Accelerating the Development of New Therapies
THE STAFF
Process development and GMP production
Jung-Hee Woo, Soo Kang, Shi-Yan Li, Randall Alfano, Yizhen Liu
Jung-Hee Woo, Associate Director of the CRI, has a PhD in Biotechnology and more than 20 years of experience in molecular biology research and targeted toxin development. As Associate Executive Director, he oversees all aspects of process development activities, scale-up and GMP production. He directed the process development, GMP production and release tests and formal pharmacology/ toxicology studies of a T cell lymphoma immunotoxin and compiled the INDA application. Dr. Woo supervises the process development and GMP production of a chronic pain immunotoxin and a bladder cancer immunotoxin.
Other staff members Shi-Yan Li, PhD in Biochemistry, with experience in fermentation, protein purification and protein characterization; Soo Kang, MS in Biotechnology, with experience in gene construction, fermentation, protein purification and protein characterization; Randall Alfano, PhD with experience in molecular biology research and targeted toxin development; and Yizhen Liu with experience in quality control, molecular biology research and protein purification.
Woo, J.H., Liu, J., Kang, S.H., Singh, R., Park, S.K., Su, Y., Ortiz, J., Neville Jr., D.M., Willingham, M.C. and Frankel, A. E., 2008. GMP production and characterization of the bivalent anti-human T cell immunotoxin, AdmDT390-bisFv(UCHT1) for phase I/II clinical trials. Protein Expr. Purif. 58(1):1-11.
Woo, J. H., Bour, S., Dang, T., Lee, Y., Park, S.K., Andreas, E., Kang, S. H., Liu, J., Neville Jr., D.M. and Frankel, A.E., 2008. Preclinical studies in rats and squirrel monkeys for safety evaluation of the bivalent anti-human T cell immunotoxin, A-dmDT390- bisFv(UCHT1). Cancer Immunol. Immunother. 57(8):1225-1239.
Awasthi, S., Singhal, S.S., Awasthi, Y.C., Martin, B., Awasthi, S., Woo, J.H., Cunningham, C.C. and Frankel, A.E., 2008. RLIP76 and cancer. Clin. Cancer Res. 14(14):4372-4377.
Wang, Z., Kim, G.B., Woo, J.H., Liu, Y.Y., Mathias, A., Stavrou, S. and Neville, Jr., D. M., 2007. Improvement of a recombinant anti-monkey anti-CD3 diphtheria toxin based immunotoxin by yeast display affinity maturation of the scFv. Bioconjugate Chemistry 18(3):947-955.
Woo, J.H., Liu, J. S., Kang, S.H., Singh, R., Park, S.K., Su, Y., Ortiz, J., Neville, D.M., Willingham, M.C., Frankel, A.E., GMP production and characterization of the bivalent antihuman T cell immunotoxin, AdmDT390- bisFv(UCHT1) for phase I/II clinical trials. Protein Expr Purif 2007; Nov 22, Epub.
Woo, J.H., Bour, S.H., Dang, T., Lee, Y.J., Park, S.K., Andreas, E., Kang, S.H., Liu, J.S., Neville, D.M., Frankel, A.E., Preclinical studies in rat and squirrel monkeys for safety evaluation of the bivalent anti-human T-cell immunotoxin, A-dmDT390-bisFv(UCHT1). Cancer Immunol Immunother 57: 1225-1239, 2008.
Woo, J.H., Liu, J., Kang, S.H., Singh, R., Park, S.K., Su, Y., Ortiz, J., Neville Jr., D.M., Willingham, M.C. and Frankel, A. E., 2008. GMP production and characterization of the bivalent anti-human T cell immunotoxin, AdmDT390-bisFv(UCHT1) for phase I/II clinical trials. Protein Expr. Purif. 58(1):1-11.
Woo, J. H., Bour, S., Dang, T., Lee, Y., Park, S.K., Andreas, E., Kang, S. H., Liu, J., Neville Jr., D.M. and Frankel, A.E., 2008. Preclinical studies in rats and squirrel monkeys for safety evaluation of the bivalent anti-human T cell immunotoxin, A-dmDT390- bisFv(UCHT1). Cancer Immunol. Immunother. 57(8):1225-1239.
Woo, J.H., Liu, J. S., Kang, S.H., Singh, R., Park, S.K., Su, Y., Ortiz, J., Neville, D.M., Willingham, M.C., Frankel, A.E., GMP production and characterization of the bivalent antihuman T cell immunotoxin, AdmDT390- bisFv(UCHT1) for phase I/II clinical trials. Protein Expr Purif 2007; Nov 22, Epub.
Woo, J.H., Bour, S.H., Dang, T., Lee, Y.J., Park, S.K., Andreas, E., Kang, S.H., Liu, J.S., Neville, D.M., Frankel, A.E., Preclinical studies in rat and squirrel monkeys for safety evaluation of the bivalent anti-human T-cell immunotoxin, A-dmDT390-bisFv(UCHT1). Cancer Immunol Immunother 57: 1225-1239, 2008.
Liu, S., Wang, H., Currie, B.M., Molinolo, A., Leung, H.J., Moayeri, M., Basile, J.R., Alfano, R.W., Gutkind, J.S., Frankel, A.E., Bugge, T.H., Leppla, S.H.. Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature. J Biol Chem 2008; 283(1):529-40.
Alfano, R.W., Leppla, S.H., Liu, S., Bugge, T.H., Duesbery, N.S., Frankel, A.E., Potent inhibition of tumor angiogenesis by the matrix metalloproteinase-activated anthrax lethal toxin: implications for broad anti-tumor efficacy. Cell Cycle 2008; 7(6):745-9.
Alfano, R.W., Leppla, S.H., Liu, S., Bugge, T.H., Herlyn, M., Smalley, K.S., Bromberg-White, J.L., Duesbery, N.S., Frankel, A.E., Cytotoxicity of the matrix metalloproteinase-activated anthrax lethal toxin is dependent on gelatinase expression and B-RAF status in human melanoma cells. Mol Cancer Ther 2008; 7(5):1218-26.
Alfano, R.W., Leppla, S.H., Liu, S., Bugge, T., Meininger, C.J., Lairmore, T.C., Mulne, A.F., Davis, S.H., Duesbery, N.S., Frankel, A.E., Matrix metalloproteinase-activated anthrax lethal toxin inhibits endothelial invasion and neovasculature formation during in vitro morphogenesis. In review.
Liu Y, Dolence J, Ren J, Rao M. N.A, Sreejayan N (2008) Inhibitory effect of dehydrozingerone on vascular smooth muscle cell function. Journal of Cardiovascular Pharmacology. 52:422-9.
Li SY, Li Q, Shen JJ, Dong F, Sigmon VK, Liu Y, Ren J. (2006) Attenuation of acetaldehyde-induced cell injury by overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene in human cardiac myocytes: role of MAP kinase signaling. J Mol Cell Cardiol. 40:283-94.
Li SY, Liu Y, Sigmon VK, McCort A, Ren J. (2005) High-fat diet enhances visceral advanced glycation end products, nuclear O-Glc-Nac modification, p38 mitogen-activated protein kinase activation and apoptosis. Diabetes Obes Metab. 7:448-54.
Li S-Y, Yang X, Ceylan-Isik AF, Du M, Ren BH, Sreejayan N, Ren J. 2006. Cardiace contracticle dysfunction in ob/ob obesity is accompanied with oxidative modification of sarco(endo)plasmic reticulum Ca2_-ATPase and myosin heavy chain isozyme switch. Diabetologia. 49:1434-46.
Yang, X, Li S-Y, Dong F, Ren J, Sreejayan N. 2006. Insulin-sensitizing and cholesterol-lowering effects of chromium (d-Pheylalanine)(3). J Inorg Biochem. 100:1187-93.
Li S-Y, Li Q, Shen JJ, Dong F, Sigmon VK, Liu Y, Ren J. 2006. Attenuation of acetaldehyde-induced cell injury by overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene in human cardiac myoctes: role of MAP kinase signaling. J. Mol. Cell Cardiol. 40:283-294.
Xu P. Li S-Y, Li Q, Ren J, Van Kirk EA, Murdoch WJ, Radosz M, Shen Y. 2006. Biodegradable cationic polyester as an efficient carrier for gene delivery to neonatal cardiomyocytes. Biotecnology and Bioengineering 95:893-903.
Quality control
Yunpeng Su, Carol Carter
The QC unit has two scientists - Dr. Yunpeng Su, Assistant Director of R&D/QC and Carol Carter. Both scientists have been working in biochemistry and translational biomedical research for more than 10 years and have substantial experience in drug development processes from a QC perspective with preclinical execution experience. Carol Carter is a certified medical technologist with years of training in pharmacology and microbiology-related studies.
Woo, J.H., Liu, J., Kang, S.H., Singh, R., Park, S.K., Su, Y., Ortiz, J., Neville Jr., D.M., Willingham, M.C. and Frankel, A. E., 2008. GMP production and characterization of the bivalent anti-human T cell immunotoxin, AdmDT390-bisFv(UCHT1) for phase I/II clinical trials. Protein Expr. Purif. 58(1):1-11.
Su Y, Ortiz, J., Singh, R., Liu, S., Bugge, T.H., Leppla, S.H. and Frankel, A.E., 2006. Systematic urokinase-activated anthrax toxin therapy produces regressions of subcutaneous human non-small cell lung tumor in athymic nude mice. Cancer Research. 2007 April 67, 3329-3336.
Su,Y., Vanderlaag, K., Ireland, C., Ortiz, J., Grage, H., Safe, S. and Frankel, A.E., 2006. 1, 1-bis(3'- indolyl)-1-(p-biphenyl)methane inhibits basal-like breast cancer growth in athymic nude mice. Breast Cancer Res. 2007 Aug 31;9(4):R56 Epub.
Vanderlaag, K., Su,Y., Frankel, A.E., Grage, H., Smith R. 3rd, Khan, S., Safe, S. 1,1-Bis(3'-indolyl)-1 (psubstituted phenyl) methanes inhibit proliferation of estrogen receptornegative breast cancer cells by activation of multiple pathways. Breast Cancer Research and Treatment. 2007 Jul 12, Epub.
Woo, J.H., Liu, J. S., Kang, S.H., Singh, R., Park, S.K., Su, Y., Ortiz, J., Neville, D.M., Willingham, M.C., Frankel, A.E., GMP production and characterization of the bivalent antihuman T cell immunotoxin, AdmDT390- bisFv(UCHT1) for phase I/II clinical trials. Protein Expr Purif 2007; Nov 22, Epub.
Pharmacology/toxicology
Jennifer Lane, Rebecca Blackwood
Rebecca Blackwood, DVM is the CRI veterinarian. She performs formal pharmacology and toxicology research in whole-animal systems while ensuring compliance with federal and state laws, regulations and policies. She advocates animal well-being and adheres to appropriate guidelines for animal care and use when conducting research. Dr. Blackwood graduated from Texas A&M College of Veterinary Medicine and completed her residency in laboratory animal medicine at the University of California, Davis.
Jennifer Lane, DVM is the Scott & White attending veterinarian and the Director of the Department of Comparative Medicine, which employs seven technicians who assist with CRI animal work and maintain the CRI vivarium. All Scott & White animal facilities are AAALAC-accredited. Dr. Lane graduated from Virginia-Maryland College of Veterinary Medicine and completed her residency in laboratory animal medicine at the University of California, Davis.
Clinical pharmacology
Jen-Sing Liu, Shu-Ru Kuo
Dr. Jen-Sing Liu leads the clinical pharmacology studies at the Institute. Under the leadership of Drs. Frankel and Woo, and technical assistance from Dr. Shu-Ru Kuo, our clinical pharmacology team is conducting analysis of patient blood samples as part of the Phase I/II clinical trials at Scott & White as well as several other sites around the world.
Woo, J.H., Liu, J. S., Kang, S.H., Singh, R., Park, S.K., Su, Y., Ortiz, J., Neville, D.M., Willingham, M.C., Frankel, A.E., GMP production and characterization of the bivalent antihuman T cell immunotoxin, AdmDT390- bisFv(UCHT1) for phase I/II clinical trials. Protein Expr Purif 2007; Nov 22, Epub.
Frankel, A.E., Liu, J.S., Rizzieri, D.A. and Hogge, D.E. (2008) Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia. Leukemia & Lymphoma 49:543-553
Kuo, S.R., Bour, S.H., Andreas, E.A., Park, S.K., Jackson, C., Duesbery, N., Leppla, S.H., Tang, W.J., Frankel, A.E., Anthrax toxin-induced shock in rats is associated with pulmonary edema and hemorrhage. Microbial Pathog 44: 467-472, 2008.
Jeremy P. Mauldin, PhD
Compliance Officer
Jeremy P. Mauldin, PhD, Compliance Officer, comes to the CRI from the University of Virginia where he received his doctorate in pharmacology. He has held research positions and worked directly for the FDA. Dr. Mauldin's primary responsibility is to ensure that the CRI meets the rigorous standards set forth by the US Food & Drug Administration for our drug manufacturing campaigns, our pharmacological / toxicological animal studies, our phase 1 clinical studies, and preparation of our investigational new drug applications (INDAs). Dr. Mauldin also oversees the administrative staff and ensures fiduciary compliance.
Clinical Trials
Allison Mankin, Margarite Grable, Arthur Frankel, MD
Arthur Frankel, MD created the CRI model that zeroes in on work that goes from bench to bedside. He is assisted by a full-time clinical research coordinator in our clinical trials office. Margarite Grable has a BS in biology and has been active in the field of science for the past 12 years. Allison Mankin works in all aspects of clinical research trials, including management of the data collection process, design relevant data collection instruments, and collaborate with other study coordinators to ensure integrity of research data.
Administration
Anjie Colvin, Marla Franco, Jeremy Mauldin
Marla Franco has a BS in Finance and serves as our Financial Analyst. She assists with oversight of all financial transactions, including effective accounting and internal controls, so that funds are used conservatively and appropriately for a successful research program. Anjie Colvin, Executive Assistant to Arthur Frankel, MD, has held administrative support roles for executives within the professional community for the past 10 years; including McLane Company and Performance Food Group.