Drug Dynamics Institute
DDI's TherapeUTex Collaborating Faculty
The TherapeUTex Preclinical Core interacts with a wide-variety of researchers. Collaborating faculty participate in TherapeUTex projects on an "as needed" basis for interested researchers or companies. These include faculty through The University of Texas system with frequent and/or direct research activities involving Preclinical Drug Development.
Carla Van Den Berg, Pharm. D.
Director, TherapeUTex
Associate Professor
Pharmacology & Toxicology
Models and Expertise:
- Perform various phenotypic in vitro assays including cell cycle analysis, cell death, proliferation, migration and invasion assays.
- Mouse models for cancer. For human cell lines, the cells can be engrafted for orthotopic (usually solid) tumor studies to assay for response to a drug treatment. Some cell lines can also be injected either through intra-cardiac or tail vein injection to provide models for tumor metastasis. We use mouse and human mammary tumor cell lines that metastasize to either the lung and/or bone.
- In vivo assays for angiogenesis including quantification of micro-vessel density, and MatrigelTM plug assays.
- Use of genetically modified mouse models for cancer:
- Transgenic mouse models that spontaneously develop mammary tumors that metastasize to the lung.
- Transgenic mice where a gene can be overexpressed in a tetracycline-inducible manner in mammary epithelial cells.
- Genetic knockout mice for the p53, jnk2-/- and jnk1-/- mice. The p53-/- mice frequently develop sarcomas and lymphomas but they can also be used for other tumor models with modifications.
- Primary tumor cell and circulating tumor cell culture.
- Study of other tumor types using similar in approaches.
Techniques and Equipment:
- Live cell imaging assays using bright field or fluorescent tags.
- Immunofluorescent cytochemistry.
- Stereomicroscopy that can be used to detect color, GFP, RFP, and cy5 tagged proteins or probes in animal tissues.
- Tissue processing, paraffin embedding, and tissue sectioning for subsequent tissue staining and analyses including immunohistochemistry.
- Target validation using qPCR, immunohistochemistry, ELISA, Western blot analysis or kinase assays
Note: Animal experiments require prior IACUC approval. Use of some of these cell lines or mice may require revision of the current Materials Transfer Agreements from various institutions.
David Burgess, Pharm.D.
Clinical Professor
Pharmacotherapy Division Head
Expertise: Anti-infective (i.e., bacteria and fungi) drug development from preclinical through post-marketing.
- Measuring the in vitro potency (i.e., MIC, MBC, zone of inhibition) of anti-infectives through performing susceptibility testing via broth microdilution, agar dilution, Kirby-Bauer, or E-test.
- Measuring the in vitro activity (i.e., bacteriostatic vs bactericidal) of anti-infectives through using traditional time-kill methods and in vitro models.
- Determining the interaction (i.e., synergy, indifference, antagonism) between mutliple anti-infectives using checkerboard, time-kill, or E-test.
- Identifying bacterial mechanisms of resistance using molecular assays.
- Measuring protein binding of anti-infectives using ultracentrifugation.
- Measuring anti-infectives in biological samples using HPLC or bioassay.
- Determining anti-infective pharmacokinetic parameters using compartmental and noncompartmental analysis.
- Determining the relationship between microbiological activity and pharmacokinetic parameters (pharmacokinetic-pharmacodynamic indices) to develop the optimal dosing regimen while minimizing the development of resistance and toxicity.
- Modeling the pharmacokinetic-pharmacodynamic indices of anti-infectives using Monte Carlo simulation to optimize the dosing regimen and determine the appropriate in vitro susceptibility breakpoint.
Maria Croyle, Ph.D.
Associate Professor
Pharmaceutics
Expertise:
- Drug/delivery(intravenous, nasal, oral) and formulation, specifically unique to my lab is large scale lyophilization.
- PK/PD assessment of drugs as well as recombinant DNA based preparations
- unique to my lab is the establishment of techniques for proper harvesting of
tissues/organs for biodistribution studies using real-time PCR.
- Drug metabolism via the cytochrome P450 enzyme families
- have experience in vivo in mice, rats and primates
- have in vitro primary hepatocyte culture system in rats established and
are working on one for wild type and genetically altered mice
- have assessed changes in gene expression patterns using real-time PCR
and microarray technology
- Immunological Animal models (for assessment of infectious disease and vaccine development)
- current expertise is in mouse, Guinea Pig and primate models hope to add
ferrets within the next year.
- along with this have expertise in tissue/organ processing/harvest for immunohistochemical staining, immunocytochemistry
Kevin Dalby, Ph.D.
Associate Professor
Medicinal Chemistry
Expertise: Protein biochemistry and intracellular signaling
Protein expression and purification
- Expression of proteins using prokaryotic and eukaryotic expression systems
Enzymology
- In vitro enzyme assays using a variety of biophysical techniques:
- Radioactive liquid scintillation assays
- spectrophotometric assays (uv and visible)
- fluorescence (emission and polarization)
- Potential for high throughput assays in 96-well and 384-well format
- IC50 determinations
- inhibitor characterization (mechanism and potency)
Characterization of inhibitors of signal transduction processes (cellular)
- protein kinase assays
- radioactive immune complex assays
- Western blot analysis
Duvauchelle, Christine L., Ph.D.
Associate Professor
Pharmacology & Toxicology
Expertise: In vivo models of drug self-administration
Intravenous drug delivery - Experimenter-administered
Dr. Duvauchelle's primary interests concerning drug development relate to drug abuse and candidate compounds affecting voluntary drug intake. Additional behavioral techniques can identify compounds that enhance or attenuate learning, memory and motor abilities. These assessments are relevant treatment issues for clients on minor medication regimens and for patients undergoing more serious neurological challenges.
In vivo models:
- Drug abuse (stimulants, narcotics, polydrug abuse)
- Intravenous drug delivery
- Learning and memory assessment - Pharmacological effects on consolidation, retrograde/anterograde amnesia
Methodologies and Equipment:
- Microdialysis-analysis of extracellular concentrations of neurotransmitters such as dopamine, serotonin
- Rodent surgery including: Intravenous catheterization- implantation of juguluar catheters for self-administration or experimenter-administered drugs; stereotaxic surgery for implantation of indwelling cannula enabling drug injections into specific brain regions and/or placement of microdialysis probes for neurotransmitter sample collection
- Behavioral testing/Learning and memory
- Motoric Activity Assessment
- Histology- analysis of probe placements in brain slices
Walter Fast, Ph.D.
Associate Professor
Medicinal Chemistry
Expertise: Enzymology, HTS, compound development
- Guanidine-modifying enzymes and inhibitors: as possible therapeutic targets to treat cancer, infectious disease, rheumatoid arthritis, multiple sclerosis
- Quorum-sensing pathways: Use of catabolic enzymes to disrupt interbacterial signaling and associated pathogenecity and/or biofilm growth.
Rueben Gonzales, Ph.D.
Professor
Pharmacology & Toxicology
Expertise: In vivo models of self-administration of drugs of abuse
Dr. Gonzales' primary interests concerning drug development relate to diseases of alcoholism and drug abuse; however, his techniques (in collaboration with Dr. Christine Duvauchelle) and overall areas of emphasis on neurochemistry and behavior would enable him to help the development of drugs in many different neurological diseases (epilepsy, neurodegenerative disorders and neurotoxicity as in stroke, schizophrenia, Parkinsonism and related diseases of the basal ganglia and motor deficits).
In vivo models:
- Alcoholism
- Drug addiction (cocaine, opiates)
Methodologies and Equipment:
- Microdialysis-analysis of extracellular concentrations of neurotransmitters such as dopamine, glutamate, GABA, and peptides.
- Histology- analysis of probe placements in brain slices
- Rodent surgery including: Intravenous catheterization- implantation of juguluar catheters for self-administration of drugs; brain cannulation-implantation of an indwelling cannula for placing microdialysis probes and microinjectors into various brain areas
- Ethanol analysis-determination of blood and dialysate alcohol concentration
Adron Harris, PhD
Professor/Joint
Neurobiology
College of Natural Sciences
Expertise: Drug actions on ion channels and genetic mouse models for studying drug action.
- ion channel mutations
- functional protein expression in Xenopus oocytes transcriptome analysis by microarrays mouse genetic models of disease
Sean M. Kerwin, Ph.D.
Associate Professor
Medicinal Chemistry
Expertise: Synthetic Medicinal Chemistry and DNA-Interactive Agents
- Chemical synthesis of a wide range of compound classes including heterocycles, phospholipids, terpenoids, molecular hosts, and nucleic acids.
- Synthesis of isotope-labeled compounds.
- Spectroscopic, PAGE, and SPR-based methods for elucidating the affinity and specificity of small molecule-DNA interactions, DNA cleavage, and DNA adduct formation.
- Special focus on G-quadruplex DNA targets and metal-mediated DNA binding agents.
- Biochemical assays: Helicases, in vitro DNA replication, topoisomerases, telomerase.
Jason McConville, Ph.D.
Associate Professor
Pharmaceutics
Expertise: Drug formulation and delivery
- Pre-formulation studies with APIs
- Formulation design (inhalation, and oral delivery)
- Pharmacopeial testing
- Site specific drug delivery
- Animal testing with mouse, rat, rabbit models:
- Parenteral administration
- Inhalation, lung deposition studies
- Oral drug administration
- Liquid gavage (suspension or solution)
- Capsule administration (dry powders/APIs)
- Buccal patch delivery (Rabbits)
- Surgical procedures (jugular catheterization etc.)
- Pharmacokinetic modeling
Methodologies and Equipment:
- Dissolution Paddle/Basket Apparatus with flow through analysis and sample collection
- UV/Vis spectrophotmetry
- Next Generation Cascade Impactor
(Aerosol Particle Sizing)
- Dynamic Vapor Sorption Analysis
(Surface Properties: Morphology, Surface energy of Powders/Particles by Adsorption)
- HPLC- extraction assays performed from tissue/blood
Other Equipment (regularly used on campus):
- Viscometer
- Scanning Electron Microscope - equipped with elemental analysis
- Atomic Absorption Spectrometer - ICP or Flame
- DSC
- Surface Area analyzer
- X-ray diffraction
- Laser diffraction particle sizing
- Radiolabel scintigraphic analysis possible offsite
James W. McGinity, Ph.D.
Professor, Pharmaceutics
Johnson & Johnson
Centennial Chair
Expertise: Research and development of novel drug delivery systems, controlled and targeted drug delivery systems
- Solid dosage forms, aqueous film coating of pellets and tablets, powder technology, materials science, transdermal systems, hot-melt extrusion
- Concentration on specific therapeutic targets or drug delivery systems (e.g. microparticulate technology)
- Hot-melt extrusion technology, investigated as a pharmaceutical process to prepare transmucosal films, transdermal patches, tablets, granules, pellets, and fast-dissolving oral dosage forms
Richard Morrisett, Ph.D.
Professor
Pharmacology & Toxicology
Expertise: Neuronal models (animal, primary cells, and cell lines), ion channel biology, and imaging
Dr. Morrisett's primary interests concerning drug development broadly relate to diseases involving ion channels (eg "channelopathies"). His expertise is related to alcoholism and drug abuse; however, his techniques and overall areas of emphasis in ion channels would enable him to help the development of drugs in many different neurological diseases (epilepsy, neurodegenerative disorders and neurotoxicity as in stroke, schizophrenia, Parkinsonism and related diseases of the basal ganglia and motor deficits). Peripheral diseases would mainly include as cardiovascular and related diseases (arrhythmias, hypertension, angina, cardiomyopathies, diabetes).
John Richburg, Ph.D.
Associate Professor
Pharmacology & Toxicology Division Head
Expertise: Evaluation of the adverse effects of toxicants on male (and female) reproductive system.
Complete histopathological and phenotypic analysis of the male reproductive system including:
- Epididymal and testicular sperm counts.
- Grading of the severity and specificity of spermatogenic disturbances (characterizing germ cell subtypes involved; Sertoli cell or Leydig cell toxicity).
- Assessment of male testis development
- Monitoring of endocrine function (testosterone, inhibin ect).
- Assessment of accessory sex glands (epididymis, vas deferens, seminal vesicle and prostate).
Testicular germ cell transplantation for assessing germ cell versus somatic cell disruptions.
Mating studies of rodents and determination of fertility/fecundity indexes.
Nathan Wiederhold, Pharm. D.
Assistant Professor
Pharmacotherapy
Expertise: Studying different cellular pathways in pathogenic fungi that are up-regulated in response to antifungal challenge.
- Cellular viability assays, time-kill methods, and microscopy (DIC optics and fluorescence) and molecular assays (real-time PCR) are utilized. The goal is to better understand how these organisms adapt in hopes of developing more effective treatment strategies. Also, because of structural similarities between these lower eukaryotes and mammalian cells resulting in collateral toxicities associated with the use of various antifungal agents, different strategies that aim to minimize such toxicities are also being investigated.
- Animal models of invasive fungal infections (including invasive aspergillosis, candidiasis, fusariosis, and zygomycosis) can be utilized to assess in vivo drug activity and different dosing strategies.
Robert O. (Bill) Williams III,
Ph.D.
Professor
Pharmaceutics Division Head
Models and Expertise: Drug delivery technologies
- Drug delivery through various routes of administration including oral, pulmonary, parenteral and topical.
- Use of nanoparticles to enhance bioavailability by oral and pulmonary routes.
- Preformulation, formulation, analytical methods development, material characterization
- Use of small rodent animal models for delivery of drugs by the oral and inhaled routes.
Last Reviewed: August 11, 2009
