Neurology - Neurobiology

Monica Aleman

Department of Medicine & Epidemiology; VMTH: Large Animal Clinic (see also: Internal Medicine, Genetics)

Dr. Monica Aleman obtained her veterinary degree at the University UNAM-Mexico. She completed residencies in large animal internal medicine (equine emphasis) and neurology and neurosurgery at UC Davis; and achieved board certification for both specialties by the American College of Veterinary Internal Medicine. She completed a PhD in comparative pathology of neuromuscular diseases at UC Davis. Her research and clinical interest has focused in neurology, neuromuscular and muscle disorders in all species with equine emphasis. Currently, she is a faculty member of the equine internal medicine and neurology services, and Director of the Neuromuscular Disease Laboratory at UC Davis. Dr. Aleman is one of the founding members of the Comparative Neurology Research Group, and is affiliated with the Clinical Neurophysiology Laboratory at UC Davis. Dr. Aleman is author of over 90 peer reviewed medical publications, over 100 proceedings and abstracts, and over 25 book chapters; and is a regular speaker in national and international meetings. Currently, she works in the investigation of neuromuscular disorders in multiple species including humans.

For more information, please contact Dr. Aleman at mraleman@ucdavis.edu.

Marie E. Burns, PhD

College of Biological Sciences (see also: Biochemistry, Immunology, Translational Research)

The first steps in vision begin in the rod and cone photoreceptors of the retina, which transduce photons of light into electrical signals. Our lab examines the biochemical and biophysical properties of signaling in photoreceptors, as well as the consequences of defective signaling on visual performance.  We are also trying to understand why and how photoreceptors die, which is the ultimate leading cause of untreatable blindness in humans. Photoreceptor degeneration, like all neurodegenerative diseases, leads to microglial activation and neuroinflammation. We are trying to understand the regulation of neuroinflammation, its relationship to neovascularization, and its helpful vs harmful consequences for perserving neuronal and synaptic function.  To this end, we are also exploring how resident and infiltrating immune cells and glial cells can be used to manipulate the local micro environments within the nervous system to mitigate tissue damage and promote regenerative repair.

Burns Lab website

College of Biological Sciences Faculty Page

Chao-Yin Chen, PhD

Cardiovascular regulation (see also: Cardiology)

Dept. of Pharmacology

Blood pressure and heart rate are regulated by CNS on a moment-to-moment basis. Depending on the interaction between the genetic and environmental factors, the CNS regulatory output can result in either a normal or a pathological outcome.  My current research focuses on cigarette smoke (both conventional and e-cigarette)- induced changes in central regulation of cardiovascular function. 

Potential summer research projects: 

1.  Secondhand smoke- and vaping-induced cardiovascular consequences and their interaction with high fat diet. 

2.  Sex difference in secondhand smoke- and vaping-induced cardiovascular consequences.

Potential techniques involved: BP/ECG recordings using telemetry, heart rate variability and baroreflex sensitivity analysis, whole-cell patch clamp in brain slices.

Website: http://www.ucdmc.ucdavis.edu/publish/providerbio/pharmacology/faculty/701

Please email Dr. Chen for more information at: cych@ucdavis.edu.

Gino Cortopassi

VM: Dept. of Molecular Biosciences (See also: Biochemistry/Cell Biology)

Mitochondrial disease results from inherited defects in mitochondrial genes or exposure to mitochondrial toxins. We investigate pathomechanism, including mitochondrial defect ->neuroinflamation->neurodegeneration. We screen for protective molecules for mitochondrial disease.  We are interested in canine distemper and its relationship to human multiple sclerosis.

Please visit Dr. Cortopassi's website at: http://cortopassilab.com/

Lillian Cruz-Orengo, Ph.D.

VM: Anatomy, Physiology & Cell Biology

(See also: Immunology/Infectious Disease, Pharmacology/Toxicology)

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 pharmacology/toxicology)

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

Peter Dickinson BVSc, PhD, Diplomate ACVIM

VM: Neurology

Dr Dickinson is a board certified neurologist/neurosurgeon with a 50% clinical appointment at the VMTH. His research focus is on brain tumors and covers 3 basic areas.

1) Molecular characterization of spontaneous small animal brain tumors.
2) Development of novel therapeutic strategies for the treatment of brain tumors.
3) Translation of novel therapies into the veterinary clinic.

Dr Dickinson has a laboratory (Paul & Borghild Petersen Brain Tumor Research Laboratory) in Tupper Hall and collaborates closely with Dr Rick LeCouteur and Dr Robert Higgins.

Projects currently underway include:

  • Characterization of growth factor expression in canine spontaneous gliomas.
  • NF2-gene expression in canine meningiomas.
  • Characterization of 1p19q chromosomal deletions in canine oligodendrogliomas.
  • Adeno-associated viral vector delivery of VEGF-TRAP for the treatment of glioblastoma
  • Convection enhanced delivery (CED) of liposomal CPT-11 for the treatment of canine glioma. (clinical trial)

The laboratory utilizes core molecular biology techniques and has several rodent brain tumor models, including models of canine gliomas that are used to investigate novel therapies.

Please visit Dr. Dickinson's website at: http://faculty.vetmed.ucdavis.edu/faculty/pjdickinson/

Melanie Gareau, Ph.D.

Microbiota-gut-brain axis

VM: Anatomy, Physiology and Cell Biology

(See also: GI/Gastroenterology, Immunology and Behavior)

Dr. Gareau is a physiologist primarily interested in studying the microbiota-gut-brain axis. It is increasingly being recognized that the microbes that live the gastrointestinal tract, collectively referred to as the intestinal microbiota, can contribute to modulating cognition and mood. The research focus of her laboratory is in determining how manipulating the microbiota within the gut, using models of infection with bacterial pathogens or administration of beneficial probiotic bacteria, can change cognitive function, anxiety, and depression-like behaviors in mouse models of disease. Dr. Gareau has a particular interest in how the microbiota-gut-brain axis responds to stimulation with psychological stressors and under conditions of intestinal inflammation, such as in models of inflammatory bowel disease (IBD). Ongoing projects in the laboratory include studying behavior in mouse models of IBD and following pathogenic E. coli infection.

If interested, please contact Dr. Gareau: mgareau@ucdavis.edu

Cecilia Giulivi

VM: Molecular Biosciences (see also: biochemistry and genetics/genomics)

Bioenergetics: changes in intermediary metabolism with diets deficient of essential amino acids. Role of mitochondria dysfunction in Huntington's disease. Fragile X, ataxia and tremor syndrome. Autism Neurodegeneration in Alaskan huskies Type 2 diabetes. Role of mitochondria in different organs during prediabetes and diabetes. Citrullinemia: changes in nitric oxide pathways in cerebellum. Aging and protein nitration, oxidative and nitrative stress pathways.

Research: My laboratory focuses at understanding the mechanisms of mitochondrial dysfunction in a variety of phisiopathologies such as triplet nucleotide diseases (Huntington's disease. Fragile X, ataxia and tremor syndrome), autism, and metabolic diseases (diabetes, essential amino acid deficiency, thiamine deficiency).  We use a variety of techniques ranging from biophysics and biochemistry to molecular biology including in silico modeling.

Please visit Dr. Giulivi's website at: http://faculty.vetmed.ucdavis.edu/faculty/cgiulivi/

Pamela Lein

Neurodevelopment, neuroinflammation, neurodegeneration, neurotoxicology, seizures, asthma

VM: Molecular Biosciences (See also: Pharmacology/Toxicology, 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: Pharmacology/Toxicology)

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.

David Pleasure, MD

Dept. of Neurology and Pediatrics, Director, IPRM

School of Medicine:  Neurology and Pediatrics

I am a clinical neurologist with long-standing interests in glial development, glial diseases, and glial/neuronal relationships.  My research is conducted in The Institute for Pediatric Regenerative Medicine (IPRM), which I founded in 2005, and still direct.  The IPRM occupies 27,000 square feet of laboratory space in Shriners Hospitals for Children Northern California on the UC Davis Biomedical Campus in Sacramento, maintains well-equipped optical imaging and molecular cores, and is in close proximity to a veterinarian-staffed, AALAC-approved UC Davis mouse vivarium.   I have served as the primary mentor for 6 predoctoral fellows and 23 postdoctoral fellows.  The majority of my trainees have chosen academic careers, and, thus, far 11 have attained a tenured position.

Click here for more information about Dr. Pleasure

Please visit the IPRM website http://www.iprmd.org for more details.

Dr. Pleasure's email david.pleasure@ucdmc.ucdavis.edu

Michael Rogawski, MD, Ph.D.

Department of Neurology (see also: Pharmacology-Toxicology)

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/

David J. Segal, Ph.D.


Genome Center, Biochemistry and Molecular Medicine, Pharmacology, and MIND Institute

(See also: Genetics/Genomics, Translational Research, Biochemistry/Cellular Biology)

Research in the Segal Lab revolves around engineering zinc finger, TALE, and CRISPR/Cas nucleases and transcription factors. Almost every disease has a genetic component. Often this information is used only to determine how condemned a person is to develop disease. We would like to use the genetic information to fix the disease. A guiding principle for our work has been to study how nature does what it does, then attempt to use that knowledge to make useful tools to improve public health. We continue to develop new methodologies for genome editing. Our most recent efforts focus on creating epigenomic editing tools that can precisely manipulate epigenetic information at specific loci. Such tools can be used for the long-term control of gene expression for both research and therapeutic applications. Angelman syndrome is a rare neurogenetic disease that is the textbook example of an imprinting disorder. We are using artificial transcription factors to activate the epigenetically silenced gene in in the brains of mice and other animal models. 

Please visit Dr. Segal's website at: http://www.ucdmc.ucdavis.edu/biochem/faculty/segal/index.html

Christina Sigurdson, DVM, Ph.D., DACVP

Department of Pathology, Microbiology, and Immunology, UC Davis

Department of Pathology, UC San Diego

(See also: Pathology/Virology)

Our laboratory investigates the spread of prion diseases. We are focused on understanding the molecular basis for prion transmission between species, for example, human and animal susceptibility to prions of deer and elk, known as chronic wasting disease. To this end, we have identified a  loop region in the prion protein that has a major impact on the cross-species transmission of prions. We also study how the biophysical properties of the prion aggregate enable or prevent prion spread into the brain, leading to fatal neurodegeneration.

A second area of interest is in understanding the molecular basis of a highly prevalent amyloid disease that is occurring in island foxes off the coast of southern California.

We would welcome veterinary students to our laboratory at UC San Diego to participate in projects related to either prion disease or island fox amyloidosis.

Please visit Dr. Sigurdson’s website at:  http://www.sigurdsonlab.ucsd.edu/

James S. Trimmer, Ph.D.

Director, UC Davis/NIH NeuroMab Facility

James S. Trimmer studies how voltage-gated ion channels are modulated in response to physiological and pathophysiological alterations in hippocampal neuronal activity. His primary experimental approach is to manipulate hippocampal neuronal activity, in either animals in vivo, in organotypic slice cultures or in dissociated neuronal cultures, and analyze effects on phosphorylation as a regulator of ion channel expression, localization and function. These studies use time-lapse and confocal imaging, patch-clamp recording, analyses of phosphorylation state employing phospho-specific antibodies and mass spectrometry, immunohistochemistry, and immuno-electron microscopy. Much of our recent work involves the colocalization of ion channels proteins to specific sub cellular domains, a subject that would be greatly enhanced by studies at the ultra structural level. Access to this highly specialized technology is absolutely essential for our future research plans.

Please visit Dr. Trimmer's website at: http://www.ucdmc.ucdavis.edu/search/faculty/trimmer

Kevin D. Woolard, DVM, PhD, Dipl, ACVP

Assistant Professor of Anatomic Pathology

(See also: Oncology/Cancer Biology)

The Woolard Laboratory is primarily focused on comparative biology of human and canine glioma brain tumors. These tumors have an aggressive biologic behavior, with median survival times of around 14 months in people, in spite of surgery, chemo-, and radiotherapy. Much of our efforts are focused on identifying how sub-populations within an individual patient’s tumor communicate with each other to establish a dominant population of tumor cells, as well as how cells re-grow following initial treatment. We are also examining how cellular metabolism in glioma may impact epigenetic dysregulation, with the goal of providing a druggable target to delay tumor progression. Finally, we also routinely isolate canine embryonic neural stem cells, which are used as physiologic comparisons to glioma tumor cells. Additionally, we are using these cells to model Zika virus infection in mammalian neural stem cells.

Please contact Dr. Woolard (kdwoolard@ucdavis.edu) for more information.