A5049482789- Cancer Cells and Metastasis
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Renal Diseases and Glomerulopathies
- Radiopharmaceutical Chemistry and Applications
- Cancer Immunotherapy and Biomarkers
- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Chronic Kidney Disease and Diabetes
- Metabolism, Diabetes, and Cancer
- Medical Imaging Techniques and Applications
- Protein Tyrosine Phosphatases
- Prostate Cancer Treatment and Research
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- Nanoplatforms for cancer theranostics
- Cancer, Stress, Anesthesia, and Immune Response
- PARP inhibition in cancer therapy
- Ultrasound and Hyperthermia Applications
- Pancreatic function and diabetes
- CAR-T cell therapy research
- Chemokine receptors and signaling
- Wnt/β-catenin signaling in development and cancer
- Amino Acid Enzymes and Metabolism
- Ultrasound Imaging and Elastography
University of Michigan
1997-2023
Johns Hopkins University
2016-2021
Johns Hopkins Medicine
2020-2021
Sidney Kimmel Comprehensive Cancer Center
2016-2018
Pediatric Nephrology of Alabama
2005-2010
Michigan United
2006
Michigan Medicine
2006
Glomerular injury and proteinuria in diabetes (types 1 2) IgA nephropathy is related to the degree of podocyte depletion humans. For determining causal relationship between glomerulosclerosis, a transgenic rat strain which human diphtheria toxin receptor specifically expressed podocytes was developed. The rodent homologue does not act as (DT) receptor, thereby making rodents resistant DT. Injection DT into rats but wild-type resulted dose-dependent from glomeruli. Three stages glomerular...
Recent investigations have focused on characterizing the molecular components of podocyte intercellular junction, because several these components, including Nephrin, are functionally necessary for development normal structure and filter integrity. Accumulating evidence suggests that Nephrin-associated protein complex is a signaling nexus. As such, Nephrin-dependent might be mediated in part through Nephrin phosphorylation. Described biochemical mouse genetics experiments demonstrating...
Because loss of podocytes associates with glomerulosclerosis, monitoring podocyte by measuring products in urine may be clinically useful. To determine whether a single episode injury would cause persistent loss, we induced limited depletion using diphtheria toxin receptor (hDTR) transgenic rat. We monitored detecting nephrin and podocin mRNA particulates quantitative reverse transcriptase–PCR. Aquaporin 2 served as kidney reference gene to account for variable contribution RNA amount...
The programmed death protein 1 (PD-1) and death-ligand (PD-L1) pair is a major immune checkpoint pathway exploited by cancer cells to develop maintain tolerance. With recent approvals of anti-PD-1 anti-PD-L1 therapeutic antibodies, there an urgent need for noninvasive detection methods quantify dynamic PD-L1 expression in tumors evaluate the tumor response modulation therapies. To address this need, we assessed [(64)Cu]atezolizumab tumors. Atezolizumab (MPDL3208A) humanized, human mouse...
Tumors create and maintain an immunosuppressive microenvironment that promotes cancer cell escape from immune surveillance. The checkpoint protein programmed death-ligand 1 (PD-L1) is expressed in many cancers important contributor to the maintenance of tumor microenvironment. PD-L1 a prominent target for immunotherapy. Guidance anti-PD-L1 therapy currently effected through measurement biopsy immunohistochemistry. Here, we report peptide-based imaging agent, [68Ga]WL12, detect expression...
Immune checkpoint therapies have shown tremendous promise in cancer therapy. However, tools to assess their target engagement, and hence the ability predict efficacy, been lacking. Here, we show that engagement tumor-residence kinetics of antibody therapeutics targeting programmed death ligand-1 (PD-L1) can be quantified noninvasively. In computational docking studies, observed PD-L1–targeted monoclonal antibodies (atezolizumab, avelumab, durvalumab) a high-affinity PD-L1–binding peptide,...
Podocytes are specialized epithelial cells with delicate interdigitating foot processes which cover the exterior basement membrane surface of glomerular capillary. They in part responsible for extraordinary charge and size filtration characteristics glomerulus. To better understand disease affecting filter, we searched proteins relative specificity to podocyte using a monoclonal antibody strategy. The first such protein characterized (designated 1 (GLEPP1)) is protein-tyrosine phosphatase...
Glomerular epithelial protein 1 (GLEPP1) is a receptor tyrosine phosphatase present on the apical cell surface of glomerular podocyte. The GLEPP1 gene (Ptpro) was disrupted at an exon coding for NH2-terminal region by targeting in embryonic stem cells. Heterozygote mating produced expected genotypic ratio 1:2:1, indicating that Ptpro–/– genotype does not lead to or neonatal lethality. Kidney and structure normal gross light microscopic levels. Scanning transmission electron microscopy showed...
Human renal cortex and heart cDNA libraries were screened for a human homolog of rabbit PCLP1 using the as probe. Clones spanning 5869 base pairs with an open reading frame coding 528-amino acid peptide obtained. The putative contains potential signal single membrane-spanning region. extracellular domain multiple sites N- O-linked glycosylation 4 cysteines disulfide bonding similar to PCLP1. On Northern blot major transcript is seen at 5.9 kilobases. Antibodies this protein show doublet...
The peak prevalence of ESRD from glomerulosclerosis occurs at 70 to 79 years. To understand why old glomeruli are prone failure, we analyzed the Fischer 344 rat model aging under ad libitum-fed (rapid aging) and calorie-restricted (slowed conditions. All glomerular cells contained genes whose expression changed "linearly" during adult life 2 24 months: mesangial (e.g., MMP9), endothelial ICAM VCAM), parietal epithelial ceruloplasmin), podocytes nephrin prepronociceptin). Patterns gene...
Expression of programmed cell death ligand 1 (PD-L1) within tumors is an important biomarker for guiding immune checkpoint therapies; however, immunohistochemistry-based methods detection fail to provide a comprehensive picture PD-L1 levels in entire patient. To facilitate quantification the whole body, we developed peptide-based, high-affinity imaging agent labeled with [ 18 F]fluoride positron emission tomography (PET) imaging. The parent peptide, WL12, and nonradioactive analog...
The prostate-specific membrane antigen (PSMA) is a validated target for detection and management of prostate cancer (PC). It has also been utilized targeted drug delivery through antibody–drug conjugates polymeric micelles. Polyamidoamine (PAMAM) dendrimers are emerging as versatile platform in number biomedical applications due to their unique physicochemical properties, including small size, large reactive terminal groups, bulky interior void volume, biocompatibility. Here, we report the...
Abstract Cancer cells reprogram energy metabolism through metabolic plasticity, adapting ATP-generating pathways in response to treatment or microenvironmental changes. Such adaptations enable cancer resist standard therapy. We employed a coculture model of estrogen receptor–positive (ER+) breast and mesenchymal stem (MSC) interactions with stromal microenvironments. Using single-cell endogenous engineered biosensors for cellular metabolism, MSCs increased oxidative phosphorylation,...
Biologic aging is accelerated by high-calorie intake, increased free radical production, and oxidation of key biomolecules. Fischer 344 rats that are maintained on an ad libitum diet develop oxidant injury age-associated glomerulosclerosis 24 mo. Calorie restriction prevents both glomerulosclerosis. Ceruloplasmin (Cp) a copper-containing ferroxidase functions as antioxidant in part oxidizing toxic ferrous iron to nontoxic ferric iron. Glomerular Cp mRNA protein expression were measured...
A human umbilical vein endothelial cell (EC)/monocyte (MC) coculture system was used to dissect cell:cell interactions associated with production of procoagulant activity (PCA) in response two common stimuli intravascular coagulation vivo (LPS and immune complexes). We found that the presence MC at a ratio 1 MC:10 EC increased sensitivity LPS by 4 logs maximal approximately 20-fold. Aggregated IgG alone did not stimulate system, but small amounts (1 10 ng/ml) aggregated powerful stimulus....