UB’s New York State Center of Excellence in Bioinformatics & Life Sciences (CBLS) is home to over 250 scientists and research staff with biological, physical and computational expertise, all of whom are engaged in interdisciplinary biomedical research with collaborators from across the region, the country and the globe. CBLS faculty members are affiliated with our primary research partners, including the University at Buffalo, Roswell Park Cancer Institute, and the Hauptmann-Woodward Medical Research Institute.
PK/PD; Pharmacodynamic; Pharmacokinetic
Director, Center for Protein Therapeutics with research focusing on the utilization of pharmacokinetic and pharmacodynamic analyses and mathematical modeling to guide the discovery and development of new immunotherapies for cancer and autoimmunity. Research Interests and Projects: 1. Development of antibody conjugates for targeted, intra-cellular delivery of macromolecular toxins 2. Engineering monoclonal antibodies for improved pharmacokinetic properties 3. Investigation of sources of inter-individual variability in monoclonal antibody pharmacokinetics 4. Investigation of strategies to overcome the "binding site barrier" to antibody distribution in solid tumors 5. Development of improved mathematical models for predicting the disposition and effects of monoclonal antibody drugs 6. Development of new targeting strategies to optimize the safety and efficacy of intraperitoneal chemotherapy of ovarian cancers (CA118213) 7. Development of FcRn inhibitors for treatment of humoral autoimmune diseases (e.g., myasthenia gravis, autoimmune neutropenia) (AI60687) 8. Development of new strategies to treat immune thrombocytopenic purpura (HL67347) 9. Investigation of the role of FcRn in the absorption, distribution, and elimination of IgG antibodies 10. Development of antibody-based therapies to treat and prevent infection. Efforts are currently focused on prevention of infection by Treponema denticola (DE023080), S. aureus, and A. baumannii
Research interest is in the area of protein delivery and immunotherapy. Current research projects: 1. Development of lipidic nano particle containing therapeutic proteins and is supported by NHLBI/NIH. The overall goal of the project is to improve therapeutic efficacy of protein based therapies for bleeding and lysosomal disorders using a multidisciplinary approach involving Biophysics/Bioengineering, immunology and pharmacokinetics/Pharmacodynamics. 2. Re-activating Memory T Cells in the Microenvironment of Human Tumors and development of in situ vaccination. This project is supported by NCI/NIH (Dr. Bankert, PI, Balu-Iyer Co-PI). Our aim is to to rationally develop therapeutic intervention by understanding the molecular mechanism of TCR arrest. 3. Develop novel strategies to treat food allergies and autoimmune conditions using the tolerogenic properties of biomolecules. 4. Formulation and delivery of Monoclonal antibody based products: Understand and develop strategies to improve efficacy of antibody based therapeutics particularly given via sc route of administration
Research focus areas: Proteomics and Pharmaceutical Analysis. Major research programs in the proteomic field involve i) high-resolution and large-scale expression profiling of pathological proteomes (e.g. for cardiovascular diseases, colon cancer and infectious diseases) for the discovery of disease/therapeutic biomarkers by gel-free LC/MS methods; ii) Sensitive identification, localization and quantification of post-translational modifications in complex proteomes, with the emphases on arginine methylation and phosphorylation. Novel anti-PTM-peptides capture procedure and alternating collision induced dissociation (CID)/electron transferring dissociation (ETD) are employed to obtain abundant PTM information; iii) targeted quantification of regulatory, marker proteins for clinical study. Dr. Qu‘s lab possesses many state-of-the-art LC/MS instruments, including a high resolution/accuracy LTQ/Orbitrap XL with ETD, a highly sensitive TSQ Quantum Ultra EMR triple-quadrupole instrument, two ultra-high pressure nano-LC systems, and several HPLC instruments for pre-fraction and ion chromatography. A number of key analytical advances have been developed by his lab that greatly enhanced the proteomic coverage, sensitivity and throughput for proteomic research. As for the Pharmaceutical Analysis of small-molecule drug/markers, Dr. Qu‘s lab is focusing on the ultra-sensitive quantifications of drug, metabolites and endogenous markers (e.g. corticosteroids, di-hydroxyl-vitamin D metabolites, androgens, etc.) using a novel combination of selective enrichment and micro- or nano- LC/MS.
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.