Pharmacology and Toxicology

Lillian Cruz-Orengo, Ph.D.

VM: Anatomy, Physiology & Cell Biology

(See also: Immunology/Infectious Disease, Neurology)

Multiple Sclerosis (MS) is a devastating disease and the second leading cause of neurologic deficits in young adults, characterized by the pathological trafficking of autoreactive-leukocytes into the central nervous system (CNS). MS exhibits a high sex-bias, affecting three times more women than men a phenomenon that we could replicate in the lab when inducing Experimental Autoimmune Encephalomyelitis (EAE) on SJL mice. Specifically, my research focuses on sexual dimorphism of the blood-brain barrier (BBB) as a relevant contributor to MS neuropathogenesis, aiming to develop sex-specific therapeutic targets. Additionally, we are in the developing an animal model using transgenic zebrafish to assess for changes in brain microvasculature as a result to pesticide exposure. This model of BBB disruption will lead to greater understanding of the influences environmental factors may play in this process and consequent induction of neurological and neurodevelopmental disorders.

Keywords:

Autoimmunity, sexual bias/dimorphisms, blood-brain barrier, neuroinflammation/neurodegeneration

Example of research projects:

  1. Developmental onset of sexual dimorphisms of CXCL12 apicobasal polarity among SJL mice.
  2. Assessment of therapeutic outcomes of IL-20 monoclonal antibody treatment during EAE.
  3. Clinical assessment and neuro-immune interactions IL-20RB-/- mice versus wild type.
  4. Quantitation of BBB permeability on juvenile Tg(1-fabp:DBP-EGFP:flk1-mCherry) zebrafish after Chlorpyrifos exposure.
  5. Expression of ZO-1, Claudin-5 and VE-cadherin on Tg(1-fabp:DBP-EGFP:flk1-mCherry) zebrafish during exposure to Diazinon.

Dr. Cruz-Orengo can be reached at (530) 752-7318 or cruzorengo@ucdavis.edu.

Elva Diaz, PhD

Med: Pharmacology (see also: biochemistry, genetics/genomics and neuroscience)

Dr. Diaz is trained in molecular and cellular biochemistry and functional genomic approaches to understanding nervous system development. The two main areas of interest are neural proliferation and synaptic differentiation in rodent model systems. The Diaz lab uses genomic approaches such as DNA microarrays to identify genes differentially regulated in nervous system development. Individual candidates genes are studied with molecular and cellular techniques including primary neuronal culture, immunocytochemistry, electrophysiology, and transgenic mouse models. Potential projects include: 1) understanding the role of transcription factors during neural proliferation in the cerebellum and potential implications for diseases such as brain tumors; 2) dissecting the role of a novel family of transmembrane proteins in synapse development and potential implications for neurological diseases such as mental retardation and schizophrenia.

Please visit Dr. Diaz's website at:

http://www.ucdmc.ucdavis.edu/publish/providerbio/pharmacology/faculty/1368

Kristin Grimsrud, DVM, PhD

Assistant Clinical Professor, Dept of Pathology, School of Medicine 

Associate Director of Vivaria and Veterinary Care, Mouse Biology Program (MBP)

(See also: Anesthesia/Pain Management, Genetics/Genomics, Translational Research)

Dr. Grimsrud is a laboratory animal veterinarian and her research focuses on translational medicine and animal model optimization and development. Her current major research efforts are in collaboration with the Knockout Mouse Project, Metabolic Mouse Phenotyping Center and Mutant Mouse Resource and Research Center. Additionally, she is involved in a variety of microbiota bariatric surgery research projects that utilize mouse models. Lastly, Dr. Grimsrud has a strong interest in translational clinical pharmacology where she investigates variation in pharmacokinetics and pharmacodynamics in special populations (e.g. burn patients, pediatrics) and assess the influences of polymorphisms on drug efficacy.

Research projects that students could be involved with relate to studies to optimize anesthesia and analgesia protocols, optimizing superovulation techniques in rodents and a variety of other projects related to the genetically engineered rodent models and microbiota/gnotobiotic research.

Contact Information:

Email: kngrimsrud@ucdavis.edu

Office Phone: 530-757-3220

Bruce Hammock

(See also: Anesthesia/Pain Managment, Arthritis, Dentistry/Oral Biology, Food Animal Medicine)

Dr. Hammock’s laboratory has a long collaboration with faculty and students in the school of veterinary medicine.  His laboratory develops mass spectral and biosensor analytical methods for environmental contaminants and drugs in companion animals.  The laboratory is working on a new branch of the arachidonic acid cascade and is developing drugs to block arthritic and laminitic inflammation in horses and inflammatory and post surgical pain in dogs and cats associated with injury, diabetes, age and other criteria.

Projects:

Use of inhibitors of the soluble epoxide hydrolase to potential treat disease in companion animals such as dogs and cats as well as horses and livestock species.

Pharmacokinetic analysis in development of novel pharmaceuticals for veterinary use.

Fundamental mechanism of action of regulatory lipids.

Natural food additives to expand the efficacy of omega 3 fatty acid supplements in food of companion animal and livestock species.

See   http://www.biopestlab.ucdavis.edu/ for additional information.

Pamela Lein

Neurodevelopment, neuroinflammation, neurodegeneration, neurotoxicology, seizures, asthma

VM: Molecular Biosciences (See also: Neurology, Biochemistry/Cell Biology)

The overarching goal in the Lein laboratory is to determine how environmental stressors interact with genetic susceptibilities to influence the risk and severity of neurodevelopmental disorders, neurodegenerative disease, seizures and airway hyperreactivity. Altered patterns of connectivity are associated with functional deficits in the central and peripheral nervous systems; therefore, we are investigating how environmental contaminants, chemical convulsants and inflammation perturb neuronal connectivity as determined using biochemical, morphogenic, functional and electrophysiological endpoints. We are also developing biomarkers of OP neurotoxicity and testing novel therapeutic approaches for protecting against the neurodegenerative effects associated with chemical convulsants.

If interested, please contact Dr. Pamela Lein at pjlein@ucdavis.edu

Visit our website: http://www.vetmed.ucdavis.edu/lein-lab/

Isaac Pessah, PhD

(See also: Neurology/Neurobiology)

Assoc. Dean of Research and Graduate Education

Research focuses investigating the molecular and cellular mechanisms by which neuromodulators, neurotoxicants, and natural products influence Ca2+ signaling pathways in excitable cells (muscle and neurons). The approaches available are highly interdisciplinary and use cutting-edge in vivo and in vitro methods with transgenic and knock-in mice and cells isolated from them. The major disorders currently being studied include malignant hyperthermia (MH) susceptibility conferred by mutations in RYR1 and CACNA1S, FMR1 related disorders, Rett syndrome, and most recently development of model of Timothy Syndrome mutation CACNA1C. Students will be trained basic biophysical, chemical, and cellular physiological methods to answer important questions about etiological factors contributing to neurological and muscle disorders.

Please visit Dr. Pessah's website.

Kent E. Pinkerton, Ph.D.

Professor of Anatomy, Physiology and Cell Biology

(see also: cardiology, immunology, pathology/virology and pulmonary medicine)

1) To take an innovative approach in addressing air quality issues in dairy and cattle operations by the examination of direct health effects on the cardiopulmonary systems of mice and rats exposed to ambient particles using a concentrator system at the Tulare Veterinary Medicine Teaching and Research Center.

2) To examine the effects of environmental factors (gases and particles in the air) on peri-natal development to affect lung anatomy and pulmonary function in the rat. From conception to adulthood in the rats takes approximately 6 weeks, an easy fit for one summer!

3) To measure heart rate variability as an indicator of change in autonomic control in the mouse exposed to Davis, CA summer particulates.

4) To take a comparative biology approach to elucidate mechanistic environmental pathways leading to increased susceptibility (fetal onset of adult disease).

5) To examine the role of secondhand smoke on increased susceptibility to infection (influenza).

6) To explore the role of metabolomics as an early indicator of disease (asthma, altered immune function, increased susceptibility to infection).

Please visit Dr. Pinkerton's website for more information.

Birgit Puschner, DVM, PhD

VM: Molecular Biosciences

Dr. Puschner is a toxicologist whose research focuses on the detection of toxicants and drugs in source material and biological specimens with a focus on assessing exposure in the context of clinical outcome. The laboratory uses mass spectrometry techniques to identify and quantitate compounds in matrices such as feed, food, blood, milk and urine. My work currently focuses on compounds found in the environment or produced naturally including algal toxins, plant toxins, and persistent organic pollutants. Students in the STAR program will work with a senior researcher in Dr. Puschner’s laboratory on an independent project related to one of the diverse projects of interest to the group. Research in the laboratory utilizes analytical chemistry approaches. Students have an opportunity to gain experience with sample extraction techniques, as well as method validation and mass spectrometry analyses.   

Some of the ongoing research studies include the metabolism of vitamin E in various animal species, THC analogues in foods for animal and human use, microcystin determination in recreational waters, and PCB and PBDE detection in tissues.

Please visit Dr. Puschner’s website at:  http://www.vetmed.ucdavis.edu/faculty/results.cfm?fid=14622

Michael Rogawski, MD, Ph.D.

Department of Neurology (see also: Neurology-Neurobiology)

Dr. Rogawski is a neurologist and pharmacologist whose research focuses on new treatment approaches for seizures, epilepsy, headache and other neurological conditions. Many of the treatment approaches involve targeting of ion channels, including GABA-A receptors, glutamate receptors, voltage-gated sodium channels and voltage-gated potassium channel. Students in the STAR program will work with a senior researcher in Dr. Rogawski’s laboratory on an independent project related to one of the diverse areas of interest to the group. Research in the laboratory utilizes animal models and also cellular electrophysiology (brain slice and tissue culture). Students have an opportunity to gain experience with animal surgery, EEG recording, and testing of novel treatments in various neurobehavioral and seizure paradigms. The laboratory also conducts pharmacokinetic studies and operates a UPLC-quadrapole mass spectrometer for the measurement of drug levels.  Some of the therapeutic strategies under investigation include: AMPA receptor antagonists, neuroactive steroids, dietary therapies, cannabinoids, and treatments for genetic epilepsies. Dr. Rogawski’s laboratory is a component of the UC Davis CounterACT Center of Excellence, which investigates treatments for nerve agent seizures. STAR program students may choose a project related to the activities of the CounterACT Center. Students successfully completing a summer project may have an opportunity to present their research at a national meeting.

Please visit Dr. Rogawski's website at: http://mr.ucdavis.edu/

Swee Teh, Ph.D.

Department of Anatomy, Physiology, and Cell Biology (see also: aquatic health, pathology and reproductive biology)

Independent research in the fields of developmental biology, nutrition, pathology, and ecotoxicology. Special emphasis on adverse effects of environmental endocrine disruptors and other contaminants in the embryonic development, growth, and reproduction of invertebrates, fish and shellfish populations. Development of biomarkers of exposure and deleterious effects in aquatic organisms. Development of a screening assay for endocrine disrupting chemicals utilizing microarray technology.

Research will include:

1. The culture of native (salmon, delta smelt, and splittail) and surrogate (Medaka) fish models for use in carcinogens, endocrine disruptors and toxicants testing;
2. Design QA/QC & safety protocols for animal care & exposure experiment. Acute and chronic toxicity testing of contaminants and toxicants using native and non-native fish;
3. The long-term, sublethal growth and reproductive effects of fish exposed to contaminant-laden diets (metals, and organic chemicals including endocrine disruptors and pesticides);
4. Development and use of biochemical, molecular, and histopathologic indicators (biomarkers) of exposure to determine the sublethal deleterious effects of environmental pollutants on fish and aquatic invertebrate populations;
5. Development and the application of toxicogenomics in aquatic toxicology testing;
6. Effects of toxicants on quality and quantity of food chain organisms and resultant consequences on the higher trophic organisms.
7. Integrate growth, biochemical, molecular, histopathologic, and reproductive indicators into an individual and population health effects and extrapolation of population level effects to ecosystem health effects.

Active Projects's

1. Groundwater ambient monitoring and assessment program - Hexavalent chromium and endocrine disrupting chemicals.
2. Using a Sensitive Japanese Medaka (Oryzias Latipes) Fish Model for Endocrine Disruptors Screening.
3. Histopathological examinations of larval and juvenile pelagic fish.
4. Biomass and Toxicity of a Newly Established Bloom of the Cyanobacteria Microcystis Aeruginosa and its Potential Impact on Beneficial Use in the Sacramento-San Joaquin Delta.

Please visit Dr. Teh's website at: http://faculty.vetmed.ucdavis.edu/faculty/sjteh/

Lisa A. Tell, DVM

Department of Medicine and Epidemiology (See also: Food Animal Medicine/Food Safety, Zoo Animals/Wildlife)

Dr. Tell is the Director of the Veterinary Drug Residue Laboratory and serves as the Regional Director for the Minor Use Animal Drug and the Food Animal Avoidance Database Programs. She has been a full-time faculty member of the School of Veterinary Medicine since 1994. Dr. Tell's research interests are veterinary drug pharmacokinetic studies for zoological and food animal species. She has a particular interest in treatment options for fungal diseases in birds.

Research studies in Dr. Tell's laboratory vary from pivotal data studies seeking label claims for minor food animal species (particularly goats) to clinically related pharmacokinetic studies for companion birds. Many of the food animal related studies focus on drug residues and residue avoidance in the interest of protecting public health. Research experience gained from working in Dr. Tell's laboratory varies from the in life phase of the pharmacokinetic study to the good laboratory practice bench-top research activities.

Dr. Tell is also the lead investigator for the UC Davis Hummingbird Health program that investigates diseases in free ranging hummingbirds in California.  This program bands the birds, takes biometric measurements, and evaluates birds for infectious diseases.

PLEASE CONTACT DR. TELL : latell@ucdavis.edu

Laura S. Van Winkle, Ph.D., DABT

VM: Anatomy, Physiology & Cell Biology (See also: Pulmonary Medicine)

My research focus is on toxicology and pulmonary cell biology. I study cellular responses in the lung.. Airways are a key site for many human lung diseases such as asthma, bronchitis, cystic fibrosis and lung cancer. Exposure to toxic air pollutants contributes to development of these diseases in humans and animals. We utilize unique in vivo and in vitro models to study airway epithelial injury and repair in diverse species from mice to monkeys. We have a substantial archive of tissue sections.  My laboratories are located at the Center for Health and the Environment. Projects available include studies of: 1) The effect of inhaled particles on airway toxicology and histopathology in rats 2) Effect of inhaled toxic vapors, such as naphthalene on cytotoxicity in the nose and lung 3) Using nanoparticles to understand ultrafine particle dosimetry.

Students are invited to participate in any of these ongoing projects. Students may also conduct an original project of special interest to be completed during the summer session. Ongoing research is supported by funding from several grants from NIH.

Please visit Dr. Van Winkle's website for more information.

Luke A. Wittenburg, DVM, PhD, DACVCP

VM: Surgery & Radiology (See also: Biochemistry/Cell Biology, Oncology)

Dr. Wittenburg is a veterinary clinical pharmacologist with basic research interests in cancer biology and investigational/developmental therapeutics for treatment of cancer in pets and people.  A better understanding of the biology and response to therapy in veterinary patients with cancer is crucial to translate discoveries in our pet populations to potential therapies in humans with cancer.  Dr. Wittenburg’s current projects involve aspects of clinical pharmacology, (pharmacokinetic/pharmacodynamics studies), in vitro pharmacology (comparative metabolism of chemotherapeutic drugs across species), in silico pharmacology (physiologically based pharmacokinetic modeling of chemotherapeutic agents in animals) and molecular biology studies into the importance of protein-protein interactions with regard to transcription factors in the development and survival of osteosarcoma.  Summer projects might involve the use of inhibitors of transcription factor protein-protein interactions in human and canine osteosarcoma cell lines as molecular probes for identification of potential novel therapeutic targets, investigations into the contribution of increased drug efflux pump expression on the surface of lymphoma cell lines following curative-intent therapy and the role of epigenetics in this process, in vitro metabolism studies using isolated liver microsomes and some commonly used chemotherapeutics in veterinary and human medicine and pharmacokinetic/pharmacodynamic studies in veterinary species. 

Please contact Dr. Wittenburg (lwittenburg@ucdavis.edu) for more information.