Research Laboratories at Penn Vet

Our laboratory investigates X-chromosome Inactivation, and how this epigenetic process contributes to female-biased autoimmunity.

We are investigating how female lymphocytes maintain X-chromosome Inactivation, which is an epigenetic process responsible for equalizing gene expression between sexes.  X-chromosome Inactivation silences one X-chromosome in female cells, and this process is initiated and maintained by the long noncoding RNA Xist.

Lab Mission:

• To investigate the epigenetic regulatory mechanisms of the inactive X chromosome in immune cells that maintain transcriptional silencing of most genes while promoting X-linked gene expression of specific genes
• To determine the genetic and epigenetic contributions responsible for the female bias in autoimmune diseases such as lupus and scleroderma
• To investigate how X-linked gene expression contributes towards sex biased disease outcomes following pathogen infections

The Animal Model Core at Penn Vet New Bolton Center at the intersection of science and the rapid advancements in health care technology is an ecosystem supporting the continuum from discovery to invention to innovation in medical translation. We are invested in understanding the value proposition of emerging technologies under consideration and how they target unmet clinical needs. This process informs animal model development to enhance scientific rigor during in vivo studies in experimental or naturally occurring disease models. Studies can be iterative starting on a small scale leading towards pivotal non-clinical IND/IDE-enabling trials in support of FDA or OUS-FDA submissions.

The Agricultural Systems and Microbial Genomics (ASMG) Laboratory was established to support Dr. Dou and Dr. Pitta in their research endeavors

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

Research at the ASMG lab focuses primarily on the gut microbial composition of ruminants utilizing 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.

The advent of next generation sequencers has greatly enhanced our ability to explore community microbial populations. The ASMG lab has the capabilities to isolate bacteria and methanogens from the gastrointestinal contents of different ruminant species as well as apply multi-omic approaches to better characterize and understand the functional potential of rumen microbiota. The primary areas of focus include deciphering dietary-microbe, microbe-microbe and host-microbe interactions that play essential roles in maintaining health and production while also minimizing negative impacts on the environment. Research efforts at ASMG are to understand the role of microbiota in ruminal methanogenesis and determine the impacts of different inhibitors on enteric methane inhibition, application of precision technologies to advance animal productivity and early life microbial interventions to improve health and welfare, and productivity of dairy cattle. Please research projects for further details.

In addition, The ASMG group collaborates with other researchers and clinicians both within the University of Pennsylvania as well as at other institutions. Research findings are disseminated via publications and are presented at conferences. The ASMG group strives to educate and train next generation students in application of microbial genomics to help address global issues such as Food Insecurity, Climate Change, Sustainable Agricultural Systems, and Mitigation of Antimicrobial Resistance. Opportunities for students from diverse backgrounds, ranging from high school through postdoctoral are available at ASMG laboratory to further their careers in microbial genomics and its applications

We are interested in defining the prognostic and therapeutic role of T cells in hematologic malignancies utilizing a multispecies comparative approach. Our research involves identification and appraisal of novel strategies for T cell-based immunotherapy in clinical trials of canine cancer patients with tumors bearing translational importance for human medicine.
Graduate groups:
https://www.med.upenn.edu/camb/

Interested in Working With Us?

 

We are always seeking highly motivated students and scholars interested in identifying and appraising the novel strategies for T cell-based immunotherapy in clinical trials of canine cancer patients Please contact Dr. Matt Atherton (mattath@upenn.edu) with your background and CV.

We study the biological basis of diseases caused by microbes -- whether it be a parasitic worm, a pathogenic bacterium, or a complex microbial community in the gut. Our group makes up the Center for Host-Microbial Interactions, at Penn Vet, and our research leverages a diverse skill set that cuts across the disciplines of genomics, microbiology and immunology. We engage in collaborative projects that benefit from close interactions with veterinarians and human clinicians alike. Our research embodies the idea of 'One-Health' - that humans, animals and the environment are interconnected, and that we all live in a microbial world. We are located at the The University of Pennsylvania, in The Department of Pathobiology at the School of Veterinary Medicine.

 Our research has involved studies on mammalian germ cells and early embryos. Initially, we 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.

However, 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.

Nitrogen, Phosphorus, and Integrated Management

Nitrogen and phosphorus are essential nutrients for growing plants and animals. Insufficient nutrients diminish yields; excessive applications 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 see relevant projects and publications in 'Research Projects' and 'Publications' tab below.

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

 

Pathogens, Antimicrobial Resistance (AMR), and Livestock Farming 

Livestock animals are important reservoirs of zoonotic pathogens as well as antimicrobial resistant determinants (antibiotic residues, AMR microbes, and AMR 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 pathways to the broader terrestrial and aquatic ecosystems? What intervention may help mitigate relevant risks associated with animal farming concerning food safety and public health? The research of Dr. Dou’s group addresses some of these critical issues.

• Please see relevant projects and publications in 'Research Projects' and 'Publications' tab below.

Food Waste, Food Security, and Sustainability

Sustainable food security is an issue that intersects many of the contemporary challenges the world is struggling to deal with today, e.g. water scarcity, water pollution, resource limitation, land degradation, habitat and biodiversity loss, climate change, and hunger and poverty.  Dr. Dou collaborates with national and international experts to examine sustainable food security issues from multiple dimensions, such as food waste reduction and reuse, engaging, and empowering smallholder farmers, etc. 

• Please see relevant projects and publications in 'Research Projects' and 'Publications' tab below.

Developing Novel Feeds from Food Waste and Crop Residue Biomass from Cows

Livestock farming is at a crossroads, its sustainable future challenged by competing interests for limited resources and urgent need to mitigate environmental and climate footprints, amid a rapidly growing global demand for animal protein. One viable solution overlooked, is to leverage the innate ability of animals as nature’s most effective recyclers, able to utilize a wide variety of plant biomass materials as feed resources in producing meats, milk, and eggs. This project will deploy an innovative sequential fermentation approach to create novel feeds for dairy cows using food waste of fruit and vegetable discards and post-harvest crop residues such as wheat straw and spent mushroom substrates, abundantly available but currently wasted or landfilled. 

• Please see relevant projects and publications in 'Research Projects' and 'Publications' tab below.

Our Mission: The mission of the Equine Pharmacology Laboratory at New Bolton Center is to promote the welfare of the working horse and the integrity of sport through pharmacological and forensic research.

Learn about us and our research...

The Division of Experimental Retinal Therapies (ExpeRTs) is actively engaged in multiple research projects relating to the inheritance of retinal degenerations in dogs, humans, and other mammals. These include efforts to identify the genes and locate the mutations associated with several separately inherited forms of progressive retinal atrophy (PRA), a significant disease of dogs that is also the genetic analog of retinitis pigmentosa, a group of retinal degenerations inherited in human families. In parallel to these studies, the Division of ExpeRTs is involved in developing or applying novel therapeutic approaches for the treatment of inherited retinal degenerations.

At the Harty Laboratory, we focus our research on three main areas:

1. The molecular dynamics and biological significance of virus-host interactions during late stages of RNA virus assembly and egress.
2. The identification and development of host-oriented therapeutics as a new class of antiviral inhibitors.
3. The interplay between the host innate immune response and RNA virus infection.

Our model virus systems to interrogate these topics include:

• Filoviruses (Ebola and Marburg viruses)
• Arenaviruses (Lassa fever and Junín viruses)
• Rhabdoviruses (VSV)
• Retroviruses (HIV-1 and HTLV-1)

The Equine Behavior Program and Laboratory at New Bolton Center has grown from within the Section of Reproductive Studies.  Since the early 1980s the program, has had research as its core activity.  The program has included involvement in related clinical and teaching in the veterinary school and continuing education programs nationally and internationally.  The initial research focus of the laboratory was on stallion reproductive physiology and behavior. 

Early research concentrated on the physiology and pharmacology of libido, erection, and ejaculation, with immediate application to clinical problems in breeding stallions and with relevance to the understanding of human sexual dysfunction. 

Another long-standing research interest of our laboratory has been the effects of experience on sexual function.  In the 1990s our research and clinical work expanded beyond stallions to include reproductive and general behavior problems of horses.

The Behavior Lab is housed in The Havemeyer Barn at The Georgia and Philip Hofmann Center for Animal Reproduction. 

Dr. Christopher Hunter's research team has been working on various aspects of basic parasitology since 1984.

For nearly 25 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.

In the mammalian soma, tissue-specific stem cells capable of maintaining the proliferative output necessary for tissue organization and function exist in a state of 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.  

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 stem 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.

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.

Welcome to the Lennon Mucosal Immunology Laboratory where we study Inflammatory Bowel Disease (IBD).

We believe that by studying naturally occurring IBD in dogs and cats we can improve treatment for people and pets with this debilitating condition. 

• Visit our new lab website...

The Marshak Dairy is named in honor of Robert Marshak, the ninth dean of the School of Veterinary Medicine whose support was instrumental in establishing the farm. Built in 1996, the greenhouse dairy was the first of its kind and was recognized as a dairy of distinction in 1998. The greenhouse design uses natural lighting and excellent ventilation within the barn to promote a healthy environment for the cows.

The Marshak Dairy provides an easily accessible working dairy farm for research trials. In addition, the Dairy serves as a laboratory for teaching students on topics related to cow healthcare, preventive medicine, nutrition and food safety.

Dr. Mason's lab currently focuses on immunotherapy approaches to treat osteosarcoma, hemangiosarcoma, and lymphoma, among other cancers. 

We are interested in the genetic basis of hereditary ocular diseases in animals and people.

By learning from our canine friends affected with the ocular diseases, we strive to to understanding the molecular mechanisms of the equivalent diseases affecting human patients.

Our goal is to develop safe and effective therapies such as AAV gene therapy to prevent or reverse vision-loss in animals and people affected.

Interested in Working With Us?

We are always seeking highly motivated students and scholars interested in investigating the genetics and therapeutics of inherited ocular diseases. Please contact Dr. Keiko Miyadera (kmiya@upenn.edu) with your background and CV.

The “Modz Lab” is interested in the phenomenon of Retrotransposon Reactivation in development and disease. Making up nearly 50% of the human genome, retrotransposons have recently emerged as important features of Normal Biology across all mammalian species. Transposons have rewired regulatory networks and provided raw material for genetic innovation through co-option of innate regulatory sequences and repurposing (domestication) of proteins that were once used to invade our genomes. These events were critical in shaping evolution and are responsible for essential biological breakthroughs like the placenta, VDJ recombination, memory plasticity and much more.

Our work is aimed at understanding the exciting and emerging roles that retrotransposons have throughout development where reactivation is essential and intentional. The genome goes through great lengths to suppress the activity of retrotransposons by evolving epigenetics mechanisms to silence these parasites until the invading elements is defeated and mutated over millions of years. A small handful of these retain regulatory and coding capacity that provide some benefit to the host, but the vast majority of these cases are completely unknown. For brief instances in the early preimplantation embryo (and likely the germline), these surveillance mechanisms are paradoxically relaxed and allow the retrotransposons to reactivate for unknown reasons. My work has shown at least one mechanism is essential for development in the mouse. I have generated Retrotransposon KnockOut (KO) mouse models to study distinct mechanisms that operate in the early embryo and found they control and participate in various essential processes. This is only the tip of the iceberg in terms of what Retrotransposons are capable of. We next apply these findings to study the unintentional retrotransposon reactivations that occur during epigenetic breakdown associated with aging, disease and cancer.

Our lab primarily focuses on how retrotransposons impact preimplantation embryo development and fertility in mice and adopt comparative biology studies using various mammalian species to learn about human health and reproduction. To this end, that lab has two major but linked focuses: Developmental Biology and Genome Editing.

Research Topics:

• Study mammalian preimplantation embryos to understand the biological importance of retrotransposon reactivation.
• Phenotypical analysis and mechanistic understanding of retrotransposon knockout (KO) mouse models. 
• Develop Humanized mouse models to study Human specific retrotransposons.
• Probe embryos, germline and stem cells to understand retrotransposon regulation.
• Explore retrotransposon reactivation consequences outside of the embryo, where epigenetic breakdown occurs, such as aging, disease and cancer.
• Improvements to genome editing technologies (CRISPR-EZ) in mammalian embryos for longer inserts, higher efficiency and lower costs.

Visit www.TheModzLab.org for additional information.

Joint injuries are overwhelmingly common in both human and equine athletes. Chondrocytes, the sole cell type in cartilage, are responsible for producing and maintaining the extra-cellular matrix (ECM), which affords remarkable tensile and compressive strength to the joint surface. Once damaged, cartilage has little to no ability to heal itself. Therefore, post-traumatic osteoarthritis (PTOA) commonly develops following joint trauma, whether sustained during an acute injury or accumulated overtime.

Lab Mission

• To improve cartilage repair using stem cell and gene therapy.
• To limit the long-term effects of joint trauma through gene therapy immunomodulation of the joint.
• To further elucidate the pathogenesis of post-traumatic osteoarthritis (PTOA).

Led by Katrin Hinrichs, DVM, PhD, DACT, the Harry Werner Endowed Professor of Equine Medicine and Chair of the Department of Clinical Studies-New Bolton Center, the Penn Equine Assisted Reproduction Laboratory (PEARL) performs both research and clinical work in equine assisted reproduction. The Laboratory conducts research into equine sperm capacitation (readiness for fertilization), oocyte maturation, intracytoplasmic sperm injection (ICSI), standard in vitro fertilization, and equine embryo development, and is one of the few laboratories in the United States performing clinical ICSI to produce foals from client mares and stallions. Dr. Hinrichs has pioneered research in these areas, producing the first foal from ICSI and embryo culture in North America in 2003, and the first cloned horse foal in North America in 2005. 

Dr. Hinrichs’ research has established methods for equine assisted reproductive techniques that are now used clinically worldwide, including methods for successfully holding and shipping equine oocytes, for performing equine embryo biopsy, which allows genetic diagnosis of embryos before transfer to avoid production of foals with genetic diseases, and methods for successful vitrification (freezing) of expanded equine blastocysts, which allows embryos to be produced from older or valuable mares year-round while still supporting the production of foals that have early birth dates.

The Section of Medical Genetics at the University of Pennsylvania's School of Veterinary Medicine has been in the forefront of reporting and characterizing hereditary diseases in companion animals for more than 40 years, including research to uncover the genetic basis and developing genetic tests for canine and feline diseases.

PennGen is a genetic testing facility operated through the Section of Medical Genetics as a collection of not-for-profit laboratories offering testing for a variety of genetic diseases, metabolic screening for inborn errors of metabolism, hematological, and other diagnostic services. 

Research Interests

Our main research interest is innate immune recognition and elimination of pathogens. Our work focuses on the interaction between mosquitoes and the animal and human pathogens they transmit. As the most species-rich group of animals on the planet occupying a vast array of ecological niches, insects are a fantastic example of the potency of innate defenses.

Rather than passive or willing carriers of pathogenic organism, mosquitoes are actually amazing pathogen killers. Taking mosquito interactions with malaria parasites as an example, the vast majority of the parasites ingested when a mosquito bites a malarious person are attacked and eliminated before they can mount an infection in the mosquito. It is the few parasites that survive (even one is sufficient), that are ultimately responsible for disease transmission. Similar interactions occur between mosquitoes and the other pathogens they transmit, like canine heartworm (Dirofilaria) and arboviruses (Zika, Dengue, Yellow Fever, West Nile, and Chikungunya).

Arthropod vectors such as mosquitoes, sand flies and ticks are responsible for transmission of a large number of animal and human diseases worldwide. Studying these organisms may reveal general insights about innate immune defense mechanisms as well as provide novel avenues for controlling the terrible diseases they spread.

Some of the questions we are addressing:

• What is the basis of pathogen recognition by the mosquito innate immune system and how do some pathogens manage to escape?
• What is the biochemical mechanism leading from innate recognition to pathogen killing?
• How is mosquito complement regulated?
• How does steroid hormone signaling regulate mosquito immunity?

Dr. Puré’s research focuses on the cellular and molecular basis of inflammation and fibrosis and her laboratory has made seminal contributions to our understanding of the roles of stromal cells and extracellular matrix remodeling in tissue fibrosis and in cancer risk, initiation, progression, and metastasis.

Join us in our quest to transform the landscape of chronic disease understanding and treatment. Contact Ellen Puré, PhD if you are interested in being a part of the lab.

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. 

All cells consisting of our body are originated from a single cell called zygote, which is formed by a fusion of a sperm and egg. However, little is known about the origin of eggs and sperms and how they are formed in humans. In Sasaki lab, we employ genetic, stem cell and system biology approaches to uncover the mystery of germ cell development occurring in early human life.

The mission of the Sasaki Laboratory is We will continue to develop robust and innovative research in human reproduction to transform humanity and overcome diseases and death.

Visit our site and learn more about our research and who we are. 

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 infectious 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.

Welcome to the Striepen lab

We study the cell and molecular biology of parasites, and use our findings to develop new treatments. Most of our research is focused on Cryptosporidium and Toxoplasma, two protozoan parasites that threaten small children and those with weakened immune systems.

For the latest updates on our research, please visit https://www.striepenlab.org/.

 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 adaptive 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.

The van Eps Laminitis and Endocrinology Laboratory at New Bolton Center is focused on understanding the key events that drive laminitis under different circumstances in order to develop reliable means of prevention and treatment.  

We take a multidisciplinary approach to the study of laminitis utilizing 

• Advanced imaging and sensor-based techniques to evaluate structure and function of the foot in health and disease 

• Molecular techniques to examine events at a tissue level. 

• Biomechanical testing to study mechanical function both in vivo and ex vivo 

We are also focused on developing and refining tests and novel biomarkers of endocrine dysfunction, the most common cause of laminitis in horses and ponies.

More about the van Eps Lab

Check out the new Vaughan Laboratory Website

Dr. Vaughan’s research is focused on defining and understanding the relevant cell types and molecular mechanisms by which the mammalian lung is able to regenerate after severe injury. He is especially interested in elucidating the means by which epithelial progenitors contribute to repaired airway and alveolar units after various lung insults (influenza, ARDS, fibrosis). His studies suggest that physiological lung function is in fact dictated by progenitor cell fate choices after injury.

Dr. Vaughan and his group have developed a novel orthotopic cell transplantation assay which allows for the direct assessment of engraftment, proliferation, and differentiation potential of these stem cells. Further, he is actively investigating the roles of the Notch, Wnt, and BMP pathways in regulating the differentiation potential and fate of expanded progenitor cells post-injury.

Dr. Vaughan is part of the CAMB (DSRB) graduate group, and is a member of the Penn Institute for Regenerative Medicine (IRM).

• Read a recent interview with Dr. Vaughan by the Institute of Regenerative Medicine at the University of Pennsylvania...

Dr. Vaughan is currently seeking new graduate students to join his laboratory team. He welcomes inquiries for potential rotations from incoming students. Contact Dr. Vaughan directly at andrewva@vet.upenn.edu

Our group focuses on the study of regulation of meiosis, the biology of small non-coding RNAs (piRNAs), epigenetics of transposable elements, and biology of spermatogonial stem cells.

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.

Welcome to the Wolfe Lab, supervised by John H. Wolfe, Professor of Pathology and Medical Genetics in Pediatrics and Director, Walter Flato Goodman Center for Comparative Medical Genetics.

 Description of Research 

Our lab works on transferring disease correcting genes into the central nervous system (CNS) in animal models of human genetic diseases. In these diseases, the CNS is often not rescued by the therapies that help the rest of the body. The lab studies both ex vivo gene transfer into neural stem cells that are then transplanted and in vivo transfer using vectors injected directly into the brain.

Our studies involve comparisons of both the vectors used to introduce the genes into cells and the properties of the genes themselves. Additionally, we examine the ability of different cell types and subregions of the brain to be corrected. We also pursue new methods to follow the corrected cells and the expression of the correcting gene in the live animal using MRI and PET techniques. For a complete understanding of the therapy, we also are working on achieving a better understanding of the mechanism of these diseases in the brain.

Projects

Projects involve the molecular design and engineering of vectors, the understanding of the fate of vector-transferred genes in the brain, the regulation of gene expression from vectors, the biology of neural stem cell, the study of induced pluripotent stem cells (iPS), the use of imaging studies in genetic disease and gene therapy, and the proteomic and genomics analysis of the neurodegenerative brain. For students, projects can be tailored to interests, learning goals, and experience.