Paloma Giangrande, Ph.D. (Full Member)
Assistant Professor, University of Iowa

http://www.int-med.uiowa.edu/divisions/Cardiology/Directory/PalomaGiangrande.html

Research Interest    

Dr. Giangrande's research interests include developing RNA-based therapeutics to modulate cellular pathways that underlie pathological cell proliferation in the setting of cancer and cardiovascular disease. One focus area of Dr. Giangrande?s laboratory is the selection of RNA aptamers to receptors expressed on the surface of target cells using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) for the purpose(s) of: 1) modulating receptor function and/or 2) delivering therapeutic molecules (e.g. siRNAs, antimirs, drugs) to specific cell types. The ultimate goal is to develop safer, more effective therapeutic reagents that can be systemically delivered in vivo. A second area of interest is the optimization of aptamer-siRNA technology. The laboratory is currently looking at optimizing three aspects of this methodology: 1) silencing potential, 2) intracellular delivery, and 3) pharmaco kinetics/pharmacodynamics of systemic delivery. A third interest is the use of genomic/proteomic methodologies to acquire important insights into the mechanisms of pathological cell proliferation. In addition to providing useful mechanistic information, this knowledge will be helpful in identifying novel membrane proteins that may serve as effective targets for therapeutic RNAs ? in the treatment of cancer or pathological vascular hyperplasia.

Selected Publications:

McNamara JO, Kolonias D, Pastor F, Mittler RS, Chen L, Giangrande PH, Sullenger B, Gilboa E. Multivalent 4-1BB binding aptamers costimulate CD8 T cells and inhibit tumor growth in mice. J Clin Invest. 118(1):376-386 (2008).

Giangrande PH, Zhang J, Tanner A, Eckhart AD, Rempel RE, Andrechek ER, Layzer JM, Keys JR, Hagen PO, Nevins JR, Koch WJ, Sullenger BA. Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia. Proc Natl Acad Sci U S A.104(32):12988-93 (2007).

McNamara JO 2nd, Andrechek ER, Yong Wang, Kristi D. Viles, Rempel RE, Gilboa E, Sullenger BA, Giangrande PH. Cell-type specific delivery of siRNAs with aptamer-siRNA chimeras. Nat. Biotechnol. 24(8): 1005-15 (2006).

Mi J, Zhang X, Giangrande PH, McNamara JO 2nd, Nimjee SM, Sarraf-Yazdi S, Sullenger BA, Clary BM. Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival. Biochem Biophys Res Commun. 338(2):956-63 (2005).

Publications from PubMed