Susan Dymecki Explained

Susan Dymecki
Birth Date:19 June 1960
Birth Place:Philadelphia, Pennsylvania, U.S.
Fields:Neuroscience, genetics
Workplaces:Harvard Medical School
Alma Mater:University of Pennsylvania, Johns Hopkins University School of Medicine
Known For:Flp-FRT genetic recombination tools, mapping serotonergic heterogeneity and function
Awards:Rita Allen Foundation Scholar, Gulf Oil Outstanding Achievement in Biomedical Science Award, AAAS Member

Susan M. Dymecki (born June 19, 1960) is an American geneticist and neuroscientist and director of the Biological and Biomedical Sciences PhD Program at Harvard University.[1] Dymecki is also a professor in the Department of Genetics and the principal investigator of the Dymecki Lab at Harvard. Her lab characterizes the development and function of unique populations of serotonergic neurons in the mouse brain. To enable this functional dissection, Dymecki has pioneered several transgenic tools for probing neural circuit development and function. Dymecki also competed internationally as an ice dancer, placing 7th in the 1980 U.S. Figure Skating Championships.[2] [3] [4]

Early life and education

Dymecki was born in Philadelphia, Pennsylvania, on June 19, 1960.[5] Before becoming a scientist, Dymecki was a competitive ice dancer. She started ice dancing when she was 13 years old and competed at the national level within the United States during high school.

Dymecki pursued a Bachelor of Science in Engineering at the University of Pennsylvania, and during this time she competed internationally in ice dancing. When Dymecki was 20 years old, her and her ice dancing partner ranked 6th in the United States. After taking a year off to compete, she completed her bachelor's degree and then stayed at UPenn to complete a Master of Science in Engineering. During her Master's, she worked in the lab of Carl Theodore Brighton exploring the use of electric current in stimulating osteogenesis.[6]

After completing her master's degree, she pursued her MD-PhD in 1985 at the Johns Hopkins School of Medicine, studying under Stephen Desiderio.[7] During her PhD, Dymecki discovered a new gene expressed in B cells, called blk for B Lymphoid Kinase, which helps to initiate an immune response. After completing her MD-PhD training in 1992, Dymecki became a Helen Hay Whitney Fellow and John Merck Scholar at the Carnegie Institution for Science in the Department of Embryology in Washington, DC. While completing her postdoctoral training, she pioneered novel genetic tools with which to study development in the mammalian nervous system. In 1997, Dymecki filed a patent for her genetic tool, which consisted of DNA constructs that enable transgenic expression of FRT recombination sites and a Flp recombinase in non-human mammals.[8]  Her technology has aided many researchers in achieving gene insertion, deletion, and modulation as well as label cell lineages to explore developmental stages.

Identification of B Lymphoid Kinase

During graduate school, Dymecki isolated and characterized a novel gene, blk, named after B Lymphoid Kinase.[9] This gene encodes a tyrosine kinase protein, and is specifically expressed in B cell lineages. Through further characterization of the transcriptional of blk, Dymecki found that none of its transcriptional start sites are preceded by TATA elements, AT-rich elements, or other common start site motifs.[10] Dymecki also found that blk is expressed in pro-, pre-, and mature B cells, but not the antibody producing plasma cells.

Flp recombinase tool development

During Dymecki's postdoctoral work at the Carnegie Institute, she pioneered the development of novel vectors that enabled targeted genetic manipulation of specific populations of mammalian cells.[11] Using Flp recombinase, Dymecki shows that her genetic constructs can be expressed in mammalian cells to activate specific genes. In a following paper in 1996, Dymecki showed that her tool not only worked in cell culture, but also in vivo in living transgenic mice to mediate gene insertion and deletion via recombination at FRT sites.[12] Dymecki's paper was the inaugural paper to show that Flp technology could be used to make specific alterations to the mouse genome.

Career and research

In 1998, Dymecki joined the faculty at Harvard Medical School and became an associate professor in the Department of Genetics. Dymecki's involvement with graduate education led her to become the associate director of the Biological and Biomedical Sciences PhD program in 2004. By 2010, Dymecki was promoted to Full Professor in the Department of Genetics, and the following year she became the Director of the Biological and Biomedical Science PhD Program at Harvard.[13]

As the Principal Investigator of the Dymecki Lab, Dymecki runs a research program dedicated to exploring the development and function of serotonin neurons in the rodent brain. Since Dymecki has found that serotonergic neurons are implicated in a wide range of critical processes from respiration, to thermal regulation, to emotional state, her research addresses fundamental questions about how the specific neural subtypes and circuits underlying these processes develop such that they can be targeted in the future to treat disease.

Innovation of Flp recombinase transgenic tools

After establishing Flp recombinase as an available genetic tool for site specific recombination in the mouse brain, Dymecki further optimized this tool.[14] By creating the FLPe deleter strain, which uses an enhanced, thermostable version of Flp, Dymecki found that her tool was just as effective as the already established Cre-loxP tools. Since highly specific targeting of cell populations requires combinatorial genetic strategies, Dymecki's optimization enabled Flp and Cre to be used together in mammalian transgenic systems to perform highly targeted mutations. Following this optimization, Dymecki and her team created a FLPer (“flipper”) mouse line that has global, constitutive Flp expression that can be used to label specific cell populations, or to be crossed with other strains to create opportunities for cell-type specific conditional knockouts.[15]

Serotonergic diversity in mouse brain

Dymecki's lab uses their transgenic tools to probe the diversity of serotonin neurons in the central nervous system.[16] Using a variety of genetic profiling and developmental mapping techniques, Dymecki and her team were able to identify various subpopulations of serotonin neurons within the brainstem, and show the immense transcriptional diversity both between and within anatomically defined subpopulations of serotonin neurons. They also found that these transcriptional, anatomical, and molecular differences, lead to differences in function.

Serotonin neurons in aggression

Narrowing in on specific subtypes of serotonin neurons has enabled Dymecki and her team to identify the unique behaviors modulated by specific populations of serotonin neurons. For example, the Pet1+ serotonin neurons that also express either dopamine receptor 1 or dopamine receptor 2 were shown to be implicated in aggression.[17] When these neural subtypes were silenced, male aggressive behavior in mice was increased, suggesting the unique role played in a behavior by a very specific population of brainstem serotonergic neurons. Dymecki and her colleagues then found that serotonergic neurons also mediate aggression in Drosophila.[18]  They found two serotonergic projections, a GABAergic projection that decreased aggression when stimulated, and a cholinergic projection that increased aggression when stimulated.

Serotonin in respiration

Dymecki and her team have characterized the role of serotonin neurons in the regulation of breathing dynamics.[19] By chemogenetically manipulating single sub-populations of serotonin neurons, they found one population, expressing Egr1-Pet1 that increases ventilation in response to acidosis. Following this study, Dymecki and her colleagues identified another unique serotonin population, this time characterized by Tac1-Pet1 that are also implicated in driving ventilation but differ in their projection targets and methods of sensing inhaled .[20]

Awards and honors

Select publications

References

  1. Web site: Susan Dymecki. dymeckilab.hms.harvard.edu. 2020-03-07.
  2. Web site: Skating Results U.S. Figure Skating Championships. UPI. en. 2020-03-07.
  3. Web site: Susan Dymecki: Serotonin Circuit Master . Rita Allen Foundation. May 27, 2016. en-US. 2020-03-07.
  4. Web site: As ice dancer or researcher...plenty of smooth skating Even at benchework,Susan Dymecki turns up a winner. Crockett. Sandra. baltimoresun.com. en-US. 2020-03-07.
  5. Web site: As ice dancer or researcher...plenty of smooth skating Even at benchework,Susan Dymecki turns up a winner. Crockett. Sandra. baltimoresun.com. en-US. 2020-05-08.
  6. Dymecki. S. M.. Black. J.. Nord. D. S.. Jones. S. B.. Baranowski. T. J.. Brighton. C. T.. 1985. Medullary osteogenesis with platinum cathodes. Journal of Orthopaedic Research. en. 3. 2. 125–136. 10.1002/jor.1100030201. 3998890. 25227264. 1554-527X.
  7. Web site: Susan M. Dymecki-Susan M.-1992 Hopkins BCMB. bcmb.bs.jhmi.edu. 2020-05-08.
  8. Web site: Use of FLP recombinase in mice - Dimensions. app.dimensions.ai. en. 2020-05-08.
  9. Dymecki. S. M.. Niederhuber. J. E.. Desiderio. S. V.. 1990-01-19. Specific expression of a tyrosine kinase gene, blk, in B lymphoid cells. Science. en. 247. 4940. 332–336. 10.1126/science.2404338. 0036-8075. 2404338. 1990Sci...247..332D.
  10. Dymecki. S. M.. Zwollo. P.. Zeller. K.. Kuhajda. F. P.. Desiderio. S. V.. 1992-03-05. Structure and developmental regulation of the B-lymphoid tyrosine kinase gene blk. The Journal of Biological Chemistry. 267. 7. 4815–4823. 10.1016/S0021-9258(18)42905-5. 0021-9258. 1537861. free.
  11. Dymecki. S. M.. 1996-06-01. A modular set of Flp, FRT and lacZ fusion vectors for manipulating genes by site-specific recombination. Gene. 171. 2. 197–201. 10.1016/0378-1119(96)00035-2. 0378-1119. 8666272.
  12. Dymecki. S. M.. 1996-06-11. Flp recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenic mice. Proceedings of the National Academy of Sciences of the United States of America. 93. 12. 6191–6196. 10.1073/pnas.93.12.6191. 0027-8424. 8650242. 39212. 1996PNAS...93.6191D. free.
  13. Web site: New Appointments to Full Professor (12/22/10). hms.harvard.edu. en. 2020-05-08.
  14. Rodríguez. C. I.. Buchholz. F.. Galloway. J.. Sequerra. R.. Kasper. J.. Ayala. R.. Stewart. A. F.. Dymecki. S. M.. June 2000. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nature Genetics. 25. 2. 139–140. 10.1038/75973. 1061-4036. 10835623. 9327391.
  15. Farley. F. W.. Soriano. P.. Steffen. L. S.. Dymecki. S. M.. November 2000. Widespread recombinase expression using FLPeR (flipper) mice. Genesis. 28. 3–4. 106–110. 10.1002/1526-968X(200011/12)28:3/4<106::AID-GENE30>3.0.CO;2-T. 1526-954X. 11105051.
  16. Okaty. Benjamin W.. Freret. Morgan E.. Rood. Benjamin D.. Brust. Rachael D.. Hennessy. Morgan L.. deBairos. Danielle. Kim. Jun Chul. Cook. Melloni N.. Dymecki. Susan M.. 2015-11-18. Multi-Scale Molecular Deconstruction of the Serotonin Neuron System. Neuron. 88. 4. 774–791. 10.1016/j.neuron.2015.10.007. 1097-4199. 4809055. 26549332.
  17. Niederkofler. Vera. Asher. Tedi E.. Okaty. Benjamin W.. Rood. Benjamin D.. Narayan. Ankita. Hwa. Lara S.. Beck. Sheryl G.. Miczek. Klaus A.. Dymecki. Susan M.. 15 November 2016. Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior. Cell Reports. 17. 8. 1934–1949. 10.1016/j.celrep.2016.10.063. 2211-1247. 5156533. 27851959.
  18. Alekseyenko. Olga V.. Chan. Yick-Bun. Okaty. Benjamin W.. Chang. YoonJeung. Dymecki. Susan M.. Kravitz. Edward A.. 8 July 2019. Serotonergic Modulation of Aggression in Drosophila Involves GABAergic and Cholinergic Opposing Pathways. Current Biology. 29. 13. 2145–2156.e5. 10.1016/j.cub.2019.05.070. 1879-0445. 6633915. 31231050.
  19. Brust. Rachael D.. Corcoran. Andrea E.. Richerson. George B.. Nattie. Eugene. Dymecki. Susan M.. 2014-12-24. Functional and developmental identification of a molecular subtype of brain serotonergic neuron specialized to regulate breathing dynamics. Cell Reports. 9. 6. 2152–2165. 10.1016/j.celrep.2014.11.027. 2211-1247. 4351711. 25497093.
  20. Hennessy. Morgan L.. Corcoran. Andrea E.. Brust. Rachael D.. Chang. YoonJeung. Nattie. Eugene E.. Dymecki. Susan M.. 15 February 2017. Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex. The Journal of Neuroscience. 37. 7. 1807–1819. 10.1523/JNEUROSCI.2316-16.2016. 1529-2401. 5320611. 28073937.
  21. Web site: Susan Dymecki Elected to American Academy of Arts and Sciences. genetics.hms.harvard.edu. en. 2020-05-07.
  22. Web site: Susan Dymecki Joins Rita Allen Foundation Scientific Advisory Committee - Rita Allen Foundation. December 18, 2017. en-US. 2020-05-07.
  23. Web site: Brain and Behavior Magazine. May 7, 2020.
  24. Web site: Susan Dymecki – Giovanni Armenise Harvard Foundation. en-US. 2020-05-07.
  25. Web site: Susan M. Dymecki. genetics.hms.harvard.edu. en. 2020-05-08.

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