Harvard Medical School
 
Michael Goldberg
 

Contact Information:

Dept. of Microbiology and Immunobiology
Dana-Farber Cancer Institute
450 Brookline Avenue
Smith 770C
Boston, MA 02215

phone: 617-582-9840
fax: 617-582-9610
email:

     

Research Summary

Our laboratory is interested to develop and deliver novel therapeutics to address cancer. Cancer is a leading cause of death worldwide, and ­ unlike other leading causes of death such as heart disease and infectious disease ­ its incidence is increasing. Indeed, cancer is now the primary cause of death among Americans under the age of 85. Conventional therapeutic approaches involve harsh treatment regimens that entail severe side effects. Clearly, the establishment of disruptive therapeutic molecules and platforms would be desirable.

The ability to regulate the expression of specific genes either positively or negatively in specific cells in animal models and in patients would be of great utility. To this end, our laboratory seeks to develop targeted systems for the delivery of mRNA and RNAi therapeutics. These molecules provide the tremendous specificity of genetic therapies but, owing to their impermanence, allow for dosage control like traditional therapeutic modalities. By combining applied chemical tools with an understanding of basic RNA biology and immunology, we aim to generate innovative technologies.

Indeed, through evolution, the immune system has been selected to serve as the greatest drug delivery system developed to date. By modulating genes encoding stimulatory and inhibitory signals, we will attempt to leverage the host immune system¹s ability to expand, to communicate with complementary cell types, to penetrate deeply into tumor parenchyma, and to develop a memory response. This strategy is designed to be as broadly applicable as possible as it is indifferent to the type of cancer and its underlying mutations.

Three current areas of research in the lab are:
I)     Targeting RNA delivery to specific immune cells
II)    Generating improved cancer vaccines
III)   Developing tumor-homing and tumor-penetrating drug delivery systems

While the principal focus of our work is to develop tools to study and treat cancer, the same tools should be relevant to the evaluation and manipulation of other biological systems of inquiry, ranging from autoimmune disease to virology.


Selected Publications

1. Schroeder A*, Goldberg M*, Kastrup C, Levins CG, Langer RS, Anderson DG. Remotely-activated protein-producing nanoparticles. Nano Lett. Epub ahead of print (2012).
*These authors contributed equally

2. Goldberg MS, Sharp PA. Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression. J Exp Med. 209(2):217-24 (2012).

3. Goldberg MS*, Xing D*, Ren Y, Orsulic S, Bhatia S, Sharp PA. Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival of mice bearing tumors derived from Brca1-deficient ovarian cancer cells. Proc Natl Acad Sci USA. 108(2):745-50 (2011).
*These authors contributed equally

4. Akinc A, Goldberg M, Qin J, Dorkin JR, Gamba-Vitalo C, Maier M, Jayaprakash KN, Jayaraman M, Rajeev KG, Manoharan M, Koteliansky V, Röhl I, Leshchiner ES, Langer R, Anderson DG. Development of lipidoid-siRNA formulations for systemic delivery to the liver. Mol Ther. 17(5):872-9 (2009).

5. Akinc A, Zumbuehl A, Goldberg M, Leshchiner ES, Busini V, Hossain N, Bacallado SA, Nguyen DN, Fuller J, Alvarez R, Borodovsky A, Borland T, Constien R, de Fougerolles A, Dorkin JR, Narayanannair Jayaprakash K, Jayaraman M, John M, Koteliansky V, Manoharan M, Nechev L, Qin J, Racie T, Raitcheva D, Rajeev KG, Sah DW, Soutschek J, Toudjarska I, Vornlocher HP, Zimmermann TS, Langer R, Anderson DG. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat Biotechnol. 26(5):561-9 (2008).

6. Goldberg M, Mahon K, Anderson D. Combinatorial and rational approaches to polymer synthesis for medicine. Adv Drug Deliv Rev. 60(9):971-8 (2008).

7. John M, Constien R, Akinc A, Goldberg M, Moon YA, Spranger M, Hadwiger P, Soutschek J, Vornlocher HP, Manoharan M, Stoffel M, Langer R, Anderson DG, Horton JD, Koteliansky V, Bumcrot D. Effective RNAi-mediated gene silencing without interruption of the endogenous microRNA pathway. Nature. 449(7163):745-7 (2007).

8. Goldberg M, Langer R, Jia X. Nanostructured materials for applications in drug delivery and tissue engineering. J Biomater Sci Polym Ed. 18(3):241-68 (2007).