Pathology and Virology

Lark L. Coffey, Ph.D.

Davis Arbovirus Research and Training
Center for Vectorborne Diseases
Assistant Professor
Department of Pathology, Microbiology and Immunology

(See also: Microbiology/Parasitology, Vector-Borne Disease Research)

Dr. Coffey  studies the ecology, evolution, and transmission dynamics of mosquito-borne viruses including chikungunya, Zika, West Nile, and St. Louis encephalitis that are significant causes of human disease with no licensed human vaccines or treatments beyond supportive care. The goal of her research is to understand patterns of viral molecular evolution and the viral genetic factors that promote arbovirus emergence and severe disease. Her work focuses on how intrahost viral genetic diversity generated by error-prone viral replication influences infectivity and transmissibility between mosquitoes and people or animals. She and her team also developing cheap and convenient improvements to surveillance in mosquitoes by detecting viral RNA in saliva expectorated by sugar-feeding West Nile virus vectors in California. They are also developing approaches to increase safety of candidate live-attenuated chikungunya virus vaccines by restricting their potential to develop revertant mutations that cause illness in vaccinees. Together with the California National Primate Research Center, the team is developing a non-human primate model of human Zika virus in pregnancy that is being used to define the roles of Zika virus mutations in fetal disease and for pre-clinical testing of therapies and vaccines. 

Please see http://coffeylab.ucdavis.edu for more information.

Laurel J. Gershwin, DVM, PhD

VM: Pathology, Microbiology & Immunology (See also: Immunology, Pulmonary Medicine)

Dr. Gershwin is a veterinary immunologist who studies immunopathogenesis of disease in several species. The laboratory studies bovine respiratory disease, with particular emphasis on Bovine Respiratory Syncytial Virus (BRSV).  Ongoing projects focus on effects of anti-viral compounds and anti-inflammatory drugs on bovine respiratory syncytial virus (BRSV) infection, testing in cattle a new potential BRSV subunit vaccine, and evaluating gene usage during acute and chronic infection. Human and bovine RSV are very similar and cause almost identical disease in their respective hosts. One of our projects has uses a human anti-RSV drug to evaluate its effectiveness in bovine calves.

The Gershwin lab is working with VMTH equine clinicians to evaluate the cellular immune response of grey horses with melanoma that are receiving Merial’s canine melanoma vaccine (off label). This DNA vaccine appears to have great potential and the goal is to document at the cell and molecular level how it works to decrease tumor growth.

STAR projects for summer can involve either of these research areas.

Please visit Dr. Gershwin's website at: http://faculty.vetmed.ucdavis.edu/faculty/ljgershwin/

Smita Iyer, PhD

Department of Pathology, Microbiology, and Immunology

(See also: Infectious Disease/Immunology, Microbiology/Parasitology)

Our lab’s primary research interests center around delineating immunological and molecular mechanisms of CD4 T cell help. Our ultimate goal is to use this information to design an effective HIV vaccine and in parallel understand mechanisms of HIV susceptibility and pathogenesis.

Well-defined projects in the lab in the area of HIV immunology provide motivated students opportunities to contribute to publications while training in biomedical research. Research projects provide opportunities to learn, implement, and analyze data using powerful tools such as flow cytometry in combination with RNA sequencing analysis.

Contact information:

Email: smiyer@ucdavis.edu

Phone: (530) 752-5716 Office
           (530) 754-2688 Lab

Richard Levenson, MD, FCAP

Department of Pathology and Laboratory Medicine (see also: Global Health, Oncology)

BACKGROUND

Richard Levenson, MD, FCAP, is Professor and Vice Chair for Strategic Technologies in the Department of Pathology and Laboratory Medicine, UC Davis. He trained in medicine at University of Michigan and pathology at Washington University, and is Board-certified in Anatomic Pathology. A faculty position at Duke was followed by an appointment at Carnegie Mellon University to explore multispectral imaging approaches for pathology and biology. In 1999, he joined Cambridge Research & Instrumentation (now part of PerkinElmer) to become VP of Research, and helped develop commercially successful multispectral microscopy systems and software for molecular pathology and diagnostics, multispectral and three-dimensional small-animal imaging systems, optical dynamic contrast techniques, and birefringence microscopy. He serves on NIH, NCI and NSF review panels, is section editor for Archives of Pathology, and is on the editorial boards of Laboratory Investigation. Current research includes mass-tagged enabled multiplexed immunohistochemistry, and novel slide-free microscopy.

MUSE MICROSCOPY

How microscopes work in actual clinical pathology has not changed materially in well over a century. Microscopy with Ultraviolet Surface Excitation. MUSE is a novel approach for obtaining high-resolution, diagnostic-quality histological images from unsectioned thick tissue specimens, avoiding the need to perform extensive tissue processing and thin physical sectioning. MUSE is notable for its optical and mechanical simplicity. Micron-deep images of the specimen surface are generated with 280-nm UV excitation provided by off-axis light-emitting diodes (LEDs).  Excitation with such short-wavelength UV light excites a wide range of exogenous dyes, and the resulting visible-band fluorescence images can be captured using ordinary microscopic optics and standard CMOS or CCD cameras. These multicolor fluorescence images have novel contrast but can also be converted to resemble conventional hematoxylin- and eosin-staining. A sample can be prepared for MUSE in around a minute. Extended fields of view can be captured from whole organs with microscopic detail. This non-destructive process leaves the sample intact for subsequent downstream molecular or genetic analysis. In addition, images can include shading and depth cues that reveal surface profiles important in understanding the three-dimensional organization of complex specimens. This inexpensive, rapid, and slide-free, sample-sparing method has potential to replace frozen sections, and may have other applications in both high- and low-resource settings.

EXAMPLES OF POSSIBLE PROJECTS:

1.            Survey a suite of familiar and unfamiliar fluorescent stains to learn what work best for either recapitulating standard hematoxylin-and-eosin stain appearance, or for staining new tissue components that are not easily detected just with H&E, like collagen, elastin, amyloid, PAS, etc.

2.            One of the things we have not yet been quite successful with is getting immunofluorescence to work with MUSE. The problem may be inadequate excitation light power (so we would need different sources), or alternatively, we need brighter labels. There are ways of approaching both these things, but this may be a more difficult project without guarantee of success. Still, it’s very important, and a lot would be learned along the way.

3.            Application to vet path cases would be very relevant, as MUSE can both provide intra-operative guidance, as well as point-of-care histology in veterinarian offices, which could be very helpful in decreasing the need for return visits and accelerating care.

Contact - levenson@ucdavis.edu

Christopher Miller, DVM, PhD

Center for Comparative Medicine

Christopher J. Miller, D.V.M., Ph.D. is a Professor of Pathology, Microbiology and Immunology in the School of Veterinary Medicine and an Adjunct Professor of Medicine in the School of Medicine. Dr Miller is a veterinarian and virologist, a core faculty member of the Center for Comparative Medicine and a Staff Scientist at the California National Primate Research Center. His laboratory utilizes non-human primate models of AIDS, Herpes simplex virus, Zika virus and influenza A virus infection to define the pathogenesis of these viral infections, study the nature of protective antiviral immunity, and test vaccines and immunotherapeutic strategies to prevent infections with these agents.

Please visit Dr. Miller's website at: http://faculty.vetmed.ucdavis.edu/faculty/cjmurphy/

Brian Murphy, DVM, PhD

VM: Pathology, Microbiology & Immunology (see also: orthopedics/biomechanical engineering)

I am an anatomical pathologist with an interest in viral pathogenesis.   My laboratory has a feline model of lentiviral latency and we our examining the mechanisms of viral persistence in the FIV-infected cat model.   We also have projects exploring FIP pathogenesis and a collaboration with Gilead Sciences to identify pharmacologic agents that will block replication of the FIP virus.  I am also interested in retroviral promoter function and how specific promoter sequences relate to viral tropism and pathogenesis. 

Please visit Dr. Murphy's website at: http://faculty.vetmed.ucdavis.edu/faculty/bmurphy/

Sean Owens, DVM

VM: Pathology, Microbiology & Immunology (See also: Transfusion Medicine)

Dr. Owens, DVM, Diplomate ACVP, Assistant Professor, is a veterinary graduate of Colorado State University. Following an internship in small animal medicine and surgery, he completed a fellowship in small animal transfusion medicine at the University of Pennsylvania's Penn Animal Blood Bank. Dr. Owens completed his residency training in clinical pathology at UC Davis in 2004, and worked as a clinical pathologist with IDEXX Reference Laboratories, Inc., for two years prior to returning to UC Davis. His research interests include stem cell cell compatibility issues as they relate to the development of cell-derived therapeutics, veterinary blood banking, and equine transfusion medicine.

Dr. Owens may be reached via email at sdowens@ucdavis.edu

Please visist Dr. Owens's website at http://faculty.vetmed.ucdavis.edu/faculty/sdowens/

Patricia Pesavento, DVM, PhD, dip ACVP

Pathology, Viral Diseases

Vet Med: Pathology, Microbiology & Immunology

The Pesavento laboratory is interested in pathogens that emerge from intensive housing situations such as shelters, or from free ranging wildlife populations. The approach is one of translational research; from examination of the clinical disease and pathology of outbreaks of infectious disease, to molecular and cellular analysis of the causative pathogen/pathogens and their particular virulence.  We extend studies by using cell culture models of primary host target tissues, with the overall aim of the laboratory to form a basic understanding of the pathogen: host relationship. Our laboratory has projects in viral oncogenesis (Raccoon neuroglial tumors) and on emerging viral pathogens (Canine circovirus).

Previous projects accomplished include:
Polarity of Feline Caliciviral invasion of epithelium
Expression of the capsid protein VP1 of Raccoon Polyomavirus
Monoclonal antibodies to the oncogenic Tag protein of the Raccoon polyomavirus

Potential 10 week projects for Summer 2016:
Polyomavirus and brain tumors: identifying proteins that interact with Tag  
Serologic prevalence of exposure to Canine circovirus: a comparison between owned and intensively housed (shelter) dogs

Please visit Dr. Pesavento's website at: http://www.vetmed.ucdavis.edu/pesavento_lab/

Kent E. Pinkerton, Ph.D.

Professor of Anatomy, Physiology and Cell Biology

(see also: cardiology, immunology, pharmacology/toxicology 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.

Christina Sigurdson, DVM, Ph.D., DACVP

Department of Pathology, Microbiology, and Immunology, UC Davis

Department of Pathology, UC San Diego

(See also: Neurology/Neurobiology)

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/

Esteban Soto-Martinez, MSc, DVM, PhD, Dipl. ACVM

VM: Medicine and Epidemiology (See also: Microbiology, Immunology, WIldlife/Zoonoses)

Dr. Esteban Soto is a board certified veterinary microbiologist who has an interest in aquatic animal health. Our laboratory main research interests are to understand the pathogenesis of important infectious diseases of wild and aquatic animals, and to develop strategies to protect animals from these diseases. Members in our laboratory study One Health, Aquatic Animal Disease, and Fish Disease through a combination of microbiological, molecular, and epidemiological methods. Current projects involve studying the ecology, diversity and host-pathogen interaction of Francisella noatunensis, Piscirickettsia salmonis, Veronaea botryosa, Erysipelothrix rhusiopathiae, Flavobacterium spp., Saprolegnia ferax, Koi herpes virus and other fish pathogens; and studying the ecology, diversity and host-pathogen interaction of hypermucoid Klebsiella pneumoniae in marine mammals.

Please email Dr. Soto-Martinez for more information - sotomartinez@ucdavis.edu

Swee Teh, Ph.D.

Department of Anatomy, Physiology, and Cell Biology (see also: aquatic health, pharmacology/toxicology 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/

Nam K. Tran, PhD, MS, FACB

SOM: Department of Pathology and Laboratory Medicine

(See also: Microbiology/Parasitology)

My expertise is in clinical chemistry and point-of-care testing for critical care and emergency settings. This includes the development and implementation of innovative biomedical devices and technologies for improving the quality of patient care. These technologies include molecular pathogen detection methods for early detection of sepsis, novel biomarkers of organ dysfunction (e.g., acute kidney injury, myocardial infarction, etc), and point-of-care devices (i.e., medical testing at or near the site of patient care) for testing in emergency medicine and critically ill populations. Our team works closely with Biomedical Engineering, as well as the Divisions of Burn Surgery, and Trauma/Emergency Surgery from the School of Medicine. We are also heavily involved with clinical trials including a large multicenter randomized controlled study evaluating the impact of quantitative, PCR-based detection of Staphylococcus aureus in burn sepsis patients. Translational studies with the veterinary medicine involve the use of anti-fibrinolytic therapy in severe hemorrhage models (e.g., swine and sheep), and pharmacokinetic/pharmacodynamic (PK/PD) modeling of drugs in both animal and human models of injury.

Contact: nktran@ucdavis.edu

Please visit Dr. Tran's website at: https://www.ucdmc.ucdavis.edu/pathology/our_team/faculty/tranN.html

Nissi Varki, M.D.*

Comparative pathology, mouse models of human disease

Affiliated with UC Veterinary Medical Center – San Diego

Director of Histopathology Resources, Cancer and Mouse Histopathology
Professor of Pathology

(See also: Immunology/Infectious Diseases, Oncology, Cardiology)

Dr. Nissi Varki's research interests include comparative histopathology analysis of genetically altered mice, and models of human diseases including cancer, inflammatory disorders and microbial infections. She is investigating the role of glycosylated molecules in tumor progression and metastasis, including evidence for a human-specific mechanism for diet and antibody-mediated inflammation in human carcinogenesis. Another area of recent exploration is the tissue and species-specific expression of sialic-acid binding lectin receptors known as Siglecs, which play an important role in regulating host innate immune responses and inflammation. Dr. Varki also has a longstanding interest in immunological mechanisms operating at the gastrointestinal mucosal epithelium and their role in chronic colitis and colon cancer development. Dr. Varki serves as Director of the Histopathology Core laboratories Mouse Phenotyping Services at UC San Diego and teaches in the histology and pathology laboratory sessions for medical students, mentors numerous undergraduate students and high school students and serves on the Recruitment and Admissions Committee for the UC San Diego School of Medicine.
Link to Dr. Varki’s current publications
Link to Dr. Varki’s website

*Please contact Peter Ernst pernst@ucsd.edu or Christina Sigurdson csigurdson@ucsd.edu first for more information