A5036204423- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Advanced Radiotherapy Techniques
- Radiopharmaceutical Chemistry and Applications
- Congenital heart defects research
- Immune Cell Function and Interaction
- Prostate Cancer Diagnosis and Treatment
- Cancer Research and Treatments
- interferon and immune responses
- Radiation Dose and Imaging
- Nanoplatforms for cancer theranostics
- Cardiomyopathy and Myosin Studies
- Advanced Breast Cancer Therapies
- CAR-T cell therapy research
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Mathematical Biology Tumor Growth
- Photodynamic Therapy Research Studies
- Brain Metastases and Treatment
- Ultrasound and Hyperthermia Applications
- Cancer Mechanisms and Therapy
- Biosimilars and Bioanalytical Methods
- Chromatin Remodeling and Cancer
- IL-33, ST2, and ILC Pathways
- Drug Transport and Resistance Mechanisms
Northwestern University
2023-2025
University of Glasgow
2025
Medical College of Wisconsin
2020-2024
University of Wisconsin–Madison
2018-2021
St George Hospital
2018-2021
Cardiff Metropolitan University
2018
Amgen (United States)
2012-2016
Neoantigens induced by random mutations and specific to an individual's cancer are the most important tumor antigens recognized T cells. Among immunologically "cold" tumors, limited recognition of neoantigens results in absence a de novo antitumor immune response. These tumors present clinical challenge as they poorly responsive immunotherapies, including checkpoint inhibitors (ICIs). Radiation therapy (RT) can enhance resulting more diversified T-cell response, yet RT alone rarely systemic...
Abstract Finding improved therapeutic strategies against T-cell Non-Hodgkin’s Lymphoma (NHL) remains an unmet clinical need. We implemented a theranostic approach employing tumor-targeting alkylphosphocholine (NM600) radiolabeled with 86 Y for positron emission tomography (PET) imaging and 90 targeted radionuclide therapy (TRT) of NHL. PET biodistribution performed in mouse models NHL showed vivo selective tumor uptake retention Y-NM600. An initial toxicity assessment examining complete...
Clinical interest in combining targeted radionuclide therapies (TRT) with immunotherapies is growing. External beam radiation therapy (EBRT) activates a type 1 interferon (IFN1) response mediated via stimulator of genes (STING), and this critical to its therapeutic interaction immune checkpoint blockade. However, little known about the time course IFN1 activation after EBRT or whether may be induced by decay TRT source.
Abstract Influenza virus infection causes increased morbidity and mortality in the elderly. Aging impairs immune response to influenza, both intrinsically because of altered interactions with endothelial pulmonary epithelial cells. To characterize these changes, we performed single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk (bulk RNA-seq) on lung tissue from young aged female mice at days 0, 3, 9 post-influenza infection. Our analyses identified dozens key genes...
Due to the complex molecular structure and proprietary manufacturing processes of monoclonal antibodies (mAbs), differences in function may be expected during development biosimilar mAbs. Important regulatory requirements for approval products involve comprehensive assessments any potential between proposed biosimilars reference mAbs, including all known mechanisms action, using sensitive relevant methods. Any identified structural should not result biofunctional or clinical activity. A...
During chronic viral infection and cancer, it has been established that a subset of progenitor CD8+ T cells continuously gives rise to terminally exhausted cytotoxic effector cells. Although multiple transcriptional programs governing the bifurcated differentiation trajectories have previously studied, little is known about chromatin structure changes regulating cell-fate decision. In this study, we demonstrate remodeling complex PBAF restrains expansion promotes exhaustion during cancer....
We report two synthetic strategies for the preparation of dibenzofuran α-amino acids, expanding structural toolbox fluorescent probes. The involved synthesis via a Pd(II)-catalyzed C–O cyclization, alongside an efficient Negishi coupling approach faster access to analogues. These rigid tyrosine mimics possess enhanced properties compared proteinogenic amino acids as demonstrated by application lead compound FRET donor monitoring peptide hydrolysis serine protease.
Effective co-stimulation of CD8 T cells is critical for maintenance TCF-1+ stem-like necessary long-term tumor control. NKG2D via binding stress ligands such as membrane-bound MIC enhances cell effector functions and important promoting memory development. Cancer often shed into a soluble form (sMIC) that inhibits activation. TRAMP prostate mice expressing human MICB (TRAMP/MICB) treated with anti-sMIC/MIC antibody elicited potent anti-tumor responses re-invigorated immunity. However,...
Abstract Purpose The aim of this project was to design and manufacture a cost‐effective end‐to‐end (E2E) phantom for quantifying the geometric dosimetric accuracy linear accelerator based, multi‐target single‐isocenter ( MTSI ) frameless stereotactic radiosurgery SRS technique. Method A perspex Multi‐Plug device from Sun Nuclear ArcCheck (Sun Nuclear, Melbourne, FL) enhanced make it more applicable E2E testing. following steps in chain were then analysed using phantom: magnetic resonance...
β-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted hydroxyethylamine-derived such as 1 with low nanomolar potency against β-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound was also shown to significantly reduce Aβ40 levels plasma, brain, and cerebral spinal fluid. Herein, we report further optimizations that led the discovery of inhibitor 16 a novel, potent,...
Introduction Combining CpG oligodeoxynucleotides with anti-OX40 agonist antibody (CpG+OX40) is able to generate an effective in situ vaccine some tumor models, including the A20 lymphoma model. Immunologically “cold” tumors, which are typically less responsive immunotherapy, characterized by few infiltrating lymphocytes (TILs), low mutation burden, and limited neoantigen expression. Radiation therapy (RT) can change microenvironment (TME) of immunologically tumor. This study investigated...
Abstract During chronic viral infection, CD4+ T cells help in the form of IL-21 is critical for development highly cytolytic effector CD8+ cells. However, exact signaling pathways from that regulate cell function remain unclear. The current dogma states predominantly signals through STAT3, to generate during infection. Here, we reveal a novel mechanism via STAT4 following LCMV Furthermore, STAT4-mediated differentiation epigenetically regulated by BAF, SWI/SNF chromatin remodeling complex....
Abstract T cell exhaustion, a state of dysfunction occurring during chronic infections and cancer, is marked by progressive loss effector functions increased expression inhibitory receptors. In infection, CD8 cells differentiate into TCF1+ progenitor (TPRO), CX3CR1+ (TEFF), terminally exhausted (TEXH) subsets. The differentiation pathways are governed complex transcription factor (TF) networks. Employing regulon analysis enabled single-cell RNA+ATAC multiome sequencing, we dissected the TF...
Abstract Repetitive T cell receptor (TCR) engagement on CD8 cells during chronic infection is a critical driver of the dysfunctional state termed exhaustion. These exhausted are characterized by additional heterogeneity including memory-like progenitor (Tpro) that continuously gives rise to either non-cytolytic (Texh) or cytotoxic effector (Teff). While we and others have shown TCR avidity influence fate commitment Texh Teff, it not certain if sequence features this choice. In study,...
We demonstrate here that iPSCs derived from patients with Ebstein’s anomaly and left ventricular noncompaction, when differentiated into cardiomyocytes, display significant structural functional changes offer insight disease pathogenesis, including altered ER/SR mitochondrial morphology, contractility, calcium signaling.
Hypoplastic left heart syndrome (HLHS) is a complex form of congenital disease (CHD) characterized by hypoplasia the ventricle and proximal aorta, as well stenosis or atresia mitral aortic valves. Our lab previously identified that rare, predicted-damaging variants in gene encoding for α-myosin heavy chain ( MYH6, α-MHC), key contractile protein heart, are enriched HLHS. It has been shown pathological MHC head domain directly alter force generation, but mechanisms which tail cause defects...
Surgical resection or hypo-fractionated radiation therapy (RT) in early-stage non-small cell lung cancer (NSCLC) achieves local tumor control, but metastatic relapse remains a challenge. We hypothesized that immunotherapy with anti-CTLA-4 and bempegaldesleukin (BEMPEG; NKTR-214), CD122-preferential IL2 pathway agonist, after primary RT would reduce metastases syngeneic murine NSCLC model. Mice bearing Lewis Lung Carcinoma (LLC) tumors were treated combinations of BEMPEG, anti-CTLA-4,...