(Top row, left to right) Drs. Peter Ernst, Tim Kurt*, Kent Osborn, Christina Sigurdson, Keith Jenné, Tyler Hockman* (Bottom row) Drs. Patricia Gaffney*, Victoria Castillo*, Jennifer Frohlich*, Carla Fernandez Cuadros* *Current residents, graduate students and post-doctoral fellows.
Our primary goal is to provide outstanding training in basic research to highly qualified veterinarians from across the country so they are equipped for careers in biomedical research that impact human and animal health.
Given their specialized training in comparative pathology and comparative medicine, veterinarians have unique skills that enable them to contribute to multidisciplinary teams pursuing biomedical research. The Training Program at UCSD will offer advanced research training to DVM/VMD graduates enrolled fulltime in a formal degree-granting program (i.e. PhD) as well as postdoctoral training to DVM/VMD/PhD graduates.
The graduate degree component of the proposed Training Program is structured within the Biomedical Sciences Graduate Program at UCSD. Eligible candidates will be DVM/VMD graduates who will pursue a didactic curriculum that has been tailored to reflect the years of training they have already completed. The majority of their experience in the program will be conducting original research under the mentorship of highly-qualified faculty.
The cadre of 25 faculty mentors draws from several departments at UCSD and adjacent institutions to provide an outstanding training experience. The research topics are focused on host-microbial interactions and comparative medicine. There is a particular emphasis on mucosal immunology including diseases of the digestive tract, lung and reproductive tract. This focus reflects the expertise of the associated faculty as well as the significance of disease in these tissues for human and veterinary medicine.
Further, the trainees will benefit from the mentorship and role models provided by the faculty associated with the Training Program who are veterinarians themselves. Despite the absence of a veterinary school in San Diego, there are several collaborations with the School of Veterinary Medicine at UC Davis as well as more than 20 veterinarians from UCSD and adjacent institutions who are associated with the Lab Animal Residency Program and the proposed Training Program. These veterinarians contribute to the advanced, post-graduate training environment through mentoring, teaching, organized symposia and rounds in comparative pathology or laboratory animal medicine as well as the Laboratory Animal Medicine Residency.
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Kim E. Barrett, Ph.D.
Dr. Barrett’s interests involve epithelial transport and barrier function in human health and disease and it’s inter- and intracellular regulation. The laboratory has a primary focus on chloride secretory mechanisms in the gastrointestinal tract and the pathogenic mechanisms in diseases of epithelial dysfunction. Regulatory mechanisms for many electrolyte transport processes converge on the EGF receptor with transactivation of this tyrosine kinase recruiting in MAP kinase-dependent signaling. Other studies explore mechanisms of infection-induced diarrhea, with a particular focus on changes in epithelial transport function evoked by invasive bacterial pathogens such as Salmonella spp. Dr. Barrett is the Dean of Graduate studies at UCSD.
Lars Bode, Ph.D.
Dr. Bode’s lab is dedicated to research on Human Milk Oligosaccharides (HMO) and comparative glycobiology that is relevant to the understanding of the differences between human and bovine milk. Their objective is to elucidate how HMO are synthesized in the mother’s mammary gland and how they benefit the breast-fed infant. Several of these projects led to investigations of the epithelial barrier permeability, both in the mother’s mammary gland and in the infant’s intestine as well as the ability of HMO to modify the microbial communities in the intestine. His lab has discovered that HMO prevent necrotizing enterocolitis (NEC), a devastating intestinal disorder that frequently occurs in preterm infants and that is also associated with intestinal epithelial barrier failure.
David Brenner, M.D.
Dr. Brenner investigates the pathogenesis of liver inflammation and fibrosis. He employs a spectrum of cell biologic and physiologic models in human and murine species. For example, primary cultures of hepatic stellate cells are used to examine the regulation of collagen expression. Angiotensin II was identified as a fibrogenic agonist that activates NADPH oxidase to produce reactive oxygen species in the stellate cell. Isolated Kupffer cells are used to demonstrate their primary role in hepatic production of TGFb-1, the most potent fibrogenic cytokine in the liver. Other studies characterize chemokines and their receptors that recruit macrophages to the injured liver and the role of hepatocyte apoptosis in inducing liver inflammation and fibrosis.
David Broide, MD.
Dr. Broide’s laboratory investigates mechanisms of allergic mucosal inflammation. From his background in asthma, he brings expertise in studies of human disease and mouse models of asthma. He has also collaborated in studies using equine chronic obstructive pulmonary disease as a model of COPD exacerbated by inflammation. Dr. Broide has utilized his techniques used to study asthma to understand mechanisms of eosinophilic inflammation and remodeling in eosinophilic esophagitis in mouse models and patients (including children) with the disease.
Jack Bui, M.D., Ph.D.
Dr. Bui’s laboratory studies the molecular basis of tumor rejection by the immune system. His lab uses mouse models to elucidate pathways that activate appropriate anti-tumor immune responses while blocking pro-tumor inflammatory responses. He has expertise in primary models of sarcoma and breast cancer, transplantable syngeneic models of various cancer cell lines, and xenogeneic transplantation models of human cancer cell lines. He is especially interested in mobilizing innate immune cells such as natural killer cells and macrophages to destroy cancer cells. Dr. Bui also studies human immune responses using flow cytometry assays and is the Director of the UCSD Clinical Flow Cytometry Laboratory.
John Chang, M.D., Ph.D.
Dr. Chang investigates the molecular basis of pathogenic adaptive immune responses in inflammatory bowel disease, with a focus on the role of polarity and asymmetric cell division in the differentiation of colitogenic CD4+ T cells. His studies have shown a novel role for an evolutionarily conserved mechanism of asymmetric cell division and the network of polarity proteins that regulates this process, in initiating the dysregulated immune response that leads to inflammatory bowel disease.
Lynette B. Corbeil, D.V.M., Ph.D.
Dr. Corbeil investigates microbial pathogenesis and immunoprophylaxis of mucosal infections in the airway and reproductive tracts.
Sheila E. Crowe, M.D.
Dr. Crowe investigates mechanisms of epithelial cell damage in gastrointestinal inflammation to increase our understanding of inflammatory and malignant disorders of the digestive tract. In particular, she studies oxidative damage to epithelial cells by H. pylori, which has been shown to control the transcription of genes that regulate cell growth, repair and programmed death processes. Dr. Crowe was recruited to the Division of Gastroenterology as part of the major expansion of the Digestive Health Research program at UCSD.
Pieter Dorrestein, Ph.D.
Dr. Dorrestein’s research aims to develop new mass spectrometry based methods to link biological, including disease and health phenotypes to the underlying chemistry and genotypes. In short, he developed tools that translate the chemical language between cells. This research requires the understanding of (microbial) genomics, proteomics, imaging mass spectrometry, genome mining, enzymology, small molecules structure elucidation, bioactivity screening and an understanding of small molecule structure elucidation methods.
Lars Eckmann, M.D.
Dr. Eckmann investigates the cellular and molecular pathogenesis of infections with enteric pathogens and the mechanisms underlying the regulation of intestinal inflammation. His studies employ animal models of intestinal infection and inflammation and apply molecular, microbiological and histological approaches to elucidate the key genes and cellular and molecular mechanisms that govern intestinal host defenses against enteric pathogens and regulate inflammatory responses in the gastrointestinal tract. Current studies define host defense mechanisms against the protozoan pathogen Giardia and the bacterial pathogens Escherichia coli and Salmonella.
Peter Ernst, D.V.M., Ph.D.
Dr. Ernst’s principal research interest is in immune-epithelial cell interactions involved in the microbial pathogenesis of acute and chronic diseases in the stomach and intestine. He has developed programs in comparative immunology to validate models using immune and inflammatory cells isolated from human gastrointestinal tissue. One aspect of the work has identified receptors for gastroenteric pathogens including class II MHC for Helicobacter pylori and Brain Angiogenesis Factor 1 (BAI1) as a pattern recognition receptor that binds LPS. Ongoing studies include an examination of the role of the BAI1/Rac1 pathway in loading autophagomes. The role of these pathways in regulating helper T cell function, particularly through the production of ATP and its metabolism to adenosine and their impact on G protein linked signally through cAMP is being studied.
Pascal Gagneux, Ph.D.
Dr. Gagneux is interested in primate molecular diversity. His lab investigates the evolutionary mechanisms responsible for the generation and maintenance of primate diversity, its potential roles in protecting populations from pathogens as well as potential consequences for reproductive compatibility. He is currently studying cell-surface molecules of sperm cells in closely related primate species. His focus is on glycans, the oligosaccharides attached to glycolipids and glycoproteins of the cell surface. The numerous parallels between the surface molecules of successful pathogens and those found on the surface of mammalian sperm, invite the analogy between internal fertilization and “extremely successful infection”. These interests examine the differences in sperm surface molecules and sexual selection (via sperm competition and cryptic female choice) and whether such differences might contribute to reproductive incompatibility and speciation due to female immune rejection of sperm with incompatible glycoconjugates. Dr. Gagneux has studied the behavioral ecology of wild chimpanzees in the Taï Forest, Ivory Coast, population genetics of West African chimpanzees, and differences in sialic acid biology between humans and great apes with special consideration of their differing pathogen regimes. His great concern is that the current surge in interest for comparative genomics is not being translated into direct support for the conservation of primates in their endangered natural habitats.
Steven Gonias, MD, PhD.
Dr. Gonias’ laboratory explores the function of proteases and their inhibitors as regulators of cell physiology. They are particularly interested in the role of proteases as ligands for cell signaling receptors, including the urokinase receptor (uPAR) and low density lipoprotein receptor-related protein (LRP1). Using transgenic and other mouse model systems, mass spectrometry/proteomics, and high resolution imaging, they examine the role of these molecules in the control of inflammatory cell function and the development of neurological diseases and cancers of the nervous system.
Luca Guidotti, DVM, PhD.
Dr. Guidotti was educated in veterinary medicine before completing his training virology. He has worked for the past 20 years as an immunovirologist studying host responses to hepatitis B virus. In particular, he has studied the role of innate immunity in the activation of CD8+ cytotoxic T cells in protection against infection and its sequelae, including liver cancer.
Michael Karin, Ph.D.
studies signaling and transcriptional pathways and their functions in inflammation and cancer. The laboratory has generated several mouse models, both general and tissue-specific in order to characterize the importance of the inflammatory cascade. Dr. Karin has also produced transgenic mice that express a degradation resistance mutant of NF-kB in various cell types. His group investigates the signaling pathways leading from the TNF and IL-1 receptors to activate various MAP kinases, including JNKs and p38.
Victor Nizet, M.D.
Dr. Nizet is a Pediatric Physician-Scientist, Infectious Diseases Specialist and Chief of the Division of Pediatric Pharmacology & Drug Discovery at UCSD School of Medicine and Skaggs School of Pharmacy & Pharmaceutical Sciences. Dr. Nizet leads a large and productive basic and translational research program focused upon the innate immune system, bacterial pathogenesis and the development of new immune-based infectious disease treatment strategies including novel antibiotics, targeted neutralization of bacterial virulence phenotypes, and pharmacologic augmentation of host phagocyte function.
Mana Parast, M.D., Ph.D.
The focus of Dr. Parast’s research is the molecular mechanisms of trophoblast lineage specification, proliferation and differentiation as related to placental development and disease. She is a pathologist who has worked to develop protocols for optimal banking of human placental tissues and uses these tissues and mouse models to study comparative placental pathobiology and how specific signaling pathways direct placental function and fetal growth and the differentiation of stem cells. Dr. Parast follows a long-standing tradition in comparative placentation at UCSD that was started by Dr. Kurt Benirschke who has been instrumental in developing research programs in Comparative Pathology on campus and created and led the Center for the Reproduction of Endangered Species at the San Diego Zoo as well as their “Frozen Zoo” program which is a repository of cell lines from multiple species.
Sharon Reed, M.D.
Dr. Reed’s laboratory studies protozoal research, particularly with Entamoeba histolytica. A major focus of her work has been on virulence factors of E. histolytica, particularly released cysteine proteinases (CP) as drug targets. She cloned and characterized a unique cysteine proteinase of invasive E. histolytica, EhCP1, as well as the most up-regulated CP in vivo, EhCP4, which could be blocked in vitro and in vivo with specific peptide inhibitors. These findings led to a project developing novel therapeutics for the Class B agents, Entamoeba and Giardia.
Philip J. Richter, D.V.M., Ph.D.
Dr. Richter is the Director of the Lab Animal Medicine residency program and also leads the UCSD Animal Care Program. From 1997-2006 Dr. Richter and his team played a critical role in the development of eight UCSD research facilities comprising over 200,000 square feet. The developed expertise has been sought out by private and outside entities where he has acted in a consultant role. During this past year, three additional facilities have been completed which contain significant in vivo research components where Dr. Richter served as the key technical consultant for design. Dr. Richter and his team continue to serve in the design and development of seven additional facilities, one of which includes a novel and innovative approach to centralized sanitation and processing of in vivo research equipment.
Robert Rickert, Ph.D.
Dr. Rickert’s laboratory focuses on B lymphocyte differentiation in the normal and diseased states. These studies explore the in vivo environments of the primary (bone marrow) and secondary (spleen and lymph node) lymphoid tissues, but also extend to tertiary sites to investigate mechanisms of infection, inflammation, autoimmunity and B cell neoplasia. Conditional gene targeting is applied to assess gene function and establish key signaling networks operating at distinct stages of B cell differentiation. In addition, in vitro cell culture systems, microscopy, flow cytometry and signal transduction approaches are utilized to examine cell-cell interactions and the molecular basis of B cell responses to antigen, cytokines, growth factors and metabolites.
Jesus Rivera-Nieves, M.D.
Dr. Rivera-Nieves works on the pathogenesis of Crohn’s disease. Leukocytes of the granulocytic, monocytic and lymphocytic lineages are active participants in the chronic inflammatory process. Their recruitment from the circulation is regulated by adhesion molecules and chemokine receptors interacting with their respective ligands expressed or presented by intestinal endothelia cells. These adhesive interactions represent attractive therapeutic targets for the modulation of the destructive chronic inflammatory process. Proof of concept for the viability of this strategy has been provided by the efficacy of natalizumab, which interferes with integrin alpha-4-VCAM-1, MAdCAM-1 interactions. Using novel murine models of Crohn’s-like ileitis, Dr. Rivera-Nieves has continued to explore potential molecules that may be targeted, within the leukocyte recruitment cascade.
Christina Sigurdson, D.V.M., Ph.D.
Dr. Sigurdson is a veterinary pathologist and has maintained a focused research program on neurodegenerative diseases. Her group has studied the pathogenesis of prion strains as well as the role of specific amino acid sequences in species barriers to prion infection. The lab studies human, food animal, or wildlife prions as well as systemic amyloid in channel island foxes.
Ajit Varki, M.D.
Dr. Varki’s research interests are focused on a family of sugars called sialic acids and their roles in biology, evolution and disease. Sialic acids are found at the outermost position on the glycan chains of all vertebrate cell surfaces and glycoproteins and the highest levels are found in the nervous system. Currently, active projects are relevant to the roles of sialic acids in microbial infection; the regulation of the immune response; the progression of cancer and unique aspects of human evolution. Dr. Varki is particularly interested in understanding the multiple differences in sialic acid biology between humans and the closest evolutionary cousins, the great apes. These differences are a signature of the events that occurred during the last few million years of human evolution and may be relevant to understanding aspects of the current human condition, both in health and disease.
Nissi Varki, M.D.
Dr. Varki has studied the interpretation and analysis of the histopathology of genetically altered mice in the field of Glycosciences. Being board certified in human anatomic and clinical pathology has provided her with an interesting perspective on comparative pathology as she is able to relate animal models of human disease to human disease processes. Other studies are related to morphological approaches to study mouse models of cancer metastasis. As the director of the histology core and phenotyping services, her laboratory provides a relevant opportunity for research training in advanced interpretation of pathology in animal models of human disease.