Karl-Dimiter Bissig

Pediatrics, Medical Genetics

Chen Family Associate Professor of Pediatrics

Karl-Dimiter Bissig Profile Photo

Research Interests

Our group is interested in diseases of the liver, ranging from viral hepatitis to metabolic liver disorders and liver cancer. The lab specializes in human liver chimeric mice and created the first xenograft model for metabolic liver disease as well as a novel patient derived cancer model. We use these next generation humanized mouse models to develop new therapeutic approaches, such as metabolic pathway reprogramming - a CRISPR based gene therapy approach.

Bio

Education

MD./PhD. Universitat Bern (Switzerland), 2000

Trainings & Certifications

Residency, Inselspital (Switzerland), INTERNAL MEDICINE 2001 - 2005 (2001 - 2005) Inselspital (Switzerland)
Postdoctoral Fellow, Salk Institute for Biological Studies 2005 - 2011 (2005 - 2011) Salk Institute for Biological Studies

Positions

Chen Family Associate Professor of Pediatrics
Associate Professor in Pediatrics
Associate Professor in Pharmacology and Cancer Biology
Associate Professor of Biomedical Engineering
Member of the Duke Cancer Institute
Affiliate of the Duke Regeneration Center

Courses Taught

PHARM 494: Research Independent Study
PHARM 493: Research Independent Study
PHARM 394: Research Independent Study
BME 791: Graduate Independent Study
BME 493: Projects in Biomedical Engineering (GE)

Publications

Liao K-A, Han S-O, Barzi M, Yi H, Eisner W, Bissig-Choisat B, et al. High-potency MyoAAV capsids enhanced skeletal muscle correction in a mouse model of GSD IIIa. Mol Ther Methods Clin Dev. 2025 Sep 11;33(3):101567.
Hemmingsen MG, Zhang G-F, Ma Y, Marchuk H, Patel KR, Chen T, et al. Dissecting the effect of mitochondrial BCAT inhibition in methylmalonic acidemia. JCI Insight. 2025 Sep 9;10(17).
Chen T, Barzi M, Furey N, Kim HR, Pankowicz FP, Legras X, et al. CRISPR/Cas9 gene therapy increases the risk of tumorigenesis in the mouse model of hereditary tyrosinemia type I. JHEP Rep. 2025 Apr;7(4):101327.
De Giorgi M, Park SH, Castoreno A, Cao M, Hurley A, Saxena L, et al. In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene. Sci Transl Med. 2025 Feb 12;17(785):eadk3920.
Ates I, Stuart C, Rathbone T, Barzi M, He G, Major AM, et al. Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1. Hepatol Commun. 2024 May 1;8(5).
Espinoza AF, Patel RH, Patel KR, Badachhape AA, Whitlock R, Srivastava RK, et al. A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma. J Hepatol. 2024 Apr;80(4):610u201321.
Barzi M, Chen T, Gonzalez TJ, Pankowicz FP, Oh SH, Streff HL, et al. A humanized mouse model for adeno-associated viral gene therapy. Nat Commun. 2024 Mar 4;15(1):1955.
Padilla J, Osman NM, Bissig-Choisat B, Grimm SL, Qin X, Major AM, et al. Circadian dysfunction induces NAFLD-related human liver cancer in a mouse model. J Hepatol. 2024 Feb;80(2):282u201392.
Barzi M, Johnson CG, Chen T, Rodriguiz RM, Hemmingsen M, Gonzalez TJ, et al. Rescue of glutaric aciduria type I in mice by liver-directed therapies. Sci Transl Med. 2023 Apr 19;15(692):eadf4086.
Qin X, Xie C, Hakenjos JM, MacKenzie KR, Boyd SR, Barzi M, et al. The roles of Cyp1a2 and Cyp2d in pharmacokinetic profiles of serotonin and norepinephrine reuptake inhibitor duloxetine and its metabolites in mice. Eur J Pharm Sci. 2023 Feb 1;181:106358.
Qin X, Xie C, Hakenjos JM, Mackenzie KM, Barzi M, Nyshadham P, et al. Cyp1a2-knockout increases the systemic exposure of a serotonin and norepinephrine reuptake inhibitor duloxetine in mice. FASEB J. 2022 May;36 Suppl 1.
Qin X, Hakenjos JM, MacKenzie KR, Barzi M, Chavan H, Nyshadham P, et al. Metabolism of a Selective Serotonin and Norepinephrine Reuptake Inhibitor Duloxetine in Liver Microsomes and Mice. Drug Metab Dispos. 2022 Feb;50(2):128u201339.
Kinstlinger IS, Saxton SH, Calderon GA, Ruiz KV, Yalacki DR, Deme PR, et al. Author Correction: Generation of model tissues with dendritic vascular networks via sacrificial laser-sintered carbohydrate templates. Nat Biomed Eng. 2021 Aug;5(8):941.
De Giorgi M, Li A, Hurley A, Barzi M, Doerfler AM, Cherayil NA, et al. Targeting the Apoa1 locus for liver-directed gene therapy. Mol Ther Methods Clin Dev. 2021 Jun 11;21:656u201369.
Bissig-Choisat B, Alves-Bezerra M, Zorman B, Ochsner SA, Barzi M, Legras X, et al. A human liver chimeric mouse model for non-alcoholic fatty liver disease. JHEP Rep. 2021 Jun;3(3):100281.
Kruse RL, Barzi M, Legras X, Pankowicz FP, Furey N, Liao L, et al. A hepatitis B virus transgenic mouse model with a conditional, recombinant, episomal genome. JHEP Rep. 2021 Apr;3(2):100252.
MacKenzie KR, Zhao M, Barzi M, Wang J, Bissig K-D, Maletic-Savatic M, et al. Metabolic profiling of norepinephrine reuptake inhibitor atomoxetine. Eur J Pharm Sci. 2020 Oct 1;153:105488.
Kinstlinger IS, Saxton SH, Calderon GA, Ruiz KV, Yalacki DR, Deme PR, et al. Generation of model tissues with dendritic vascular networks via sacrificial laser-sintered carbohydrate templates. Nat Biomed Eng. 2020 Sep;4(9):916u201332.
Stripecke R, Mu00fcnz C, Schuringa JJ, Bissig K-D, Soper B, Meeham T, et al. Innovations, challenges, and minimal information for standardization of humanized mice. EMBO Mol Med. 2020 Jul 7;12(7):e8662.
Minor MM, Hollinger FB, McNees AL, Jung SY, Jain A, Hyser JM, et al. Hepatitis B Virus HBx Protein Mediates the Degradation of Host Restriction Factors through the Cullin 4 DDB1 E3 Ubiquitin Ligase Complex. Cells. 2020 Mar 30;9(4).
Johnson CG, Chen T, Furey N, Hemmingsen MG, Bissig K-D. Somatic Liver Knockout (SLiK): A Quick and Efficient Way to Generate Liver-Specific Knockout Mice Using Multiplex CRISPR/Cas9 Gene Editing. Curr Protoc Mol Biol. 2020 Mar;130(1):e117.
Akkina R, Barber DL, Bility MT, Bissig K-D, Burwitz BJ, Eichelberg K, et al. Small Animal Models for Human Immunodeficiency Virus (HIV), Hepatitis B, and Tuberculosis: Proceedings of an NIAID Workshop. Curr HIV Res. 2020;18(1):19u201328.
Alves-Bezerra M, Furey N, Johnson CG, Bissig K-D. Using CRISPR/Cas9 to model human liver disease. JHEP Rep. 2019 Nov;1(5):392u2013402.
Pankowicz FP, Barzi M, Kim KH, Legras X, Martins CS, Wooton-Kee CR, et al. Rapid Disruption of Genes Specifically in Livers of Mice Using Multiplex CRISPR/Cas9 Editing. Gastroenterology. 2018 Dec;155(6):1967-1970.e6.
Bissig K-D, Han W, Barzi M, Kovalchuk N, Ding L, Fan X, et al. P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity. Drug Metab Dispos. 2018 Nov;46(11):1734u201344.
Kho J, Tian X, Wong W-T, Bertin T, Jiang M-M, Chen S, et al. Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension. Am J Hum Genet. 2018 Aug 2;103(2):276u201387.
Kruse RL, Shum T, Tashiro H, Barzi M, Yi Z, Whitten-Bauer C, et al. HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice. Cytotherapy. 2018 May;20(5):697u2013705.
Valanejad L, Cast A, Wright M, Bissig K-D, Karns R, Weirauch MT, et al. PARP1 activation increases expression of modified tumor suppressors and pathways underlying development of aggressive hepatoblastoma. Commun Biol. 2018;1:67.
Woodfield SE, Shi Y, Patel RH, Jin J, Major A, Sarabia SF, et al. A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma. Sci Rep. 2017 Dec 19;7(1):17751.
Kruse RL, Shum T, Legras X, Barzi M, Pankowicz FP, Gottschalk S, et al. In Situ Liver Expression of HBsAg/CD3-Bispecific Antibodies for HBV Immunotherapy. Mol Ther Methods Clin Dev. 2017 Dec 15;7:32u201341.
Barzi M, Pankowicz FP, Zorman B, Liu X, Legras X, Yang D, et al. Erratum: A novel humanized mouse lacking murine p450 oxidoreductase for studying human drug metabolism. Nat Commun. 2017 Oct 17;8(1):984.
Pankowicz FP, Jarrett KE, Lagor WR, Bissig K-D. CRISPR/Cas9: at the cutting edge of hepatology. Gut. 2017 Jul;66(7):1329u201340.
Barzi M, Pankowicz FP, Zorman B, Liu X, Legras X, Yang D, et al. A novel humanized mouse lacking murine P450 oxidoreductase for studying human drug metabolism. Nat Commun. 2017 Jun 28;8(1):39.
Jarrett KE, Lee CM, Yeh Y-H, Hsu RH, Gupta R, Zhang M, et al. Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease. Sci Rep. 2017 Mar 16;7:44624.
Velasquez-Mao AJ, Tsao CJM, Monroe MN, Legras X, Bissig-Choisat B, Bissig K-D, et al. Differentiation of spontaneously contracting cardiomyocytes from non-virally reprogrammed human amniotic fluid stem cells. PLoS One. 2017;12(5):e0177824.
Pankowicz FP, Barzi M, Legras X, Hubert L, Mi T, Tomolonis JA, et al. Reprogramming metabolic pathways in vivo with CRISPR/Cas9 genome editing to treat hereditary tyrosinaemia. Nat Commun. 2016 Aug 30;7:12642.
Bissig K-D, Paust S, Barzi M. Liver is liver and blood is blood, and finally the twain have met. J Hepatol. 2016 Aug;65(2):245u20138.
Bissig-Choisat B, Kettlun-Leyton C, Legras XD, Zorman B, Barzi M, Chen LL, et al. Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer. J Hepatol. 2016 Aug;65(2):325u201333.
Billioud G, Kruse RL, Carrillo M, Whitten-Bauer C, Gao D, Kim A, et al. In vivo reduction of hepatitis B virus antigenemia and viremia by antisense oligonucleotides. J Hepatol. 2016 Apr;64(4):781u20139.
Shih Y-M, Sun C-P, Chou H-H, Wu T-H, Chen C-C, Wu P-Y, et al. Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice. Sci Rep. 2015 Oct 20;5:15259.
Lin F, Marcelo KL, Rajapakshe K, Coarfa C, Dean A, Wilganowski N, et al. The camKK2/camKIV relay is an essential regulator of hepatic cancer. Hepatology. 2015 Aug;62(2):505u201320.
Bissig-Choisat B, Wang L, Legras X, Saha PK, Chen L, Bell P, et al. Development and rescue of human familial hypercholesterolaemia in a xenograft mouse model. Nat Commun. 2015 Jun 17;6:7339.
Goldman O, Han S, Sourisseau M, Dziedzic N, Hamou W, Corneo B, et al. Erratum: KDR identifies a conserved human and murine hepatic progenitor and instructs early liver development (Cell Stem Cell (2013) 12 (748-760)). Cell Stem Cell. 2013 Dec 5;13(6):769.
Bissig K-D, Grompe M. Response to "Can 'humanized' mice improve drug development in the 21st century?". Trends Pharmacol Sci. 2013 Aug;34(8):425.
Goldman O, Han S, Sourisseau M, Dziedzic N, Hamou W, Corneo B, et al. KDR identifies a conserved human and murine hepatic progenitor and instructs early liver development. Cell Stem Cell. 2013 Jun 6;12(6):748u201360.
Ruiz S, Panopoulos AD, Herreru00edas A, Bissig K-D, Lutz M, Berggren WT, et al. A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity. Curr Biol. 2011 Jan 11;21(1):45u201352.
Bissig K-D, Wieland SF, Tran P, Isogawa M, Le TT, Chisari FV, et al. Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment. J Clin Invest. 2010 Mar;120(3):924u201330.
Bissig K-D, Le TT, Woods N-B, Verma IM. Repopulation of adult and neonatal mice with human hepatocytes: a chimeric animal model. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20507u201311.
Bissig K-D, Honer M, Zimmermann K, Summer KH, Solioz M. Whole animal copper flux assessed by positron emission tomography in the Long-Evans cinnamon rat--a feasibility study. Biometals. 2005 Feb;18(1):83u20138.
Bissig KD, Voegelin TC, Solioz M. Tetrathiomolybdate inhibition of the Enterococcus hirae CopB copper ATPase. FEBS Lett. 2001 Nov 2;507(3):367u201370.
Multhaup G, Strausak D, Bissig KD, Solioz M. Interaction of the CopZ copper chaperone with the CopA copper ATPase of Enterococcus hirae assessed by surface plasmon resonance. Biochem Biophys Res Commun. 2001 Oct 19;288(1):172u20137.
Bissig KD, Wunderli-Ye H, Duda PW, Solioz M. Structure-function analysis of purified Enterococcus hirae CopB copper ATPase: effect of Menkes/Wilson disease mutation homologues. Biochem J. 2001 Jul 1;357(Pt 1):217u201323.
Bissig KD, Mayerle J, Lerch MM, Friess H, Bu00fcchler MW. Pancreatic tumour of uncertain pathology: When is stenting or surgical intervention indicated? Deutsche Medizinische Wochenschrift. 2001 Jun 8;126(SUPPL. 2):S107u201314.
Bissig KD, La Fontaine S, Mercer JF, Solioz M. Expression of the human Menkes ATPase in Xenopus laevis oocytes. Biol Chem. 2001 Apr;382(4):711u20134.
Bissig KD, Marti U, Solioz M, Forestier M, Zimmermann H, Lu00fcthi M, et al. Epidermal growth factor is decreased in liver of rats with biliary cirrhosis but does not act as paracrine growth factor immediately after hepatectomy. J Hepatol. 2000 Aug;33(2):275u201381.
Solioz M, Bissig KD. [How (deficient) copper causes illness]. Schweiz Med Wochenschr. 1998 Aug 4;128(31u201332):1175u201380.

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