Ph.D. 1991 UMDNJ-Robert Wood Johnson Medical School

B.S. 1984 Universidad Austral de Chile

Dr. Cortes's laboratory studies the mechanisms of V(D)J recombination and non-homologous end joining (NHEJ) and investigates the etiology of human diseases related to these processes. As Dr. Cortes develops these studies, she mentors new generations of students, postdocs and research assistants, giving them solid foundations to become outstanding contributors in their individual careers.

V(D)J recombination and NHEJ are essential for the generation of antibodies, T cell receptors and to maintain genomic stability. Early studies done by her group demonstrated that RAG2, one of the specific components of V(D)J recombination, bridges the RAG recombinase with chromatin through histone interaction; showing that mutations in the PHD domain of RAG2-identified in patients with SCID and Omenn Syndrome-affected RAG2 stability, cellular localization, and histone interaction. This work defined novel mechanisms of RAG2 mediated immunodeficiency. More recently, her team has identified novel roles of Artemis and Ligase IV, two DNA repair proteins, on V(D)J recombination and DNA repair by showing that Artemis facilitates  efficient V(D)J recombination and DNA repair through its interaction with DNA Ligase IV and DNA-PKcs. The specificity, structural, and biophysical properties of the indicated interaction were defined at a molecular level using state of the art technology.

The current focus of the laboratory is on elucidating the molecular mechanisms that control DNA Ligase IV function and on exploring the potential applications of these findings in the modulation of DNA repair. In addition, her laboratory continues to develop national and international collaborations to investigate yet uncharacterized molecular mechanisms of immunodeficiency.

MED204/MED305 Molecules to Cells – Course co-Director and lecturer

Organ Systems: PBL facilitator

1.- Maffucci, P., Chavez, J., Jurkiw, T.J., O’Brien, P.J., Abbott, J.K., Reynolds, P.R., Worth, A., Notarangelo, L.D., Felgentreff, K., Cortes, P., Boisson, B., Radigan, L., Cobat, A., Dinakar, C., Ehlayel, M., Ben-Omran, T., Gelfand, E.W., Casanova, J-L., Cunningham-Rundles, C. (2018). DNA LIG1 Mutations lead to a Spectrum of Immune Deficiencies. J Clin. Invest. In press.

2.- Charlier, C., Bouvignies, G., Pelupessy, P., Walrant, A., Marquant, R., Kozlov, M., De Ioannes, P., Bolik-Coulon, N., Sagan, S., Cortes, P., Aggarwal, A., Carlier, L., Ferrage, F. (2017). Structure and dynamics of an intrinsically disordered protein region that partially folds upon binding by chemical-exchange NMR. J. Am. Chem. Soc. 139 (35): 12219-12227.

3.- Francis, D. B., Kozlov, M., Chavez, J., Chu, J., Malu, S., Hanna, M., and Cortes, P. (2014). DNA Ligase IV regulates XRCC4 nuclear localization. DNA Repair 21, 36-42

4.- Van Til NP, Sarwari, R., Visser, T.P., Hauer, J., Lagresle-Peyrou, C., van der Velden, G., Malshetty, V., Cortes, P., Jollet, A., Danos, O., Cassani, B., Zhang, F., Thrasher, A.J., Fontana, E., Poliani, P.L., Cavazzana, M., Verstegen, M.M., Villa, A., and Wagemaker, G. J. (2014). Recombination-activating gene 1 (Rag1)-deficient mice with severe combined immunodeficiency treated with lentiviral gene therapy demonstrate autoimmune Omenn-like syndrome. Allergy Clin Immunol 133, 1116-1123.

5.- De Ioannes, P., Malu, S., Cortes, P.*, and Aggarwal, AK.* (2012). Structural Basis of DNA Ligase IV-Artemis Interaction in Nonhomologous End-Joining. Cell Reports 2, 1505-15012. *corresponding authors.

6.- Mayer, L.*, Lira, S., Ting, A., and Cortes, P. (2012). Introduction to the special issue on Immunology at Mount Sinai. *corresponding author. Immunol Res. 54, 1-3.

7.- Malu, S., Malshetty, V., Francis, D., and Cortes, P. (2012). Role of non-homologous end joining in V(D)J recombination. Immunol Res. 54, 233-246.

8.- Malu, S., De Ioannes, P., Kozlov, M., Green, M., Francis, D., Hanna, M., Pena, J., Escalante, C.R., Kurosawa, A., Erdjument-Bromage, H., Tempst, P., Adachi, N., Vezzoni, P., Villa, A., Aggarwal, A., and Cortes, P.  (2012). Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs. J. Exp. Med. 209 (5), 955-963.

9.- Couedel, C., Roman, C., Jones, A., Vezzoni, P., Villa, A., and Cortes, P.  (2010). Mutations isolated from patients with SCID and Omenn Syndrome reveal the central role of RAG2 PHD domain in regulating V(D)J recombination. J Clin. Invest. 120 (4), 1337-1344.

10.- Matangkasombut, P., Pichavant, M., Saez, D.E., Giliani, S., Mazzolari, E., Finocchi, A., Villa, A., Cortes, P., Umetsu, D.T., and Notarangelo, L. (2008).  Lack of iNKT cells in patients with combined immune deficiency due to hypomorphic RAG mutations. Blood 111, 271-274.