User:PabloCironi

Current Position

3rd year Postdoctoral Fulbright fellow at Pam Silver's lab (http://silver.med.harvard.edu/.)

Background

B.S (1995-2000): I got my B.S. in chemistry at the University of Buenos Aires (School of Exact and Natural Science), in Argentina. In 1997 I started to work as an undergraduate researcher in “Asymmetric electrosynthesis” under the supervision of Prof. Fabio Doctorovich at the Inorganic, Physicochemical and Analytical Department. In 1998 I joined Prof. Oscar Varela's group at the Organic Chemistry Department where I worked on “Asymmetric synthesis, using abundant natural products as chirals scaffolds” until I finished my B.S/M.S. in 2000.

Ph.D (2001-2004): Looking for an experience abroad to do my Ph.D. I moved to Barcelona, Spain where I joined Prof. Albericio's group at the Biomedical Research Institute, Barcelona Scientific Park – University of Barcelona. Under F. Albericio and M. Alvarez's supervision I started to work in solid-phase synthesis of natural products and heterocyclic compounds where my major success was to achieve the first Solid-Phase Total Synthesis of the Pentacyclic System Lamellarins U and L.

Research projects

Wicked Awesome.

1) Functional nucleus-cytoplasmic shuttling analysis by cell-based-screening of miRNAs:

Human immunodeficiency virus type 1 (HIV-1) Rev protein is essential for viral replication. Rev functions to export unspliced or singly spliced HIV precursor mRNAs from the nucleus. This nuclear transit requires two signal sequences: a nuclear localization signal (NLS) that overlaps the RNA-binding domain, and an export signal (NES) that enables Rev to shuttle. The Rev-type export sequences function by directly binding to a nuclear export receptor, named CRM1/exportin. In order to understand more about the mechanism of the Rev mediated transport and general transport factors between the nucleus and the cytoplasm, we engineered a cell line that allows us to study this shuttling process by modulating the expression of different proteins. Our approach uses HTS (high throughput screening) and high throughput microscopy by using miRNAs, a human kinase library and also small molecules as nuclear transport modulators.

2) Engineering Breast Cancer Therapies with Quantitatively Designed Protein “Parts”

Overexpression of EGFR is a hallmark of many breast cancers where the EGF/EGFR system plays a key role in driving cell proliferation. On the other hand cytokines have demonstrated efficacy in the treatment of some cancers. Using a rational synthetic approach we computationally modeled a fusion protein that carries the information for targeting specific tumor cells. Combining the affinity and dissociation constants (Kon and Koff) of both receptor-ligand systems we modulate the activity of our synthetic protein in order to generate the desired response.

Publications

Articles

1) P. Cironi & O. Varela. “Synthesis of 3,4-di-O-benzyl-1-O-methyl-L-galactitol a key precursor of the C33-C37 fragment of calyculins”. J Braz. Chem. Soc., 2001, 12, 667-672.

2) P. Cironi , I. Manzanares, F. Albericio, M. Álvarez. “Solid-Phase Total Synthesis of the Pentacyclic System Lamellarins U and L”. Org. Lett., 2003, 5, 2959-2962.

3) P. Cironi, M. Álvarez, F. Albericio. “1H NMR Spectroscopy with Internal and External Standards for the Quantification of Libraries”. Molecular Diversity, 2003, 6, 165-168.

4) P. Cironi, M. Álvarez, F. Albericio. “A Combination of different spectroscopy techniques to monitor “in situ” solid-phase synthesis of organic molecules”. QSAR & Comb. Sci., 2004, 23, 61-68.

5) P. Cironi, J. Tulla-Puche, G. Barany, F. Albericio, M. Álvarez. “Solid-phase Syntheses of Furopyridine and Furoquinoline Systems”. Org. Lett., 2004, 6, 1405-1408.

6) D. Fernández, A. Ahaidar, G. Danelón, P. Cironi, M. Marfil, O. Pérez, C. Cuevas, F. Albericio, J. A. Joule, M. Álvarez. “Synthesis of Polyheterocyclic Nitrogen-Containing Marine Natural Products”. Monatshefte fur chemie, 2004, 135, 615-627.

7) P. Cironi, C. Cuevas, F. Albericio, M. Álvarez. “Gaining Diversity in Solid-Phase Synthesis by Modulation of Cleavage Conditions from Hydroxymethyl-based Supports. Application to Lamellarin Synthesis”. Tetrahedron, 2004, 60, 8669-8675.

8) P. Cironi, F. Albericio, M. Álvarez. “Solid-Phase Synthesis of 4H-2-(3-Hydroxy-4-methoxyphenyl)naphtho[1,2-b]pyran-1-one”. Tetrahedron Lett. 2004, 45, 7311-7314.

9) F. Albericio, M. Álvarez, P. Cironi, C. Cuevas, M. Marfil. “Total Solid-phase Synthesis of Heterocycles from Marine Source with Antitumoral Activity”. Innovation and perspectives in: Solid Phase Synthesis & Combinatorial Libraries (R. Epton, ed.) Mayflower Worldwide Ltd., Kingswinford, England. 2004, p.25-28.

10) N. Roque-Rosell, P. Cironi, X. Solans, F. Albericio, M. Alvarez. “1-Hydroxy-6,7-dimethoxy-8-nitro-1,2,3,4-tetrahydroisoquinoline”. Acta Crystallographica, Section E: Structure Reports Online 2006, 62, 2285-2287.

11) Z. Zhou*, P. Cironi*, AJ. Lin*, Y. Xu, S. Hrvatin, DE. Golan, PA. Silver, CT. Walsh, J. Yin, “Genetically encoded short peptide tags for orthogonal protein labeling by Sfp and AcpS phosphopantetheinyl transferases”. ACS Chemical Biology, 2007, 2, 337-346. (* These authors contribute equally)

PATENTS

12) F. Albericio, M. Álvarez, P. Cironi, C. Cuevas, A. Francesch, M. Marfil. “Solid phase synthesis of antitumoral compounds”. PCT Int. Appl. WO 2004/073598 A2. Publication day: 2 September 2004.

REVIEWS AND BOOK CHAPTERS

13) P. Cironi, F. Albericio, M. Álvarez. “Lamellarins: Isolation, activity and synthesis”. Progress in Heterocyclic Chemistry, 2004, Vol. 16, Ch. 1 p.1-26 Ed G. W. Gribble, J. A. Joule, Pergamon, Oxford, U.K.

14) P. Cironi, M. Álvarez, F. Albericio. “Solid-phase chemistry in the total synthesis of non-peptidic natural products”. Mini-reviews in Medicinal Chemistry, 2006, 6, 15.

Contact Info

Pablo Cironi Ph D.

Department of Systems Biology

Harvard Medical School

200 Longwood Ave. WAB 536

Boston, MA 02115

Tel: (1) 617-432-6402

Fax: (1) 617-432-6405

pablo_cironi@hms.harvard.edu