Kristian Almstrup

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The Almstrup group is mainly located at the Department of Growth and Reproduction, at Copenhagen University Hospital - Rigshospitalet but is also affiliated with the Department of Cellular and Molecular Medicine, at University of Copenhagen. Our research focus on studies that connect genetic and epigenetic variation to reproductive endpoints, testicular gene expression and functional studies of sperm cells.

 

Group homepage: https://www.rigshospitalet.dk/almstrup 

 

Primary fields of research

Genetic and epigenetic variation in relation to reproductive endpoints, testicular gene expression and functional studies of sperm cells.

Teaching

Medical genetics course (Medicine and Molecular Biomedicine)

Possible conflicts of interest

None

Current research

Genetic and epigenetic variation

The Almstrup group has been pioneering in describing genetic and epigenetic variation associated with several reproductive endpoints. This includes genetic variants causing non-obstructive azoospermia (GEMINI, IMIGC consortia), genetic variants associated with testicular germ cell cancer (TECAC consortia) as well as genetic variants and DNA methylation patterns that have a significant effect on the age of pubertal onset.

Small RNAs

Small RNAs, like micro RNAs (miRNAs) and the PIWI-interacting RNAs (piRNAs), is an area of great interest to our group. We have shown that the piRNAs, which are nearly unique to male germ cell, are essential for human spermatogenesis and have identified piRNAs in seminal plasma and in circulation that may serve as markers of testicular function. However, also specific miRNAs show great promise as novel sensitive biomarker of testicular germ cell cancer.

Testicular gene expression

The testis is a complex tissue with many different cell types and studies of testicular gene expression, therefore, needs to take into account the composition of cell types that are present in the analysis. The Almstrup group has been involved in studies of testicular gene expression since the pre-omics era, using differential display techniques, and are now working with single-cell/nuclei methods and spatial transcriptomics.

Sperm cell function

Sperm cells are unique because they have a tightly packed haploid genome, are extremely differentiated, and has the sole purpose of fertilising an egg. We have shown that the number of viable sperm cells with an intact acrosome is important for the fertility of men and that environmental chemicals can influence sperm cell function directly.

Selected publications

1. Published

   Variant PNLDC1, Defective piRNA Processing, and Azoospermia

   Nagirnaja, L., Mørup, N., Nielsen, J. E., Stakaitis, R., Golubickaite, I., Oud, M. S., Winge, S. B., Carvalho, F., Aston, K. I., Khani, F., Van Der Heijden, G. W., Marques, C. J., Skakkebæk, Niels Erik, Rajpert–de Meyts, E., Schlegel, P. N., Jørgensen, N., Veltman, J. A., Lopes, A. M., Conrad, D. F. & Almstrup, Kristian, 19 Aug 2021, In: New England Journal of Medicine. 385, 8, p. 707-719 13 p.

   Research output: Contribution to journal › Journal article › peer-review

2. Published

   PIWI ‐interacting RNAs and human testicular function

   Saritas, G., Main, A. M., Winge, S. B., Mørup, N. & Almstrup, Kristian, 2022, In: WIREs Mechanisms of Disease. 14, 6, e1572.

   Research output: Contribution to journal › Journal article › peer-review

3. Diverse monogenic subforms of human spermatogenic failure

   Nagirnaja, L., Lopes, A. M., Charng, W., Miller, B., Stakaitis, R., Golubickaite, I., Stendahl, A., Luan, T., Friedrich, C., Mahyari, E., Fadial, E., Kasak, L., Vigh-Conrad, K., Oud, M. S., Xavier, M. J., Cheers, S. R., James, E. R., Guo, J., Jenkins, T. G., Riera-Escamilla, A., Barros, A., Carvalho, F., Fernandes, S., Gonçalves, J., Gurnett, C. A., Jørgensen, N., Jezek, D., Jungheim, E. S., Kliesch, S., McLachlan, R. I., Omurtag, K. R., Pilatz, A., Sandlow, J. I., Smith, J., Eisenberg, M. L., Hotaling, J. M., Jarvi, K. A., Punab, M., Rajpert-De Meyts, E., Carrell, D. T., Krausz, C., Laan, M., O'Bryan, M. K., Schlegel, P. N., Tüttelmann, F., Veltman, J. A., Almstrup, Kristian, Aston, K. I. & Conrad, D. F., 26 Dec 2022, In: Nature Communications. 13, 1, p. 7953

   Research output: Contribution to journal › Journal article › peer-review

4. Published

   The molecular evolution of spermatogenesis across mammals

   Murat, F., Mbengue, N., Winge, S. B., Trefzer, T., Leushkin, E., Sepp, M., Cardoso-Moreira, M., Schmidt, J., Schneider, C., Mößinger, K., Brüning, T., Lamanna, F., Belles, M. R., Conrad, C., Kondova, I., Bontrop, R., Behr, R., Khaitovich, P., Pääbo, S., Marques-Bonet, T., Grützner, F., Almstrup, Kristian, Schierup, M. H. & Kaessmann, H., 2023, In: Nature. 613, p. 308–316

   Research output: Contribution to journal › Journal article › peer-review

5. Published

   Environmental factors in declining human fertility

   Skakkebæk, Niels Erik, Lindahl-Jacobsen, R., Levine, H., Andersson, A., Jørgensen, N., Main, Katharina Maria, Lidegaard, Øjvind, Priskorn, Lærke, Holmboe, S. A., Bräuner, E. V., Almstrup, Kristian, Franca, L. R., Znaor, A., Kortenkamp, A., Hart, R. J. & Juul, Anders, 2022, In: Nature Reviews Endocrinology. 18, p. 139–157

   Research output: Contribution to journal › Review › peer-review

6. Published

   Identification of 22 susceptibility loci associated with testicular germ cell tumors

   Pluta, J. & The Testicular Cancer Consortium, T. T. C. C., 2021, In: Nature Communications. 12, 1, 4487.

   Research output: Contribution to journal › Journal article › peer-review

7. Application of miRNAs in the diagnosis and monitoring of testicular germ cell tumours

   Almstrup, Kristian, Lobo, J., Mørup, N., Belge, G., Rajpert-De Meyts, E., Looijenga, L. H. J. & Dieckmann, K. P., 1 Apr 2020, In: Nature Reviews Urology. 17, 4, p. 201-213 13 p.

   Research output: Contribution to journal › Review › peer-review

Selected activities

1. Andrology (Journal)

   Almstrup, Kristian (Editor)

   1 Jan 2023

   Activity: Peer-review and editorial work types › Editor of Research journal › Communication

2. Scientific Reports (Journal)

   Almstrup, Kristian (Editor)

   17 Aug 2020

   Activity: Peer-review and editorial work types › Editor of Research journal › Research

3. Frontiers in Cell and Developmental Biology (Journal)

   Almstrup, Kristian (Editor)

   9 Nov 2021

   Activity: Peer-review and editorial work types › Editor of Research journal › Research