Research Interests: Cancer Metabolism, Targeted Drug Delivery, Bacteriolytic Therapy
Our laboratory focuses on developing therapeutics to treat regions of tumors that are inaccessible to standard cancer therapies. Blood-borne therapeutics rely on diffusion for delivery and do not accumulate in effective concentrations distant from vasculature. This problem will be especially compounded for the next generation of therapeutics, especially antibodies, liposomes, and viral vectors, because of their larger size and subsequently reduced interstitial diffusivity. To address this limitation, we are currently quantifying the microenvironment of the inaccessible tumor regions and designing bacterial vectors targeted to those regions. We are also using surgical techniques to investigate how bacteria migrate and proliferate in subcutaneous mouse tumors. By applying engineering principles to the design of cancer therapeutics, we hope to create more effective strategies to treat these tumor regions in order to reduce local failure and metastasis, which both lead to patient morbidity and mortality.
Rays of Hope Center for Breast Cancer Research
Center of Excellence in Apoptosis Research
Ganai S, Arenas RB, Sauer JP, Bentley B, Forbes NS. In tumors Salmonella migrate away from vasculature toward the transition zone and induce apoptosis. Cancer Gene Ther. In press.
Forbes NS. Engineering the perfect (bacterial) cancer therapy. Nat Rev Cancer. 2010;10(11):785-794.
Venkatasubramanian R, Arenas RB, Henson MA, Forbes NS. Mechanistic modeling of dynamic MRI data predicts that tumor heterogeneity decreases therapeutic response. Br J Cancer. 2010;103(4):486-497.
Kim BJ, Han G, Toley BJ, Kim CK, Rotello VM, Forbes NS. Tuning payload delivery in tumor cylindroids using gold nanoparticles. Nat Nanotechnol. 2010;5(6):465-472.
Hunnewell M, Forbes NS. Active and inactive metabolic pathways in tumor spheroids: determination by GC-MS. Biotechnol Prog. 2010;26(3):789-796.
Ganai S, Arenas RB, Forbes NS. Tumor-targeted delivery of TRAIL using Salmonella typhimurium enhances breast cancer survival in mice. Br J Cancer. 2009;101(10):1683-1691.
Walsh CL, Babin BM, Kasinskas RW, Foster JA, McGarry MJ, Forbes NS. A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics. Lab Chip. 2009;9(4):545-554.
Ghosh PS, Kim CK, Han G, Forbes NS, Rotello VM. Efficient gene delivery vectors by tuning the surface charge density of amino-acid functionalized gold nanoparticles. ACS Nano. 2008;2(11):2213-2218.
Forbes NS. A module to foster engineering creativity: an interpolative design problem and an extrapolative research project. Chem Eng Educ. 2008;42:166-172.
St. Jean A, Zhang M, Forbes NS. Bacterial therapies: completing the cancer treatment toolbox. Curr Opin Biotechnol. 2008;19(5):511-517.
Kim BJ, Forbes NS. Single cell sorting in cylindroids demonstrates how nutrient deprivation creates apoptotic and quiescent cell populations in tumors. Biotechnol Bioeng. 2008;101(4):797-810.
Venkatasubramanian R, Henson MA, Forbes NS. Integrating cell-cycle progression, drug penetration and energy metabolism to identify improved cancer therapeutic strategies. J Theor Biol. 2008;253(1):98-117.
Ganai S, Arenas RB, Sauer JP, Bentley B, Forbes NS. Tumor-targeting attenuated Salmonella typhimurium accumulates within therapeutically-resistant microenvironments adjacent to tumor necrosis. J Am Coll Surg. 2008;207(3)(suppl):S101-S102.
Ganai S, Arenas RB, Forbes NS. Tumor-targeted delivery of TRAIL using Salmonella typhimurium enhances breast cancer survival. Ann Surg Oncol. 2008;15:64.
Kasinskas RW, Forbes NS. Salmonella typhimurium lacking ribose chemoreceptors localize in tumor quiescence and induce apoptosis. Cancer Res. 2007;67:3201-3209.
Kim BJ, Forbes NS. Flux analysis shows that hypoxia-inducible-factor-1-alpha minimally affects intracellular metabolism in tumor spheroids. Biotechnol Bioeng. 2007;96:1167-1182.
Ganai S, Arenas RB, Bentley B, Forbes NS. Targeting bacteriolytic therapy of solid tumors using Salmonella typhimurium. Annuls Surgical Oncology. 2007;14:71.
Forbes NS. Profile of a bacterial tumor killer. Nat. Biotech. 2006;24:1484-1485.
Forbes NS, Meadows AL, Clark DS, Blanch HW. Estradiol stimulates the biosynthetic pathways of breast cancer cells: detection by metabolic flux analysis. Metabolic Engineering. 2006;8:639-652.
Venkatasubramanian R, Henson MA, Forbes NS. Incorporating energy metabolism into a growth model of multicellular tumor spheroids. J Theor Biol. 2006;242:440-453.
Kasinskas RW, Forbes NS. Salmonella typhimurium specifically chemotax and proliferate in heterogeneous tumor tissue in vitro. Biotechnology Bioengineering. 2006;94:710-721.
Han G, You CC, Kim BJ, Turingan RS, Forbes NS, Martin CT, Rotello VM. Light-regulated release of DNA and its delivery to nuclei by means of photolabile gold nanoparticles. Angew Chem Int Ed Engl. 2006;45:3165-3169.
Hong R, Han G, Fernandez JM, Kim BJ, Forbes NS, Rotello VM. Glutathione-mediated delivery and release using monolayer protected nanoparticle carriers. J Am Chem Soc. 2006;128:1078-1079.
Pinelis M, Kasinskas RW, Borno RT, Park JH, Chu E, Forbes NS, Maharbiz MMI. Microfluidic devices for the assembly and culture of three-dimensional multi-cellular constructs with diffusion-limited microenvironments. In: Proceedings of the 10th International Conference on Miniaturized Systems for Chemistry and Life Sciences; November 8-11, 2006; Tokyo, Japan. Abstract µTAS2006.
Crichton MA, Forbes NS, Bhatia SR. 2005. USANS as a probe of large-scale structure in attractive colloidal glasses of block copolymer micelles. MRS Symp. Proc. v. 840 - Neutron and X-Ray Scattering as Probes of Multiscale Phenomena. Q7.11.1-Q7.11.6.
Kim BJ, Forbes NS. In situ characterization of cell-cycle populations in multi-cell cylindroids. In Progress.
Venkatasubramanian R, Henson MA, Forbes NS. Incorporating cell cycle progression and drug penetration into metabolic models of multicellular tumor spheroid growth. Submitted.
Kasinskas RW, Forbes NS. Distribution of cellular microenvironments of tumor cylindroids and quantification of metabolites in tumor spheroids. In Progress.
Forbes NS. Teaching engineering creativity and problem solving. Submitted.
Hunnewell M, Forbes NS. Measurement of isotope enrichment to quantify intracellular metabolism in multicellular spheroids. In Progress.
Forbes NS, Munn LL, Fukumura D, Jain RK. Sparse initial entrapment of systemically injected Salmonella typhimurium leads to heterogeneous accumulation within tumors. Cancer Res. 2003;63:5188-5193.
Helmlinger G, Sckell A, Dellian M, Forbes NS, Jain RK. Acid production in variant, glycolysis-deficient and parental tumors in vivo: support for hypothesized tumor metabolism. Clin Cancer Res. 2002;8:1284-1291.
Jain RK, Forbes NS. Can engineered bacteria help control cancer? PNAS. 2001;98:14748-14750.
Forbes NS, Clark DS, Blanch HW. Using isotopomer path tracing to quantify metabolic fluxes in pathway models containing reversible reactions. Biotech Bioeng. 2001;74:196-211.
Forbes NS, Clark DS, Blanch HW. Analysis of metabolic fluxes in mammalian cells. In: Schügerl K, Bellgardt KH, eds. Bioreaction Engineering: Modeling and Control. Berlin: Springer Verlag; 2000.