Paula A. Witt‐Enderby

ORCID: 0000-0002-1844-4457
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About
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Research Areas
  • Circadian rhythm and melatonin
  • Receptor Mechanisms and Signaling
  • Estrogen and related hormone effects
  • Free Radicals and Antioxidants
  • Neurobiology and Insect Physiology Research
  • Neuroendocrine regulation and behavior
  • Photoreceptor and optogenetics research
  • Spaceflight effects on biology
  • Vitamin D Research Studies
  • Mast cells and histamine
  • Periodontal Regeneration and Treatments
  • Stress Responses and Cortisol
  • Endometriosis Research and Treatment
  • Growth Hormone and Insulin-like Growth Factors
  • Asthma and respiratory diseases
  • Sleep and Wakefulness Research
  • Complementary and Alternative Medicine Studies
  • Birth, Development, and Health
  • Sleep and related disorders
  • Synthesis and Biological Evaluation
  • Bioactive Compounds and Antitumor Agents
  • Biochemical Acid Research Studies
  • Nitric Oxide and Endothelin Effects
  • Bone health and osteoporosis research
  • Problem and Project Based Learning

Duquesne University
2013-2023

UPMC Hillman Cancer Center
2009-2020

University of Pittsburgh Medical Center
2019

University of Würzburg
2009-2019

Tulane University
2019

Purdue University West Lafayette
2019

Indiana University – Purdue University Indianapolis
2019

Indiana University School of Medicine
2019

German University in Cairo
2019

Mylan (United States)
2006-2018

The goals of this study were to determine (a) if melatonin enhances human adult mesenchymal stem cell (hAMSC) differentiation into osteoblasts as assessed by measuring alkaline phosphatase (ALP) enzyme activity, and (b) identify potential signal transduction pathways that mediate process. ALP activity significantly increased in hAMSCs following a 10-day incubation osteogenic medium, relative incubated basal growth medium alone. Melatonin (50 nm), added combination with the Co-exposure...

10.1111/j.1600-079x.2006.00318.x article EN Journal of Pineal Research 2006-02-22

The purpose of this double-blind study was to assess the effects nightly melatonin supplementation on bone health and quality life in perimenopausal women. A total 18 women (ages 45-54) were randomized receive (3mg, p.o., n=13) or placebo (n=5) for 6months. Bone density measured by calcaneal ultrasound. turnover marker (osteocalcin, OC formation NTX resorption) levels bimonthly serum. Participants completed Menopause-Specific Quality Life-Intervention (MENQOL) Pittsburgh Sleep Index (PSQI)...

10.1111/j.1600-079x.2011.00956.x article EN Journal of Pineal Research 2011-12-15

Numerous physiological functions of the pineal gland hormone melatonin are mediated via activation two G-protein-coupled receptors, MT1 and MT2. The melatonergic drugs on market, ramelteon agomelatine, as well most advanced drug candidates under clinical evaluation, tasimelteon TIK-301, high-affinity nonselective MT1/MT2 agonists. A great number MT2-selective ligands and, more recently, several MT1-selective agents have been reported to date. Herein, we review recent advances in field...

10.1021/jm401343c article EN Journal of Medicinal Chemistry 2013-11-14

The Melatonin Osteoporosis Prevention Study (MOPS) demonstrated that nightly melatonin resulted in a time-dependent decrease equilibrium ratios of serum osteoclasts and osteoblasts perimenopausal women. This study examines mechanisms related to the using coculture models (transwell or layered) human mesenchymal stem cell (MSC) peripheral blood monocytes (PBMCs). Human MSC/PBMC cocultures exposed osteogenic (OS+) medium for 21 days induced osteoblast differentiation mineralization; however,...

10.1111/jpi.12465 article EN Journal of Pineal Research 2017-12-29

The phenomenon of acute desensitization G-protein-coupled receptors has been associated with several events, including receptor phosphorylation, loss high affinity agonist binding, receptor:G-protein uncoupling, and internalization. However, the biochemical events underlying these processes are not fully understood, their contributions to signaling remain correlative. In addition, nature kinases domains which involved in modulation activity have only begun be investigated. order directly...

10.1074/jbc.270.48.29004 article EN cc-by Journal of Biological Chemistry 1995-12-01

Abstract: The purpose of this study was to determine the critical time periods melatonin treatment required induce human mesenchymal stem cells (hAMSCs) into osteoblasts and which osteogenic genes are involved in process. design consisted adding for different times (2, 5, 10, 14 or 21 days) toward end a 21-day containing (OS+) medium at beginning then withdrawn. results show that continuous both alkaline phosphatase (ALP) activity calcium deposition these effects were mediated through MT2Rs....

10.1111/j.1600-079x.2010.00784.x article EN Journal of Pineal Research 2010-07-06

This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and K2 (MK7; MSDK) on bone mineral density (BMD) quality life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD lumbar spine (4.3%) left femoral neck (2.2%), with an upward trend for total hip (p=0.069). serum P1NP levels reduced turnover (CTx:P1NP). Psychometric analyses indicated that mood sleep improved group....

10.18632/aging.101158 article EN cc-by Aging 2017-01-26

The human ML1A melatonin receptor is expressed in the suprachiasmatic nucleus of hypothalamus and believed to regulate circadian rhythms. We report kinetic characteristics pharmacological profile 2-[125I]iodomelatonin binding signaling pathway agonist regulation stably Chinese hamster ovary cells. Association was maximal by 1.5 hr at 37 degrees fully dissociated on addition 1 microM melatonin. saturable high affinity (KD = 74 +/- 14 PM, Bmax 679 88 fmol/mg protein; three experiments)....

10.1016/s0026-895x(25)09133-3 article EN Molecular Pharmacology 1996-07-01

Abstract: Over 500,000 bone graft or bio‐implant procedures are performed annually in the United States. It has been reported that osseous autograft procurement may result donor site complications and allografts have associated with disease transmission. Ceramic scaffolds only osteoconductive, limiting their clinical use. The objective of this study was to create a filler substitute regenerating properties similar natural bone. Therefore, melatonin platelet‐rich plasma (PRP) were utilized...

10.1111/j.1600-079x.2012.00989.x article EN Journal of Pineal Research 2012-03-02

In this study, the effects of light/dark cycle, hormone replacement therapy (HRT), and nocturnal melatonin supplementation on osteogenic markers serum levels were examined in a blind mouse model (MMTV-Neu transgenic mice). Melatonin strain (FVB/N) with retinal degeneration (rd-/-) fluctuate diurnal manner, suggesting that these mice, although blind, still perceive light. Real-time RT-PCR analyses demonstrated Runx2, Bmp2, Bmp6, Bglap, Per2 mRNA coincide levels. The effect chronic HRT (0.5 mg...

10.1111/j.1600-079x.2012.01007.x article EN Journal of Pineal Research 2012-05-03

Anticancer drug conjugates may benefit from simultaneous action at two targets potentially overcoming the drawbacks of current cancer treatment, such as insufficient efficacy, high toxicity, and development resistance. Compared to a combination single-target drugs, they offer an advantage pharmacokinetic simplicity fewer drug-drug interactions. Here, we report series compounds connecting tamoxifen or endoxifen with EGFR-inhibitor gefitinib via covalent linkage. These hybrid ligands retain...

10.1021/acs.jmedchem.1c01646 article EN Journal of Medicinal Chemistry 2022-03-14

Tamoxifen is used to prevent and treat estrogen receptor-positive (ER+) breast cancer (BC); however, its chronic use can increase uterine risk induce tamoxifen resistance. Novel melatonin-tamoxifen drug conjugates may be promising BC help offset the adverse effects of usage alone due presence melatonin. We synthesized screened five (C2, C4, C5, C9, C15 linked) for their on cell (MCF-7, tamoxifen-resistant MCF-7, mouse mammary carcinoma, MDA-MB-231, BT-549) viability, migration, binding...

10.1124/mol.119.116202 article EN Molecular Pharmacology 2019-06-20

Melatonin has gained recent popularity as a treatment for insomnia and other sleep disorders; however, its cellular effects are unknown. We report the of melatonin on morphology Chinese hamster ovary (CHO) cells transformed to express human receptors, mt1 MT2. Our results show that exerts strong influence shape cytoskeletal organization in receptor-dependent possibly subtype-selective manner. The cell change we see after 5-h these non-neuronal with pharmacological concentration consists...

10.1002/(sici)1097-0169(200005)46:1<28::aid-cm4>3.0.co;2-5 article EN Cell Motility and the Cytoskeleton 2000-05-01
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