GeneSys Research Institute

Boston, MA, United States

GeneSys Research Institute

Boston, MA, United States
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PubMed | Lawrence Livermore National Laboratory, Boston University, Yale University, GeneSys Research Institute and 2 more.
Type: | Journal: Frontiers in oncology | Year: 2015

[This corrects the article on p. 231 in vol. 5, PMID: 26528440.].


PubMed | Lawrence Livermore National Laboratory, Boston University, Yale University, GeneSys Research Institute and 2 more.
Type: | Journal: Frontiers in oncology | Year: 2015

Exposure of individuals to ionizing radiation (IR), as in the case of astronauts exploring space or radiotherapy cancer patients, increases their risk of developing secondary cancers and other health-related problems. Bone marrow (BM), the site in the body where hematopoietic stem cell (HSC) self-renewal and differentiation to mature blood cells occurs, is extremely sensitive to low-dose IR, including irradiation by high-charge and high-energy particles. Low-dose IR induces DNA damage and persistent oxidative stress in the BM hematopoietic cells. Inefficient DNA repair processes in HSC and early hematopoietic progenitors can lead to an accumulation of mutations whereas long-lasting oxidative stress can impair hematopoiesis itself, thereby causing long-term damage to hematopoietic cells in the BM niche. We report here that low-dose (1)H- and (56)Fe-IR significantly decreased the hematopoietic early and late multipotent progenitor (E- and L-MPP, respectively) cell numbers in mouse BM over a period of up to 10months after exposure. Both (1)H- and (56)Fe-IR increased the expression of pluripotent stem cell markers Sox2, Nanog, and Oct4 in L-MPPs and 10months post-IR exposure. We postulate that low doses of (1)H- and (56)Fe-IR may induce endogenous cellular reprogramming of BM hematopoietic progenitor cells to assume a more primitive pluripotent phenotype and that IR-induced oxidative DNA damage may lead to mutations in these BM progenitors. This could then be propagated to successive cell lineages. Persistent impairment of BM progenitor cell populations can disrupt hematopoietic homeostasis and lead to hematologic disorders, and these findings warrant further mechanistic studies into the effects of low-dose IR on the functional capacity of BM-derived hematopoietic cells including their self-renewal and pluripotency.


The invention features methods and compositions feature lapatinib and/or rapamycin for treating or preventing a cardiac condition induced by anthracycline treatment.


Patent
Genesys Research Institute | Date: 2013-10-04

The invention generally features isolated platelets, compositions, methods, and kits useful for targeted delivery of one or more therapeutic agents to a site of injury, inflammation, disease, or disorder. Also featured are methods and kits for producing a platelet loaded with one or more therapeutic agents. Platelets loaded with one or more therapeutic agents are useful for treating neoplasia, hemophilia, wounds, and other pathologies or conditions involving sites of injury, inflammation, disease, or disorder where platelets are able to localize.


Patent
Genesys Research Institute | Date: 2011-08-24

The invention features compositions comprising microRNAs that are differentially regulated in dormant versus fast growing neoplasias, and related methods of using the microRNAs for inducing or prolonging dormancy in a neoplastic cell or otherwise inhibiting the growth of a neoplastic cell.


Patent
Massachusetts Eye, Ear Infirmary and Genesys Research Institute | Date: 2013-11-04

The invention provides compositions for inducing expression in hair cells, and provides methods of using these compositions for modulating cochlear expression. Such compositions are further useful in treatment of sensorineural hearing loss, e.g., increasing proliferation or survival of mechanosensory hair cells.


Patent
Genesys Research Institute | Date: 2014-08-19

The invention provides methods for the treatment of radiation exposure featuring agents that interfere with the expression, production, release, accumulation, or activity of a TNF, IL6, EGF, IL1-alpha, IL1-beta, G-CSF, MCP-1, MIP-1, SCF, or RANTES receptor; or a TNF-, IL6, EGF, IL1-alpha, IL1-beta, G-CSF, MCP-1, MIP-1, SCF, or RANTES peptide or fragment thereof.


Patent
Genesys Research Institute | Date: 2014-01-31

Provided herein are an isolated or enriched population of tumor initiating cells derived from normal cells, cells susceptible to neoplasia, or neoplastic cells. Methods of use of the cells for screening for anti-hyperproliferative agents, and use of the cells for animal models of hyperproliferative disorders including metastatic cancer, diagnostic methods, and therapeutic methods are provided.


PubMed | Boston University, GeneSys Research Institute, H. Lee Moffitt Cancer Center and Research Institute and Tufts University
Type: | Journal: Stem cells international | Year: 2016

[This corrects the article DOI: 10.1155/2015/496512.].


PubMed | Boston University, GeneSys Research Institute, H. Lee Moffitt Cancer Center and Research Institute and Tufts University
Type: | Journal: Stem cells international | Year: 2015

Bone-marrow- (BM-) derived endothelial progenitor cells (EPCs) are critical for endothelial cell maintenance and repair. During future space exploration missions astronauts will be exposed to space irradiation (IR) composed of a spectrum of low-fluence protons ((1)H) and high charge and energy (HZE) nuclei (e.g., iron-(56)Fe) for extended time. How the space-type IR affects BM-EPCs is limited. In media transfer experiments in vitro we studied nontargeted effects induced by (1)H- and (56)Fe-IR conditioned medium (CM), which showed significant increase in the number of p-H2AX foci in nonirradiated EPCs between 2 and 24h. A 2-15-fold increase in the levels of various cytokines and chemokines was observed in both types of IR-CM at 24h. Ex vivo analysis of BM-EPCs from single, low-dose, full-body (1)H- and (56)Fe-IR mice demonstrated a cyclical (early 5-24h and delayed 28 days) increase in apoptosis. This early increase in BM-EPC apoptosis may be the effect of direct IR exposure, whereas late increase in apoptosis could be a result of nontargeted effects (NTE) in the cells that were not traversed by IR directly. Identifying the role of specific cytokines responsible for IR-induced NTE and inhibiting such NTE may prevent long-term and cyclical loss of stem and progenitors cells in the BM milieu.

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