A5081339867- Phagocytosis and Immune Regulation
- Cancer Mechanisms and Therapy
- Pancreatic and Hepatic Oncology Research
- Prostate Cancer Treatment and Research
- Muscle Physiology and Disorders
- Mass Spectrometry Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Vitamin D Research Studies
- Liver physiology and pathology
- Heat shock proteins research
- Endoplasmic Reticulum Stress and Disease
- Hormonal Regulation and Hypertension
- Muscle metabolism and nutrition
- Exercise and Physiological Responses
- Adipose Tissue and Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- Adrenal Hormones and Disorders
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Structural Engineering and Vibration Analysis
- Cancer Genomics and Diagnostics
- Coenzyme Q10 studies and effects
- Pancreatitis Pathology and Treatment
Duke University
2020-2025
Duke Medical Center
2024
The Ohio State University
2015-2022
Wiss Janney Elstner Associates
2010
Heat shock factor 1 (HSF1) is a cellular stress-protective transcription exploited by wide range of cancers to drive proliferation, survival, invasion, and metastasis. Nuclear HSF1 abundance prognostic indicator for cancer severity, therapy resistance, shortened patient survival. The gene was amplified, nuclear markedly increased in prostate particularly neuroendocrine (NEPC), which there are no available treatment options. Despite genetic validation as therapeutic target cancers, direct...
After failing primary and secondary hormonal therapy, castration-resistant neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in PCa potentially synergizing inhibiting metastasis growth are urgently needed. Phosphorylated (activated) AXL expression human metastases was assessed by immunohistochemical staining. We evaluated effects of...
Early treatment with heart failure drugs lisinopril and spironolactone improves skeletal muscle pathology in Duchenne muscular dystrophy (DMD) mouse models. The angiotensin converting enzyme inhibitor mineralocorticoid receptor (MR) antagonist indirectly directly target MR. presence function of MR have not been explored. mRNA protein are present all tested muscles from both wild-type mice DMD expression is cell autonomous undifferentiated myoblasts differentiated myotubes human cultures. To...
Abstract An understanding of the molecular features associated with prostate cancer progression (PCa) and resistance to hormonal therapy is crucial for identification new targets that can be utilized treat advanced disease prolong patient survival. The glycome, which encompasses all sugar polymers (glycans) synthesized by cells, has remained relatively unexplored in context PCa despite fact glycans have great potential value as biomarkers therapeutic due their high density on cell surface....
Abstract Neuroendocrine (NE) cells comprise ~1% of epithelial in benign prostate and prostatic adenocarcinoma (PCa). However, they become enriched hormonally treated castration‐resistant PCa (CRPC). In addition, close to 20% tumors recur as small cell NE carcinoma (SCNC), composed entirely cells, which may be the result clonal expansion or lineage plasticity. Since do not express androgen receptors (ARs), are resistant hormonal therapy contribute failure. Here, we describe identification...
Abstract There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and an actionable target. In this manuscript, we identify HSF1 regulates the conversion of homocysteine to cystathionine transsulfuration pathway by altering levels cystathionine-β-synthase (CBS). find directly binds CBS gene upregulates mRNA levels. Targeting decreases growth induces tumor cell death while benign...
<p>Figure S4. Quantification of bone mineral density in mouse tibia specimen after treatment for 30 days. Batiraxcept and docetaxel as single agents or combination increased (BMD) the tibiae to a similar extent determined by microCT.</p>
<p>Figure S6. IHC staining (continuing Fig. 6A) demonstrates batiraxcept alone or in combination with docetaxel reduced p-ERK1/2 protein levels compared to vehicle-treated controls intratibial LuCaP 147CR PDX model while total AKT proteins were similar. Scale bar = 10 μm.</p>
<p>Figure S5. Mouse body weight change (%) after treatment for 30 days. None of the groups displayed significant differences in weight, indicating overall low toxicity from batiraxcept and docetaxel at doses administered.</p>
<p>Figure S3. Mouse serum PSA after treatment for 30 days. Batiraxcept and docetaxel as single agents or in combination significanty reduced mouse detected by ELISA.</p>
<p>Figure S1. The levels of murine serum GAS6 before treatment in the LuCaP 147 PDX model. There were no significant differences among groups detected by ELISA</p>
<div>AbstractPurpose:<p>After failing primary and secondary hormonal therapy, castration-resistant neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in potentially synergizing inhibiting metastasis growth are urgently needed.</p>Experimental Design:<p>Phosphorylated (activated) AXL expression human metastases...
<p>Figure S2. Batiraxcept and docetaxel alone or in combination significantly inhibited bone tumor growth metastasis LuCaP mPCa AC PDX models. A-B, Representative images of Masson-Goldner staining Ku70 IHC cells the tibiae 147 (A), 35 (B). Human PCa marked by were decreased after 30 days treatment intraperitoneal injection with batiraxcept (20 mg/kg/QOD, n = 8–9, (10 mg/kg/QW, 9) compared to vehicle controls (n 8,10). C-D, Quantification Ku70-positive areas mouse tibia specimens...
Duchenne muscular dystrophy (DMD) is an X-linked inherited disease due to dystrophin deficiency causing skeletal and cardiac muscle dysfunction. Affected patients lose ambulation by age 12 usually die in the second third decades of life from respiratory failure. Symptomatic treatment includes use anti-inflammatory corticosteroids, which are associated with side effects including weight gain, osteoporosis, increased risk cardiovascular disease. Novel options include blockade...
Mineralocorticoid and glucocorticoid receptors are closely related steroid hormone that regulate gene expression through many of the same response elements. However, their transcriptional activities effects in skeletal muscles largely unknown. We recently identified mineralocorticoid (MR) after finding combined treatment with angiotensin-converting enzyme inhibitor lisinopril MR antagonist spironolactone was therapeutic Duchenne muscular dystrophy mouse models. The receptor (GR) agonist...
Abstract Background Prostate cancer (PCa) continues to be one of the leading causes deaths in men. While androgen deprivation therapy is initially effective, castration‐resistant PCa (CRPC) often recurs and has limited treatment options. Our previous study identified glutamine metabolism critical for CRPC growth. The antagonist 6‐diazo‐5‐oxo‐ l ‐norleucine (DON) blocks both carbon nitrogen pathways but dose‐limiting toxicity. prodrug DRP‐104 expected preferentially converted DON tumor cells...
Mineralocorticoid receptor (MR) drugs have been used clinically for decades to treat cardiovascular diseases. MR antagonists not only show preclinical efficacy heart in Duchenne muscular dystrophy (DMD) models but also improve skeletal muscle force and membrane integrity. The mechanisms of action muscles are entirely unknown. Since present many cell types the microenvironment, it is critical define cell-intrinsic functions each type ultimately optimize antagonist use widest variety We...
Suppressing mineralocorticoid receptor (MR) activity with MR antagonists is therapeutic for chronic skeletal muscle pathology in Duchenne muscular dystrophy (DMD) mouse models. Although mechanisms underlying clinical antagonist efficacy DMD cardiomyopathy and other cardiac diseases are defined, muscles not fully elucidated. Myofiber knockout improves force a subset of dystrophic pathology. However, signaling myeloid cells known to be major contributor efficacy. To define contributions...
Acute skeletal muscle injury is followed by a temporal response of immune cells, fibroblasts, and progenitor cells within the microenvironment to restore function. These same cell types are repeatedly activated in muscular dystrophy from chronic injury, but eventually, regenerative portion cycle disrupted fibrosis replaces degenerated fibers. Mineralocorticoid receptor (MR) antagonist drugs have been demonstrated increase function, decrease fibrosis, directly improve membrane integrity mice,...
Our lab identified a potential new treatment for Duchenne Muscular Dystrophy using the mineralocorticoid receptor (MR) antagonist spironolactone and ACE inhibitor lisinopril. Drug studies dystrophic Het (utrn+/-;mdx) mice showed dramatic improvement in both respiratory limb muscle force reduction of ongoing damage, addition to preventing cardiomyopathy. We show MR is present skeletal tissue myogenic cultures, supporting direct affect by antagonists on muscle. Global analysis gene expression...
Instability at beam-over-column connections in continuous steel frame building construction has resulted numerous failures. Despite these failures, and well-publicized stability research about this subject by others, many engineers still fail to appreciate the critical nature of omitting either beam web stiffeners, bottom flange lateral bracing, or both, connections. One reason cited for omission is that was designed preclude use stiffeners bracing beam-to-column intersection. It been...