Pioneer Valley Life Sciences Institute

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Forbes Laboratory

Neil S. Forbes, Ph.D.

Telephone: 413.577.0132
Fax: 413.545.1647
Email
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Assistant Professor, Chemical Engineering and Adjunct Professor, Molecular and Cell Biology, University of Massachusetts Amherst
Principal Investigator, PVLSI

Education

B.S., Chemical Engineering, Case Western Reserve University
Ph.D., Chemical Engineering, University of California, Berkeley

Postdoctoral Experience

Radiation Oncology/Tumor Biology, Harvard Medical School / Massachusetts General Hospital, 2000-2002

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 they hope to create strategies more effective at treating these tumor regions in order to reduce local failure and metastasis, which both lead to patient morbidity and mortality.

Working Groups:
Breast Cancer Working Group
Center of Excellence in Apoptosis Research


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Selected papers:

Kasinskas RW, Forbes NS. 2007. Salmonella typhimurium lacking ribose chemoreceptors localize in tumor quiescence and induce apoptosis. Cancer Res. 67:3201-9.

Kim BJ, Forbes NS. 2007. Flux analysis shows that hypoxia-inducible-factor-1-alpha minimally affects intracellular metabolism in tumor spheroids. Biotechnol Bioeng. 96:1167-82.

Ganai S, Arenas RB, Bentley B, Forbes NS. 2007. Targeting bacteriolytic therapy of solid tumors using Salmonella typhimurium. Annuls Surgical Oncology 14:71-71.

Forbes NS. 2006. Profile of a bacterial tumor killer. Nat. Biotech. 24:1484-1485.

Forbes NS, Meadows AL, Clark DS, Blanch HW. 2006. Estradiol stimulates the biosynthetic pathways of breast cancer cells: detection by metabolic flux analysis. Metabolic Engineering. 8:639-652.

Venkatasubramanian R, Henson MA, Forbes NS. 2006. Incorporating energy metabolism into a growth model of multicellular tumor spheroids. J Theor Biol. 242:440-453.

Kasinskas RW, Forbes NS. 2006. Salmonella typhimurium specifically chemotax and proliferate in heterogeneous tumor tissue in vitro. Biotechnology Bioengineering, 94:710-721.

Han G, You CC, Kim BJ, Turingan RS, Forbes NS, Martin CT, Rotello VM. 2006. Light-regulated release of DNA and its delivery to nuclei by means of photolabile gold nanoparticles. Angew Chem Int Ed Engl. 45:3165-3169.

Hong R, Han G, Fernandez JM, Kim BJ, Forbes NS, Rotello VM. 2006. Glutathione-mediated delivery and release using monolayer protected nanoparticle carriers. J Am Chem Soc. 128:1078-9.

Pinelis M, Kasinskas RW, Borno RT, Park JH, Chu E, Forbes NS, Maharbiz MM. 2006. Microfluidic devices for the assembly and culture of three-dimensional multi-cellular constructs with diffusion-limited microenvironments. Proceedings of the 10th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS2006). Japan

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. 2003. Sparse initial entrapment of systemically injected Salmonella typhimurium leads to heterogeneous accumulation within tumors. Cancer Res. 63:5188-5193.

Helmlinger G, Sckell A, Dellian M, Forbes NS, Jain RK. 2002. Acid production in variant, glycolysis-deficient and parental tumors in vivo: support for hypothesized tumor metabolism. Clin. Cancer Res. 8:1284-1291

Jain RK, Forbes NS. 2001. Can engineered bacteria help control cancer? PNAS 98:14748-14750

Forbes NS, Clark DS, Blanch HW. 2001. Using isotopomer path tracing to quantify metabolic fluxes in pathway models containing reversible reactions. Biotech. Bioeng. 74:196-211

Forbes NS, Clark DS, Blanch HW. 2000. Analysis of metabolic fluxes in mammalian cells. Chap 4.4 in: Schügerl K, Bellgardt KH, editors. Bioreaction Engineering: Modeling and Control. Berlin: Springer Verlag

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