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Research Laboratories at Penn Vet


Penn Vet faculty are engaged in ongoing groundbreaking research. Here are examples of faculty laboratories and the projects being investigated, both at our Philadelphia campus and at New Bolton Center.

Faculty Laboratories

Anguera Laboratory

  • Our laboratory investigates epigenetic gene regulation involving long noncoding RNAs. XIST FISH, Anguera Lab, Penn Vet

    We use human pluripotent stem cells as a model system to determine how long noncoding RNAs regulate gene expression required for normal development. 

    We study mechanisms of X-Chromosome Inactivation (XCI), an epigenetic phenomenon responsible for silencing one X-chromosome in females. 

    This chromosome-wide silencing is initiated by the long noncoding RNA XIST.

    Lab Mission:

    • To understand how long noncoding RNAs regulate X-Chromosome Inactivation during early human development
    • To determine the epigenetic regulators of the human long noncoding RNA gene XIST
    • To investigate the function and mechanisms for novel X-linked long noncoding RNAs expressed in human pluripotent stem cells and early germ lineage progenitor cells
    • To identify therapeutic opportunities for correcting X-linked dosage imbalances and diseases using insight from human pluripotent stem cell model system

    Anguera Lab Slide Show
    Read More About The Anguera Laboratory

ASMG Laboratory - Microbial Genomics

  • The Agricultural ASMG Lab, New Bolton CenterSystems and Microbial Genomics Laboratory (ASMG Laboratory) was established to support Dr. Dou and Dr. Pitta in their research endeavors.  

    Dr. Pitta is the ruminant nutrition and microbiologist at the Center for Animal Health and Productivity (CAHP), New Bolton Center, University of Pennsylvania.

    Microbial Genomics

    Research in the Microbial Genomics section of the ASMG lab focuses primarily on the New Bolton Center, ASMG Lab-Microbial Genomicsgut microbial composition of ruminants, utilizing both culture-based and advanced molecular methodologies. The alimentary tract of a ruminant is colonized by millions of microbes living in a symbiotic relationship with the host. Therefore, knowledge of the microbial composition of the entire gut can provide insights into improving the overall health and productivity of the animal.

    Microbiology Component

    The recent advent of next generation sequencers has greatly enhanced the ability to explore community microbial populations. The ASMG lab has the capabilities to perform metagenomic studies including sample preparation, genomic DNA extraction and generating 16S amplicon libraries for sequencing on next generation platforms. The sequenced data is analyzed at the ASMG laboratory utilizing the appropriate bioinformatics tools for data interpretation. The lab is in the process of streamlining the protocols for generating 18S libraries for protozoa and fungal communities.

    Read More About The ASMG Laboratory - Microbial Genomics

Avadhani Laboratory

  • The research in Dr. Avadhani's laboratory is focused on the following aspects of mitochondrial genetics and regulation of mitochondrial membrane biogenesis in mammalian cells:

    1. Mechanisms of dual targeting of cytochrome P450 and related proteins to ER and mitochondria and mechanisms of activation of the chimeric N-terminal signal by cAMP and other physiological factors. 

    2. Characterization of a novel mitochondria-to-nucleus stress signaling in cells subjected to mitochondrial specific genetic, and or, metabolic stress, which operates through altered [Ca2+]c, and the role of mitochondrial stress signaling in tumor progression and metastasis.

    3. Regulation of cytochrome oxidase gene expression, and modulation of enzyme assembly/activity under chemical and oxidative stress conditions. 

    4. Role of mitochondrial stress signaling in Embryonic Stem Cell function/differentiation, and mammalian mitochondrial transcription under chemical and oxidative stress in ES cells.
    Read More About The Avadhani Laboratory

Bale Laboratory

  • Our research focuses on developing mouse models of stress sensitivity related to neurodevelopmental and neuropsychiatric disease. We utilize genetic and prenatal manipulations to elucidate mechanisms contributing to disease predisposition.

    We have focused on utilizing approaches that range from fetal antecedents in programming of long-term disease risk to genetic targeting of cell type specific knockout mice.

    We have focused on developing models of disease including affective disorders and obesity utilizing approaches that range from fetal antecedents, involved in programming of long-term disease risk, to genetic targeting of cell type specific knockouts.

    We have initiated multiple lines of investigation that will provide insight into the timing and sex specificity of early life events promoting disease susceptibility, the maturation of central pathways during key periods of development, and the epigenetic mechanisms involved in long-term effects following stress exposure.

     

    Read More About The Bale Laboratory

Brinster Laboratory of Reproductive Physiology

  •  Our research has involved studies on mammalian germ cells and early embryos. Initially, Ralph Brinster on transgenesiswe developed a culture system and manipulation techniques for mouse eggs that are the foundation for subsequent mammalian egg and embryo experiments in the field, including nuclear transfer and in vitro fertilization of human eggs.

    We then used these methods to show that mouse blastocysts can be colonized by foreign stem cells and result in chimeric adults, which led to the development of embryonic stem cells. Subsequently, we used these culture and manipulation techniques to develop transgenic mice. In recent years, our research has focused on male germline stem cells, and these studies demonstrated that spermatogonial stem cells (SSCs) from a fertile male mouse can be transplanted to the testes of an infertile male where they will colonize the seminiferous tubules and generate donor cell-derived spermatozoa, thereby restoring fertility.

    In addition, SSCs of mice and other rodents can be cultured in vitro and their number increased, and the SSCs can be frozen and preserved for long periods. The ability to culture, transplant and cryopreserve SSCs makes the germline of individual males immortal. The transplantation and freezing methods are readily transferrable to the SSCs of all mammalian species.

    Ralph Brinster in ScienceHowever, a culture system for SSCs of nonrodent species has proven to be difficult to develop, and published reports of success have not been independently confirmed and are not universally accepted. Therefore, in recent studies we have attempted to develop a reliable system to culture human SSCs, which is essential to preserve and expand for later use the SSCs of prepubertal boys who will receive germ cell destroying treatment for cancer.

    As part of these studies, we are establishing the genes and regulating mechanism used by mouse and human SSCs to survive and replicate, which will contribute to the understanding necessary for human SSC culture and expansion. In the long term, a culture system will also allow the development of techniques to support SSC differentiation in vitro with production of spermatozoa capable of fertilizing eggs.

    In addition, the SSC assay system provides a powerful technique in which to test the conversion of somatic cells to functional SSCs. Over the past 10 years, we and others have identified transcription factors and micro RNAs that play key roles in SSC self-renewal. In current research, we plan to use this information to reprogram somatic cells into germ cells, specifically SSCs. The transplantation assay provides an unequivocal conformation of this reprogramming for a single cell.

    Moreover, it allows for the identification of gene activation during the differentiation process in vivo and production of progeny from sperm produced from reprogrammed cells. In the future, the approach could be used to address fertility problems in humans and possibly the correction of genetic defects.

    This research is supported by grants from National Institutes of Child Health and Human Development and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.

    Read More About The Brinster Laboratory of Reproductive Physiology

Comparative Orthopedic Research Laboratory

  • CORL surgery, Penn Vet

    The Comparative Orthopedic Research Laboratory at the University of Pennsylvania School of Veterinary Medicine (Penn Vet CORL) is focused on clinical and non-clinical translational services.

    The Translational Services Program partners with pharmaceutical and medical-device companies, government agencies, and academic institutions to meet a broad range of R&D needs.

    Penn Vet CORL has over ten years experience in the successful translation of novel therapeutic interventions from design and development to regulatory submission. The laboratory supports both GLP and VICH-GL9 compliant studies.

    Please contact us for more information or to schedule a consultation.


    Read More About The Comparative Orthopedic Research Laboratory

Dou Laboratory

  • Integrated System Approach for Nutrient Management

    Nitrogen and phosphorus are essential nutrients for growing plants and animals. Insufficient nutrients diminish yields; excessive nutrients translate to wasted resources and environmental pollution. The work of Dr. Dou’s group features an integrated system nutrient management approach, coupling nutrient optimization in animal feeding with manure management and targeted nutrient application to crops for enhanced production efficiency and reduced environmental footprint.

    • Please review relevant publications in 'Publications' tab below.

    Integrated whole farm management based on nutrients (pathogen) flow pathway

     

    Whole Farm Management 

    Pathogens, Antimicrobials, and the Environmental Fate

    Food animals are important reservoirs of zoonotic pathogens as well as antimicrobial resistant genes.  What happens to these “microbial pollutants” in the post-shed environment? How long do they survive under different management conditions? What is their distribution pattern in the intrinsically linked farming sectors and the dissemination pathway? The research of Dr. Dou’s group addresses some of these critical issues.

    • Please review relevant publications in 'Publications' tab below.

    Food Security and Sustainability

    Global food security and sustainability is an issue that intersects nearly all of the contemporary challenges the world is struggling to deal with today, e.g. water shortage, energy crisis, resource inefficiency, biodiversity decline, inequality and hunger and poverty.  Dr. Dou collaborates with national and international experts to examine this topic from different perspectives.

    • Please review relevant publications in 'Publications' tab below.

    Latest News

    The Last Food Mile Conference is being held at the University of Pennsylvania on December 8-9, 2014:

    This conference will bring together experts from national and international, academic and industrial, public and private sectors, to discuss:

    • Where food losses occur along the food supply chain, why, and how much
    • What food waste reduction measures work effectively, lessons learned and barriers encountered
    • What policies and interventions are critically needed for moving forward

    Read More About The Dou Laboratory

Equine Pharmacology Laboratory

  • Equine Pharmacology at New Bolton CenterIn 2006, Dr. Lawrence R. Soma, VMD, and professor of Large Animal Medicine at New Bolton Center, and Dr. Cornelius E. Uboh, director of the Pennsylvania Equine Toxicology and Research Laboratory (PETRL) in West Chester, PA, and their respective teams at Penn Vet and PETRL became the first research group in the world to develop and establish a method for confirming blood-doping agents in racehorse serum.

    Previously only the antibodies caused by the drug, not the drug itself, were detectable in the blood. Used in human and small animal veterinary medicine to treat conditions that produce anemia such as cancer and renal disease, erythropoetin (EPO) is a natural hormone protein produced in the kidneys that stimulates red blood cell production. Recombinant human eythropoietin (rhEPO) and darbepoetin-alfa (DPO) are genetically engineered versions of EPO.

    Read More About The Equine Pharmacology Laboratory

Hunter Laboratory

  • Dr. Christopher Hunter's research team has been working on various aspects of basic parasitology since 198Hunter Laboratory, Penn Vet4.

    For the past 16 years, Dr. Hunter's team has focused on understanding how the immune response to Toxoplasma gondii is regulated to allow the development of protective immunity as well as to limit T cell mediated pathology in multiple sites including the gut and brain.

    Read More About The Hunter Laboratory

Laminitis Laboratory at New Bolton Center

  • Laminitis is a common and debilitating disease that affects the folded and interdigitating tissues, called the lamellae, which connect the hoof wall to the underlying tissues of the horse’s foot. The lamellae normally allow the transfer of the horse's weight from the skeletal elements of the digit to the hoof wall.

    Dr. Galantino-Homer founded the Laminitis Laboratory at New Bolton Center  in 2008. The Laminitis Laboratory was formed in part due to the tragic loss of the 2006 Kentucky Derby winner, Barbaro, to laminitis in January, 2007.

    Our goal is to better understand laminitis pathogenesis in order to improve the prevention, diagnosis, and treatment of this disease.

    Our studies include the investigation of laminitis pathogenesis using protein biochemistry and histopathological analysis, characterization of the epidermal stem cell population in the lamellae, identification of diagnostic serum biomarkers for laminitis, and establishing an in vitro culture system for equine hoof epidermal cells to minimize the use of live horses for laminitis research.

    The Laminitis Laboratory is home to the Laminitis Discovery Database, an archive of pathology images, histology slides, and frozen lamellar tissue and serum from naturally occurring cases of laminitis and unaffected control horses. These materials are being used for several published and ongoing multi-institutional collaborative studies.

    Read More About The Laminitis Laboratory at New Bolton Center

Lengner Laboratory

  • Our lab is broadly interested in the mechanisms by which stem cells acquire and maintain developmental potency. We are also exploring how deregulation of these mechanisms can contribute to oncogenic transformation, tumorigenesis, and tissue regeneration in response to injury, while looking forward to learn how we might manipulate these mechanisms for application in disease modeling and regenerative medicine.
     
    In the mammalian soma, tissue-specific stem cells capable of maintaining the proliferative output necessary for tissue organization and function exist in a state Lengner image 6 copyof multipotency (the ability to generate any cell type of that particular tissue, in contrast to the pluripotent state embodied by embryonic stem cells capable of generating all cell types of the mammalian organism). In highly proliferative tissues such as the epithelial lining of the intestine, data from our lab and others has begun to establish a model in the stem cell compartment is organized into a hierarchy, with a mostly dormant population of long-live, radio-resistant reserve stem cells at the top of this hierarchy. When activated, these reserve stem cells give rise to a second, highly proliferative, radiosensitive short-term stem cell that bears the daily proliferative burden required to maintain tissue homeostasis.  
     
    Our lab is focused on understanding the relationship between these two stem cell populations, the molecular determinants of reserve intestinal stem cell activation, and how deregulation of the reserve intestinal stem cell compartment contributes to disease states such as colorectal cancer or acute gastrointestinal radiation injury.
     
    We have recently identified the Msi family of RNA binding proteins as potent oncoproteins in both hematopoietic and intestinal malignancies. Msi proteins are expressed in putative somatic Lengner image 8 copystem cell compartments, are frequently found to be overexpressed in advanced cancers, and are known to govern asymmetric cell division in Drosophila melanogaster (a process thought to maintain the somatic stem cell niche in mammals). Using mouse genetic approaches integrated with human patient data, we have recently demonstrated that MSI2 acts as an intestinal oncogene, driving activation of the mTORC1 complex and uncontrolled stem cell expansion. We are currently pursuing the role of Msi proteins in epithelial stem cell compartments using tissue-specific gene ablation and drug-inducible gene activation. The effects of Msi proteins on stem cell maintenance and oncogenic transformation are being tied to their RNA binding capacity using CLIP-Seq analysis (immunoprecipitation of Msi-interacting RNAs followed by massively parallel sequencing) in order to determine how specific Msi-RNA interactions affect stem cell self-renewal and oncogenic transformation.
     
    While murine genetic systems are the primary tool of the laboratory, we also work to model human genetic gastrointestinal disorders using induced pluripotent stem (iPS) cells generated from patients. Generation of isogenic diseased and disease-allele corrected iPS cell lines using nuclease-mediated homologous recombination followed by directed differentiation into intestinal tissue provides a controlled platform not only for studying the molecular mechanisms underlying  

    Photos above: Label retaining cells of the intestinal crypts are identified by loading all cells with a Histone H2B protein fused to a green fluorescent protein (left). Several weeks later, only cells that do not divide retain the fluorescent label in their chromatin.

    A glimpse of the rare reserve intestinal stem cell (red).   This cell is capable of regenerating the entire intestinal lining after injury such as exposure to high doses of radiation.
    Read More About The Lengner Laboratory

Lopez Laboratory

  • Virus-Host Interactions and Innate Immunity

    Our body, as well as that of all other animals, is equipped with a complex defense system that protects us from microbes that cause disease. Our laboratory studies the signals that turn on and regulate this defense system –the immune system- when we are infected with common viruses, such as the influenza virus or the respiratory syncytial virus. These viruses can cause or exacerbate chronic lung diseases, such as asthma, and can be fatal in some patients. 

    The immune response that prevents the virus from growing to dangerous levels and causing disease can be very damaging to our own body if turned on in the absence of real threat from disease-causing microbes; thus, the immune response it is tightly regulated and is only active upon recognition of specific signals from the invading pathogens by specialized cellular proteins. 

    By identifying the viral and cellular molecules involved in initiating the immune response during infection and by elucidating how our body protects itself from the ammunitions of the immune system, we hope to contribute to the development of better antiviral treatments and vaccines to protect humans and other animals from these infections.

    Read More About The Lopez Laboratory

Mason Laboratory

  • Cancer cells, Mason Lab research, Penn VetInvestigating canine cancer, Dr. Nicola Mason and her team of researchers at Penn Vet's Mason Laboratory focus on developing novel approaches to generate functional, tumor-specific cytotoxic T lymphocytes.

    One approach involves active immunization using whole tumor RNA loaded CD40 activated B cells, aimed at activating tumor specific T cells in vivo.

    A second approach involves the passive adoptive transfer of genetically modified autologous T cells that are capable of MHC-independent tumor antigen recognition and activaton/effector function in the absence of co-stimulatory ligands.

    Read More About The Mason Laboratory

Reference Andrology Laboratory

  • The Reference Andrology Laboratory provides complete testing of neat, cooled and frozen-thawed semen from mammalian and avian species. The primary purpose of these services is to aid practitioners in their differential diagnosis of individual/herd/flock reproductive problems.

    These services are also frequently used by practitioners and studs as a third-party quality control component in an ongoing stud auditing process.

    The laboratory strives to perform objective, validated techniques for assessing samples for the basic spermiogram parameters of sample volume, motility, morphology, and concentration. With advanced notification, we will also try to accommodate requests for supplemental assessment techniques on sperm subcellular structures. We also offer semen extender analysis and microbiological testing of the extended semen product and purified water used in extenders.
    Read More About The Reference Andrology Laboratory

Scott Laboratory

  • Dr. Scott's current research is focused on understanding the development, regulation and maintenance of CD4+ and CD8+ T cells in order to design new vaccines and immunotherapies for infectioleishmaniaus diseases.

    The laboratory primarily focuses on experimental murine infections with the protozoan parasite, Leishmania, which provides a well-characterized model of T helper cell differentiation.

    Read More About The Scott Laboratory

Sunyer Laboratory

  • Sunyer nature fig 1 The studies of Dr. Sunyer's lab focus on basic and applied aspects of the fish immune system. Moreover, as teleost fish represent the most ancient living bony species with an immunoglobulin-based adaptive immune system, we use these species to study key aspects of the evolution of sunyer JLB fig 2adaptive immunity. Our main animal model is Rainbow trout.  While earlier work focused on investigating the structure, function and evolution of fish complement  (see below refs# 1-7), during the last 7 years our studies have mainly focused on B cells and mucosal immunity aspects of teleost fish.

    Read More About The Sunyer Laboratory

Vite Laboratory

  • The focus of the Vite lab is to improve the characterization and treatment of neurological Niemann-Pick Disease, Penn Vet, Vite Laboratorydiseases by studying naturally-occurring feline and canine models of human diseases.

    Our lab develops and identifies ante-mortem biochemical and nuclear magnetic resonance markers of disease severity and progression and uses these markers to evaluate the efficacy of gene therapy, cell-based therapy, and pharmacotherapy to treat disease. 

    Read More About The Vite Laboratory

Volk Laboratory

  • In the postnatal organism, adult stem cells provide a source of new cells for the routine Penn Vet, Volk Laboratory, migrating keratinocytesmaintenance or repair, in response to injury, of tissues or organs.  These stem cells hold particular promise in the field of tissue engineering to replace tissue or improve organ function damaged by congenital defects, age, disease or trauma.  

    Read More About The Volk Laboratory

Wang Laboratory

  • Our group focuses on the study of regulation of meiosis and the biology of small non-coding RNAs - piRNAs in mice and humans.

    Meiosis, a cell division unique to germ cells, allows the reciprocal exchange of genetic material between paternal and maternal genomes. Meiosis generates the genetic diversity necessary for evolution of species.

    Abnormality in meiosis is a leading cause of birth defects and infertility. Our research interests include molecular genetics of chromosomal synapsis, DNA double-strand break repair, homologous recombination, genetic causes of male infertility in humans, piRNA biogenesis, and epigenetic silencing of transposable elements.

    We have performed two genome-wide screens to identify novel factors that regulate germ cell development in mice: a genomics screen has identified 36 germ cell-specific genes; a proteomics screen has uncovered more than 50 meiotic chromatin-associated proteins.

    Functional characterization of a number of new genes in our laboratory has uncovered novel regulatory mechanisms underlying key biological processes unique to germ cells. On one hand, our studies provide molecular insights into the development of germ cells in mice. On the other hand, these mouse studies have important implications for understanding the genetic causes of male infertility in humans.

    We employ a battery of the state-of-the-art technologies in our research: gene targeting, genome editing, genomics, proteomics, cell biological and molecular biological approaches.

    Read More About The Wang Laboratory