Honors and Awards
- Animals, Genetically Modified
- DNA Transposable Elements
- Genetic Engineering
- Genetic Research
- Organisms, Genetically Modified
Methodologies and Techniques
- Animals, Genetically Modified
- Cloning, Molecular
- Embryonic Stem Cells
- Genetic Vectors
- Organisms, Genetically Modified
- Rats, Inbred BN
- Rats, Inbred Dahl
- Rats, Inbred Strains
- Sequence Analysis, DNA
MCW Program / Core Facilities
- Rat Transgenic Service Center
Continuing research efforts in the Geurts lab are being driven by our interests in developing genetic approaches toward understanding human health and disease. For the past 12 years, we have been developing tools for genetic manipulation in a variety of cell and animal systems including stem cells, zebrafish, mice and laboratory rats. These systems are among the most widely preferred models for genetic and physiological investigation into human disease, however, genetic approaches, especially in non-mouse systems, have traditionally been limited by a lack of technologies.
After joining the Medical College in 2006, we implemented new approaches to accelerate transgenic and gene knockout studies for the PhysGen Program for Genomic Applications by adapting the Sleeping Beauty transposable element system for use in rats. Transposons are currently the most reproducible and efficient tool available for adding new genes to the rat genome and since then, we have worked with several other local investigators to create new transgenic rat models.
In 2009, we were fortunate to be the first to demonstrate that engineered proteins called Zinc Finger Nucleases (ZFNs) could be applied to rat embryos to generate the world’s first targeted gene knockout rats. This breakthrough revolutionized the local and broader research communities who use laboratory rats as a model system and other researchers are now applying these methods to other animal models such as mice, pigs, and rabbits. Site-specific modification of the rat genome using ZFNs is used to disrupt (knockout) or introduce specific gene alleles (knockin) to modify gene function. To date, we have created more than 100 knockout and knockin genetic models for several research areas related to our collaborative interests in complex diseases such as hypertension, renal disease, Type 1 Diabetes, and drug abuse.
More recently, the Geurts lab has been developing TAL Effector Nuclease (TALEN) technology for targeted genome engineering. TALENs are a relatively new technology which are analogous to ZFNs, but have some attractive attributes including reduced cost and design flexibility which will facilitate their use in the field. This new technique is complemented by our recent development of the first rat embryonic stem cells from a hypertensive rat model in collaboration with the laboratory of Dr. Howard Jacob. The availability of stem cells from this disease model rat now provides unique possibilities for creating more complicated genetic models. We are currently establishing whether these cells are capable of supporting our engineering approaches for producing genetically modified rats.
Recently, Dr. Geurts' creative and innovative contributions to the field of genetics and technology were recognized by the granting of a New Innovator Award from the Office of the Director of the National Institutes of Health. This prominent award will propel efforts in the Geurts lab toward pushing the limits of these technologies to create better models of human disease. These techniques, animal models, and resources broadly benefit the local and broader research communities and advance our collective understanding of complex human genetic diseases.
MDA5-dependent responses contribute to autoimmune diabetes progression and hindrance.
(Blum SI, Taylor JP, Barra JM, Burg AR, Shang Q, Qiu S, Shechter O, Hayes AR, Green TJ, Geurts AM, Chen YG, Tse HM.) JCI Insight. 2023 Jan 24;8(2) PMID: 36512407 PMCID: PMC9977297 SCOPUS ID: 2-s2.0-85147047458 12/14/2022
Genetic Mapping of Multiple Traits Identifies Novel Genes for Adiposity, Lipids, and Insulin Secretory Capacity in Outbred Rats.
(Hong-Le T, Crouse WL, Keele GR, Holl K, Seshie O, Tschannen M, Craddock A, Das SK, Szalanczy AM, McDonald B, Grzybowski M, Klotz J, Sharma NK, Geurts AM, Key CC, Hawkins G, Valdar W, Mott R, Solberg Woods LC.) Diabetes. 2023 Jan 01;72(1):135-148 PMID: 36219827 PMCID: PMC9797320 10/12/2022
Knockout of the Circadian Clock Protein PER1 (Period1) Exacerbates Hypertension and Increases Kidney Injury in Dahl Salt-Sensitive Rats.
(Zietara A, Spires DR, Juffre A, Costello HM, Crislip GR, Douma LG, Levchenko V, Dissanayake LV, Klemens CA, Nikolaienko O, Geurts AM, Gumz ML, Staruschenko A.) Hypertension. 2022 Nov;79(11):2519-2529 PMID: 36093781 PMCID: PMC9669134 SCOPUS ID: 2-s2.0-85140407817 09/13/2022
Lack of xanthine dehydrogenase leads to a remarkable renal decline in a novel hypouricemic rat model.
(Dissanayake LV, Zietara A, Levchenko V, Spires DR, Burgos Angulo M, El-Meanawy A, Geurts AM, Dwinell MR, Palygin O, Staruschenko A.) iScience. 2022 Sep 16;25(9):104887 PMID: 36039296 PMCID: PMC9418856 08/31/2022
Sleeve Gastrectomy Improves High-Fat Diet-Associated Hepatic Steatosis Independent of the Glucagon-like-Petpide-1 Receptor in Rats.
(Barron M, Hayes H, Fernando DG, Geurts AM, Kindel TL.) J Gastrointest Surg. 2022 Aug;26(8):1607-1618 PMID: 35618993 PMCID: PMC9444920 SCOPUS ID: 2-s2.0-85130689967 05/27/2022
Btg2 mutation induces renal injury and impairs blood pressure control in female rats.
(Hoffman MJ, Takizawa A, Jensen ES, Schilling R, Grzybowski M, Geurts AM, Dwinell MR.) Physiol Genomics. 2022 Jul 01;54(7):231-241 PMID: 35503009 PMCID: PMC9208437 SCOPUS ID: 2-s2.0-85132453480 05/04/2022
Hybrid Rat Diversity Program (HRDP): A rat resource for mapping complex traits.
(Dwinell M, Takizawa A, Lazcares L, Tutaj M, Schilling R, Geurts A, Kwitek A.) FASEB J. 2022 May;36 Suppl 1 PMID: 35560431 SCOPUS ID: 2-s2.0-85130045442 05/14/2022
Keratinocyte-associated Protein 3May Participate in the Stress Response to Impact Adiposity
(Szalanczy AM, Giorgio G, Goff E, Seshie O, Grzybowski M, Klotz J, Roberts M, Geurts AM, Redei EE, Solberg Woods LC.) FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 1 May 2022;36 PMID: 35554436 SCOPUS ID: 2-s2.0-85130034963 05/01/2022
Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females.
(Szalanczy AM, Goff E, Seshie O, Deal A, Grzybowski M, Klotz J, Chuang Key CC, Geurts AM, Solberg Woods LC.) Front Genet. 2022;13:942574 PMID: 36212147 PMCID: PMC9535360 10/11/2022
Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females
(Szalanczy AM, Goff E, Seshie O, Deal A, Grzybowski M, Klotz J, Chuang Key CC, Geurts AM, Solberg Woods LC.) Frontiers in Genetics. 21 September 2022;13 SCOPUS ID: 2-s2.0-85139449376 09/21/2022
Lack of xanthine dehydrogenase leads to a remarkable renal decline in a novel hypouricemic rat model
(Dissanayake LV, Zietara A, Levchenko V, Spires DR, Burgos Angulo M, El-Meanawy A, Geurts AM, Dwinell MR, Palygin O, Staruschenko A.) iScience. 16 September 2022;25(9) SCOPUS ID: 2-s2.0-85136236916 09/16/2022
Advancing Physiology with Expanded Multi-Omics.
(Liang M, Cowley AW Jr, Greene AS, Geurts AM, Liu P, Liu Y, Rao S.) Function (Oxf). 2022;3(4):zqac031 PMID: 35801086 PMCID: PMC9247404 07/09/2022