab is interested in auxiliary machinery that directly couples to the core replisome, handling these obstacles in coordination with the DNA replication apparatus to achieve high fidelity chromosome duplication. Using replisomes and chromatin reconstituted from protein complexes purified in yeast, we study these molecular mechanisms in detail with single-molecule fluorescence techniques in addition to traditional biochemistry.
My interests lie in STEM educational research and student learning. I teach a large Principles of Biochemistry (BC351) class designed for non-majors as well as two inquiry-based labs (BC404 and BC406) and a course on metabolism (BC403). In all settings I am attempting to conform my teaching practices with those demonstrated in the literature to increase learning outcomes for students.
Computational design, simulation, and experimental validation of new enzymes, and crystalline biomolecular assemblies. We convert porous protein crystals into “3D molecular pegboards” for the controlled assembly of nanoparticles, enzymes, fluorescent proteins, oligonucleotides, and other functional molecules.
Transcription initiation by RNA polymerase II involves a highly regulated series of events dependent upon many protein-protein and protein-DNA interactions. By combining yeast genetics, molecular biology, biochemistry, and biophysical techniques, we are using a multi-faceted approach to understand the functions of the transcription machinery in the chromatin context of living cells.
My lab combines fluorescence microscopy, novel fluorescent probe development, genetic engineering, and computational modeling to visualize and quantify single-gene expression in living cells. We dream of creating 'lightbulbs" for genes at the level of DNA transcription and mRNA translation to visualize gene activity in real-time and in-vivo. The hope is to create technology to literally see which genes are on in a specific cell. By visualizing the cell genotype in real-time, we hope to predict and ultimately control its future phenotype during important processes, such as differentiation and cancer development.
Our lab studies the interface between the ubiquitin-proteasome pathway and transcriptional regulation. Modification of components of the transcription machinery by ubiquitin can serve as a regulatory switch that both activate and limit gene expression. We are using a variety of biochemical and genetic approaches to define the molecular mechanisms that underlie these seemingly opposite processes.