A5088071259- Hepatitis B Virus Studies
- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Hepatitis Viruses Studies and Epidemiology
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Animal Virus Infections Studies
- Immune cells in cancer
- interferon and immune responses
- Phagocytosis and Immune Regulation
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Adenosine and Purinergic Signaling
- Erythrocyte Function and Pathophysiology
- Retinal Imaging and Analysis
- Viral gastroenteritis research and epidemiology
- HIV/AIDS drug development and treatment
- Signaling Pathways in Disease
- Immune Cell Function and Interaction
- Digital Imaging for Blood Diseases
- Tissue Engineering and Regenerative Medicine
- COVID-19 diagnosis using AI
- Power Line Inspection Robots
- Cytokine Signaling Pathways and Interactions
Georgetown University
2016-2024
Georgetown University Medical Center
2016-2024
Vince Lombardi Cancer Clinic
2023-2024
SB 9200, an oral prodrug of the dinucleotide 9000, is being developed for treatment chronic hepatitis B virus (HBV) infection and represents a novel class antivirals. 9200 thought to activate viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) nucleotide-binding oligomerization domain-containing protein 2 (NOD2) resulting in interferon (IFN) mediated antiviral immune responses virus-infected cells. Additionally, binding these proteins could also sterically block ability polymerase...
Background and Aims GS‐9688 (selgantolimod) is an oral selective small molecule agonist of toll‐like receptor 8 in clinical development for the treatment chronic hepatitis B. In this study, we evaluated antiviral efficacy woodchucks chronically infected with woodchuck virus (WHV), a hepadnavirus closely related to B virus. Approach Results WHV‐infected received eight weekly doses vehicle, 1 mg/kg GS‐9688, or 3 GS‐9688. Vehicle had no effect, whereas induced >5 log 10 reduction serum viral...
Histone deacetylase 6 (HDAC6) inhibition is associated with an increased pro-inflammatory tumor microenvironment and antitumoral immune responses. Here, we show that the HDAC6 inhibitor AVS100 (SS208) had effect in SM1 melanoma CT26 colon cancer models efficacy of anti–programmed cell death protein 1 treatment, leading to complete remission response cancer. treatment tumor-infiltrating macrophages CD8 effector T cells inflammatory gene signature. Acquired immunity long-term protection were...
SB 9200, an orally bioavailable dinucleotide, activates the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) causing induction of interferon (IFN) signaling cascade for antiviral defense. The present study evaluated overall response in woodchucks upon immune response, first with 9200 followed by Entecavir (ETV) versus reduction burden ETV immunomodulation. Woodchucks chronically infected woodchuck...
Current therapeutics for chronic infection with hepatitis B virus (HBV) rarely induce functional cure due to the immunotolerant status of patients. Small molecule agonists targeting toll‐like receptor 7 (TLR7) have been shown elicit a in animal models HBV but sometimes poor tolerability immune‐related toxicities. In an effort increase therapeutic window TLR7 treat (CHB), we developed oral agonist, APR002, designed act locally gastrointestinal tract and liver, thus minimizing systemic...
Viral and/or host factors that are directly responsible for the acute versus chronic outcome of hepatitis B virus (HBV) infection have not been identified yet. Information on immune response during early stages HBV in humans is mainly derived from blood samples patients with (AHB), which usually obtained after onset clinical symptoms. Features intrahepatic these less studied due to difficulty obtaining multiple liver biopsies. Woodchuck (WHV) woodchucks a model humans. In present study, five...
RG7834 is a small‐molecule inhibitor of hepatitis B virus (HBV) gene expression that significantly reduces the levels surface antigen (HBsAg) and HBV DNA in humanized liver mouse model. In current study, we evaluated potency woodchuck model chronic infection, alone combination with entecavir (ETV) and/or interferon‐α (wIFN‐α). reduced (WHV) (WHsAg) by mean 2.57 log 10 from baseline WHV 1.71 . ETV + wIFN‐α WHsAg means 2.40 6.70 , respectively. The RG7834, ETV, profoundly 5.00 7.46 However,...
This research project focuses on the development and evaluation of an advanced algorithm for retinal vessel segmentation, a critical component in automated analysis images diagnosing ocular diseases. Leveraging state-of-the-art image processing techniques deep learning models, we propose novel segmentation that significantly enhances accuracy efficiency identifying blood vessels from fundus photographs. Our methodology encompasses comprehensive data preparation phase, including normalization...
As current interventions for chronic hepatitis B (CHB) rarely induce cure, more effective drugs are needed. Short-term treatment of woodchucks with the novel immunomodulator AIC649, a parapoxvirus-based stimulator toll-like receptor 9 dependent and independent pathways, has been shown to reduce viral DNA surface antigen via unique, biphasic response pattern. The present study evaluated long-term AIC649 in combination Entecavir potency safety woodchucks. monotreatment induced modest...
Current treatment options for patients infected with hepatitis B virus (HBV) are suboptimal, because the approved drugs rarely induce cure due to persistence of viral DNA genome in nucleus hepatocytes, and associated either severe side effects (pegylated interferon-alpha) or require life-long administration (nucleos(t)ide analogs). We report here evaluation safety therapeutic efficacy a novel, humanized antibody (hzVSF) woodchuck model HBV infection. hzVSF has been shown act as entry...
Conventional treatment of chronic hepatitis B (CHB) is rarely curative due to the immunotolerant status patients. RG7854 an oral double prodrug a toll-like receptor 7 (TLR7) agonist that developed for CHB. The therapeutic efficacy, host immune response, and safety were evaluated in woodchuck model Monotreatment with two highest doses combination dose entecavir (ETV) suppressed viral replication, led loss antigens, induced seroconversion responder woodchucks. Since suppression high-titer...
Immune modulation for the treatment of chronic hepatitis B (CHB) has gained more traction in recent years, with an increasing number compounds designed targeting different host pattern recognition receptors (PRRs). These agonistic molecules activate receptor signaling pathway and trigger innate immune response that will eventually shape adaptive immunity control infection virus (HBV). While definitive HBV nucleic acids by PRRs during viral still needs to be elucidated, several RNA sensing...
Abstract Introduction: Aging of the immune system is a critical risk factor for chronic diseases, including cancer. Globally, cancer incidence higher between 45 to 75 years age and declines thereafter. However, implications aging in are understudied, aged populations underrepresented, both preclinical clinical studies. The role macrophages progression has gained attention as tool target anticancer therapies. Tumor-associated (TAMs) mainly exhibit an anti-inflammatory M2 phenotype, promote...
Abstract The interplay between tumor cells and immune within the microenvironment (TME) dictates protumor or antitumor responses. Tumor-associated macrophages (TAMs) respond to signals of TME exhibit a spectrum phenotypes ranging M1 (antitumor) M2 (protumor) macrophages. In most types, including melanoma, balance is critical with higher M1/M2 ratio favoring immunity. Therefore, strategies enhancing can significantly alter towards this study, we administered luciferase GFP-expressing as an...
Abstract Histone Deacetylases (HDACs) are enzymes that modify histones and non-histone proteins. Our group has previously demonstrated HDAC6 inhibitors (HDAC6is) modulate multiple immune pathways, including those suppress the antitumoral M2 phenotype, leading to improved antitumor immunity. Despite potential of HDAC6is, current have poor selectivity off-target effects only work at micromolar concentrations. In this work, we designed a screening pipeline HDAC6i, considering selectivity,...
Abstract Inhibition of HDAC6 was associated with an increased proinflammatory tumor microenvironment and antitumoral response. Here, we show that a highly specific inhibitor AVS100 (SS208), blocks M2 polarization in murine human macrophages while partially affecting M1 polarization. effects were observed as blocked upregulation M2-related gene signature under polarizing conditions generation CD206+ Arg1+ macrophages. Oral administration had effect SM1 melanoma CT26 colon cancer models the...
Abstract Patients with advanced melanoma are often treated radiation therapy (RT) in combination immunotherapies. Immunogenic tumor cell death induced by is known to activate innate and adaptive immunity. Macrophage activity the irradiated microenvironment (TME) has been implicated play a critical role post-RT immune responses. However, tumor-associated macrophages (TAMs) due their phenotypic plasticity convert from initial antitumor M1 phenotype protumor M2 resulting relapse metastasis of...