Oncology & Cancer Biology

Alexander Borowsky, MD

Center for Comparative Medicine

Dr. Borowsky is a surgical pathologist with expertise in diagnostic breast pathology. His research is focused on development of a mouse model of prostate cancer, focusing on the molecular pathways that are activated or disrupted in various genetically engineered mice, and correlating these findings with the tumor phenotype. Among genes of interest are tumor suppressor genes such as Nes1, which is down regulated by methylation during early breast and prostate cancer. Conditional targeted knockouts of these genes are being developed in mouse models. These findings are being validated and compared with data derived from human tumors, using microarrays, quantitative RNA and laser capture microscopy.

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

Ching-Hsien (Jean) Chen, PhD

SOM: Nephrology/Internal Medicine (See also: Biochemistry/Cell Biology, Internal Medicine)

Dr. Chen’s research strives to elucidate the molecular mechanisms underlying cancer malignancy and thereby identify useful biomarkers and/or druggable targets. She seeks to develop peptide-based therapeutics to mitigate cancer metastasis and drug resistance by targeting aberrant oncogenic signaling. Research in her laboratory focuses on how the phospholipids such as PIP2 and PIP3 are regulated during the development of malignancies and inflammatory diseases.

Potential summer research projects: 1) examine the feasibility of phospholipid retention strategies for cancer immunotherapy. This project will use genetic manipulations and pharmacological approaches to elucidate mechanisms of tumor immune evasion and develop targeted therapies for increasing the efficacy of immune checkpoint inhibitors; 2) characterize the mechanisms of cancer stemness in order to discover therapeutic targets for combating cancer progression and overcoming drug resistance. This study will help the development of novel treatments that destroy cancer stem-like cells without adversely affecting self-renewal of normal stem cells.

Please visit Dr. Chen's website at: http://www.ucdmc.ucdavis.edu/publish/providerbio/internalmedicine/22056

Xinbin Chen, BVM, PhD

VM: Veterinary Oncology, Surgical and Radiological Sciences; Med: Internal Medicine

The p53 family proteins are transcription factors and consist of p53, p63, and p73. Each member regulates a diverse array of both common and unique target genes. These target genes mediate various activities for the p53 family proteins, including the cell cycle control, apoptosis, differentiation, senescence, DNA repair, normal development and tumor suppression. p53 is a tumor suppressor and found to be mutated or inactivated in greater than 60% of all human cancers. Mutant p53 is not only defective in tumor suppression but also promotes tumor formation. However, p63 and p73 appear to be necessary for the development of various tissues and immune response. To address these diverse activities for the p53 family proteins, we focus on the following areas of research: (1) to identify both common and unique target genes for each p53 family member and their functions in tumor suppression and development; (2) to determine the mechanism by which the p53 family proteins differentially regulate gene expression; (3) to determine the mechanism by which mutant p53 obtains a gain of function in promoting tumor formation; and (4) to determine the mechanism by which the expression and activity for each p53 family protein is regulated.

Potential Projects for STAR Students:

  • The p53 pathway, including p53, p63, p73, Mdm2 and MdmX, in dog osteosarcoma, sarcomas, histocytic sarcomas, and melanoma

  • The p53 pathway in cat sarcomas and other cat tumors

Please visit Dr. Chen's website at: http://faculty.vetmed.ucdavis.edu/faculty/xchen/

Richard Levenson, MD, FCAP

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

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

Paul Luciw, PhD

Center for Comparative Medicine

Dr. Luciw is a molecular virologist who leads an internationally recognized research program that interdigitates with research programs all over campus. His group has expertise in virology, cell biology, and molecular virology. The main emphasis of his research is on molecular mechanisms that regulate replication and pathogenesis of viruses that establish chronic infections. Additionally, knowledge of virus/host relationships is being used to design and test live-attenuated viral vaccines and to develop novel DNA immunization strategies aimed at preventing viral infection. Dr. Luciw's group focuses on lentivirus models for AIDS, including SIV and SIV/HIV chimeras in macaques, and FIV in cats. As director of viral oncology research on campus, he works on herpesviruses in macaques as models for Kaposi's sarcoma. In addition, he is developing novel multiplex detection methods for serodiagnosis of infectious diseases of mice and non-human primates, analysis of cytokines and chemokines in various disease states in animal models and humans, and studies on cell signaling pathways in cell culture models for cancer.

Please visit Dr. Luciw's website at: paluciw@ucdavis.edu

Robert B. Rebhun, DVM, PhD, DACVIM

VM: Veterinary Oncology, Surgical and Radiological Sciences

Dr. Rebhun is a clinical veterinary oncologist with basic research interests in the biology and therapy of cancer metastasis.  The majority of human and veterinary cancer-related deaths result from metastases that are resistant to traditional therapies. Studies aimed at identifying, isolating, and characterizing the specific cells that are capable of forming metastasis may lead to more effective therapies.  Tumor initiating cells (sometimes called cancer stem cells) have been shown to possess high metastatic potential in mouse models of human cancer and stem-cell signaling pathways such as hedgehog/Gli/BMI1 signaling have been recently implicated in metastasis and resistance to traditional cytotoxic therapies.  My lab is primarily focused on studying molecular factors that drive proliferation and metastasis of osteosarcoma, with specific projects aimed at targeting metastatic osteosarcoma cells within the lung microenvironment.  

Please contact Dr. Rebhun (rbrebhun@ucdavis.edu) for more information.

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, Cardiology, Pathology/Virology)

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

Luke A. Wittenburg, DVM, PhD, DACVCP

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

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.

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

Assistant Professor of Anatomic Pathology

(See also: Neurology/Neurobiology)

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.