
Honors and Awards
Research Interests
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.
Publications
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Gamma secretase activating protein promotes end-organ dysfunction after bacterial pneumonia.
(Gwin MS, Alexeyev MF, Geurts AM, Lee JY, Zhou C, Yang XM, Cohen MV, Downey JM, Barrington RA, Spadafora D, Audia JP, Frank DW, Voth S, Pastukh VV, Bell J, Ayers L, Tambe DT, Nelson AR, Balczon R, Lin MT, Stevens T.) Am J Physiol Lung Cell Mol Physiol. 2023 Aug 01;325(2):L174-L189 PMID: 37366533 PMCID: PMC10396227 SCOPUS ID: 2-s2.0-85166442544 06/27/2023
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(Zietara A, Palygin O, Levchenko V, Dissanayake LV, Klemens CA, Geurts A, Denton JS, Staruschenko A.) Am J Physiol Renal Physiol. 2023 Aug 01;325(2):F177-F187 PMID: 37318990 PMCID: PMC10393338 SCOPUS ID: 2-s2.0-85164294757 06/15/2023
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Robustness of single-cell RNA-seq for identifying differentially expressed genes.
(Liu Y, Huang J, Pandey R, Liu P, Therani B, Qiu Q, Rao S, Geurts AM, Cowley AW Jr, Greene AS, Liang M.) BMC Genomics. 2023 Jul 03;24(1):371 PMID: 37394518 PMCID: PMC10316566 SCOPUS ID: 2-s2.0-85163598768 07/03/2023
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A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.
(de Jong TV, Pan Y, Rastas P, Munro D, Tutaj M, Akil H, Benner C, Chitre AS, Chow W, Colonna V, Dalgard CL, Demos WM, Doris PA, Garrison E, Geurts A, Gunturkun HM, Guryev V, Hourlier T, Howe K, Huang J, Kalbfleisch T, Kim P, Li L, Mahaffey S, Martin FJ, Mohammadi P, Ozel AB, Polesskaya O, Pravenec M, Prins P, Sebat J, Smith JR, Woods LCS, Tabakoff B, Tracey A, Uliano-Silva M, Villani F, Wang H, Sharp BM, Telese F, Jiang Z, Saba L, Wang X, Murphy TD, Palmer AA, Kwitek AE, Dwinell MMR, Williams RW, Li JZ, Chen H.) bioRxiv. 2023 Apr 14 PMID: 37214860 PMCID: PMC10197727 05/22/2023
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Heterogeneity of Islet-Infiltrating IL-21+ CD4 T Cells in a Mouse Model of Type 1 Diabetes.
(Ciecko AE, Wang Y, Harleston S, Drewek A, Serreze DV, Geurts AM, Lin CW, Chen YG.) J Immunol. 2023 Apr 01;210(7):935-946 PMID: 36762954 PMCID: PMC10483376 SCOPUS ID: 2-s2.0-85151043870 02/11/2023
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(Hess EM, Kassel SN, Simandl G, Raddatz N, Maunze B, Hurley MM, Grzybowski M, Klotz J, Geurts A, Liu QS, Choi S, Twining RC, Baker DA.) J Neurosci. 2023 Mar 29;43(13):2349-2361 PMID: 36788029 PMCID: PMC10072291 SCOPUS ID: 2-s2.0-85151313130 02/15/2023
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(Shafiee S, Jagtap J, Zayats M, Epperlein J, Banerjee A, Geurts A, Flister M, Zhuk S, Joshi A.) Cancers (Basel). 2023 Feb 25;15(5) PMID: 36900252 PMCID: PMC10000786 SCOPUS ID: 2-s2.0-85149856201 03/12/2023
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(Lenarczyk M, Alsheikh AJ, Cohen EP, Schaue D, Kronenberg A, Geurts A, Klawikowski S, Mattson D, Baker JE.) Toxics. 2023 Feb 16;11(2) PMID: 36851074 PMCID: PMC9959763 SCOPUS ID: 2-s2.0-85149176377 03/01/2023
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(Arnold AP, Chen X, Grzybowski MN, Ryan JM, Sengelaub DR, Mohanroy T, Furlan VA, Grisham W, Malloy L, Takizawa A, Wiese CB, Vergnes L, Skaletsky H, Page DC, Reue K, Harley VR, Dwinell MR, Geurts AM.) bioRxiv. 2023 Feb 10 PMID: 36798326 PMCID: PMC9934672 02/18/2023
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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
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(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 SCOPUS ID: 2-s2.0-85144589577 10/12/2022
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(Lenarczyk M, Alsheikh AJ, Cohen EP, Schaue D, Kronenberg A, Geurts A, Klawikowski S, Mattson D, Baker JE.) Toxics. 2022 Dec 18;10(12) PMID: 36548630 PMCID: PMC9783591 12/23/2022