A5037263558- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- Advanced Biosensing Techniques and Applications
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- PARP inhibition in cancer therapy
- Pancreatic function and diabetes
- Nanofabrication and Lithography Techniques
- Nanoparticle-Based Drug Delivery
- Biosimilars and Bioanalytical Methods
- Photoacoustic and Ultrasonic Imaging
- Mathematical Biology Tumor Growth
- Diabetes and associated disorders
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Diabetes Treatment and Management
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Receptor Mechanisms and Signaling
- Nanoplatforms for cancer theranostics
- Protein purification and stability
- Immunotherapy and Immune Responses
University of Michigan
2016-2025
BioSurfaces (United States)
2024
Massachusetts Institute of Technology
2007-2023
Novartis (United States)
2023
Michigan United
2018-2020
Ann Arbor Center for Independent Living
2017
Harvard University
2009-2015
Center for Systems Biology
2009-2014
Massachusetts General Hospital
2009-2014
Harvard University Press
2011
We report the synthesis and in vivo characterization of an 18F modified trimodal nanoparticle (18F-CLIO). This particle consists cross-linked dextran held together core−shell formation by a superparamagnetic iron oxide core functionalized with radionuclide high yield via "click" chemistry. The can be detected positron emission tomography, fluorescence molecular magnetic resonance imaging. presence dramatically lowers detection threshold nanoparticles, while facile conjugation chemistry...
There has been intense interest in the development of selective bioorthogonal reactions or “click” chemistry that can proceed live animals. Until now however, most still require vast surpluses reactants because steep temporal and spatial concentration gradients. Using computational modeling design pharmacokinetically optimized reactants, we have developed a predictable method for efficient vivo click reactions. Specifically, show polymer modified tetrazines (PMT) are key enabler based on...
Proteases are emerging biomarkers of inflammatory diseases. In atherosclerosis, these enzymes often secreted by macrophages, digest the extracellular matrix fibrous cap, and destabilize atheromata. Protease function can be monitored with protease activatable imaging probes quantitated in vivo fluorescence molecular tomography (FMT). To address 2 major constraints currently associated murine atherosclerosis (lack highly sensitive absence anatomic information), we compared sensors (PS)...
The hallmark of type 1 diabetes is autoimmune destruction the insulin-producing β-cells pancreatic islets. Autoimmune has been difficult to study or treat because it not usually diagnosed until substantial β-cell loss already occurred. Imaging agents that permit noninvasive visualization changes in mass remain a high-priority goal. We report on development and testing near-infrared fluorescent imaging agent. Based amino acid sequence exendin-4, we created neopeptide via introduction an...
Recent advances in genome inspired target discovery, small molecule screens, development of biological and nanotechnology have led to the introduction a myriad new differently sized agents into clinic. The differences large delivery are becoming increasingly important combination therapies as well use drugs that modify physiology tumors such anti-angiogenic treatment. complexity targeting has mathematical models facilitate understanding, but unfortunately, these studies often only applicable...
Abstract Current antibody–drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, relationship between heterogeneous intratumoral distribution efficacy of ADCs is poorly understood. Here, we compared trastuzumab ado-trastuzumab emtansine (T-DM1) to study impact ADC tumor on efficacy. In a mouse xenograft model insensitive trastuzumab, coadministration with fixed dose T-DM1 at 3:1 8:1...
Monoclonal antibodies labeled with near-infrared (NIR) fluorophores have potential use in disease detection, intraoperative imaging, and pharmacokinetic characterization of therapeutic both the preclinical clinical setting. Recent work has shown conjugation NIR to can potentially alter antibody disposition at a sufficiently high degree labeling (DoL); however, other reports show minimal impact after fluorophores. In this work, we label two clinically approved antibodies, Herceptin...
Targeted delivery of chemotherapeutics aims to increase efficacy and lower toxicity by concentrating drugs at the site-of-action, a method embodied seven current FDA-approved antibody-drug conjugates (ADC). However, variety pharmacokinetic challenges result in relatively narrow therapeutic windows for these agents, hampering development new drugs. Here, we use series prostate-specific membrane antigen-binding single-domain (Humabody) ADC constructs demonstrate that tissue penetration...
Poor tissue penetration remains a major challenge for antibody-based therapeutics of solid tumors, but proper dosing can improve the and thus therapeutic efficacy these biologics. Due to dose-limiting toxicity small molecule payload, antibody-drug conjugates (ADCs) are administered at much lower dose than their parent antibodies, which further reduces penetration. We conducted an early-phase clinical trial (NCT02415881) previously reported safety antibody-dye conjugate...
Antibody-drug conjugates (ADC) are a rapidly growing class of targeted cancer treatments, but the field has experienced significant challenges from their complex design. This study examined multiscale distribution sacituzumab govitecan (SG; Trodelvy), recently clinically approved ADC, to clarify mechanism(s) efficacy given its unique design strategy. We employed quantitative pharmacokinetic approach, including near-infrared fluorescence imaging, single-cell flow cytometry measurements,...
Antibody drug conjugates (ADCs) have made impressive strides in the clinic recent years with 11 Food and Drug Administration approvals, including 6 for treatment of patients solid tumors. Despite this success, development new agents remains challenging a high failure rate clinic. Here, we show that current approved ADCs tumors can all substantial efficacy some mouse models when administered at similar weight-based [milligrams per kilogram (mg/kg)] dosing mice is tolerated Mechanistically,...
Targeting tumors with antibody-based therapeutics is a complex task presenting multiple kinetic barriers. Antibody internalization and clearance inhibit uptake both in solid tumors, limited by tumor vascular permeability, micrometastases, diffusion.A modeling exercise used to introduce 2 simple criteria that must be less than unity for saturation of micrometastases. The modulus the Thiele are ratios plasma rate antibody catabolism, respectively, tissue penetration rate.Even low rates antigen...
Abstract Antibody-based cancer treatment depends upon distribution of the targeting macromolecule throughout tumor tissue, and spatial heterogeneity could significantly limit efficacy in many cases. Antibody tissue is a function drug dosage, antigen concentration, binding affinity, internalization, extravasation from blood vessels, diffusion extracellular matrix, systemic clearance rates. We have isolated effects subset these variables by live-cell microscopic imaging single-chain antibody...
Significance In many autoimmune diseases, self-reactive lymphocytes lead to immunocyte infiltration in the target tissue, whose evolution over time is regulated. Such lesions can be well-tolerated and minimal damage, or have more drastic consequences. We show here, for insulitis of nonobese diabetic (NOD) mouse model diabetes, that infiltrate an open dynamic cell population, with a high turnover constant reseeding fresh cells coming from general lymphoid circulation; this implies such lesion...
A computational model predicting bystander payload distribution as a function of controllable design parameters for guiding efficient clinical ADC development.