Karl-Dimiter Bissig, M.D., Ph.D.
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Positions
- Associate Professor
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Molecular and Cellular Biology
Center for Cell and Gene Therapy
Baylor College of Medicine
- Member
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Texas Medical Center Digestive Diseases Center (DDC)
Dan L Duncan Comprehensive Cancer Center (DLDCCC)
Baylor College of Medicine
Houston, Texas United States
Addresses
- Department of Molecular and Cellular Biology (Office)
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Stem Cells and Regenerative Medicine Center
Houston, TX 77030
United States
Education
- MD from School of Medicine, University of Bern
- 01/1996 - Bern, Switzerland
- PhD from School of Medicine, University of Bern
- 01/2000 - Bern, Switzerland
- Clinical Fellowship at University Hospital Bern
- 01/2005 - Bern, Switzerland
- Internal Medicine and Gastroenterology
- Postdoctoral Fellowship at Salk Institute for Biological Studies
- 02/2011 - La Jolla, California
Professional Interests
- Genome engineering in the liver
- Metabolic liver disease
- Human liver chimeric mice
- Liver cancer
- Hepatitis B virus
- Cell based therapy for liver disease
Professional Statement
We are interested in translating basic science breakthroughs into therapeutic approaches for liver disorders. Our research is therefore best described as from “bench to bedside”. We are not focused on one liver disorder in particular but our interest ranges from liver cancer to viral hepatitis to metabolic liver disorders.Basic science is often poorly translated into the clinic due to lack of experimental animal models for human disease. Indeed, metabolic pathways differ significantly across the animal kingdom. Therefore, we spend considerable effort generating new in vivo systems for primary and diseased human hepatocytes.
Our therapeutic strategies include new concepts and biologics. The advent of CRISPR/Cas9 technology has generated enormous excitement throughout the many fields of biology and biomedical research, though its broad therapeutic application has been stymied by lack of a feasible approach for genome editing that obviates its chief risks. We recently developed a therapeutic genome editing approach, called metabolic pathway reprogramming, that couples the power of CRISPR/Cas9 technology with a strategy from pharmacology, namely, inhibition of an enzymatic pathway rather than direct editing of a disease-causing gene. We have demonstrated the efficacy of this approach using CRISPR/Cas9 to convert the fatal type I tyrosinemia into benign type III tyrosinemia in mice.
Websites
Selected Publications
- Barzi M, Pankowicz FP, Zorman B, Liu X, Legras X, Yang D, Borowiak M, Bissig-Choisat B, Sumazin P, Li F, Bissig KD. "A novel humanized mouse lacking murine P450 oxidoreductase for studying human drug metabolism.." Nat Commun. 2017 Jun 28;39:s41467-017. Pubmed PMID: 28659616
- Pankowicz FP, Jarrett KE, Lagor WR, Bissig KD "CRISPR/Cas9: at the cutting edge of hepatology." Gut. 2017 Jul;66(7):1329-1340. Pubmed PMID: 28487442
- Pankowicz FP, Barzi M, Legras X, Hubert L, Mi T, Tomolonis JA, Ravishankar M, Sun Q, Yang D, Borowiak M, Sumazin P, Elsea SH, Bissig-Choisat B, Bissig KD. "Reprogramming metabolic pathways in vivo with CRISPR/Cas9 genome editing to treat hereditary tyrosinaemia.." Nat Commun. 2016 Aug 30;7:12642. Pubmed PMID: 27572891
- Bissig KD, Paust S, Barzi M "Liver is liver and blood is blood, and finally the twain have met.." J Hepatol.. 2016 Aug;65(2):245-8. Pubmed PMID: 27221221
- Bissig-Choisat B, Kettlun-Leyton C, Legras XD, Zorman B, Barzi M, Chen LL, Amin MD, Huang YH, Pautler RG, Hampton OA, Prakash MM, Yang D, Borowiak M, Muzny D, Doddapaneni HV, Hu J, Shi Y, Gaber MW, Hicks MJ, Thompson PA, Lu Y, Mills GB, Finegold M, "Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer.." J Hepatol.. 2016 Aug;65(2):325-33. Pubmed PMID: 27117591
- Billioud G, Kruse RL, Carrillo M, Whitten-Bauer C, Gao D, Kim A, Chen L, McCaleb ML, Crosby JR, Hamatake R, Hong Z, Garaigorta U, Swayze E, Bissig KD, Wieland S. "In vivo reduction of hepatitis B virus antigenemia and viremia by antisense oligonucleotides.." J Hepatol.. 2016 Apr;64(4):781-9. Pubmed PMID: 26658683
- Shih YM,, Sun CP, Chou HH, Wu TH, Chen CC, Wu PY, Enya Chen YC, Bissig KD, Tao MH,. "Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice.." Sci Rep. 2015 Oct 20;5 Pubmed PMID: 26482836
- Bissig-Choisat B, Wang L, Legras X, Saha PK, Chen L, Bell P, Pankowicz FP, Hill MC, Barzi M, Kettlun Leyton C, Leung HC, Kruse RL, Himes RW, Goss JA, Wilson JM, Chan L, Lagor WR, Bissig KD. "Development and rescue of human familial hypercholesterolaemia in a xenograft mouse model.." Nat Commun.. 2015 Jun 17; Pubmed PMID: 26081744
- Lin F, Marcelo KL, Rajapakshe K, Coarfa C, Dean A, Wilganowski N,, Robinson H, Sevick E,, Bissig KD, Goldie LC, Means AR,, York B,. "The camKK2/camKIV relay is an essential regulator of hepatic cancer.." Hepatology. 2015 Aug;62(2):505-20. Pubmed PMID: 25847065
- Goldman O, Han S, Sourrisseau M, Dziedzic N, Hamou W, Corneo B, D'Souza S, Sato T, Kotton DN, Bissig KD, Kalir T, Jacobs A, Evans T, Evans MJ, Gouon-Evans V "KDR Identifies a Conserved Human and Murine Hepatic Progenitor and Instructs Early Liver Development." Cell Stem Cell. 2013 Jun 6;12(6):748-60. Pubmed PMID: 23746980
- Bissig KD, Wieland SF, Tran P, Isogawa M, Le TT, Chisari FV, Verma IM "Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment." J. Clin. Invest. 2010 Mar 1;120(3):924-30. Pubmed PMID: 20179355
- Bissig KD, Le TT, Woods NB, 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):20507-11. Pubmed PMID: 18077355
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