Joshua P. Earnest
- Courses2
- Reviews3
- School: Georgetown University
- Campus:
- Department: Nursing
- Email address: Join to see
- Phone: Join to see
-
Location:
3700 O St NW
Washington, DC - 20057 - Dates at Georgetown University: August 2014 - November 2016
- Office Hours: Join to see
Biography
Georgetown University - Nursing
Product Developer
Information Technology & Services
JP
Earnest
Washington D.C. Metro Area
Building, automating and supporting web apps and cloud services at CARFAX.
Teaching MSN students Pathophysiology at Georgetown.
Offering therapeutic and medical massage at Skin+Touch Therapy.
Experience
Georgetown University
Research Assistant
Investigated the oncological role of NPY using:
Immunohistochemistry
Immunocytochemistry
MRI analysis (Image J)Skin+Touch Therapy
Certified Massage Therapist
Offering Relaxation and Medical Massage, as well as Shiatsu and Thai Yoga Massage.
CARFAX
Product Developer
Responsible for migrating Carfax.com applications from on-premise datacenter to AWS. Designed, implemented and now supporting multi-region Kubernetes clusters. Rewriting and enhancing CI/CD pipelines. Also performed front and mid stack work on Used Cars Listings application.
Georgetown University School of Nursing and Health Studies
Adjunct Instructor
Leading live sessions in online MSN course Advanced Concepts in Physiology and Pathophysiology.
Created asynchronous lecture content for the course.
Education
Georgetown University
MS
Physiology and Biophysics
Concentration in Complementary and Alternative MedicineGeorgetown University
Research Assistant
Investigated the oncological role of NPY using: Immunohistochemistry Immunocytochemistry MRI analysis (Image J)New York Institute of Technology
BA
Interdisciplinary Studies
Concentrations in: Math/Physics Communications Arts Social SciencesThinkful
Web Development
Fullstack Javascript
Learning front and back-end web application development with technologies including: HTML5, CSS3, Javascript / ES6, jQuery, React / Redux, Node.js / Express, MongoDB / Mongoose, PostgreSQL
Publications
Hypoxia shifts activity of neuropeptide Y in Ewing sarcoma from growth-inhibitory to growth-promoting effects
Oncotarget
Complete author list: Jason U. Tilan, Congyi Lu, Susana Galli, Ewa Izycka-Swieszewska, Joshua Patrick Earnest, Asim Shabbir, Lindsay M. Everhart, Shuo Wang, Samantha Martin, Meredith Horton, Akanksha Mahajan, David Christian, Alison O’Neill, Hongkun Wang, Tingting Zhuang, Magdalena Czarnecka, Michael D. Johnson, Jeffrey A. Toretsky, Joanna Kitlinska Ewing sarcoma (ES) is an aggressive malignancy driven by an oncogenic fusion protein, EWS-FLI1. Neuropeptide Y (NPY), and two of its receptors, Y1R and Y5R are up-regulated by EWS-FLI1 and abundantly expressed in ES cells. Paradoxically, NPY acting via Y1R and Y5R stimulates ES cell death. Here, we demonstrate that these growth-inhibitory actions of NPY are counteracted by hypoxia, which converts the peptide to a growth-promoting factor. In ES cells, hypoxia induces another NPY receptor, Y2R, and increases expression of dipeptidyl peptidase IV (DPPIV), an enzyme that cleaves NPY to a shorter form, NPY3-36. This truncated peptide no longer binds to Y1R and, therefore, does not stimulate ES cell death. Instead, NPY3-36 acts as a selective Y2R/Y5R agonist. The hypoxia-induced increase in DPPIV activity is most evident in a population of ES cells with high aldehyde dehydrogenase (ALDH) activity, rich in cancer stem cells (CSCs). Consequently, NPY, acting via Y2R/Y5Rs, preferentially stimulates proliferation and migration of hypoxic ALDHhigh cells. Hypoxia also enhances the angiogenic potential of ES by inducing Y2Rs in endothelial cells and increasing the release of its ligand, NPY3-36, from ES cells. In summary, hypoxia acts as a molecular switch shifting NPY activity away from Y1R/Y5R-mediated cell death and activating the Y2R/Y5R/DPPIV/NPY3-36 axis, which stimulates ES CSCs and promotes angiogenesis. Hypoxia-driven actions of the peptide such as these may contribute to ES progression. Due to the receptor-specific and multifaceted nature of NPY actions, these findings may inform novel therapeutic approaches to ES.
