Sophie La Salle, Ph.D.

Associate Professor, Department of Biochemistry


Midwestern University
Chicago College of Osteopathic Medicine
College of Dental Medicine - Illinois
Department of Biochemistry
Science Hall 421-E
555 31st St.
Downers Grove, IL 60515

Office: (630) 515-6047
e-mail: slasal@midwestern.edu

 

EDUCATION

B.Sc. Biochemistry Université de Sherbrooke 2000
Ph.D. Pharmacology & Therapeutics McGill University 2007

RESEARCH SUMMARY

Genetic regulation of meiosis, gametogenesis and fertility

Our laboratory investigates the genetic regulation of male and female germ cell development. We focus on meiosis, a specialized cell division unique to germ cells which allows the production of haploid gametes. Events occurring during meiosis, particularly meiotic recombination, ensure that chromosomes are physically linked by favoring the exchange of DNA segments between homologous chromosomes. In addition to promoting genetic diversity, correct execution of meiosis ensures fertility and prevents gamete aneuploidy (abnormal chromosome number). We study the mechanism(s) leading to proper completion of meiotic recombination using the mouse as a model organism. Our studies are providing new insight into the repair of DNA double strand breaks induced at the onset of meiosis. Furthermore, because the trait we study - namely meiotic arrest - occurs in many cases of unexplained human infertility, we hope to uncover novel, testable avenues to explore to better understand the requirements for fertility.

RESEARCH PROJECTS

We previously characterized the mouse repro42 mutation which causes both male and female infertility (La Salle et al., 2012). Positional cloning localized the mutation to chromosome 11 and sequencing analysis identified a nonsense mutation in exon 8 of spermatogenesis associated 22 (Spata22). Spata22 is a gene of unknown function conserved across vertebrates but absent in yeast, D. melanogaster and C. elegans. Characterization of the infertility phenotype of repro42 mutant males and females suggest that SPATA22 is involved in DNA repair during meiosis.

Project I:  Dissect the molecular phenotype of meiotic arrest in mice deficient in SPATA22.

Extensive characterization of the repro42 mutant phenotype will give insight into the function of SPATA22. Characterization of the synapsis defect as well as localization of additional components of the synaptonemal complex, proteins involved in telomere tethering at the nuclear envelop and factors involved in meiotic recombination are currently underway using immunolabeling of spermatocyte and oocyte spread chromatin with appropriate antibodies.

Project II: Identify the meiotic interacting partners of SPATA22.

Determining protein interacting partners of SPATA22 is critical to elucidating its function. Immunoprecipitation (IP) of SPATA22-interacting proteins followed by mass spectrometry will be used to uncover theses interactions. Based on bioinformatics analyses, SPATA22 contains a number of predicted motifs. This analysis will direct biased/candidate-based IPs which can be validated using co-immunolocalization analyses or genetic approaches.

Project III:  Determine if Spata22 acts epistatically to genes required for DNA double-strand break (DSB) repair.

If Spata22 is required for initiation of recombination (i.e. formation of DBSs) then it should be epistatic to genes required for DSB repair, such as Dmc1; the phenotype of Dmc1; repro42 double mutants should be identical to the phenotype of repro42 mutants alone. Additionally, since repair of DSBs is impaired, the localization of DNA-repair proteins from various pathways will be examined to evaluate the activity of repair mechanisms in the absence of SPATA22 in both mutant oocytes and spermatocytes. A combination of genetic approaches (breeding of appropriate mutants) and immunocytological techniques will be used. 

SELECTED PUBLICATIONS (See Full PubMed Results)

MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination.
M. Luo, F. Yang, N.A. Leu, J. Landaiche, M.A. Handel, R. Benavente, S. La Salle S and P.J. Wang. Nat. Commun. (2013); 4:2788; doi: 10.1038/ncomms3788

Spata22, a novel vertebrate-specific gene, is required for meiotic progress in mouse germ cells.
S. La Salle
, K. Palmer, M. O'Brien, J. Schimenti, J. Eppig and M.A. Handel.  Biol Reprod. (2012); 86 (2): 45 (1-12).

Critical period of nonpromoter DNA methylation acquisition during prenatal male germ cell development.
K.M. Niles, D. Chan, S. La Salle, C.C. Oakes, J.M. Trasler. PLoS One (2011); 6 (9): e24156.

Isolation and short-term culture of mouse spermatocytes for analysis of meiosis.
S. La Salle
, F. Sun, and M.A. Handel.  Methods Mol Biol. (2009); 558: 279-97.

Restriction digestion and real-time PCR (qAMP).
C.C. Oakes, S. La Salle, J.M. Trasler, B. Robaire. Methods Mol Biol. (2009); 507:271-80.

Developmental control of sumoylation pathway proteins in mouse male germ cells.
S. La Salle
, F. Sun, X.D. Zhang, M.J. Matunis, and M.A. Handel.  Dev. Biol. (2008); 321(1):227-37.

Loss of spermatogonia and wide-spread DNA methylation defects in newborn male mice deficient in DNMT3L.
S. La Salle
, C.C. Oakes, O.R. Neaga, D. Bourc'his, T.H. Bestor and J.M. Trasler.  BMC Developmental Biology (2007); 7: 104.

A unique configuration of genome-wide DNA methylation patterns in the testis.
C.C. Oakes, S. La Salle, D.J. Smiraglia, B. Robaire and J.M. Trasler.    PNAS (2007); 104: 228-233.

Dynamic expression of DNMT3a and DNMT3b isoforms during male germ cell development in the mouse.
S. La Salle
and J.M. Trasler.  Dev. Bio. (2006); 296:71-82.

Specific DNA methyltransferases mark putative windows for sex-specific methylation in the mouse germ line. 
S. La Salle, C. Mertineit, T. Taketo, P.B. Moens, T.H. Bestor and J.M. Trasler.  Dev. Bio. (2004); 268: 403- 415.