Academic Appointments


Administrative Appointments


  • Director, Comparative Medicine Necropsy Service (2018 - Present)

Honors & Awards


  • Department of Comparative Medicine Distinguished Clinician Award, Stanford University School of Medicine (2018)
  • Dr. Donald R. Cordy Prize in Veterinary Anatomic Pathology, University of California, Davis (2016)
  • Gerald V. Ling Award - Outstanding Small Animal Research Study and Presentation, University of California, Davis (2016)
  • Henry L. Foster DVM Scholar, Tufts Cummings School of Veterinary Medicine (2012-2013)
  • Norman J. MacLeod Endowed Scholar, Tufts Cummings School of Veterinary Medicine (2012)

Boards, Advisory Committees, Professional Organizations


  • Member, Geropathology Research Network (2017 - Present)
  • Member, Digital Pathology Association (2017 - Present)
  • Member, American College of Veterinary Pathologists (2016 - Present)

Professional Education


  • Fellow, Stanford University School of Medicine, Post-Doctoral Research Fellowship (2018)
  • Diplomate, American College of Veterinary Pathologists (ACVP), Anatomic Pathology (2016)
  • Resident, University of California - Davis, Anatomic Pathology (2016)
  • DVM, Tufts University, Veterinary Medicine (2013)
  • BA, Connecticut College, Behavioral Neuroscience (2007)

2018-19 Courses


Graduate and Fellowship Programs


All Publications


  • Investigating circulating tumor cells and distant metastases in patient-derived orthotopic xenograft models of triple-negative breast cancer. Breast cancer research : BCR Ramani, V. C., Lemaire, C. A., Triboulet, M., Casey, K. M., Heirich, K., Renier, C., Vilches-Moure, J. G., Gupta, R., Razmara, A. M., Zhang, H., Sledge, G. W., Sollier, E., Jeffrey, S. S. 2019; 21 (1): 98

    Abstract

    BACKGROUND: Circulating tumor cells (CTCs) represent a temporal "snapshot" of a patient's cancer and changes that occur during disease evolution. There is an extensive literature studying CTCs in breast cancer patients, and particularly in those with metastatic disease. In parallel, there is an increasing use of patient-derived models in preclinical investigations of human cancers. Yet studies are still limited demonstrating CTC shedding and metastasis formation in patient-derived models of breast cancer.METHODS: We used seven patient-derived orthotopic xenograft (PDOX) models generated from triple-negative breast cancer (TNBC) patients to study CTCs and distant metastases. Tumor fragments from PDOX tissue from each of the seven models were implanted into 57 NOD scid gamma (NSG) mice, and tumor growth and volume were monitored. Human CTC capture from mouse blood was first optimized on the marker-agnostic Vortex CTC isolation platform, and whole blood was processed from 37 PDOX tumor-bearing mice.RESULTS: Staining and imaging revealed the presence of CTCs in 32/37 (86%). The total number of CTCs varied between different PDOX tumor models and between individual mice bearing the same PDOX tumors. CTCs were heterogeneous and showed cytokeratin (CK) positive, vimentin (VIM) positive, and mixed CK/VIM phenotypes. Metastases were detected in the lung (20/57, 35%), liver (7/57, 12%), and brain (1/57, less than 2%). The seven different PDOX tumor models displayed varying degrees of metastatic potential, including one TNBC PDOX tumor model that failed to generate any detectable metastases (0/8 mice) despite having CTCs present in the blood of 5/5 tested, suggesting that CTCs from this particular PDOX tumor model may typify metastatic inefficiency.CONCLUSION: PDOX tumor models that shed CTCs and develop distant metastases represent an important tool for investigating TNBC.

    View details for DOI 10.1186/s13058-019-1182-4

    View details for PubMedID 31462307

  • Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses GENOME RESEARCH Benayoun, B. A., Pollina, E. A., Singh, P., Mahmoudi, S., Harel, I., Casey, K. M., Dulken, B. W., Kundaje, A., Brunet, A. 2019; 29 (4): 697–709
  • Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Napier, B. A., Andres-Terre, M., Massis, L. M., Hryckowian, A. J., Higginbottom, S. K., Cumnock, K., Casey, K. M., Haileselassie, B., Lugo, K. A., Schneider, D. S., Sonnenburg, J. L., Monack, D. M. 2019; 116 (9): 3688–94
  • Validation of a geropathology grading system for aging mouse studies. GeroScience Snyder, J. M., Snider, T. A., Ciol, M. A., Wilkinson, J. E., Imai, D. M., Casey, K. M., Vilches-Moure, J. G., Pettan-Brewer, C., Pillai, S. P., Carrasco, S. E., Salimi, S., Ladiges, W. 2019

    Abstract

    An understanding of early-onset mechanisms underlying age-related changes can be obtained by evaluating changes that precede frailty and end of life using histological characterization of age-related lesions. Histopathology-based information as a component of aging studies in mice can complement and add context to molecular, cellular, and physiologic data, but there is a lack of information regarding scoring criteria and lesion grading guidelines. This report describes the validation of a grading system, designated as the geropathology grading platform (GGP), which generated a composite lesion score (CLS) for comparison of histological lesion scores in tissues from aging mice. To assess reproducibility of the scoring system, multiple veterinary pathologists independently scored the same slides from the heart, lung, liver, and kidney from two different strains (C57BL/6 and CB6F1) of male mice at 8, 16, 24, and 32 months of age. There was moderate to high agreement between pathologists, particularly when agreement within a 1-point range was considered. CLS for all organs was significantly higher in older versus younger mice, suggesting that the GGP was reliable for detecting age-related pathology in mice. The overall results suggest that the GGP guidelines reliably distinguish between younger and older mice and may therefore be accurate in distinguishing between experimental groups of mice with more, or less, age-related pathology.

    View details for DOI 10.1007/s11357-019-00088-w

    View details for PubMedID 31468322

  • Pravastatin improves fetal survival in mice with a partial deficiency of heme oxygenase-1. Placenta Tsur, A., Kalish, F., Burgess, J., Nayak, N. R., Zhao, H., Casey, K. M., Druzin, M. L., Wong, R. J., Stevenson, D. K. 2019; 75: 1–8

    Abstract

    Statins induce heme oxygenase-1 (HO-1) expression in vitro and in vivo. Low HO-1 expression is associated with pregnancy complications, e.g. preeclampsia and recurrent miscarriages. Here, we investigated the effects of pravastatin on HO-1 expression, placental development, and fetal survival in mice with a partial HO-1 deficiency.At E14.5, untreated pregnant wild-type (WT, n=13-18), untreated HO-1+/- (Het, n=6-9), and Het mice treated with pravastatin (Het+Pravastatin, n=12-14) were sacrificed. Numbers of viable fetuses/resorbed concepti were recorded. Maternal livers and placentas were harvested for HO activity. Hematoxylin and eosin (H&E) and CD31 immunohistochemical staining were performed on whole placentas.Compared with WT, HO activity in Het livers (65±18%, P<0.001) and placentas (74±7%, P<0.001) were significantly decreased. Number of viable fetuses per dam was significantly lower in Untreated Het dams (6.0±2.2) compared with WT (9.1±1.4, P<0.01), accompanied by a higher relative risk (RR) for concepti resorption (17.1, 95% CI 4.0-73.2). In Hets treated with pravastatin, maternal liver and placental HO activity increased, approaching levels of WT controls (to 83±7% and 87±14%, respectively). The number of viable fetuses per dam increased to 7.7±2.5 with a decreased RR for concepti resorption (2.7, 95% CI 1.2-5.9). In some surviving Untreated Het placentas, there were focal losses of cellular architecture and changes suggestive of reduced blood flow in the labyrinth. These findings were absent in Het+Pravastatin placentas.Pravastatin induces maternal liver and placental HO activity, may affect placental function and improve fetal survival in the context of a partial deficiency of HO-1.

    View details for PubMedID 30712660

  • Proliferative Typhlocolitis With Multinucleated Giant Cells: A Nonspecific Enteropathy in Immunodeficient Sentinel Mice VETERINARY PATHOLOGY Casey, K. M., Johnson, A. L., Hunrath, M. N., Fraser, J. K., McCowan, N. C., Wasson, K., Doty, R. A., Griffey, S. M., Imai, D. M. 2019; 56 (1): 157–68
  • What is your diagnosis? Conjunctival smear in a dog. Veterinary clinical pathology Gonzales-Viera, O., Casey, K., Keel, M. K. 2018

    View details for PubMedID 29989194

  • Pravastatin Induces Heme Oxygenase Activity and Enhances Placental Development in a Murine Model. Tsur, A., Kalish, F., Burgess, J., Zhao, H., Casey, K. M., Druzin, M. L., Wong, R. J., Stevenson, D. K. SAGE PUBLICATIONS INC. 2018: 155A–156A
  • Pravastatin improves pregnancy outcome and placental development in heme oxygenase-1 deficient mice Tsur, A., Kalish, F., Burgess, J., Zhao, H., Casey, K., Druzin, M. L., Wong, R. J., Stevenson, D. K. MOSBY-ELSEVIER. 2018: S202
  • SETD3 is an actin histidine methyltransferase that prevents primary dystocia. Nature Wilkinson, A. W., Diep, J., Dai, S., Liu, S., Ooi, Y. S., Song, D., Li, T. M., Horton, J. R., Zhang, X., Liu, C., Trivedi, D. V., Ruppel, K. M., Vilches-Moure, J. G., Casey, K. M., Mak, J., Cowan, T., Elias, J. E., Nagamine, C. M., Spudich, J. A., Cheng, X., Carette, J. E., Gozani, O. 2018

    Abstract

    For more than 50 years, the methylation of mammalian actin at histidine 73 has been known to occur1. Despite the pervasiveness of His73 methylation, which we find is conserved in several model animals and plants, its function remains unclear and the enzyme that generates this modification is unknown. Here we identify SET domain protein 3 (SETD3) as the physiological actin His73 methyltransferase. Structural studies reveal that an extensive network of interactions clamps the actin peptide onto the surface of SETD3 to orient His73 correctly within the catalytic pocket and to facilitate methyl transfer. His73 methylation reduces the nucleotide-exchange rate on actin monomers and modestly accelerates the assembly of actin filaments. Mice that lack SETD3 show complete loss of actin His73 methylation in several tissues, and quantitative proteomics analysis shows that actin His73 methylation is the only detectable physiological substrate of SETD3. SETD3-deficient female mice have severely decreased litter sizes owing to primary maternal dystocia that is refractory to ecbolic induction agents. Furthermore, depletion of SETD3 impairs signal-induced contraction in primary human uterine smooth muscle cells. Together, our results identify a mammalian histidine methyltransferase and uncover a pivotal role for SETD3 and actin His73 methylation in the regulation of smooth muscle contractility. Our data also support the broader hypothesis that protein histidine methylation acts as a common regulatory mechanism.

    View details for PubMedID 30626964

  • Identification of occult micrometastases and isolated tumour cells within regional lymph nodes of previously diagnosed non-metastatic (stage 0) canine carcinomas VETERINARY AND COMPARATIVE ONCOLOGY Casey, K. M., Steffey, M. A., Affolter, V. K. 2017; 15 (3): 785–92

    Abstract

    Metastatic dissemination of carcinomas to lymph nodes impacts prognosis and treatment recommendations in human and veterinary medicine. Routine histopathologic evaluation of regional lymph nodes involves haematoxylin and eosin (H&E) staining to identify intra-nodal neoplastic cells; however, identification of small volume metastases (micrometastases and individual tumour cells) may be missed without the aid of immunohistochemistry or additional step-sections. The aim of this study was to identify occult carcinoma metastases in previously diagnosed non-metastatic lymph nodes using step-sections and pancytokeratin (panCK) immunohistochemistry. Samples from 20 regional lymph nodes diagnosed as non-metastatic were serially sectioned and evaluated with panCK. Of these, 25% (n = 5) contained micrometastases (n = 1) or isolated tumour cells (n = 4). This study demonstrates the increased efficacy of serial step-sections combined with panCK immunohistochemistry to identify small volume metastases in regional lymph nodes. The prognostic significance of micrometastases and isolated tumour cells in regional lymph nodes warrants further investigation in veterinary medicine.

    View details for DOI 10.1111/vco.12219

    View details for Web of Science ID 000408772500013

    View details for PubMedID 27135991

  • Partial gastrectomy for resection of a gastric leiomyoma in a guinea pig (Cavia porcellus) JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION Gardhouse, S. M., Guzman, D., Sadar, M. J., DeRouen, A. J., Bucy, D. S., Adedeji, A. O., Vernau, W., Casey, K. M., Mohr, F., Steffey, M. A. 2016; 249 (12): 1415–20

    Abstract

    CASE DESCRIPTION A 4-year-old sexually intact male pet guinea pig (Cavia porcellus) was evaluated for a routine wellness examination. CLINICAL FINDINGS During physical examination, a small mass was palpated in the cranial aspect of the abdomen. Abdominal radiographic and ultrasonographic findings were suggestive of a gastric mass. Cytologic evaluation of a fine-needle aspirate of the mass was indicative of spindle cell proliferation most consistent with a sarcoma. TREATMENT AND OUTCOME The patient was anesthetized, and an exploratory laparotomy and partial gastrectomy were performed to resect the gastric mass. Histologic and immunohistochemical examinations of the mass revealed that it was a gastric leiomyoma. The patient recovered from surgery without complications. No evidence of mass recurrence was observed during an abdominal ultrasonographic examination performed approximately 19 months after surgery. CLINICAL RELEVANCE To our knowledge, this was the first report of the clinical diagnosis and successful surgical treatment of a gastric neoplasm in a guinea pig. Gastric leiomyomas are not uncommon in guinea pigs, and although benign, they can cause clinical signs if they become large enough to impair gastric function. Gastrointestinal surgery should be considered as a treatment option for guinea pigs with similar gastric neoplasms.

    View details for DOI 10.2460/javma.249.12.1415

    View details for Web of Science ID 000388906500016

    View details for PubMedID 27901456

  • Bilateral Aural Adenocarcinoma in a Congo African Grey Parrot (Psittacus erithacus erithacus) JOURNAL OF AVIAN MEDICINE AND SURGERY Houck, E. L., Keller, K. A., Hawkins, M. G., Burton, A. G., Casey, K. M., Keel, K., Tong, N., Guzman, D. 2016; 30 (3): 257–62

    Abstract

    A 28-year-old female Congo African grey parrot ( Psittacus erithacus erithacus) was evaluated because of a mass in the left external auditory meatus. Results of a computed tomography scan revealed an osteolytic left hemimandibular mass with irregular bone production and a soft tissue mass in the left external auditory meatus. Results of cytologic examination of fine needle aspirates of the hemimandible were interpreted as adenocarcinoma with reactive osteoblasts. The owner chose palliative treatment, and a debulking procedure was performed on the left external auditory meatus mass 52 days after initial presentation to control self-trauma. Euthanasia was elected 67 days after initial presentation because of poor prognosis associated with the development of bilateral masses of the external auditory meatus and lateral deviation of the mandible, findings that were confirmed by postmortem examination. Histopathologic results confirmed the diagnosis of bilateral aural adenocarcinoma with invasion of both temporal bones and hemimandibles.

    View details for Web of Science ID 000385596600006

    View details for PubMedID 27736232

  • Bilaterally Symmetric Focal Cortical Dysplasia in a Golden Retriever Dog JOURNAL OF COMPARATIVE PATHOLOGY Casey, K. M., Bollen, A. W., Winger, K. M., Vernau, K. M., Dickinson, P. J., Higgins, R. J., Siso, S. 2014; 151 (4): 375–79

    Abstract

    A 10-year-old golden retriever dog was referred with a 24-h history of generalized seizures. Magnetic resonance imaging of the brain found no abnormalities on 3 mm transverse sections and the dog was subsequently humanely destroyed. Microscopically there was bilaterally symmetrical focal disorganization of cortical grey matter within the tips of the right and left suprasylvian gyri of the temporal cortex. The focal abnormal cortical lamination was characterized by loss of pyramidal neurons with abnormal, irregular, angular, remaining neurons occasionally forming clusters, surrounded by fibrillary astrogliosis and microgliosis and vascular proliferation. These histological findings are consistent with focal cortical dysplasia, a cerebral cortical malformation that causes seizures in people, but not reported previously in the dog.

    View details for DOI 10.1016/j.jcpa.2014.08.002

    View details for Web of Science ID 000347662200011

    View details for PubMedID 25246180

  • Reproductive Experience Alters Neural and Behavioural Responses to Acute Oestrogen Receptor alpha Activation JOURNAL OF NEUROENDOCRINOLOGY Byrnes, E. M., Casey, K., Carini, L. M., Bridges, R. S. 2013; 25 (12): 1280–89

    Abstract

    Reproductive experience (i.e. parturition and lactation) leads to persistent alterations in anxiety-like behaviour that are influenced by the oestrous cycle. We recently found that repeated administration of the selective oestrogen receptors (ER)α agonist propyl-pyrazole triol (PPT) results in anxiolytic-like behaviours on the elevated plus maze (EPM) in primiparous (but not nulliparous) female rats. The present study examined the effects of the acute administration of PPT on EPM behaviour in primiparous and aged-matched, nulliparous female rats. In addition, corticosterone secretion, corticotrophin-releasing hormone (CRH) gene expression and expression of the immediate early gene product Fos in the paraventricular nucleus (PVN) and amygdala were measured either after EPM testing or in home cage controls. Acute PPT administration significantly modified EPM behaviour as a function of reproductive experience, with nulliparous females tending toward increased anxiety-like behaviours and primiparous females tending toward decreased anxiety-like behaviours. In home cage controls, PPT increased corticosterone secretion in all females; however, both vehicle- and PPT-treated, primiparous females had reduced corticosterone levels compared to their nulliparous counterparts. Significant effects of PPT on CRH mRNA within the PVN were observed after the administration of PPT but only in primiparous females tested on the EPM. PPT also increased Fos expression within the PVN of EPM-exposed females; however, both vehicle- and PPT-treated primiparous females had reduced Fos expression compared to nulliparous females. In the amygdala, PPT increased Fos immunoreactivity in the central but not the medial or basolateral amygdala, although these effects were only observed in home cage females. Additionally, both vehicle- and PPT-treated home cage, primiparous females had increased Fos in the central nucleus of the amygdala compared to nulliparous controls. Overall, these data demonstrate that reproductive experience alters the behavioural response to acute ERα activation. Moreover, the findings suggest that central regulation of the hypothalamic-adrenal-pituitary axis is modified as a consequence of reproductive experience.

    View details for DOI 10.1111/jne.12113

    View details for Web of Science ID 000327295200006

    View details for PubMedID 24118285

    View details for PubMedCentralID PMC4269101

  • Reproductive experience modifies the effects of estrogen receptor alpha activity on anxiety-like behavior and corticotropin releasing hormone mRNA expression HORMONES AND BEHAVIOR Byrnes, E. M., Casey, K., Bridges, R. S. 2012; 61 (1): 44–49

    Abstract

    Previous studies have demonstrated that prior reproductive experience can influence anxiety-like behaviors, although neural mechanisms underlying this shift remain unknown. Studies in virgin females suggest that activation of the two estrogen receptor subtypes, ERα and ERβ, have differing effects on anxiety. Specifically, ERβ activation has been shown to reduce anxiety-like behaviors, while ERα activation has no significant effect. The purpose of the present study was to examine the possible roles of ERα and ERβ subtypes in parity-induced alterations in anxiety-like behavior, as tested on the elevated plus maze (EPM). Groups of ovariectomized, age-matched, nulliparous and primiparous females were tested on the EPM following administration of the ERα agonist 4,4',4''-(4-Propyl-{1H}-pyrazole-1,3,5-tryl)trisphenol (PPT; 1 mg/kg), the ERβ agonist Diarylpropionitrile (DPN; 1 mg/kg) or vehicle (DMSO). All drugs were administered once daily for 4 days prior to testing as this dosing paradigm has previously been used to demonstrate anxiolytic effects of DPN in virgin rats. In addition, as exposure to the EPM is a psychological stressor, physiological markers of the stress response were measured in both plasma (corticosterone) and brain (corticotropin releasing hormone; CRH) post-EPM testing. Unexpectedly, the ERα agonist PPT selectively increased the time spent exploring the open arms of the EPM in non-lactating, primiparous females, with no significant effects of DPN observed in either nulliparous or primiparous subjects. All females administered PPT and tested on the EPM demonstrated significantly reduced corticosterone secretion when compared to vehicle-treated controls. In addition, significant effects of both reproductive experience and PPT administration on CRH mRNA expression were observed in both the paraventricular nucleus and amygdala using qPCR. These findings indicate that reproductive experience modulates the effects of ERα activation on both EPM behavior related to anxiety and CRH gene expression.

    View details for DOI 10.1016/j.yhbeh.2011.10.001

    View details for Web of Science ID 000300120000008

    View details for PubMedID 22033279

    View details for PubMedCentralID PMC3264805