A5082420242- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Galectins and Cancer Biology
- Bone Metabolism and Diseases
- Bone health and treatments
- Bone health and osteoporosis research
- Biosimilars and Bioanalytical Methods
- Connexins and lens biology
- Peptidase Inhibition and Analysis
- Heat shock proteins research
- Cytokine Signaling Pathways and Interactions
- CRISPR and Genetic Engineering
- Muscle Physiology and Disorders
- Asthma and respiratory diseases
- Advanced Biosensing Techniques and Applications
- Protein purification and stability
- Adenosine and Purinergic Signaling
- Toxin Mechanisms and Immunotoxins
- Biomarkers in Disease Mechanisms
- Psoriasis: Treatment and Pathogenesis
- Estrogen and related hormone effects
- Genetics and Physical Performance
- DNA Repair Mechanisms
- Genetic Syndromes and Imprinting
- PI3K/AKT/mTOR signaling in cancer
Eli Lilly (United States)
2015-2025
Indiana University School of Medicine
2009-2019
Indiana University – Purdue University Indianapolis
2009-2019
Indiana University
2011-2012
University School
2012
University of Udine
2005-2011
University of Manchester
2009
Universidad Nacional del Sur
2009
Institute for Experimental Endocrinology and Oncology
2005
Connexin 43 (Cx43) mediates osteocyte communication with other cells and the extracellular milieu regulates osteoblastic cell signaling gene expression. We now report that mice lacking Cx43 in osteoblasts/osteocytes or only osteocytes (Cx43(ΔOt) mice) exhibit increased apoptosis, endocortical resorption, periosteal bone formation, resulting higher marrow cavity total tissue areas measured at femoral mid-diaphysis. Blockade of resorption reversed but not area, demonstrating apposition are...
BackgroundPhysicians treating patients with coronavirus disease 2019 (COVID-19) increasingly believe that the hyperinflammatory acute stage of COVID-19 results in a cytokine storm. The circulating biomarkers seen across spectrum have not been characterized compared healthy controls, but such analyses are likely to yield insights into pursuit interventions adequately reduce burden these storms.ObjectiveTo identify and characterize host inflammatory response severe respiratory syndrome 2...
The periosteal and endocortical surfaces of cortical bone dictate the geometry overall mechanical properties bone. Yet cellular molecular mechanisms that regulate activity on these are far from being understood. Parathyroid hormone (PTH) has profound effects in bone, stimulating expansion at same time accelerating intracortical remodeling. We report herein transgenic mice expressing a constitutive active PTH receptor osteocytes (DMP1-caPTHR1 mice) exhibit increased area an elevated rate...
Abstract The osteocyte network is crucial for the response of bone to mechanical force. Within this network, connexin43 (Cx43) thought mediate communication osteocytes and osteoblasts among themselves exchange small molecules with extracellular milieu. Despite recent advances in understanding Cx43 role cells stimulation, contribution specifically mechanotransduction vivo not well‐known. We examined anabolic ulnar axial loading mice lacking (Cx43 ΔOt ). Loading induced a greater increase...
Abstract Purpose: Investigate the safety and efficacy of LY3415244, a TIM-3/PD-L1 bispecific antibody that blocks TIM-3 PD-L1 in patients with advanced solid tumors. Patients Methods: A phase I, multicenter, open-label study was conducted were dosed every 2 weeks intravenously flat doses LY3415244 escalating from 3 to 70 mg. The primary endpoints safety, tolerability, identification recommended II dose. Results: Between November 2018 October 2019, 12 enrolled into four cohorts received at...
Chronic heart failure, a progressive disease with limited treatment options currently available, especially in failure preserved ejection fraction (HFpEF), represents an unmet medical need as well economic burden. The development of novel therapeutic to slow or reverse progression would be highly impactful patients and society. Relaxin-2 (relaxin) is human hormone regulating cardiovascular, renal, pulmonary adaptations during pregnancy. A short-acting recombinant relaxin, Serelaxin,...
The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place Orlando, FL, USA June 19–23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned 1 week allow an exhaustive thorough coverage all major issues bioanalysis biomarkers, immunogenicity, gene therapy, cell therapy vaccines....
Parathyroid hormone (PTH) promotes osteoblast survival through a mechanism that depends on cAMP-mediated signaling downstream of the G protein-coupled receptor PTHR1. We present evidence herein PTH-induced is impaired in cells lacking connexin43 (Cx43). Thus, expression functional Cx43 dominant negative proteins or knock-down abolished cAMP-target genes and anti-apoptosis induced by PTH osteoblastic cells. In contrast, were still responsive to stable cAMP analog dibutyril-cAMP. was rescued...
Abstract Because development of reliable biomarkers in psoriasis and atopic dermatitis has lagged behind therapeutic progress, we created a blood-based test to fill the void objective methods available for dermatological assessments. Our novel interleukin-19 (IL-19) immunoassay was initially tested determine concentrations IL-19 serum levels, then correlated with activity severity index (PASI) psoriasis, eczema area (EASI) dermatitis. Not only increased PASI, but ixekizumab administration...
The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place San Antonio, TX, USA May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned 1 week allow an exhaustive thorough coverage all major issues bioanalysis biomarkers, immunogenicity, gene therapy, cell therapy vaccines....
APE1/Ref-1, the mammalian ortholog of E. coli Xth, and a multifunctional protein possessing both DNA repair transcriptional regulatory activities, has dual role in controlling cellular response to oxidative stress. It is rate-limiting damage including strand breaks also co-transcriptional activity by modulating genes expression directly regulated Egr-1 p53 transcription factors. PTEN, phosphoinositide phosphatase, acts as an 'off' switch PI-3 kinase/Akt signalling pathway regulates cell...
The 2022 16th Workshop on Recent Issues in Bioanalysis (WRIB) took place Atlanta, GA, USA September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned 1 week order allow exhaustive thorough coverage all major issues bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy...
Signal transducer and activator of transcription 3 (Stat3) is a member the Stat family proteins involved in signaling many different cell types, including osteocytes. Osteocytes are considered major mechanosensing cells bone due to their intricate dendritic networks able sense changes physical force orchestrate response osteoclasts osteoblasts. We examined role Stat3 osteocytes by generating mice lacking these using Dmp-1(8kb)-Cre promoter (Stat3cKO mice). Compared age-matched littermate...
Despite recent advances in the development of tools to predict immunogenicity risk biotherapeutic molecules, ability a protein elicit formation anti-drug antibodies (ADA) remains one most common causes for termination clinical programs. In this study, we use ADA assays detect and measure pre-existing reactivity or molecule produce an ADA-like response serum from treatment-naïve, healthy donors. We report herein that magnitude evaluated pre-clinically expressed as 90th percentile Tier 2...
The Early Growth Response protein (Egr-1) is a C(2)H(2)-zinc finger-containing transcriptional regulator involved in the control of cell proliferation and apoptosis. Its DNA-binding activity redox regulated vitro through oxidation-reduction Cys residues within its domain. APE/Ref-1 DNA-repair enzyme with modulating activities on several transcription factors. In this study, by evaluating effects different stimuli, we found similar timing activation being suggestive for common co-linear...
Inactivation of the breast cancer susceptibility gene 1 (BRCA1) plays a significant role in development subset familial and ovarian cancers, but increasing evidence points to also sporadic tumors. BRCA1 is multifunctional nuclear protein involved regulation many cellular processes, including DNA repair, cell cycle, transcription chromatin remodeling. To identify novel proteins participating network, two-dimensional gel electrophoresis MALDI-TOF mass spectrometry were used compare...
Nitrogen-containing bisphosphonates are the elected drugs for treatment of diseases in which excessive bone resorption occurs, example, osteoporosis and cancer-induced diseases. The only known target nitrogen-containing is farnesyl pyrophosphate synthase, ensures prenylation prosurvival proteins, such as Ras. However, it likely that action involves additional unknown mechanisms. To identify novel targets bisphosphonates, we used a genome-wide high-throughput screening 5,936 Saccharomyces...
We combined high-throughput screening of differential mRNAs with mass spectrometric characterization proteins obtained from osteocytes untreated and treated Risedronate. Microarray analysis revealed, upon treatment, a marked upregulation messengers encoding zinc-proteins. MS identified 84 in the proteome map. Risedronate affected expression 10 proteins, associated cytoskeleton, stress-response metabolism. Data validated using gel imaging combination GLaD post digestion isotopic labeling...