My research focuses on developing biologically based models for the uptake, distribution, metabolism, and biological effects of drugs and chemicals and their application to safety assessments and quantitative health risk assessments. In recent years, my research emphasis has been on developing mathematical descriptions of control of genetic circuitry and the dose-response and risk-assessment implications of these control processes.
Tight junctions are intercellular contacts that form a barrier required for ion transport and organization of cell polarity. Our lab investigates assembly and regulation of TJ proteins and the molecular basis for ion selectivity in epithelia.
Our laboratory studies an amazing regulatory factor known as NF-kappaB. This transcription factor controls key developmental and immunological functions and its dysregulation lies at the heart of virtually all major human diseases.
We study the interface between signal transduction and cell function. Approaches employed include - molecular genetics, protein and lipid biochemistry, confocal and electron microscopy, protein crystallography, and model organisms approaches (e.g. yeast, Arabidopsis, C. elegans, mouse gene knockout technology).
We study the cell biology of the protozoan parasites that cause Toxoplasmosis and Malaria, especially the mechanism and control of parasite motility and host cell interaction.
The goal of our laboratory is to investigate mechanisms of tumorigenesis and tumor progression, and to apply genome-wide techniques to develop anti-cancer therapies. Our research focuses on transcriptional regulation of gene expression during stem cell self-renewal and differentiation and during tumorigenesis. We use artificial transcription factors (ATFs) as genetic probes to identify genes and gene pathways responsible for the appearance of specific malignant phenotypes and we investigate the ability of these ATFs to interfere with tumor cell regulatory programs. Cancer cell reprogramming with such artificial “genetic switches” may afford a new therapeutic strategy.
Our long term goal is to define the molecular mechanisms of two-component regulatory systems, which are utilized for signal transduction by bacteria, archaea, eukaryotic microorganisms, and plants. Our current focus is to understand the features that control the rates of self-catalyzed phosphorylation and dephosphorylation of response regulator proteins. The kinetics of these reactions vary dramatically (>40,000x) between different pathways and reflect the need to synchronize biological responses (e.g. behavior, development, physiology, virulence) to environmental stimuli. Member of the Molecular & Cellular Biophysics Training Program
Cell adhesion, both to other cells and to ECM, signaling, the cytoskeleton and cell migration. The Rho family of GTPases, their regulation by guanine nucleotide exchange factors and GAPs. Inflammation and leukocyte transendothelial migration.
Current research projects in the Campbell laboratory include structural, biophysical and biochemical studies of wild type and variant Ras and Rho family GTPase proteins, as well as the identification, characterization and structural elucidation of factors that act on these GTPases. Ras and Rho proteins are members of a large superfamily of related guanine nucleotide binding proteins. They are key regulators of signal transduction pathways that control cell growth. Rho GTPases regulate signaling pathways that also modulate cell morphology and actin cytoskeletal organization. Mutated Ras proteins are found in 30% of human cancers and promote uncontrolled cell growth, invasion, and metastasis. Another focus of the lab is in biochemical and biophysical characterization of the cell adhesion proteins, focal adhesion kinase, vinculin, paxillin and palladin. These proteins are involved in actin cytoskeletal rearrangements and cell motility, amongst other functions. Most of our studies are conducted in collaboration with laboratories that focus on molecular and cellular biological aspects of these problems. This allows us to direct cell-based signaling, motility and transformation analyses. Member of the Molecular & Cellular Biophysics Training Program.
Molecular evolution and mechanistic enzymology find powerful synergy in our study of aminoacyl-tRNA synthetases, which translate the genetic code. Class I Tryptophanyl-tRNA Synthetase stores free energy as conformational strain imposed by long-range, interactions on the minimal catalytic domain (MCD) when it binds ATP. We study how this allostery works using X-ray crystallography, bioinformatics, molecular dynamics, enzyme kinetics, and thermodynamics. As coding sequences for class I and II MCDs have significant complementarity, we also pursuing their sense/antisense ancestry. Member of the Molecular & Cellular Biophysics Training Program.
Our research is concerned with proteases and their inhibitors in various disease processes (thrombosis and cancer); our science tools are structure-activity, cell biology and signaling, pathobiology, immunohistochemistry, and in vivo models.
Diabetes and insulin resistance: lipid and carbohydrate metabolism; obesity: partition of energy between triacylglycerol storage and fatty acid oxidation; regulation of triacylglycerol synthesis; hepatic steatosis
Our lab is studying the molecular mechanisms which are involved in the induction and proliferation and patterning of cardiac progenitor cell populations. To identify the molecular pathways involved in these processes, we have used Xenopus and mouse as model systems with particular focus on the endogenous role of genes implicated in the early steps of cardiogenesis and human congenital heart disease. Present projects in the lab involve embryological manipulations, tissue explant cultures, molecular screens as well as protein-DNA interaction experiments, biochemistry and promoter analysis.
We study cell cycle control of DNA replication licensing, the process that renders replication origins competent to initiate DNA synthesis. We investigate how the replication process is linked to cell cycle progression and the signaling pathways that gather and transmit information about the cellular environment. Our experimental approach is to manipulate human cells in culture (both cancer cell lines and normal cells) through a variety of molecular and genetic strategies; some projects utilize budding yeast as a model system due to the sophisticated genetic tools available in that organism. We measure protein abundance and stability, chromatin localization and modifications, cell cycle progression, protein-protein interactions, and checkpoint functions. Our long-term goals are to understand the molecular events that ensure genome stability and how those events are disrupted in cancer cells.
Mechanisms of DNA replication, DNA repair, and cell cycle checkpoints are studied in cultured human cells and using biochemical assays in vitro. It includes translesion synthesis by DNA polymerase eta and its role in suppressing mutagenesis by solar radiation. Inherited and acquired defects in the network of protection of genetic stability are associated with increased risk for mutations underlying cancer pathogenesis. Current goals are to identify key molecular events in melanoma development associated with sun exposure. Other collaborative studies aim at localization of functional origins and characterization of DNA replication dynamics.
The Cyr laboratory studies cellular mechanisms for cystic fibrosis and prion disease. We seek to determine how protein misfolding leads to the lung pathology associated with Cystic Fibrosis and the neurodegeneration associated with prion disease.
We use an integrated approach (genomics, proteomics, computational biology) to study the molecular mechanisms of hormone and drug desensitization. Our current focus is on RGS proteins (regulators of G protein signaling) and post-translational modifications including ubiquitination and phosphorylation.
The Dokholyan group focuses primarily on understanding protein dynamics, more specifically on how induced changes in protein folding and aggregation lead to diseases, such as cystic fibrosis, many types of cancers, and a number of neurodegenerative diseases. The Dokholyan group focuses on several such diseases, including Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, and Huntington disease. The Dokholyan group is developing a hierarchy of molecular models, from simplified coarse-grained models to more detailed ones, to create a novel multi-scale simulation methodology. This methodology will enable simulations of large molecular complexes at the biologically-relevant time scales, thereby allowing to directly glance into processes associated with human diseases. Member of the Molecular & Cellular Biophysics Training Program.
My lab studies membrane traffic between the trans-Golgi network and endosomal organelles. This central feature of eukaryotic cell biology is important for functions of the human body; including the ability to recognize and destroy infective agents, sugar uptake in response to insulin and the proper reaction of cells to growth factors-a feature important in normal development and that is often inappropriately regulated in cancer. We have two main types of projects in the lab; characterizing protein-protein interactions important for membrane traffic and chemical genetic approach to identify compounds that regulate membrane traffic.
Our lab is interested in how signals from membrane receptors are transduced to the nucleus altering gene expression, cell shape, proliferation and differentiation. We are particularly interested in tyrosine-specific protein kinases in breast and prostate cancer, as well as lymphoma/leukemia. Particular focus of the lab include:1) roles of the EGF receptor family and related molecules HER4/ErbB4 in growth inhibition and differentiation and 2) Mer (a novel receptor tyrosine kinase) and how signals downstream from Mer enhance prostate tumorigenesis.
We are characterizing the structural signals that are responsible for moving proteases normally stored intracellularly in lysosomes into the extracellular environment, where they may participate in tumor cell metastasis. One putative mediator of this altered protease targeting is an endosomal integral membrane protein that behaves like a cellular "dirty bomb", undergoing proteolysis which releases fragments that target to various cellular sites where they serve distinct functions. The multiple proteolytic cleavages ultimately release the cytoplasmic tail from the membrane. This tail, which possesses a putative signal for import into the nucleus, can modify other proteins with ubiquitin, which causes them to be degraded rapidly. Proteolysis of the putative receptor is mediated by the same enzymes that cleave the Alzheimer's precursor protein into fragments that can aggregate to form plaques in the brain. When neurite outgrowth is stimulated, expression of this protein is upregulated, suggesting that it also plays a role in development. We are using biochemical characterization of the protein's domain structure to relate its proteolysis, cellular targeting, and signaling to the nucleus to altered targeting of lysosomal enzymes.
The research in my lab is divided into two main areas - 1) Atomic force microscopy and fluorescence studies of protein-protein and protein-nucleic acid interactions, and 2) Mechanistic studies of transcription elongation. My research spans the biochemical, biophysical, and analytical regimes.
Our work is focused on understanding how major histocompatibility complex (MHC) molecules function in the immune response to pathogens. This simple question involves the most fundamental aspect of immunology - self/non-self discrimination.
We study intracellular trafficking of the chloride channel CFTR in heterologous systems and in primary human airway epithelial cultures. The most common mutation in cystic fibrosis, deltaF508, results in a misassembled protein that is retained at the ER but can escape and proceed to the plasma membrane by addition of small molecule correctors or low temperature incubation. Temperature-rescued deltaF508 disappears rapidly from the cells surface and is subjected to lysosomal degradation, while wild-type CFTR is recycled back to the plasma membrane. Of particular interest is the mechanism that leads to elimination of detlaF508 from the cell surface.
Successful respiratory pathogens must be able to respond swiftly to a wide array of sophisticated defense mechanisms in the mammalian lung. In histoplasmosis, macrophages -- a first line of defense in the lower respiratory tract -- are effectively parasitized by Histoplasma capsulatum. We are studying this process by focusing on virulence factors produced as this "dimorphic" fungus undergoes a temperature-triggered conversion from a saprophytic mold form to a parasitic yeast form. Yersinia pestis also displays two temperature-regulated lifestyles, depending on whether it is colonizing a flea or mammalian host. Inhalation by humans leads to a rapid and overwhelming disease, and we are trying to understand the development of pneumonic plague by studying genes that are activated during the stages of pulmonary colonization. [note: Dr. Goldman will be moving to UNC in Summer 2008]
We are interested in how complex signaling systems interact to preserve homeostasis, while also optimizing the response of the organism to environmental changes. Two different projects are ongoing in the laboratory: Project 1: Matching renal salt excretion with dietary salt intake is vital for survival. We are integrating whole animal physiological studies and innovative molecular techniques to investigate the role of a new intestinal hormone, uroguanylin, in this process. Project 2: How do target organs communicate with neural circuits? We are investigating feedback regulation of a simple neural circuit that uses a novel form of muscle-to-nerve communication to control the contractions of the heart musculature.
Our lab is studying the role of mitogen and stress-activated protein kinases to regulate key aspects of cell metabolism. We are also studying signalling by tyrosine kinases in response to toxicological agents or cell stress.
We are interested in basic DNA-protein interactions as related to - DNA replication, DNA repair and telomere function. We utilize a combination of state of the art molecular and biochemical methods together with high resolution electron microscopes.
My lab studies a gene silencing phenomenon called RNA interference, or RNAi. We are interested in the role of RNAi in regulating endogenous genes, particularly those involved in cancer progression pathways.
We focus on mechanistic/structural aspects of regulatory proteins (heterotrimeric and Ras family GTPases, RGS proteins, and PLC isozymes) involved in inositol lipid signaling, and on G protein-coupled receptors for extracellular nucleotides.
Structure, dynamics and function of viral domains in biomembranes. Photomanipulation and traction mapping applied to the migration of single cells. Investigation of the mechanochemical basis of cell oscillations using systems biology approaches coupled with experiments.
Spatio-temporal regulation of signal relay systems in cells using live cell fluorescence imaging and targeted gene disruption of signaling proteins to define their role in development, physiology and pathophysiology.
My lab studies the pathogenic mechanisms of two bacterial pathogens, Haemophilus ducreyi and Francisella tularensis. H. ducreryi, the agent of the sexually transmitted infection chancroid, somehow inhibits the development of an effective immune response
Our research focuses on the structure and function of medically important proteins from the crystallographic approach. The current topics include cycolphilin, calcineurin, heat shock protein 90 (hsp90), and cyclic nucleotide phosphodiesterase.
We study protein structure and dynamics as they relate to protein function and energetics. We are currently using NMR spectroscopy (e.g. spin relaxation), computation, and a variety of other biophysical techniques to gain a deeper understanding of proteins at atomic level resolution. Of specific interest is the general phenomenon of long-range communication within protein structures, such as observed in allostery and conformational change. A. Lee is a member of the Molecular & Cellular Biophysics Training Program.
We study the blood clotting protein fibrinogen, its biochemistry and its role in disease (Curr Opin Hematol. 14:236, 2007). We synthesize variant fibrinogens to correlate structure and function using crystallographic and biochemical analyses (Biochemistry 46:5114, 2007). We examine the mechnical properties of fibrin fibers using atomic force microscopy (Science 313:634. 2006). We explore the interactions of fibrinogen with biomaterials (Acta Biomaterialia 3:663, 2007). We use patient samples and mouse models to examine the links between fibrinogen and disease (J Thromb Haemost. 2:1484, 2004). Member of the Molecular & Cellular Biophysics Training Program.
We are interested in the mechanisms by which histone protein synthesis is coupled to DNA replication, both in mammalian cell cycle and during early embryogenesis in Drosophila, Xenopus and sea urchins.
Research in our laboratory is focused on the enzymatic mechanisms and biological roles of DNA helicases. These enzymes provide the primary mechanism by which duplex DNA is converted to single-stranded DNA (ssDNA) for use as a template in DNA replication and repair or as a substrate in recombination. Indeed, these enzymes are essential for DNA replication, repair and to maintain genomic stability in all organisms. Consistent with this idea, defects in genes encoding DNA helicases in human cells have been linked to genomic instability leading to a variety of progeriod disorders and human cancers. The bacterium E. coli and the budding yeast S. cerevisiae provide attractive systems in which to pursue these studies due to the ease of genetic manipulation and the ability to isolate enzymes for biochemical studies. The long-range goal of the research program is to understand, in enzymatic and molecular terms, the mechanism of action of several helicase enzymes, and to define their individual roles in DNA metabolism.
The lab also has an interest in the process of DNA transfer by bacterial conjugation, first observed more than 50 years ago as the unidirectional and horizontal transmission of genetic information from one E. coli cell to another. Today we know that conjugative DNA transfer plays a role in increasing genetic diversity in addition to propagating the spread of antibiotic resistance and microbial virulence factors. Recent work in this laboratory and others has provided a working model of DNA transfer in the F plasmid system. The long-range goal of this research program is to define the function and regulation of the relaxosome, and each protein in this nucleoprotein complex, in conjugative DNA transfer. Based on that information we will begin to establish inhibitors of relaxosome function.
There are two ongoing projects in my lab - mechanism of binding of bacteria to plant surfaces and mechanism of carbohydrate synthesis in bacteria. We are studying the mechanisms of adhesion of the plant pathogenic and symbiotic bacteria Agrobacterium and Rhizobium to plant hosts. This binding involves protein adhesins, pilus adhesins, and carbohydrates. We are also studying the mechanisms of adhesion of the human pathogens E. coli O157 and Salmonella enterica to plant surfaces. The presence of human pathogens on produce and ready to eat fresh food has emerged as a serious concern worldwide. These bacteria bind tightly to the plant surface and can not be removed by washing. Understanding how these bacteria bind to plants is critical to preventing or inhibiting their binding and thus reducing their transmission via this route.
The second project in my laboratory concerns the mechanism of biosynthesis of polysaccharides by bacteria. We are particularly interested in cellulose and curdlan which are synthesized from the same precursor using similar proteins. We would like to understand the differences between these proteins which cause one to catalyze the synthesis of cellulose and the other to catalyze the synthesis of curdlan. We are also interested in the regulation of the biosynthesis of these exopolysaccharides, particularly in the role of cyclic diguanylic acid in this regulation.
The goal of the laboratory’s research is to define the structure and function of an intracellular Ca2+ release channel in skeletal and cardiac muscle, using molecular biological and electrophysiological methods and by creating mutant mice.
My laboratory has two main interests: 1) P2Y receptor trafficking in epithelial cells. Our laboratory investigates the cellular and molecular mechanisms by which P2Y receptors are differentially targeted to distinct membrane surfaces of
polarized epithelial cells and the role of lipid rafts and caveolae in P2Y receptor function. 2) Antibiotic resistance mechanisms. We are interested in the mechanisms of antibiotic resistance in the pathogenic bacterium, Neisseria gonorrhoeae. Our laboratory investigates how acquisition of mutant alleles of existing genes confers resistance to penicillin and cephalosporin. We also study the biosynthesis of the gonococcal Type IV pilus and its contribution to antibiotic resistance.
Our lab investigates molecular and cellular mechanisms that regulate mammalian spermatogenesis and fertilization. A major focus of our current research is sperm energy metabolism. Our gene knockout studies demonstrate that glycolysis is essential for sperm motility and male fertility, and genomic analyses indicate that male germ cells express unique enzymes for nearly every step in this central metabolic pathway. These sperm-specific glycolytic enzymes have distinctive properties, as demonstrated by biochemical and structural analyses. Understanding how sperm energy production is regulated has significant therapeutic potential, both for the development of new contraceptive strategies and the clinical management of infertility.
Fertilization leads to the formation of a new diploid individual and represents an exquisite example of the specificity of cell to cell and cell surface-extracellular matrix interaction. Our research laboratory is interested in the study of the structure and function of sperm proteins. The long-term goal of our research is to define a set of sperm molecules that are necessary for one or more steps in the fertilization process. A full understanding of the mechanisms of sperm maturation and fertilization would allow precise targets for both infertility diagnosis and contraception.
Currently, the structure and function of two different proteins are under study. These proteins are: 1) NASP a nuclear protein that binds and transports linker histones into the nucleus and is critical for mitosis and meiosis; 2) Eppin a testis and epididymal serine protease inhibitor.
An important step in the development of tests for the diagnosis of infertility and for the development of a male gamete based contraceptive is the determination of specific protein-protein interactions that are necessary for fertilization. Characterization of these interactions will
provide sites for contraceptive development.
The Patterson laboratory has 4 major focuses, each of which is funded by at least one major grant. Our longest ongoing project focuses on blood vessel growth and development, and in particular how bone morphogenetic protein signaling regulates vascular development. A second ongoing project in the laboratory is to understand at a fundamental level the cellular response to proteotoxic stress. The third major focus of our laboratory studies cardiac-specific ubiquitin ligases that regulate cardiac hypertrophy and metabolism. Finally, we have begun a human translational study that takes advantage of our expertise in genomics, proteomics, and genetics to develop an integrated DNA/RNA/protein profile database of patients with heart disease.
My graduate students and I use the formalism of equilibrium thermodynamics and the tools of molecular biology and biophysics to understand how nature designs proteins.
The end joining pathway is a major means for repairing chromosome breaks in vertebrates. My lab is using cellular and cell-free models to learn how end joining works, and what happens when it doesn’t.
We examine dynamic cellular processes using structural biology. Current projects focus on Infectious disease, particularly the spread of antibiotic resistance and host-pathogen interactions; Protein-DNA complexes involved in DNA manipulation; the Design of protein therapeutics; Nuclear receptors in transcriptional control; and Enzymes central to drug recognition and metabolism.
We have three main areas of research focus: (1) Nucleotide excision repair: The only known mechanism for the removal of bulky DNA adducts in humans. (2) DNA damage checkpoints: Biochemical pathways that transiently block cell cycle progression while DNA contains damage. (3) Circadian rhythm: The oscillations in biochemical, physiological and behavioral processes that occur with the periodicity of about 24 hours.
My lab is interested in mechanisms that (1) fine tune gene expression and (2) coordinate transcription and RNA processing in eukaryotes. Our work is based on molecular, genetic and biochemical analysis of the suppressor of sable gene of Drosophila.
My work is centered upon the characterization of the large mucin gene products and the complexes they make which are essential for the formation of the mucus gels vital for epithelial protection and function. This work is focused around the human lung where there are many human diseases including asthma, cystic fibrosis, and chronic bronchitis in which these glycoconjugates are centrally implicated. Our studies are broad ranging and seek to build up a picture of the chemistry of these complex phenotypes, the network of their interactions that constitutes a mucosal surface and the mechanisms of their biosynthesis, assembly and secretion. The laboratory is established with a wide range of methods including MALDI and ESI mass spectrometry, electron and atomic force microscopy, hydrodynamics, theoretical molecular dynamics and a variety of surface physics tools.
Regulator of G-protein signaling (RGS) proteins accelerate the GTPase activity of G-alpha subunits and thereby act as critical negative regulators of hormone and neurotransmitter signaling via G protein-coupled receptors. Our lab first recognized the existence of these critical signaling regulators in 1996. We continue to study their structural and functional diversity, as well as their roles in physiological and disease processes, including immunity, oncogenic transformation, and pain processing.
Our lab examines cytoskeletal dynamics, the molecules that regulate it and the biological processes it is involved in using live cell imaging, in vitro reconstitution and x-ray crystallography. Of particular interest are the microtubule +TIP proteins that dynamically localize to microtubule plus ends, communicate with the actin network, regulate microtubule dynamics, capture kinetochores and engage the cell cortex under polarity-based cues.
Our laboratory studies signal transduction systems controlled by heterotrimeric G proteins as well as Ras-related GTPases using a variety of biophysical, biochemical and cellular techniques. Member of the Molecular & Cellular Biophysics Training Program.
We are combining biochemistry and molecular biology to study protein synthesis in mammalian mitochondria. Factors required for the initiation and elongation steps of have been cloned and detailed protein chemistry is being carried out to study their properties. Mutations of several of these proteins are lethal in humans and these mutations are being studied to study the interactions of these factors with ribosomes and the structures of these factors bound to ribosomes are being examined using cryoelectron microscopy. Chemical probing is being used to explore the structures of mitochondrial mRNAs. The tRNAs in mammalian mitochondria are quite unusual and mutations in them can cause human diseases. The underlying defects in these tRNAs are being probed at structural and biochemical levels providing an understanding of how the mutations lead to human disease.
My laboratory at present is working on the vitamin K cycle and vitamin K-dependent proteins. The enzymes of the vitamin K cycle include, at a minimum two integral membrane proteins, both of which were purified and cloned by my laboratory. One, the vitamin K epoxide reductase is the target of warfarin for which 40 million prescriptions are written each year in the US alone. Polymorphisms in this gene are the best example to date of the use of genomics in molecular medicine. We are also interested in purifying any additional components of this cycle and trying to understand the ~50% of patients whose genotype is not informative about warfarin dose. In addition, we are interested in the mechanism of how factor VIIa works and the role of the extracellular matrix in coagulation.
Our laboratory is examining the role of histone post-translational modifications in chromatin structure and function. Using a combination of molecular biology, genetics and biochemistry, we are determining how a number of modifications to the histone tails (e.g. acetylation, phosphorylation, methylation and ubiquitylation) contribute to the control of gene transcription, DNA repair and replication.
To understand the general rules of splicing regulation, a.k.a. "splicing code", we study the splicing regulation in a systematic way. We also try to engineer molecules that can modulate splicing, and use them as drugs to treat splicing diseases.
Our vision is to address one of the great remaining and intractable problems in cellular and molecular biology -- that of determining comprehensive and quantitative structures for all cellular and viral RNAs. To this end, we are developing high-throughput RNA structure analysis technologies (called SHAPE) with the goal of making RNA secondary and tertiary structure analysis as straightforward, in principle, as DNA sequencing is today. We then use these tools to understand otherwise daunting problems that play pivotal roles in cellular function. Current projects include (i) RNA folding and protein assembly reactions central to the infectivity and pathogenesis of human viruses and (ii) assembly of large biomedically important ribonucleoprotein complexes inside living cells.
How the loss of different components of the SWI/SNF complex contributes to neoplastic transformation remains an open and important question. My laboratory concentrates on addressing this question by the combined use of biological, biochemical and mouse models for SWI/SNF complex function.
Our work focuses on molecular aspects of androgen receptor regulation of gene expression, which includes coactivator interactions with the androgen receptor and its functional importance in various clinical syndromes.
Cellular, molecular, and biochemical mechanisms of blood coagulation; Relationships between cells (monocytes, fibroblasts, endothelial cells, smooth muscle cells, platelets and others), plasma protein concentration, thrombin generation and blood clots; Fibrin formation, structure and stability; Mechanical properties of fibrin; Disorders associated with bleeding and thrombosis, including hemophilia and cardiovascular disease (heart attack, stroke, deep vein thrombosis, pulmonary embolism); Preclinical testing of hemostatic and antithrombotic drugs
Enzyme action; drug design; effects of solvent water on the structure and reactivity of biological molecules; rates of benchmark reactions for testing the catalytic prowess of enzymes.
