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 or visit her faculty profile page.
Melissa D. Bauman, PhD
Department of Psychiatry and Behavioral Sciences, School of Medicine
California National Primate Research Center
UC Davis MIND Institute
(See also: Behavior)
Dr. Bauman is an Associate Professor in the Department of Psychiatry and Behavioral Sciences at UC Davis Health. Her program of research focuses on prenatal risk factors for neurodevelopmental disorders with the goal of understanding how alterations in the maternal-fetal immune environment may increase the risk for autism and schizophrenia. Her laboratory uses preclinical animal models to evaluate potential risk factors and explore novel therapeutic interventions for neurodevelopmental and neuropsychiatric disease. In addition to her research interests, Dr. Bauman is committed to supporting the careers of women in science and medicine and she currently serves as the director of the Women in Medicine and Health Sciences (WIMHS) program at UC Davis Health.
Please email Dr. Bauman for more information at: mdbauman@ucdavis.edu
Eliza Bliss-Moreau, PhD
Department of Psychology, College of Letters and Sciences
California National Primate Research Center
(See also: Behavior/Animal Welfare, Cardiovascular Biology, Immunology/Infectious Disease)
Dr. Bliss-Moreau’s multi-method, multi-level, multi-disciplinary, multi-species research program is focused on understanding the biological mechanisms that generate healthy and unhealthy emotions and social behavior, with the goal of developing new effective treatments and interventions for emotion-related psychopathology and understanding how and why emotions evolved. Her research program adopts a lifespan approach, primarily studying nonhuman primates from infancy through old age – what the Bliss-Moreau Lab refers to as womb-to-tomb affective science. The lab works at levels from cellular neurobiology to the study of social systems (and everything in between). Additionally, the Bliss-Moreau Lab pursues topics related to variation in neural development, both during early development (following viral infection with Zika virus) and in the diseases of old age (namely Alzheimer’s disease).
Dr. Bliss-Moreau can be reached via email at eblissmoreau@ucdavis.edu or visit the lab website for more information.
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 for more information.
Lillian Cruz-Orengo, Ph.D.
VM: Anatomy, Physiology & Cell Biology
(See also: Immunology/Infectious Disease, Pharmacology/Toxicology)
My research focuses at the neuroimmune interactions at the blood-brain barrier (BBB) and its role in the neuropathogenesis of neurodegenerative disorders, like Multiple Sclerosis (MS). MS is the second leading cause of neurologic deficits in young adults and exhibits a high sex-bias affecting three times more women than men. MS is characterized by the pathologic trafficking of autoreactive-leukocytes into the central nervous system (CNS). We are interested in 1) assessing the contribution of IL-20 cytokine family signaling and 2) the role of sexual dimorphisms at the BBB using the murine MS model Experimental Autoimmune Encephalomyelitis (EAE). Likewise, we want to 3) assert if Canine Immune-Mediated Encephalitis (CIME) could be characterized as a natural MS model. CIME etiology is elusive but, but there is evidence to suggest that is due to autoimmunity. Lastly, we are in the developing a model 4) to assess changes in brain microvasculature as a result to pesticide exposure using zebrafish. This model will lead to better understanding of the role that environmental factors may play in of BBB disruption and consequently on neurological and neurodevelopmental disorders.
Keywords:
Autoimmunity, sexual bias/dimorphisms, blood-brain barrier, neuroinflammation/neurodegeneration
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 for more information. Email at ediaz@ucdavis.edu.
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 for more information, or email to pjdickinson@ucdavis.edu.
Carrie Finno, DVM, PhD, Diplomate ACVIM (Large Animal Internal Medicine)
Equine Genetics
(see also: Genetics/Genomics)
Dr. Finno investigates the molecular basis for genetic diseases in the horse and other companion animals. One of the strong translational focuses of Dr. Finno's laboratory is to investigate the role of vitamin E in neurodegeneration using a well-established mouse model and a naturally-occurring model of equine neuroaxonal dystrophy (eNAD) in the horse. The laboratory also focuses on the inherited bases of many genetic diseases in the horse including juvenile idiopathic epilepsy (in conjunction with Dr. Monica Aleman) and occipitoatlantoaxial malformation, among other diseases. Dr. Finno's research is funded by the NIH, Grayson Jockey Club Foundation and the Center for Equine Health at UC Davis. Her laboratory incorporates clinical research in the field with molecular tools in the laboratory. Website: https://www.vetmed.ucdavis.edu/labs/finno-laboratory
Please contact Dr. Finno for more information: cjfinno@ucdavis.edu
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
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: https://leinlab.vetmed.ucdavis.edu/
DaZhi Liu, PhD
Department of Neurology, SOM, UC Davis
Liu’s research leverages cancer elements (oncogene/kinase Src, tumor suppressor miR-122/125b) to develop new drugs for treatment of neurological disorders. Liu and colleagues developed a new concept “aberrant cell cycle diseases” that reveals cancers and neurological disorders share common mechanism of aberrant cell cycle re-entry (http://downloads.hindawi.com/journals/tswj/2012/491737.pdf).
In this concept, oncogenes/kinases (e.g., Src, ERK, CDK, others) promote cell division in cancers, but the same genes drive neuron to re-enter the cell cycle which results in neuronal death in neurological disorders. Liu further enriched this concept with evidence that oncogenes/kinases promote cancer cells crossing from blood into tissue to cause metastasis in cancers, whereas the same genes mediate cell infiltration and blood brain barrier (BBB) disruption in neurological disorders. Therefore, numerous approaches that treat cancers can be repurposed to treat neurological disorders, as these two diseases share common mechanism.
These ideas are strongly supported by the pharmacological data that show oncogene/kinase inhibitors can not only treat cancers, but also treat neurological disorders. For example, several labs in the UCD Cancer Center reported that Src inhibitor PP2 blocks metastasis and kills cancer cells; while Liu and colleagues showed PP2 promotes neuronal survival and improves BBB integrity after stroke an traumatic brain injury (TBI). Based on these concept & ideas, Liu established his research program that consists of four ongoing projects:
Project 1: Inhibiting oncogene/kinase Src for treatment of TBI. This project studies Src mechanism of TBI.
Project 2: Elevating tumor suppressor miR-122/125b for treatment of stroke and TBI. This project explores new generation microRNA drugs to treat neurological disorders, such as stroke and TBI.
Project 3: Developing microRNA drugs for SARS-CoV-2/Covid-19 associated brain injury in collaboration with local UCD animal biosafety level-3 (ABSL-3) facility.
Project 4: Repurposing FDA-approved cancer drugs (kinase inhibitors) to treat neurological disorders.
Student responsibility: Medical students must have experience of animal surgery and are interested in therapeutics for neurological disorders. Students working in the Liu team are expected to commit several hours per week to search literature, learn animal surgery, write a mini-review, and complete project design during the school year. The students should dedicate fixed time for research after year 1 to conduct bench work and write a grant if data and time are sufficient.
Training plan: The interested students are encouraged to participate in Project 4. Open below link for the rationale and examples of this project in a perspective entitled “Repurposing cancer drugs to treat neurological diseases–Src inhibitors as examples” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514862/.
Under Dr. Liu’s instruction, the students working in the Liu team will learn to design and execute a project by: 1) searching literature; 2) selecting a drug from the 62 FDA approved kinase-targeted cancer drugs; 3) picking animal models of an interested neurological disorders, such as TBI, stroke, AD, autism, epilepsy, MS, PD, and others (Note: In the event that the Liu team does not have animal models of a neurological disorder that a student is interested in, the student will be referred to other faculty of interest); 4) testing the therapeutic efficacy of the selected drug using animal models; 5) analyzing data and writing grant.
The long-term goal is to advance experimentally effective cancer drugs to clinical trials for treatment of certain types of neurological disorders in collaboration with physicians, which allows the students to continuously involve this project if they join Medical Schools at the UCD after graduation.
Email: dzliu@ucdavis.edu
Phone: (530) 754-5004
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.
Dr. Pessah can be reached via email at inpessah@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, PhD, 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 for more information.
Christine Toedebusch, DVM, PhD
VM: Veterinary Neurology/Neurosurgery, Surgical and Radiological Sciences
Dr. Toedebusch investigates microglial function in health and disease. While they comprise only ~10% of the brain in most species, they are essential for central nervous system (CNS) homeostasis. Microglia are dynamic cells, with a broad range of effector function. Microglia have been implicated in disease pathogenesis for many CNS diseases, including glioma tumorigenesis. The Toedebusch laboratory is focused on further understanding mechanisms of microglia phenotype determination in glioma models. Our goal is to modulate microglia activity for treatment of glioma in both canine and human patients. The laboratory currently works with the following models: microglial cell lines, mouse models, and canine tissue.
Potential summer projects include: 1) characterization of microglia response to genetic modification 2) isolation of microglia from mouse glioma model 3) further characterization of microglial response in canine glioma. These research projects will provide students with training in molecular techniques such as qRT-PCR, western blot and immunofluorescence microscopy.
Please contact Dr. Toedebusch for more information: cmtoedebusch@ucdavis.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 for more information.
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.