Our research program involves the application of drug carriers for the treatment of infectious diseases and cancer. Recent past efforts have been directed toward improving the therapy of brain tumors (as well as others) by targeting tumor blood vessels. Currently we are investigating strategies in increase the perfusion and drug permeability of pancreatic cancers by compromising the ability of cells within the tumor stroma, or extracellular matrix, to maintain the very low tumor blood supply and impermeability to drugs and nanoparticles We employ a variety of experimental approaches, including high-resolution magnetic resonance imaging, liquid chromatography/mass spectrometry, confocal fluorescence microscopy and image analysis, pharmacokinetic/dynamic analysis, and molecular techniques such as quantitative RT-PCR and proteomics. With these techniques, we examine the effects of treatment upon tumor vascular permeability and drug deposition, the localization of the carrier-delivered drug within the tumor, and the molecular mechanisms involved when tumor blood vessels or tumor stroma are attacked during therapy.
Additional interests of the lab that are being pursued actively include understanding the mechanisms of anti-cancer drug action and how they may be modified by changing exposure profile (time vs. concentration). Both genomic and proteomic analysis approaches are utilized in this work, but an approach of increasing importance to our research is the implementation of comprehensive proteomic investigations in order to understand in detail how tumors respond to standard-of-care drugs and new molecularly-targeted drugs.
E.T.S. Walton Visiting Professor, Science Foundation Ireland (2012)
Chancellor's Award for Excellence in Scholarship and Creative Activities (2009)
Elected Fellow, American Association of Pharmaceutical Scientists (2007)
3rd Place, Western New York Inventor of the Year (2003)
Rho Chi National Pharmaceutics Honor Society (1993)
: Utilizes liposomes and other carrier techniques to improve the solubility and delivery of taxol and other poorly-soluble anticancer agents.
: Methods of improving the delivery and efficacy of anticancer drugs such as taxol.
: Research interests center on the use of drug carriers such as liposomes to improve the therapy of diseases that include ovarian cancer and opportunistic infections associated with AIDS.
: Development of liposome-based therapy for ovarian cancer using in vitro and in vivo systems. Project involved developing and evaluating efficacy of ligand-directed liposomes against human ovarian carcinoma in vitro or in vivo in athymic nude mouse model.
: Intracellular traffic of membranes and membrane proteins, using molecular cloning techniques. Project involved use of recombinant DNA techniques to create chimeric proteins containing specific domains of HMG-CoA reductase and reporter genes to allow intracellular localization in living cells. Goal was to understand how membrane-spanning domains of the reductase protein affect intracellular localization. Genes for recombinant proteins were introduced into cultures cells by needle microinjection.
: Kinetics of liposome internalization into acidic and enzyme-bearing compartments following endocytosis, using novel fluorescence techniques that allow continuous observation of endocytosis in living cells. Role of cell surface receptor in determining intracellular fate of ligand-directed lipid vesicles. Intracellular vesicular traffic and sorting of model membranes microinjected into cells.
: Mechanisms of membrane fusion: development of a pure-lipid membrane system for study of pH-dependent fusion. Role of neutral-phospholipid headgroup in determining susceptibility of membranes to undergo pH-dependent fusion. Application of system to delivery of macromolecules to cytoplasm following endocytosis of liposomes into acidic intracellular compartment.
: Aerosol and intravenous administration of pentamidine and pentamidine-containing liposomes for treatment of Pneumocystis carinii. Project supplied some of the data filed in support of successful IND application for clinical trial of aerosolized pentamidine in humans. Clinical trial of this work currently is proceeding.
: Cell biology of liposome internalization and intracellular fate of liposome contents.
: Gene delivery in vitro; effect on viral DNA expression of liposome transfection procedures, liposome composition, cell incubation conditions, and chemical modifiers of cell and organelle function.
: Physical properties of liposomes: encapsulation of biologically active compounds.
: Interaction of Picornaviruses (polio and encephalomyocarditis) with cells in culture; transfection with isolated RNA to study cellular resistance to Picornavirus infection. (Under the direction of Robert L. Taber, Ph.D., Department of Medical Viral Oncology, Roswell Park Memorial Institute, Buffalo, N.Y.).
: Avian limb bud morphogenesis: in vitro assay of limb bud polarizing factor activity. (Masters thesis project carried out under the direction of John M. Cairns, Ph.D., Springville Labs Division, Roswell Park Memorial Institute, Buffalo, N.Y.).
: Extensive 'C', Fortran, Java language programming experience on mainframe and microcomputers.
Center of Excellence in Bioinformatics and Life Sciences
UB 2020 Strategic Strengths:
Integrated Nanostructured Systems
Method of complexing a protein by the use of a dispersed system and protein Type: Regular (2010)
Compositions of less immunogenic and long circulating protein-lipid complex Type: Regular (2007)
Method for treating blood coagulation disorders Type: Regular (2007)
Stabilization of taxane-containing dispersed systems Docket Number: 5214 Type: Other Other Type: PCT (2000)
Aminophospholipid compositions and uses thereof Type: Regular (1998)
Aminophospholipid compositions and uses thereof Type: Regular (1996)
TAXOL FORMULATION Docket Number: 5214 Type: Other Other Type: Germany (1994)
TAXOL FORMULATION Docket Number: 5214 Type: Other Other Type: Canada (1994)
Johnson J, Bootman J, Evans W, Hudson R, Knoell D, Simmons L, Straubinger RM, Meyer, A. Pharmacogenomics: a scientific revolution in Pharmaceutical Sciences and Pharmacy Practice. Report of the 2001/2 Academic Affairs Committee.. Am J Pharm Educ. 2002; 66.
American Association of Pharmaceutical Scientists (AAPS) (1989–present)
American Association for Cancer Research (AACR) (1980–present)
"Tumor Priming Combined with Nanoparticle Drug Formulations for Pancreatic Cancer Therapy" Department of Oral Biology, University at Buffalo, State University of New York (2016)
"Nanoparticle based chemotherapy combinations for oncology applications" Department of Pharmaceutical Sciences, University at Buffalo, State University of New York (2016)
"Tumor Priming Combinations to Enhance the Efficacy of Pancreatic Cancer Therapy" Department of Pharmacology and Toxicology, University at Buffalo, State University of New York (2016)
"From the Beginning… to the USA-Ireland Research Partnership Programme" National Inst. for Cellular Biotechnology, Dublin City University (2016)
"Tumor priming sequences combined with novel nanoparticle drug carriers for enhanced therapeutic efficacy in pancreatic cancer: a tripartite USA/Northern Ireland/Republic of Ireland consortium" Pancreatic cancer research symposium, Queen's University Belfast (2016)
"Tumor priming approaches to increase drug delivery in pancreatic cancer models" Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital (2016)
"Development and application of computational approaches to understand and overcome stromal resistance-mediated cancer treatment failure" Workshop on Quantitative Pharmacology and Systems Biology in Pharmaceutical Development, Dublin City University (2014)
"Imaging and visualization modalities supporting research in rodent models of cancer" Ireland Branch Symposium 2013, Institute of Animal Technology (2013)
"Tumour priming strategies to enhance cancer chemotherapy with nanoparticulate drug carriers" E.T.S. Walton Visiting Professor Public Lecture, Science Foundation Ireland, Dublin City University (2013)
"Tools for the development of novel cancer therapies" Fourth year elective in Biotechnology, School of Biotechnology (2013)
"Tumor Priming Strategies in Combination with Nanoparticle Delivery Carriers" School of Biotechnology, Dublin City University (2013)
"Establishment and Preclinical Applications of Patient-Derived Pancreatic Cancer Tumor Models" Presentation to pancreatic cancer therapeutics team, National Surgical Centre for Pancreatic Cancer (2013)
"Tumor priming combination chemotherapy strategies: model studies" Molecular Therapeutics for Cancer Ireland Symposium, Molecular Therapeutics for Cancer Ireland (MTCI) (2012)
"Development of tumor priming strategies combining tumor stromal modulators with nanoparticulate drug carriers" Institute Seminar, National Inst. for Cellular Biotechnology (2012)
"Liposomal mitoxantrone for intra-arterial drug delivery" 40th Annual Meeting of the Society for Neuroscience in Anesthesiology and Critical Care, Washington, DC, American Society for Neuroscience in Anesthesiology and Critical Care (2012)
"Surface charge manipulation of liposomes to enhance intraarterial delivery" 40th Annual Meeting of the Society for Neuroscience in Anesthesiology and Critical Care, Washington, DC, American Society for Neuroscience in Anesthesiology and Critical Care (2012)
"Preclinical combination therapy of pancreatic cancer using tumour stromal modulators and nanoparticulate drug" BIOTECHNOLOGY IN ACTION: Stem Cells & Tissue Engineering, Biopharmaceutical Production and Cancer Biomarkers, National Inst. for Cellular Biochemistry, Associazonione Italiana di Colture Cellulari, European Tissue Culture Society (2012)
"Pharmacokinetic/pharmacodynamic modeling of cocaine self-administration behavior in rats" 74th Annual Meeting - College on Problems of Drug Dependence, The College on Problems of Drug Dependence (CPDD) (2012)
"Modulation of Tumor Barriers to Improve Drug Delivery in Cancers" AAPS Student Chapter Lecture in Pharmaceutical Sciences, AAPS and Pharmaceutical Sciences Graduate Student Association (2012)
"Effects of sonic hedgehog inhibitor combined with nanoparticulate drug delivery on vascular permeability and efficacy in a pancreatic cancer model." Annual Meeting of the American Association for Cancer Research, American Association for Cancer Research (2012)
"Mathematical Analysis of Paclitaxel-induced Tumor Priming That Leads to Enhanced Deposition and Efficacy of Nanoparticulate Doxorubicin" American Association for Cancer Research, AACR (2012)
"Multi-scale assessment of Everolimus and Sorafenib Combination in Pancreatic Cancer" American Association for Cancer Research, AACR (2012)
"Population Physiologically-based Pharmacokinetic Models for Everolimus and Sorafenib in Pancreatic Cancer Xenograft Mice" 2011 AAPS Annual Meeting and Exposition, AAPS (2011)
"Systems Pharmacological Analysis of Molecularly Targeted Agents in Pancreatic Cancer: Pharmacodynamic Design of Novel Therapeutic Trials" Clinical and Translational Research Colloquium, University at Buffalo (2011)
"Investigation of the effect of cocaine use and withdrawal in rat models using comprehensive and reproducible ion-current-based proteomic expression profiling" 2011 American Society for Mass Spectrometry annual meeting (2011)
"Physiologically-Based Pharmacokinetics and Interactions of Everolimus and Sorafenib in Mice" American Association for Cancer Research, AACR (2011)
"Modeling chemotherapeutic interactions of sorafenib and everolimus effects on pancreatic cancer cells" AAPS Annual Meeting and Exposition, AAPS (2010)
"Pharmacodynamic Interaction of Everolimus and Sorafenib Using In Vitro Whole Blood Lymphocyte Proliferation" AAPS Annual Meeting and Exposition, AAPS (2010)
"A rapid, reproducible, on-the-fly orthogonal array optimization method for targeted protein quantification by LC/MS and its application in clinical analysis" 2010 ASMS Anuual Meeting (2010)
"Pharmacodynamic Interaction of Everolimus and Sorafenib Using In Vitro Whole Blood Lymphocyte Proliferation" Pharmacology Day 2010, University at Buffalo (2010)
"Drug Development Resources of UB Pharmaceutical Sciences and the Buffalo Life Sciences Center" NYSTEM Planning Meeting, Roswell Park Cancer Inst. (2009)
"Chemotherapy PK/PD Modeling" UB-Pfizer Annual Research Symposium, Pfizer (2007)
"Opportunities for combination therapies with liposomal formulations" , Merrimack Pharmaceuticals (2007)
Editorial Advisory Board; Journal of Pharmaceutical Sciences Advise editorial board on scientific merit of manuscripts, participate in discussions relating to journal function as requested; Other (2011)
External Scientific Advisory Board, MTCI (Molecular Therapeutics for Cancer Ireland) cluster; Science Foundation Ireland/ICORG MTCI program Meet twice yearly in Dublin Ireland to review progress on 6M Euro program funded by Science Foundation Ireland; Other (2010)
grant reviewer; Science Foundation Ireland (SFI); Other (2010)
external advisory board member; Dublin City University National Inst. for Cellular Biotechnology External scientific advisory board member; Other (2010)
External advisory board member; Dublin City University- Strategic Research Cluster in traslational cancer drug discovery External science advisory board; Other (2009)