A5081876348- Diabetes and associated disorders
- Biochemical Analysis and Sensing Techniques
- Regulation of Appetite and Obesity
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Pancreatic and Hepatic Oncology Research
- Immune Response and Inflammation
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- T-cell and B-cell Immunology
- Cancer Cells and Metastasis
- Immune cells in cancer
- Pancreatitis Pathology and Treatment
- Estrogen and related hormone effects
- Histone Deacetylase Inhibitors Research
- Cancer, Lipids, and Metabolism
- Inflammatory mediators and NSAID effects
- Nanoparticle-Based Drug Delivery
- Cancer Genomics and Diagnostics
- Folate and B Vitamins Research
- Metabolomics and Mass Spectrometry Studies
- melanin and skin pigmentation
- Genomics, phytochemicals, and oxidative stress
- Cancer, Hypoxia, and Metabolism
- Prostate Cancer Diagnosis and Treatment
University of Central Florida
2012-2024
Translational Research Institute for Metabolism and Diabetes
2019-2022
Florida Hospital Cancer Institute
2012-2022
AdventHealth Orlando
2016-2019
Fraternal Order of Eagles
2016
University of Florida
1999-2015
Sanford Burnham Prebys Medical Discovery Institute
2008-2015
Kennedy Space Center
2008-2010
University of Michigan
2007-2009
Bipar
2008
Efforts toward routine islet cell transplantation as a means for reversing type 1 diabetes have been hampered by availability well allograft rejection. In vitro transdifferentiation of mouse bone marrow (BM)-derived stem (mBMDS) cells into insulin-producing could provide an abundant source autologous this procedure. For study, we isolated and characterized single cell-derived lines obtained from BM. differentiation these mBMDS resulted in populations meeting number criteria set forth to...
The melanocortin-4 receptor (MC4R) is a G-protein coupled (GPCR) that expressed in the central nervous system and has role regulating energy homeostasis obesity. Up to remarkable 6% of morbidly obese adults children studied possess single nucleotide polymorphisms (SNPs) MC4R. Upon stimulation by agonist, MC4R signals through intracellular adenylate cyclase signal transduction pathway. Posttranslational modification pro-opiomelanocortin (POMC) gene transcript results generation several...
Prostaglandins (PGs) are lipid molecules that profoundly affect cellular processes including inflammation and immune response. Pathways contributing to PG output highly regulated in antigen-presenting cells such as macrophages monocytes, which produce large quantities of these upon activation. In this report, we demonstrate aberrant constitutive expression the normally inducible cyclooxygenase synthase 2 (PGS2/ COX-2) nonactivated monocytes humans with insulin-dependent diabetes mellitus...
The portal venous circulation provides a conduit for pancreatic ductal adenocarcinoma (PDAC) tumor cells to the liver parenchyma sinusoids, frequent site of metastasis. Turbulent flow in promotes retention PDAC shed circulating (CTC) and myeloid-derived immunosuppressor (MDSC). Excessive colony stimulating factor-1 receptor (CSF1R) signaling can induce myeloid differentiation MDSC transformation fibroblasts (M-FB). Interactions between CTC M-FB blood formation immunoresistant clusters that...
Abstract: Regulatory T cells (Treg), characterized as CD4 + /CD25 +hi cells, are critical for sustaining and promoting immune tolerance. Treg highly dependent on IL‐2 signaling to maintain their numbers function interruption of this pathway promotes autoimmunity. The transcription factor, Foxp3, is also required defective Foxp3 promotos autoimmunity in both mice humans. We previously reported a point mutation the DNA‐binding domain NOD STAT5B gene that limits DNA binding when compared...
Exercise is a mechanism for maintenance of body weight in humans. Morbidly obese human patients have been shown to possess single nucleotide polymorphisms the melanocortin-4 receptor (MC4R). MC4R knockout mice well characterized as genetic model that possesses phenotypic metabolic disorders, including obesity, hyperphagia, hyperinsulinemia, and hyperleptinemia, similar those observed humans possessing dysfunctional hMC4Rs. Using this model, we examined effect voluntary exercise were allowed...
Circulating tumor cells (CTC) enter the blood from many carcinomas and represent a likely source of metastatic dissemination. In contrast to peripheral circulation, KRAS mutation- positive CTC thrive in portal venous patients with pancreatic ductal adenocarcinoma (PDAC). To analyze essential interactions that contribute carcinoma growth immune resistance, was collected during pancreatico-duodenectomy 41 peri-ampullary pathologies (PDAC = 11; ampullary (AA) 15; distal cholangiocarcinoma (CC)...
The melanocortin-4 receptor (MC4R) is a G-protein-coupled (GPCR) that expressed in the central nervous system and has role regulating feeding behavior, obesity, energy homeostasis, male erectile response, blood pressure. Since report of MC4R knockout mouse 1997, field been searching for links between this genetic biomarker human obesity type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have identified from patients, both obese nonobese controls. Many significant studies...
Over-diagnosis and treatment of prostate cancer has been a major problem in care management. Currently the most relevant prognostic factor to predict patient's risk death due is Gleason score biopsied tissue samples. However, pathological analysis subjective, only qualitative estimate malignancy. Molecular biomarkers diagnostic tests that can accurately tumor aggressiveness are rather limited. We report here for first time development nanoparticle test not distinguish from normal benign...
Aggressive spread and liver metastases are predominant features of pancreatic ductal adenocarcinoma (PDAC). This study investigates activation PDAC circulating tumor cells (CTC) immunosuppression in the portal venous system.Portal peripheral blood were collected during pancreaticoduodenectomy from patients with (n = 21) or other non-PDAC conditions 20). Circulating isolated by fluorescence-activated cell sorting characterized for messenger RNA (mRNA) expression acetylated chromatin encoding...
The melanocortin pathway, specifically the melanocortin-4 receptor and cognate endogenous agonist antagonist ligands, have been strongly implicated in regulation of energy homeostasis satiety. Genetic studies morbidly obese human patients normal weight control resulted discovery over 70 (MC4R) polymorphisms observed as both heterozygous homozygous forms. A number laboratories studying these hMC4R attempting to understand molecular mechanism(s) that might explain phenotype. Herein, we studied...
While inflammation is associated with pancreatic cancer, the underlying mechanisms leading to cancer initiation are still being delineated. Eosinophils may promote or inhibit tumor growth, although specific role in has yet be determined. Eosinophil-supporting cytokine interleukin-5 and receptor likely have a role, but significance microenvironment unknown.Genetically engineered Akt1Myr/KRasG12D KRasG12D mice were used model changes induced by chronic inflammation. Tissue samples collected...
Loss of the actin filament capping protein CapG has no apparent effect on phenotype mice maintained under sterile conditions; however, bone marrow-derived macrophages from CapG(-/-) exhibited distinct motility defects. We examined ability to clear two intracellular bacteria, Listeria monocytogenes and Salmonella enterica serovar Typhimurium. The 50% lethal dose was 10-fold lower for than CapG(+/+) (6 x 10(3) CFU 6 10(4) mice), while difference observed Salmonella: numbers cells in spleens...
Type 1 diabetes (T1D) is a T cell-mediated disease. Various DC populations play important roles in initiating and directing cell responses thus may be critical for T1D pathogenesis. We examined peripheral blood DC1 DC2 by flow cytometry healthy controls, subjects at risk T1D, new-onset patients, established patients. found significant increase the number of DCs (including DC2) at-risk those with versus controls patients (ANOVA; p < 0.0001). Analysis subsets these same groups demonstrated...
Abstract Unstimulated monocytes of at-risk/type 1 diabetic humans and macrophages the NOD mouse have markedly elevated autocrine GM-CSF production persistent STAT5 phosphorylation. We analyzed relationship between phosphorylation in using reciprocal congenic strains containing either diabetes-susceptible (B6.NODC11), or diabetes-resistant C57L (NOD.LC11) loci on chromosome 11. These intervals contain gene for (Csf2; 53.8 Mb) those STAT3, STAT5A, STAT5B (Stat3, Stat5a, Stat5b; 100.4–100.6...
The Melanocortin‐4 Receptor is a G‐protein coupled receptor that has been physiologically linked to participate in the regulation of energy homeostasis. stimulated by endogenous melanocortin agonists derived from pro‐opiomelanocortin gene transcript and antagonized antagonist agouti‐related protein. Central administration demonstrated decrease food intake conversely, treatment with antagonists resulted increased intake. Deletion mouse genome results an obese hyperphagic phenotype....
Methods: We examined monocyte prostaglandin synthase 2 (PGS2/COX2) expression in individuals at risk for or with type 1 diabetes including: (i) 58 established and diabetic patients; (ii) 34 autoantibody positive (AA+) children adults; (iii) 164 infants young insulin-dependent mellitus (IDDM) susceptibility human leukocyte antigen (HLA) alleles; (iv) 37 healthy control individuals, over a 5-yr period. Results: Established patients (1 month to 30+ yr post-disease onset) had significantly...
STAT5 proteins are adaptor for histone acetylation enzymes. Histone at promoter and enhancer chromosomal regions opens the chromatin allows access of transcription enzymes to specific genes in rapid response cell signals, such as inflammation. acetylation-mediated gene regulation is involved expression 2 key inflammatory genes: CSF2, encoding granulocyte-macrophage colony stimulating factor (GM-CSF), PTGS2, prostaglandin synthase 2/cyclooxygenase (PGS2/COX2). Prolonged CSF2 expression, high...