Kathleen L. Gabrielson, D.V.M., Ph.D., Dip ACVP
Department of Molecular and Comparative Pathobiology
Department of Environmental Health Sciences
eBriefing "Light,Sound,Action:Imaging Tools in Toxicology Assessment"
Background, Training and Current Position
Before she entered Veterinary school, she worked in neuroscience and endocrinology research at the University of Texas, San Antonia, University of California, San Diego and the San Diego Zoo. This experience undoubtedly led her back to pursue research after her veterinary medicine training. She graduated from North Carolina State University Veterinary College of Medicine in 1989 and next entered a postdoctoral fellowship in veterinary pathology at Johns Hopkins University School of Medicine. Before entering a PhD program in toxicology at the Johns Hopkins University School of Public Health, she worked as a diagnostic pathologist and became board certified by the American College of Veterinary Pathologists. Her PhD project bought here back to the field of neuroscience, as she studied the mechanisms of toxicity behind the mitochondrial toxin 3-nitropropionic acid (3NPA). During this investigation, she discovered that 3NPA was not only a neurotoxin, but also a cardiac toxin. This finding remodeled her research focus to the study of cardiac toxicity and cardiac diseases. She joined the faculty of Comparative Medicine in 2000 and through this appointment, she is involved in the teaching and training of post-doctoral fellows in laboratory animal medicine and veterinary pathology. She also have an appointment in Environmental Health Sciences in the Johns Hopkins University School of School of Public Health, and through this appointment, developed and directs a graduate course in Toxicological Pathology, as well as co-direct a core facility for molecular imaging and pathology, sponsored by a NIEHS center grant. She also has a faculty appointment in the Center for Alternatives to Animal Testing and through this position participated in the web-based course “Enhancing Humane Science/Improving Animal Research”.
Her research efforts focus on the signal transduction of cardiovascular toxicities in vitro, in cardiomyocyte culture and in vivo, using rodent models. Specifically, the research focuses on the understanding the mechanisms of various cancer therapies that induce cardiac toxicities. Currently she is testing prevention strategies for these toxicities. She is studying the cardiac effects of the anthracycline doxorubicin (adriamycin) and the immunotherapeutic agent, Herceptin, anti-erbB2. For patients concurrently treated with Herceptin and doxorubicin, the risk of cardiac dysfunction is 28% compared to 7% in doxorubicin alone treatment. She is focusing on the signal transduction pathways in the heart that are modulated by anti-erbB2 treatment, which in turn, worsens doxorubicin toxicity. Thus, understanding the mechanisms behind the combined toxicity of doxorubicin and anti-erbB2 will pave the way for the design of strategies to reduce toxicity, identify patients at risk and potentially allow higher levels of this effective combination therapy to be used with an improved long-term survival in patients. In another doxorubicin animal model, she is using the neu mouse model that overexpresses neu (erbB2) and thus develops breast cancer, to test several strategies to prevent doxorubicin toxicity. For evaluating various cardiac protection strategies, in conjunction with molecular studies, she is also using histopathology, clinical pathology and non-invasive echocardiography in both acute and chronic models of doxorubicin toxicity. Tumor growth and regression is also being monitored during treatment. Some of the pharmacological strategies she is testing have also been show to reduce tumor burden. To complement the in vivo studies, toxicity assessments and pharmacological strategies are first screened in vitro in neonatal and adult rat cardiomyocyte cell culture. These projects are funded by a Scientist Development Grant award from the National American Heart Association program, Department of Defense- Breast Cancer Research program and from pilot project funds from the Breast Cancer SPORE and the American Cancer Society.
She is also currently collaborating with multiple investigators within JHU and other universities ranging from cancer research to cardiovascular research
Students and Post-doctoral Fellows
She has assisted in the mentoring of 7 undergraduate pre-vet and pre-med students, 5 veterinary students, 2 pre-doctoral students and 12 post-doctoral DVM fellows in Comparative Medicine since 2000.
Animal Pathology, School of Medicine, Johns Hopkins University (1992, 2000, 2003, 2006) Lecturer and Laboratory instruction
Animal Models, School of Medicine, Johns Hopkins University (2000-6) Lecturer
Toxicological Pathology, School of Public Health, Johns Hopkins University (2002-6), Director and Lecturer
Laboratory Animal Medicine and Pathology, School of Medicine, Johns Hopkins University (2001-6) Lecturer
Veterinary Anatomical Pathologist – Department of Comparative Medicine, Johns Hopkins University, School of Medicine
Carrillo AJ, Evans KL: Electrochemical stimulation of the preoptic area and luteinizing hormone in the rat: Effect of ferrous cations. Journal of Endocrinology 93: 193-199, 1982.
Sharp FR, Evans KL: Regional (14 C) 2-deoxyglucose uptake during vibrissae movement evoked by rat motor cortex stimulation. Journal of Comparative Neurology 208: 255-287, 1982.
Sharp FR, Evans KL, Bolger E: Local cerebral glucose utilization in the symptomatic thiamine deficient rat: Increase in fomix and pyramidal tract. Neurology 32: 808-814, 1982.
Sharp FR, Bolger E, Evans KL: Thiamine deficiency limits glial glucose utilization and proliferation in brain lesions of symptomatic rats. Journal of Cerebral Blood Flow and Metabolism 2: 203-207, 1982.
Matthews SA, Evans KL, Morgan WM, Petterborg U, Reiter RJ: Pineal indoleamine metabolism in the cotton rat, Siizmodon Hiwidus: Studies on norepinephrine, serotonin, N-acetyltransfemse activity and melatonin. In The Pineal and it’s Hormones, Reiter RJ, Ed. Alan Liss, New York, 1982.
Sharp FR-, Evans KL: Bilateral (14 C) 2-deoxyglucose uptake by motor pathways after unilateral neonatal cortex lesions in the rat. Developmental Brain Research 6:1-11, 1983.
Evans KL, Kasman LH, Hughes JP, Couto M, Lasley BL: Pregnancy diagnosis in the domestic horse through direct urinary estrone conjugate analysis. Theriogenology 22: 615-620, 1984.
Gabrielson KL, Remillard RL, Huso DL: Zinc toxicity with pancreatic acinar necrosis piglets receiving total parental nutrition. Vet.Pathol. 33:692-696, 1996.
Yang S, Zhu H, Li Y, Lin H, Gabrielson KL, Trush MA, Diehl AM. Mitochondrial adaptions to obesity-related oxidant stress. Archives of Biochemistry and Biophysics 378:259-268, 2000.
Nakajima W, Lange MS, Ishida A, Gabrielson KL, Blue M, Martin L, Johnston MV. Distribution of apoptotic cells in a neonatal rat model of cerebral hypoxia-ischemia. Journal of Neuroscience: 20:7994-8004, 2000.
Gabrielson KL, Hogue BA, Bohr VA, Cardounel AJ, Zweier JL, Nakajima W, Kofler J, Rodriguez ER, Martin LJ, de Souza-Pinto NC and Bressler J. Mitochondrial toxin 3-nitropropionic acid induced striatal and cardiac toxicity in multiple mouse strains. American Journal of Pathology 159:1507-1520, 2001.
Olson LE, Bedja D, Alvey SJ, Gabrielson KL, Reeves R. Protection from doxorubicin-induced cardiac toxicity in mice with a null allele of carbonyl reductase. Cancer Research 63:6602-6606, 2003
Watanabe H, Mamelak AJ, Weiss E, Brice AK, Wachtman L, Yokota N, Wang B, Freed I, Hicklin DJ, Kerbel RS, Haas M, Gabrielson KL and Sauder DN. VEGFR-2 antibody accelerates renal disease progression in the NZB/W F1 murine SLE model. Clinical Cancer Research 11:407-9, 2005.
Pointek KB, Huso D, Grinberg A, Westphal H, Gabrielson KL, Bedja D, Germino GG. A functional floxed Pkd1 allele. Am Soc Nephrol 15:3035-3043, 2004.
Ng CM, Cheng A, Myers LA, Martinez-Murillo F, Jie C, Bedja D, Gabrielson KL, Hausladen JM, Mecham RP, Judge DP, Dietz HC. "TGF?-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome." J Clin Invest 114:1586-92, 2004
Takimoto E, Li M, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Champion HC, Wang Y, Kass DA. Chronic inhibition of cyclic GMP phoshodiesteras 5A prevents and reverses Hypertrophy. Nat Med 11(2):214-22, 2005
Afanasyeva M, Georgakopoulos D, Belasrdi DF, Bedja D, Fairweather D, Wang Y, Kaya Z, Gabrielson KL, Rodriguez ER, Caturegli P, Kass DA, Rose NR. Enhanced Progression of Myocarditis to Cardiomyopathy and Heart failure in Interferon-g Deficient mice is due to Impaired Upregulation of CD25 on CD4+ T cells. PNAS 102: 180-5, 2005
Takimoto E, Champion H, Li M, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA. ROS from uncoupled eNOS plays Pivotal Role in Left ventricular Remodeling to pressure overload. J Clin Invest 15(5):1221-1231, 2005
Liddell RP, Patel TH, Weiss CR, Lee DS, Matsuhashi T, Brown PR, Gabrielson KL, Rodriguez ER, Eng J, Kimura H, Hofmann LV. Endovascular Model of Rabbit Hindlimb Ischemia: A Platform to Evaluate Therapeutic Angiogenesis. J Vasc Interv Radiol; 16:991-998. 2005
Cooper TK, Shih IM, Gabrielson KL. Uterine Epithelioid Trophoblastic Tumour in a Red-Tailed Guenon. J Comp Pathol. 133:218-222, 2005
Lee J, Jallo GI, Penno MB, Gabrielson KL, Young GD, Johnson RM, Gillis EM, Rampersaud C, Carson BS, Guarnieri M. Intracranial Drug-Delivery Scaffolds: Biocompatibility Evaluation of Sucrose Acetate Isobutyrate Gels. Toxicology and Applied Pharmacology, in press
Raju SVY, Zheng M, Schuleri K, Phan AC, Bedja D, Saraiva RM, Yiginer O, Vandegaer K, Gabrielson KL, O’Donnell CP, Berkowitz DE, Barouch LA, Hare J, Activation of the Novel Cardiac Ciliary Neurotrophic Factor Receptor Reverses LVH in Leptin Deficient and Leptin Resistant Obesity. PNAS, in press
Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson KL, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC.Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. (2006) 312 (5770):117-21
Lehrke S, Mazhari R, Durand DJ, Zheng M, Bedja D, Zimmet JM, Schuleri, KH, Chi AS, Gabrielson KL, Hare JM. Aging Impairs the Beneficial Effect of Granulocyte Colony-Stimulating Factor and Stem Cell Factor on Post-Myocardial Infarction Remodeling. Circulation Research 2006 Sept 1; Volume 99 Number 5: (2006) 553-560
Gabrielson KL, Bedja, D, Pin S, Gama L, Yuan B, Muratore N, Tsao A., HSP90 and ErbB2 in the Cardiac Response to Doxorubicin Injury, Cancer Research 2007;67(4):1-7
Wachtman, L, Bedja, D, Pin, S, Browning, M, Gabrielson, K. Validation of the use of long-term indwelling jugular catheters in model of cardiotoxicity, Contemporary Topics in Laboratory Animal Science, in press
Magno P, Giday SA, Gabrielson KL, Eun JS, Buscaglia J, Clarke JO, Ko C Jagannath SB, Canto MI, Kalloo AN, Kantsevoy, SV., Endoscopic Ultrasound (EUS)-Guided Implantation of Radio-Opaque Marker into Mediastinal and Celiac Lymph Nodes is Safe and Effective, Gastrointestinal Endoscopy, in press
Cooper TK, Gabrielson KL., Spontaneous Lesions in the Reproductive Tract and Mammary Gland of Female Non-Human Primates, Birth Defects Research Part B: Developmental and Reproductive Toxicology, in press
Lee SJ, Orita H, Gabrielson KL, Alvey S, Hagemann RL, Kuhajda FP, Gabrielson E, Pomper M., FDG-PET for Pharmacodynamic Assessment of the Fatty Acid Synthase Inhibitor C75 in an Experimental Model of Lung Cancer, Pharmacological Research, in press
Ruben D, Muratore N, Pin S, Gabrielson KL. Effects of Bedding Substrates on Microsomal Enzymes in Rabbit Liver, Journal of the American Association for Laboratory Animal Science, in press