Krawetz Lab

DR. STEPHEN A. KRAWETZ

Charlotte B. Failing Professor of Fetal Therapy and Diagnosis  
Associate Director C.S. Mott Center for Human Growth and Development,
Wayne State University School of Medicine
Department of Obstetrics and Gynecology
Center for Molecular Medicine and Genetics

 

RESEARCH INTEREST

My entry into high throughput systems-scale genomics began as I was completing my postdoctoral fellowship with the creation of the first computer video-acquisition sequencing system.  To develop appropriate base calling data interpretation algorithms, I was the first to describe and characterize sequence error rates within genomic data available with GeneBank. As a faculty member, mapping of DNase I-sensitive chromatin domains in human spermatozoa followed with in-depth developmental analysis using humanized animal models that showed a nick by topoisomerase II is one of the first events that readies a chromatin domain for transcription (1). My laboratory was one of the first to embrace a genome-wide systems approach to directly address whether we identified the exception or the rule.  This included the development of chromosome-specific aCGH to map genome-wide DNA/protein interactions supplemented with the 454 sequencing in collaboration with the Joint Genome Initiative as we transitioned to the Illumina Hi-Seq 2500.  We have extended our capabilities to the 4D metamorphosis of the male gamete's genome (2). Data acquisition and analysis required the creation of custom computer code that was not available when the projects were initiated.  The goals of my program have been expanded to include understanding the contribution of paternal RNAs at fertilization to the development of a healthy child. Contrary to dogma we showed that at the time of fertilization the spermatozoon delivers a cadre of unique mRNAs along with small RNAs, including antisense and microRNAs to the oocyte (3). This concept has now been expanded to RNA elements and directly tested as components of early human development from the human type a dark spermatogonia to blastocyst (4). The unique attributes of this transcriptionally and translationally inactive system have pushed us to develop a series of whole genome analysis tools to objectively assess fertility status as a bellwether of disease (5) as we translate this technology to the clinic. This has helped to shape public policy of the impact of environment on the father's contribution to the child (6).

REFERENCES

  1. Martins, R. P. and Krawetz, S.A. (2007) Decondensing the protamine domain for transcription.  Proceedings of the National Academy of Sciences (U.S.A.) 104:8340-8345.  PMID: 17483471 
  2. Johnson, G.D., Jodar, M., Pique-Regi, R., Krawetz, S.A., (2016) Nuclease Footprints in Sperm Project Past and Future Chromatin Regulatory Events, (Nature's) Scientific Reports.  6:25864 PMID: 27184706
  3. Ostermeier, G.C., Miller, D., Huntriss, J.D., Diamond, M.P. and Krawetz, S.A. (2004) Delivering spermatozoan RNA to the oocyte.  Nature 429:154.  PMID: 15141202
  4. Estill, M.S., Hauser, R. Krawetz, S.A. (2019) RNA element discovery from germ cell to blastocyst. Nucleic Acids Research. 18:2263-2275 PMID: 30576549   
  5. Jodar, M., Sendler, E., Moskovtsev, S. Librach, C., Goodrich, R., Swanson, S., Hauser, R., Diamond, M. and Krawetz, S.A. (2015) Absence of sperm RNA elements correlates with idiopathic male infertility. Science Translational Medicine. 7(295):295re6. PMID: 26157032.
  6. National Academies of Sciences, Engineering and Medicine Gulf War and Health: Volume 11: Generational Health Effects of Serving in the Gulf War (2018) ISBN 978-0-309-47823-6 DOI 10.17226/25162.

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Postdoctoral Positions Available