Summer Scholars Faculty Mentor Summaries

Dr. Payal Agarwal: Exploration of different immunotherapy modalities in osteosarcoma. Osteosarcoma (OS) is a highly aggressive and metastatic bone malignancy that primarily affects children and young adults. The survival rates for patients with OS have not improved significantly over the past 20 years, especially for those with metastatic disease. Cancer Immunotherapy has shown promise in treating various cancers and is a potential avenue for treating osteosarcoma. Immunotherapy reshapes the tumor microenvironment from immunologically ‘cold’ to immunologically ‘hot.’ In this study, we are exploring immunotherapies, individually, such as oncolytic virus armed with anti-PD1 anti-PDL1 sdAb and CAR T cell therapy against B7-H3 and also in combination to ascertain the advantages over using individual therapies. Anti-B7H3 CAR T cell therapy and anti-PD1 sdAbs will enhance the existing anti-tumor immunity. Oncolytic viruses will trigger immunity against tumor cells in primary as well as secondary sites. We have developed a next-generation canine adenovirus (CAV2-AU-M3) that infects and lyse tumor cells and secretes anti-PD1 sdAbs in cell vicinity. Our next step is to evaluate these oncolytic viruses for induction of cell lysis and functionality of anti-PD-1 sdAbs in vitro, in 2D and 3D canine OS cell cultures, and in vivo, in a murine xenograft model using canine OS cells. We will also assay the immunogenic cell death-inducing effects of CAV2-AU-M3 by assaying cytokine, chemokine, and DAMP (damage-associated molecular patterns) profiles in OS cells in response to oncolytic virotherapy. We will also explore and characterize the CAR T cells against B7-H3 surface antigen. CAR T cells will be assessed for their functionality (cell killing and cytokine secretion) in vitro, in 2D and 3D canine OS cell cultures, and in vivo, in a murine xenograft model of canine OS.

Dr. Benson Akingbemi: Action of xenostrogens in the male gonad and neuroendocrine axis. Our long-term research goal is to understand how developmental exposure to environmental chemicals predispose to adult-onset disease related to male infertility. The increasing incidence of testicular disorders in the population was associated with exposure to chemicals which have the capacity to mimic and/or antagonize hormone action. Of interest, there is increasing public concern that exposures to chemical mixtures may cause unpredictable effects not seen with individual compounds. However, studies on the safety profile of chemicals commonly encountered in the environment are limited. The present study is focused on chemicals which are present in consumer products, including phthalates, bisphenols, 17α-ethinyl estradiol, and soy isoflavones. We hypothesize that exposures to combinations of chemicals intensify disruption of male reproductive function due to their single counterparts. Following exposure of male rats to test chemicals, we will analyze testicular steroid hormone secretion, androgen-stimulated germ cell development, sperm function, and identify mechanisms of chemical disruption of the pituitary-hypothalamus axis.  The results will address whether chemical combinations cause additive effects in reproductive tract tissues, describe gene networks mediating chemical action, and inform development of screening protocols for risk assessment of the population. Students will be involved in executing the experimental protocol, sample analyses, data preparation, and presentation of results at scientific meetings.

Dr. Kristine Griffett: Development of Novel Non-Opioid Compounds for Chronic Pain  This project focuses on the development of characterization of novel, non-opioid compounds targeting the nuclear receptor REV-ERB for analgesia.  The opioid crisis is a substantial concern worldwide, and new efficacious pain therapies are desperately needed to reduce use and abuse of opioids.  We have developed small molecule agonists for the REV-ERB nuclear receptors that appear to have analgesic properties in our preliminary testing.  We believe that the inhibitory effects on inflammation at the site of nerve damage is one path that REV-ERB elicits its analgesic properties.  The goal is to develop novel therapeutics that will be used for veterinary and human medicine, reducing our dependency on opioids, and reducing potential for abuse among patients, clients, and even providers.  Our current model of efficacy testing is in mice, using mechanical and thermal measures to evaluate efficacy of compounds.  This work will focus on evaluating animal tolerance to the compounds, efficacy testing, and evaluation of molecular and histological changes in sensory tissues.  Techniques including QPCR, behavioral analysis, RNA-seq, IF/IHC or others may be utilized for this work.  For more information regarding our work, please check out our website (   

Dr. Erik Hofmeister:  Evidence-based decision making.  My work is aimed at finding answers to clinically relevant questions which practitioners can immediately apply to their clinical practice.  Topics vary considerably, including education, tools for researchers, and anesthesia.  Methods typically include case review, surveys, interviews, and/or direct observation.  There is no laboratory time.  Students will be expected to choose a project from a long list which interests them and follow it from inception to data collection during the summer.  If they continue with the work and write the paper, they will be first-author on a publication for a peer-reviewed journal.  A secondary project will also be chosen.  Students will work in their own time so a high degree of self-direction is essential.

Dr. Katie Horzmann: Developmental toxicity of trichloroethylene metabolites in the zebrafish model. I work with emerging and legacy environmental toxicants and study the effects of developmental exposure to these chemicals using the zebrafish (Danio rerio) biomedical model. One legacy contaminant is trichloroethylene (TCE), an industrial solvent and degreaser that contaminates over half of all Superfund sites, is a known carcinogen, and is linked to other adverse health outcomes including congenital cardiac defects and neurotoxicity. TCE is rapidly metabolized and the metabolites are thought to contribute to the overall toxicity. Our laboratory’s hypothesis is that the metabolites of TCE mediate aspects of developmental TCE toxicity. Student scholars would be able to join in a project investigating the developmental toxicity of TCE metabolites in embryonic and larval zebrafish. In addition to learning zebrafish husbandry and handling skills, scholars would evaluate embryonic mortality and hatching, embryonic behavior, larval behavior, and larval morphology in zebrafish with developmental exposure to TCE metabolites.

Dr. Dana LeVine and Dr. Andrew Leisewitz:  Evaluation of the ability of Babesia rossi to cause Neutrophil Extracellular Trap (NET) formation Babesia species cause a malaria-like disease and are the second most common infectious organisms that infect mammals and they cause severe disease in all mammals of veterinary importance. Babesiosis is also regarded as a significant emerging tick-borne zoonosis and is the most common blood transfusion acquired disease in humans. Disease in dogs is caused by several different parasite species with the most common organisms being B. gibsoni (most common in the USA), B. canis (most common in Europe) and B. rossi (most common in Africa). B. rossi causes the most severe disease of all the Babesia parasites that infect dogs. Disease is characterized by lethargy, anorexia, fever, severe hemolytic anemia, multiple organ dysfunction and failure. The mortality rate (despite intensive treatment) is around 20%. The disease is profoundly inflammatory and a great example of a sepsis-associated ‘cytokine storm’. Outcome is strongly correlated to immature neutrophil (band cell) count.

When activated, neutrophils can extrude neutrophil extracellular traps (NETs), webs of DNA, nucleosomes, histones, and granular proteases.  NETs are designed to trap and kill invading microorganisms but NETs are also very inflammatory and can cause a lot of host tissue damage.  NETs are associated with worse inflammatory disease and outcome in malaria in human patients and murine models.    Given the similarity between Babesia and malaria and the relationship between poor outcome in Babesia and high band neutrophil count, we believe that NET formation also plays a role in Babesia pathogenesis. As such, NETs could be a logical new therapeutic target in severe Babesiosis.  To test our hypothesis, we plan to look at the ability of B. rossi infected red cells and serum from B. rossi infected dogs to induce NET formation in healthy dog neutrophils in an ex vivo (outside the dog) culture system.  Knowing that NETs play a role in Babesia pathogenesis could help improve treatments and outcomes for dogs suffering from this disease.  

Through this project you will learn to culture Babesia, isolate canine neutrophils and stimulate NETosis and will image NETs with immunofluorescence microscopy and live cell imaging. You will also have the opportunity to practice venipuncture skills and you will become an expert on NETs and Babesia.

Dr. Shaan Mooyottu: Precision medicine and precisionbiomics: Comparative gut microbiomics solutions for intestinal and extra-intestinal diseases: Contrary to conventional understanding of enteric diseases, recent studies suggest that a majority of enteric infectious and inflammatory diseases are primarily caused by disruptions in the gut microbiota, a phenomenon known as dysbiosis. Interestingly, we have achieved remarkable results in reversing many of these disease conditions without directly targeting the pathogens responsible, but rather by addressing the underlying dysbiosis, thus avoiding the use of antibiotics and xenobiotics.Our laboratory is dedicated to a comprehensive multi-omics investigation of the gut microbiome across various host species, including pets, livestock, and humans. Through this extensive research, we pinpoint specific gut microbiomic factors that determine host resistance to particular diseases within specific species.  This wealth of knowledge serves as the foundation for our development of precision microbiota-based therapies tailored to treat specific diseases in susceptible species. Our diverse portfolio encompasses conditions such as canine and human inflammatory bowel disease, equine, swine, and human C. difficile colitis, as well as swine post-weaning diarrhea. Our focus extends beyond enteric diseases to encompass hepatic and neurologic conditions that involve the complex interplay between the gut, brain, and gut-liver axis.Our collaborative research group comprises a range of experts, including veterinary pathologists, surgeons, human and animal physicians, microbiologists, genomics, and microbiomics specialists. Our animal experiments encompass experimental infections and surgeries alongside tissue-based anatomic pathology and molecular techniques. Furthermore, our work incorporates advanced anaerobic microbiology techniques to study both pathogenic and commensal gut microbiota that are sensitive to oxygen. In summary, participating in our projects offers budding veterinarians a unique opportunity to gain hands-on experience in developing next-generation antibiotic-free therapeutics.

Dr. Melissa Singletary and Dr. Sarah Krichbaum: The detection canine is the most capable tool for the detection of many hazardous and other targeted substances. The Canine Performance Sciences (CPS) Program conducts research and development to enhance the technology of using dogs for detection of such substances. This effort includes research and development focused on health and welfare management of working dogs throughout all life stages from production to field operations and retirement. CPS summer scholar participants usually perform research that is at aimed toward direct application of working dog performance in a supportive partnership with the department of clinical sciences and services such as theriogenology which provide our summer scholars with an opportunity to become familiar with the production, clinical assessments, and health care of performance/working dogs. Throughout exposure and experience across the program, Summer Scholars at CPS will learn about the development, training, and application of detection dogs in addition to performing a chosen project examining metrics for working dog health, welfare and performance in behavioral/cognitive, physical fitness and olfactory-based tasks.

Dr. Maninder Sandey: Immune checkpoint inhibitors (ICIs) have shown unprecedented clinical activity in a wide range of malignancies. However, their efficacy remains limited in many malignancies due to primary or acquired resistance. Targeted therapies that activate tumor necrosis factor receptor superfamily (TNFRSF) members, like OX40 & 4-1BB, are currently explored to augment the clinical efficacy of ICIs. In this study, we have constructed a novel-nanobody (Nb) based Agonist-Redirected Checkpoint (ARC) platform that consolidates immune checkpoint blockade (ICB) and TNFRSF agonism in a single biologic. Our long-term goal is to utilize this Nb-based ARC platform to develop novel immunotherapeutics to treat canine and human cancer patients. In this project, we will: (Aim 1) assess the safety and pharmacokinetic (PK) profile of aPD1-Fc-OX40L; (Aim 2) conduct a phase II/III clinical trial of aPD1-Fc-OX40L in canine patients with oral melanoma (OM); and (Aim 3) assess the functional activities of aPD1-Fc-OX40L over monotherapies. We will perform clinical correlative studies (using flow cytometry and immunohistochemistry (IHC)) on tumor and peripheral blood samples collected before and after administration of aPD1-Fc-OX40L to understand the cellular and molecular mechanisms that determine the antitumor immune response.

Dr. Scarlett Sumner and Dr. Maria C. Naskou: Characterization of platelet derived products against wound healing Platelet alpha granules contain numerous cytokines and growth factors that can affect tissue regeneration, alleviation of inflammation and influence anabolic processes, while releasing numerous antimicrobial, anti-inflammatory and analgesic factors. Specifically, platelet derived products such as platelet rich plasma and platelet lysate from various species have been shown to aid in wound healing by promoting granulation tissue formation, epithelialization, angiogenesis, and collagen deposition. However, the manufacturing process of such products can affect growth factor and cytokine concentration as well as their antimicrobial properties. The aim of this study is to a) characterize the concentration of growth factors and cytokines related to wound healing from various preparations of platelet derived products and b) assess their anti-microbial properties against bacteria that are commonly present in skin wounds. The completion of this project will allow us to standardize the preparation method of platelet derived products while retaining its antimicrobial properties and evaluate in vivo its role in wound healing and the management of wound related microbial contamination.