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.
(Mehrotra P, Ullah MM, Collett JA, Myers SL, Dwinell MR, Geurts AM, Basile DP.) Am J Physiol Renal Physiol. 2020 11 01;319(5):F796-F808 PMID: 32924545 SCOPUS ID: 2-s2.0-85094221372 09/15/2020
(Alexeyev M, Geurts AM, Annamdevula NS, Francis CM, Leavesley SJ, Rich TC, Taylor MS, Lin MT, Balczon R, Knighten JM, Alvarez DF, Stevens T.) Am J Physiol Heart Circ Physiol. 2020 08 01;319(2):H349-H358 PMID: 32589443 PMCID: PMC7473926 SCOPUS ID: 2-s2.0-85088491118 06/27/2020
(Kitagawa A, Kizub I, Jacob C, Michael K, D'Alessandro A, Reisz JA, Grzybowski M, Geurts AM, Rocic P, Gupte R, Miano JM, Gupte SA.) Hypertension. 2020 Aug;76(2):523-532 PMID: 32507041 SCOPUS ID: 2-s2.0-85088206977 06/09/2020
(Chen YG, Ciecko AE, Khaja S, Grzybowski M, Geurts AM, Lieberman SM.) Sci Rep. 2020 07 21;10(1):12019 PMID: 32694640 PMCID: PMC7374577 SCOPUS ID: 2-s2.0-85088288172 07/23/2020
(Cheng Y, Wang D, Wang F, Liu J, Huang B, Baker MA, Yin J, Wu R, Liu X, Regner KR, Usa K, Liu Y, Zhang C, Dong L, Geurts AM, Wang N, Miller SS, He Y, Liang M.) J Am Soc Nephrol. 2020 Jul;31(7):1539-1554 PMID: 32487559 PMCID: PMC7350998 SCOPUS ID: 2-s2.0-85087468924 06/04/2020
(Johnston JG, Speed JS, Becker BK, Kasztan M, Soliman RH, Rhoads MK, Tao B, Jin C, Geurts AM, Hyndman KA, Pollock JS, Pollock DM.) Hypertension. 2020 Jun;75(6):1624-1634 PMID: 32306766 PMCID: PMC7228023 SCOPUS ID: 2-s2.0-85084695306 04/21/2020
(Prokop JW, Chhetri SB, van Veen JE, Chen X, Underwood AC, Uhl K, Dwinell MR, Geurts AM, Correa SM, Arnold AP.) Biol Sex Differ. 2020 05 12;11(1):28 PMID: 32398044 PMCID: PMC7216353 SCOPUS ID: 2-s2.0-85084627810 05/14/2020
(Shapiro MR, Yeh WI, Longfield JR, Gallagher J, Infante CM, Wellford S, Posgai AL, Atkinson MA, Campbell-Thompson M, Lieberman SM, Serreze DV, Geurts AM, Chen YG, Brusko TM.) Front Immunol. 2020;11:2180 PMID: 33013915 PMCID: PMC7500101 SCOPUS ID: 2-s2.0-85091212749 10/06/2020
(Shapiro MR, Yeh WI, Longfield JR, Gallagher J, Infante CM, Wellford S, Posgai AL, Atkinson MA, Campbell-Thompson M, Lieberman SM, Serreze DV, Geurts AM, Chen YG, Brusko TM.) Frontiers in Immunology. 4 September 2020;11 SCOPUS ID: 2-s2.0-85091212749 09/04/2020
(Kim MS, Fleres B, Lovett J, Anfinson M, Samudrala SSK, Kelly LJ, Teigen LE, Cavanaugh M, Marquez M, Geurts AM, Lough JW, Mitchell ME, Fitts RH, Tomita-Mitchell A.) Front Cell Dev Biol. 2020;8:440 PMID: 32656206 PMCID: PMC7324479 07/14/2020
(Kim MS, Fleres B, Lovett J, Anfinson M, Samudrala SSK, Kelly LJ, Teigen LE, Cavanaugh M, Marquez M, Geurts AM, Lough JW, Mitchell ME, Fitts RH, Tomita-Mitchell A.) Frontiers in Cell and Developmental Biology. 23 June 2020;8 SCOPUS ID: 2-s2.0-85087475806 06/23/2020
(Exner EC, Geurts AM, Hoffmann BR, Casati M, Stodola T, Dsouza NR, Zimmermann M, Lombard JH, Greene AS.) PLoS One. 2020;15(4):e0232067 PMID: 32324784 PMCID: PMC7179868 SCOPUS ID: 2-s2.0-85083695035 04/24/2020