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Caroline Zeiss, DACVP, DACLAM

Professor of Comparative Medicine and of Ophthalmology and Visual Science; Chief of Pathology, Comparative Medicine

Contact Information

Caroline Zeiss, DACVP, DACLAM

Mailing Address

  • PO Box 208016

    New Haven, CT 06520-8016

    United States

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Research Summary

Why do so many promising animal studies fail to translate to successful treatments for humans? Our lab uses biomedical informatics to identify large scale patterns of animal model use. This approach reveals systemic biases in the utilization of animal models that contribute to the translational gap. In particular, we are interested in developing text-mining programs and databases that can correlate interventional outcomes across human and animal species by intervention, drug class and choice of outcome measure. We focus on chronic and complex diseases, in particular neurodegenerative disease. Our text-mining approaches in Parkinson's disease (Menagerie) are being extended to accommodate Alzheimer's disease. This work, as well as neuropathologic assessment of aging macaque brains according to NIA-AA guidelines occurs in collaboration with the Alzheimer's Disease Research Center at Yale.

More recent COVID work employs principles of translational study design to determine when COVID will reach endemic status, and the other to assess the impact of concurrent influenza and SARS-CoV-2 infection in hamsters.

Specialized Terms: Biomedical informatics; Efficacy; Translational gap; Neurodegeneration; Neurobiology of movement disorders; Phenotypes of genetically engineered mice; Evolutionary biology of the eye; Veterinary Pathology; Mouse Phenotyping; Ocular pathology; Neuroanatomy of age-related gait disorders;

Coauthors

Research Interests

Animal Diseases; Neuroanatomy; Neurobiology; Ophthalmology; Pathologic Processes; Primates; Neurodegenerative Diseases; Informatics; Translational Medical Research

Selected Publications

  • Menagerie: A text-mining tool to support animal-human translation in neurodegeneration research.Zeiss CJ, Shin D, Vander Wyk B, Beck AP, Zatz N, Sneiderman CA, Kilicoglu H. Menagerie: A text-mining tool to support animal-human translation in neurodegeneration research. PloS One 2019, 14: e0226176. PMID: 31846471, PMCID: PMC6917268, DOI: 10.1371/journal.pone.0226176.
  • An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease.Mäkeläinen S, Gòdia M, Hellsand M, Viluma A, Hahn D, Makdoumi K, Zeiss CJ, Mellersh C, Ricketts SL, Narfström K, Hallböök F, Ekesten B, Andersson G, Bergström TF. An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. PLoS Genetics 2019, 15: e1007873. PMID: 30889179, PMCID: PMC6424408, DOI: 10.1371/journal.pgen.1007873.
  • Doxorubicin-Induced Cardiotoxicity in Collaborative Cross (CC) Mice Recapitulates Individual Cardiotoxicity in Humans.Zeiss CJ, Gatti DM, Toro-Salazar O, Davis C, Lutz CM, Spinale F, Stearns T, Furtado MB, Churchill GA. Doxorubicin-Induced Cardiotoxicity in Collaborative Cross (CC) Mice Recapitulates Individual Cardiotoxicity in Humans. G3 (Bethesda, Md.) 2019, 9: 2637-2646. PMID: 31263061, PMCID: PMC6686936, DOI: 10.1534/g3.119.400232.
  • Single-photon Emission Computed Tomography-Computed Tomography Using 99mTc-labeled Leukocytes for Evaluating Infection Associated with a Cranial Implant in a Rhesus Macaque (Macaca mulatta).Guerriero KA, Wilson SR, Sinusas AJ, Saperstein L, Zeiss CJ. Single-photon Emission Computed Tomography-Computed Tomography Using 99mTc-labeled Leukocytes for Evaluating Infection Associated with a Cranial Implant in a Rhesus Macaque (Macaca mulatta). Comparative Medicine 2019, 69: 249-256. PMID: 30935441, PMCID: PMC6591671, DOI: 10.30802/AALAS-CM-18-000123.
  • Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis.Price NL, Miguel V, Ding W, Singh AK, Malik S, Rotllan N, Moshnikova A, Toczek J, Zeiss C, Sadeghi MM, Arias N, Baldán Á, Andreev OA, Rodríguez-Puyol D, Bahal R, Reshetnyak YK, Suárez Y, Fernández-Hernando C, Lamas S. Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis. JCI Insight 2019, 4 PMID: 31613798, PMCID: PMC6948871, DOI: 10.1172/jci.insight.131102.
  • Pathology Study Design, Conduct, and Reporting to Achieve Rigor and Reproducibility in Translational Research Using Animal Models.Everitt JI, Treuting PM, Scudamore C, Sellers R, Turner PV, Ward JM, Zeiss CJ. Pathology Study Design, Conduct, and Reporting to Achieve Rigor and Reproducibility in Translational Research Using Animal Models. ILAR Journal / National Research Council, Institute Of Laboratory Animal Resources 2018, 59: 4-12. PMID: 30624739, DOI: 10.1093/ilar/ily020.
  • Investigating the role of interleukin-1 beta and glutamate in inflammatory bowel disease and epilepsy using discovery browsing.Rindflesch TC, Blake CL, Cairelli MJ, Fiszman M, Zeiss CJ, Kilicoglu H. Investigating the role of interleukin-1 beta and glutamate in inflammatory bowel disease and epilepsy using discovery browsing. Journal Of Biomedical Semantics 2018, 9: 25. PMID: 30587224, PMCID: PMC6307110, DOI: 10.1186/s13326-018-0192-y.
  • From Reproducibility to Translation in Neurodegenerative Disease.Zeiss CJ. From Reproducibility to Translation in Neurodegenerative Disease. ILAR Journal / National Research Council, Institute Of Laboratory Animal Resources 2017, 58: 106-114. PMID: 28444192, DOI: 10.1093/ilar/ilx006.
  • Established patterns of animal study design undermine translation of disease-modifying therapies for Parkinson's disease.Zeiss CJ, Allore HG, Beck AP. Established patterns of animal study design undermine translation of disease-modifying therapies for Parkinson's disease. PloS One 2017, 12: e0171790. PMID: 28182759, PMCID: PMC5300282, DOI: 10.1371/journal.pone.0171790.
  • β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares.Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.
  • Improving the predictive value of interventional animal models data.Zeiss CJ. Improving the predictive value of interventional animal models data. Drug Discovery Today 2015, 20: 475-82. PMID: 25448761, PMCID: PMC4417064, DOI: 10.1016/j.drudis.2014.10.015.
  • Expression of the CTCFL Gene during Mouse Embryogenesis Causes Growth Retardation, Postnatal Lethality, and Dysregulation of the Transforming Growth Factor β Pathway.Sati L, Zeiss C, Yekkala K, Demir R, McGrath J. Expression of the CTCFL Gene during Mouse Embryogenesis Causes Growth Retardation, Postnatal Lethality, and Dysregulation of the Transforming Growth Factor β Pathway. Molecular And Cellular Biology 2015, 35: 3436-45. PMID: 26169830, PMCID: PMC4561735, DOI: 10.1128/MCB.00381-15.
  • Preclinical safety evaluation of a recombinant AAV8 vector for X-linked retinoschisis after intravitreal administration in rabbits.Marangoni D, Wu Z, Wiley HE, Zeiss CJ, Vijayasarathy C, Zeng Y, Hiriyanna S, Bush RA, Wei LL, Colosi P, Sieving PA. Preclinical safety evaluation of a recombinant AAV8 vector for X-linked retinoschisis after intravitreal administration in rabbits. Human Gene Therapy. Clinical Development 2014, 25: 202-11. PMID: 25211193, PMCID: PMC4275775, DOI: 10.1089/humc.2014.067.
  • Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice.Kim JD, Toda C, D'Agostino G, Zeiss CJ, DiLeone RJ, Elsworth JD, Kibbey RG, Chan O, Harvey BK, Richie CT, Savolainen M, Myöhänen T, Jeong JK, Diano S. Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 11876-81. PMID: 25071172, PMCID: PMC4136568, DOI: 10.1073/pnas.1406000111.
  • Mutation of POLB causes lupus in mice.Senejani AG, Liu Y, Kidane D, Maher SE, Zeiss CJ, Park HJ, Kashgarian M, McNiff JM, Zelterman D, Bothwell AL, Sweasy JB. Mutation of POLB causes lupus in mice. Cell Reports 2014, 6: 1-8. PMID: 24388753, PMCID: PMC3916967, DOI: 10.1016/j.celrep.2013.12.017.
  • Translational models of ocular disease.Zeiss CJ. Translational models of ocular disease. Veterinary Ophthalmology 2013, 16 Suppl 1: 15-33. PMID: 23750503, DOI: 10.1111/vop.12065.
  • Fungal polymerase chain reaction testing in equine ulcerative keratitis.Zeiss C, Neaderland M, Yang FC, Terwilliger G, Compton S. Fungal polymerase chain reaction testing in equine ulcerative keratitis. Veterinary Ophthalmology 2013, 16: 341-51. PMID: 23227970, DOI: 10.1111/vop.12004.
  • Designing phenotyping studies for genetically engineered mice.Zeiss CJ, Ward JM, Allore HG. Designing phenotyping studies for genetically engineered mice. Veterinary Pathology 2012, 49: 24-31. PMID: 21930803, PMCID: PMC3957214, DOI: 10.1177/0300985811417247.
  • Animals as models of age-related macular degeneration: an imperfect measure of the truth.Zeiss CJ. Animals as models of age-related macular degeneration: an imperfect measure of the truth. Veterinary Pathology 2010, 47: 396-413. PMID: 20382825, DOI: 10.1177/0300985809359598.
  • Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in transgenic mice that develop ALS.Wang J, Farr GW, Zeiss CJ, Rodriguez-Gil DJ, Wilson JH, Furtak K, Rutkowski DT, Kaufman RJ, Ruse CI, Yates JR, Perrin S, Feany MB, Horwich AL. Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in transgenic mice that develop ALS. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 1392-7. PMID: 19171884, PMCID: PMC2631083, DOI: 10.1073/pnas.0813045106.
  • Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer.Bennicelli J, Wright JF, Komaromy A, Jacobs JB, Hauck B, Zelenaia O, Mingozzi F, Hui D, Chung D, Rex TS, Wei Z, Qu G, Zhou S, Zeiss C, Arruda VR, Acland GM, Dell'Osso LF, High KA, Maguire AM, Bennett J. Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer. Molecular Therapy : The Journal Of The American Society Of Gene Therapy 2008, 16: 458-65. PMID: 18209734, PMCID: PMC2842085, DOI: 10.1038/sj.mt.6300389.
  • Slc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival.Chande S, Caballero D, Ho BB, Fetene J, Serna J, Pesta D, Nasiri A, Jurczak M, Chavkin NW, Hernando N, Giachelli CM, Wagner CA, Zeiss C, Shulman GI, Bergwitz C. Slc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival. Scientific Reports 2020, 10: 3069. PMID: 32080237, PMCID: PMC7033257, DOI: 10.1038/s41598-020-59430-4.
  • Utility of spontaneous animal models of Alzheimer's disease in preclinical efficacy studies.Zeiss CJ. Utility of spontaneous animal models of Alzheimer's disease in preclinical efficacy studies. Cell And Tissue Research 2020, 380: 273-286. PMID: 32337614, DOI: 10.1007/s00441-020-03198-6.
  • Cutaneous and Pulmonary Mucormycosis in Rag1- and Il2rg-deficient Rats.Sarfaty AE, Compton SR, Smith PC, Zeiss CJ. Cutaneous and Pulmonary Mucormycosis in Rag1- and Il2rg-deficient Rats. Comparative Medicine 2020, 70: 390-395. PMID: 32736665, PMCID: PMC7446636, DOI: 10.30802/AALAS-CM-20-000015.
  • AgRP neurons control compulsive exercise and survival in an activity-based anorexia model.Miletta MC, Iyilikci O, Shanabrough M, Šestan-Peša M, Cammisa A, Zeiss CJ, Dietrich MO, Horvath TL. AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nature Metabolism 2020, 2: 1204-1211. PMID: 33106687, DOI: 10.1038/s42255-020-00300-8.
  • Dual Angiotensin Receptor-Neprilysin Inhibition With Sacubitril/Valsartan Attenuates Systolic Dysfunction in Experimental Doxorubicin-Induced Cardiotoxicity.Boutagy NE, Feher A, Pfau D, Liu Z, Guerrera NM, Freeburg LA, Womack SJ, Hoenes AC, Zeiss C, Young LH, Spinale FG, Sinusas AJ. Dual Angiotensin Receptor-Neprilysin Inhibition With Sacubitril/Valsartan Attenuates Systolic Dysfunction in Experimental Doxorubicin-Induced Cardiotoxicity. JACC. CardioOncology 2020, 2: 774-787. PMID: 33437965, PMCID: PMC7799406, DOI: 10.1016/j.jaccao.2020.09.007.
  • OCULAR ANATOMY AND PATHOLOGY IN LUMHOLTZ'S TREE-KANGAROO (DENDROLAGUS LUMHOLTZI).Shima AL, Johnson LK, Skerratt LF, Zeiss C. OCULAR ANATOMY AND PATHOLOGY IN LUMHOLTZ'S TREE-KANGAROO (DENDROLAGUS LUMHOLTZI). Journal Of Zoo And Wildlife Medicine : Official Publication Of The American Association Of Zoo Veterinarians 2021, 51: 868-878. PMID: 33480567, DOI: 10.1638/2019-0203.
  • Author Correction: AgRP neurons control compulsive exercise and survival in an activity-based anorexia model.Miletta MC, Iyilikci O, Shanabrough M, Šestan-Peša M, Cammisa A, Zeiss CJ, Dietrich MO, Horvath TL. Author Correction: AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nature Metabolism 2021, 3: 288. PMID: 33495625, DOI: 10.1038/s42255-021-00351-5.
  • Age-related calcium dysregulation linked with tau pathology and impaired cognition in non-human primates.Datta D, Leslie SN, Wang M, Morozov YM, Yang S, Mentone S, Zeiss C, Duque A, Rakic P, Horvath TL, van Dyck CH, Nairn AC, Arnsten AFT. Age-related calcium dysregulation linked with tau pathology and impaired cognition in non-human primates. Alzheimer's & Dementia : The Journal Of The Alzheimer's Association 2021, 17: 920-932. PMID: 33829643, PMCID: PMC8195842, DOI: 10.1002/alz.12325.
  • Animal Models of COVID-19. I. Comparative Virology and Disease Pathogenesis.Zeiss CJ, Compton S, Veenhuis RT. Animal Models of COVID-19. I. Comparative Virology and Disease Pathogenesis. ILAR Journal / National Research Council, Institute Of Laboratory Animal Resources 2021 PMID: 33836527, PMCID: PMC8083356, DOI: 10.1093/ilar/ilab007.
  • Animal Models of COVID-19 II. Comparative Immunology.Veenhuis RT, Zeiss CJ. Animal Models of COVID-19 II. Comparative Immunology. ILAR Journal / National Research Council, Institute Of Laboratory Animal Resources 2021 PMID: 33914873, PMCID: PMC8135340, DOI: 10.1093/ilar/ilab010.
  • DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model.Paluri SL, Burak M, Senejani AG, Levinson M, Rahim T, Clairmont K, Kashgarian M, Alvarado-Cruz I, Meas R, Cardó-Vila M, Zeiss C, Maher S, Bothwell ALM, Coskun E, Kant M, Jaruga P, Dizdaroglu M, Stephen Lloyd R, Sweasy JB. DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model. DNA Repair 2021, 105: 103152. PMID: 34186496, PMCID: PMC8635285, DOI: 10.1016/j.dnarep.2021.103152.
  • Comparative Milestones in Rodent and Human Postnatal Central Nervous System Development.Zeiss CJ. Comparative Milestones in Rodent and Human Postnatal Central Nervous System Development. Toxicologic Pathology 2021, 49: 1368-1373. PMID: 34569375, DOI: 10.1177/01926233211046933.
  • Modeling SARS-CoV-2 propagation using rat coronavirus-associated shedding and transmission.Zeiss CJ, Asher JL, Vander Wyk B, Allore HG, Compton SR. Modeling SARS-CoV-2 propagation using rat coronavirus-associated shedding and transmission. PloS One 2021, 16: e0260038. PMID: 34813610, PMCID: PMC8610237, DOI: 10.1371/journal.pone.0260038.
  • Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates.Leslie SN, Kanyo J, Datta D, Wilson RS, Zeiss C, Duque A, Lam TT, Arnsten AFT, Nairn AC. Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates. Frontiers In Aging Neuroscience 2021, 13: 767322. PMID: 34867294, PMCID: PMC8637411, DOI: 10.3389/fnagi.2021.767322.
  • Elevated 5-hydroxytryptamine in COVID-19 Stimulates ANO1 Mediated Cl Secretion in Lung & Intestinal Epithelial Cells.Hoque KM, Hayashi M, Sheikh IA, Banerjee A, Verma SC, Leblanc N, Zeiss CJ, Ameen N, Chakraborty S. Elevated 5-hydroxytryptamine in COVID-19 Stimulates ANO1 Mediated Cl Secretion in Lung & Intestinal Epithelial Cells. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2022, 36 Suppl 1 PMID: 35553771, DOI: 10.1096/fasebj.2022.36.S1.0R556.
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