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Harvey Blanch
Chief Scientific & Technology Officer, Joint BioEnergy Institute
Faculty Senior Scientist, Lawrence Berkeley National Laboratory
Professor, University of California, Department of Chemical Engineering, Berkeley
Contact Information
Lawrence Berkeley National Laboratory
Physical Biosciences Division
One Cyclotron Road
Mailstop 978-4121
Berkeley, California 94720-8118
USA
Location
Bldg. 978-4124
Phone: (510) 642-1387
Fax: (510) 643-1228
Email: Blanch@berkeley.edu
Email: HWBlanch@lbl.gov
Current Research
Synergistic Activities
Analysis of Pathway Fluxes in Cancer Cells
Current theories of cancer metabolism link these changes to evolutionary selection processes occurring within the confines of the tumor. For example, though it is widely recognized that complete glucose oxidation via the TCA cycle boasts a ~16-fold greater yield of ATP per glucose consumed relative to glycolysis, it is less widely appreciated that glycolysis can produce ATP more rapidly. Increased glucose consumption may also help supply carbons for de novo lipid synthesis and suppress tumor cell differentiation. Furthermore, increased glycolysis acidifies the extracellular space via the production of additional lactate. A lower pH is more toxic to normal cells than to cancer cells and increases the rate of extracellular matrix degeneration, thereby aiding the invasion of the surrounding tissue. Because the microenvironment of a tumor is often substantially different from the nutrient environment in healthy tissue, metabolic and morphological adaptation of cancer cells is expected. In particular, lowered pH and decreased O2 and glucose availability are recognized to be powerful selection factors, and computer simulations suggest that adaptations to these conditions may confer a significant proliferative advantage to cancerous cells. Understanding metabolic alterations in cancer cells may lead to the identification of metabolic drug targets, which could offer potentially non-toxic means of tumor inhibition. For example, an increased oxidative (glucose-6-phosphate dehydrogenase catalyzed) and nonoxidative (transaldolase and transketolase catalyzed) flux into the pentose phosphate pathway (PPP) have both been implicated in cancer cell proliferation in various cancers (including breast cancer), and drugs targeting the relevant enzymes in these pathways have shown promise. Other potential targets for cancer therapy that have been identified include ATP citrase lyase and lactate dehydrogenase-A. Given that there are healthy human populations lacking either glucose-6-phosphate dehydrogenase or lactate dehydrogenase-A activity, metabolic drug targeting may present a new avenue for non-toxic cancer therapies. JBEI will benefit from the metabolic flux analysis techniques developed for eukaryotic cells. These techniques can be applied to optimize biofuels production in a variety of host organisms.
Conversion of Lignocellulosic Biomass to Ethanol.
From 1974 to 1986, a DOE supported program on bioconversion of lignocellulosics to fuel ethanol was housed at LBNL and UC Berkeley. This project examined a number of pretreatments, including acid hydrolysis and steam explosion, and developed high-efficiency fermentations for the production of cellulase enzymes from T. reesii. Product and substrate inhibition in the yeast fermentation was studied, and energy requirements for fermentation and ethanol distillation were determined. Fermentation approaches for C5 sugars in bacteria were developed. Feedstocks examined included agricultural residues, newsprint, poplar and loblolly pine. This project provided many of the fundamental approaches to the enzymatic conversion of biomass to ethanol, including pretreatment technologies, enzymatic hydrolysis kinetics and ethanol production and recovery.
