A5104183396- Single-cell and spatial transcriptomics
- Receptor Mechanisms and Signaling
- Cancer Genomics and Diagnostics
- Extracellular vesicles in disease
- Protein Kinase Regulation and GTPase Signaling
- Immune cells in cancer
- Multiple Myeloma Research and Treatments
- Chronic Obstructive Pulmonary Disease (COPD) Research
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Chemokine receptors and signaling
- Protein Structure and Dynamics
- Neuropeptides and Animal Physiology
- Molecular Biology Techniques and Applications
- Vibrio bacteria research studies
- Phagocytosis and Immune Regulation
- Autophagy in Disease and Therapy
- Antibiotic Resistance in Bacteria
- Inhalation and Respiratory Drug Delivery
- Pancreatic function and diabetes
- Acute Myeloid Leukemia Research
- Metabolism, Diabetes, and Cancer
- Diabetic Foot Ulcer Assessment and Management
- ATP Synthase and ATPases Research
- Infective Endocarditis Diagnosis and Management
Emory University
2021-2024
Children's Healthcare of Atlanta
2021-2024
Aflac (United States)
2021-2024
Pushpagiri Medical College
2018-2023
Beth Israel Deaconess Hospital
2023
Institute of Medical Sciences
2018-2020
Center for Cancer and Blood Disorders
2020
Beth Israel Deaconess Medical Center
2019-2020
Harvard University
2019
Tufts University
2005-2010
Photoaffinity crosslinking has been utilized to probe the nature of ligand–receptor interface for a number G protein‐coupled receptor systems. Often photoreactive benzophenone moiety incorporated in ligand is found react with methionine receptor. We introduced methionines one‐at‐a‐time into region 163–176 parathyroid hormone receptor, and find that occurs side‐chain over range 11 amino acids. call this “Magnet Effect” methionine. Hence, contact points can be significantly shifted by presence domain.
Abstract Background Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, preclinical models, inhibits anti-tumor immunity following chemotherapy. Methods We conducted phase I trial (NCT02502708) oral IDO-pathway inhibitor indoximod children with recurrent or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for combination temozolomide (200...
Aryl hydrocarbon receptor (AHR) is an essential regulator of gut immunity and a promising therapeutic target for inflammatory bowel disease (IBD). Current AHR agonists are inadequate clinical translation due to low activity, pharmacokinetics, or toxicity. We synthesized structurally diverse library used integrated computational experimental studies discover mechanisms governing ligand-receptor interaction design potent drug leads PY109 PY108, which display physiochemical drug-likeness...
Sickle cell disease (SCD) is canonically characterized by reduced red blood (RBC) deformability, leading to microvascular obstruction and inflammation. Although the biophysical properties of sickle RBCs are known influence SCD vasculopathy, contribution poor RBC deformability endothelial dysfunction has yet be fully explored. Leveraging interrelated in vitro silico approaches, we introduce a new paradigm vasculopathy which poorly deformable directly cause via mechanotransduction, during...
Elucidating the bimolecular interface between parathyroid hormone (PTH) and its cognate G protein-coupled receptor (PTHR1) should yield insights into basis of molecular recognition mechanism ligand-mediated intracellular signaling for a system that is critically important in regulating calcium levels blood. We used photoaffinity scanning (PAS) to identify key ligand−receptor interactions residues from unstructured mid-region domain PTH-(1−34). Four PTH analogues, containing single...
Introduction Current multistep methods utilized for preparing and cryopreserving single-cell suspensions from blood samples RNA sequencing (scRNA-seq) are time-consuming, requiring trained personnel special equipment, so limiting their clinical adoption. We developed a method, Simple prEservatioN of Single cElls (SENSE), single-step cryopreservation whole (WB) along with granulocyte depletion during assay, to generate high quality profiles (SCP). Methods WB was cryopreserved using the SENSE...
Efforts to elucidate the nature of bimolecular interaction parathyroid hormone (PTH) with its cognate receptor, PTH receptor type 1 (PTHR1), have relied heavily on benzoylphenylalanine- (Bpa-) based photoaffinity cross-linking. However, given flexibility, size, and shape Bpa, resolution at PTH−PTHR1 interface appears be reaching limit this technique. Here we employ a disulfide-trapping approach developed by others primarily for use in screening compound libraries identify novel ligands. In...
Abstract Background Mixed phenotype acute leukemia (MPAL), a rare subgroup of characterized by blast cells with myeloid and lymphoid lineage features, is difficult to diagnose treat. A better characterization MPAL essential understand the subtype heterogeneity how it compares (AML) lymphoblastic (ALL). Therefore, we performed single-cell RNA sequencing (scRNAseq) on pediatric bone marrow (BM) samples develop granular map blasts microenvironment landscape. Methods We analyzed over 40,000 from...
Binding of hormones to their cognate G protein-coupled receptors (GPCRs) induces conformational shifts within the receptor based on evidence from a few hormone-receptor systems. Employing an engineered disulfide bond formation strategy and guided by previously established model PTH-PTH (PTHR)1 bimolecular complex, we set out document characterize nature agonist-induced changes in this family B GPCR. A mutant PTHR1 was generated which incorporates Factor Xa cleavage site third intracellular...
ABSTRACT During cell culture, trypsin, a serine protease, is applied to cells for 5-10 minutes separate them from each other and the underlying substratum so that they can be transferred different vessel, re-plating, after growth medium containing 10 % serum has been added cells, in well-known technique known as ‘passaging’. The contains alpha-1 antitrypsin, which potent inhibitor of elastase proteases. Although what used bovine levels proteins could seen humans, normal human A1AT (> 1...
Interaction of ligands with their specific receptors is accompanied by conformational shifts culminating in receptor activation and expression hormonal activity. Using an engineered disulfide bond formation strategy, we characterized the relative changes taking place within PTH type 1 (PTHR1) at interface transmembrane (TM)5 TM6 on binding agonist, PTH(1-34), compared antagonist PTH(7-34). Cysteines were singly incorporated into a portion extracellular-facing region TM5 (365-370), while...
Abstract Background Vein graft failure (VGF) following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. injury can occur during autogenous vein harvest preparation, as well after implantation into arterial system, leading development of intimal hyperplasia, stenosis, and, ultimately, failure. While previous studies have identified maladaptive pathways that shortly implantation, specific signaling preparation are not defined may result...
Abstract PTHR1 mutants lacking endogenous cysteines in transmembrane and intracellular domains were generated. Mutant receptors tested for their biological activities mRNA cell surface expression levels. C217 loop 1 was determined to play a critical role translocation function of the receptor. Introduction: Elucidating different PTH receptor (PTHR1) is essential understanding mechanism ligand–receptor interactions. Here we present study directed at determining importance cysteine residues...
Human angiotensin type 1 receptor (hAT1R) gene is regulated by hormones, second messengers, and both pathophysiological developmental states. The focus of the present study was to determine role glucose in trans-repression hAT1R transcription identify functional cis-acting response element(s). Serial deletions promoter region indicated that an area between -1717 -1543 base pairs upstream 5' end cDNA sequence has a responsive regulatory element (GluRE) down-regulate expression. Further...
Background: Acinetobacter baumannii has evolved as a common Multi Drug Resistant (MDR) microbe. This study was conducted to find the profile of antimicrobial resistance and mortality their associated factors in A. infection lower respiratory tract. Materials Methods: record based cross sectional done tertiary care teaching hospital Kerala. Records all 63, 2017, were retrieved analyzed. MDR defined at least one agent three or more classes. Proportion MDR, carbapenam other major antimicrobials...
Abstract BACKGROUND Brain tumors are the leading cause of pediatric cancer-related death. METHODS We report interim outcome data from an ongoing multi-site phase 2 study (NCT04049669) indoximod-based chemo-immunotherapy for patients 3-21 years age with either recurrent brain cancer (ependymoma, medulloblastoma, high-grade glioma) or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Treatment is oral IDO pathway-inhibitor indoximod (38.4 mg/kg/day, divided BID) plus temozolomide (200...
Polyploidy induction plays a significant role in hybridizing and improving orchids (Orchidaceae). Induction of polyploidy can help to restore fertility by doubling chromosomes thus leading the creation allotetraploids which breeders develop improved hybrids novel types contributing beautiful floral or growth characteristics unobtainable from diploid forms. The objective present study was investigate effective colchicine concentration duration exposure for Dendrobium crumenatum via vivo...