Search Grants — Free, No Account Required

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY Our overall vision and long-term goal are to obtain a more complete understanding for how cellular signaling pathways, in particular G proteins and integrin receptors, control platelet adhesion and plug formation in hemostasis and thrombosis. Furthermore, we aim to elucidate aspects of the signaling machinery that function differentially in hemostasis versus thrombosis (both arterial and venous). The conceptual framework is that human thrombotic diseases result from an otherwise protective mechanism gone awry, and that disease-induced changes to platelet reactivity (priming) are a major contributor to thrombotic disease. A detailed understanding of platelet activation pathways is critical for the development of novel antithrombotic therapies, and for the identification of new biomarker assays for a prothrombotic state. Over the last two decades, my lab has utilized state-of-the-art in vitro and in vivo approaches to redefine our understanding of the molecular mechanisms regulating platelet reactivity in circulation and at sites of vascular injury. Key findings include the identification of tightly balanced G protein networks, an integrin activation complex that is unique to platelets, and injury-specific contributions of platelets to vascular integrity and thrombotic complications. The proposed work will focus on several areas within the general conceptual framework outlined above: (1) studies on G protein networks and integrin affinity regulation in platelets; (2) studies on the role of platelets in venous thrombosis pathogenesis and novel antithrombotic strategies; (3) development of novel assays to measure levels of primed platelets in different diseases; and (4) studies to better understand and correct defects in platelet count and function associated with inherited and acquired platelet disorders. Exciting preliminary findings include the identification of a novel G protein network in platelets, the establishment of new assays to monitor an elusive intermediate affinity conformation in platelet integrins, and a critical role for intermediate affinity integrins in thrombocytopenia and/or thrombosis associated with platelet disorders and cancer. In summary, the proposed studies will investigate significant knowledge gaps in basic platelet biology and provide a new understanding for how disease states like cancer affect platelet reactivity and platelet plug formation. Our studies have high translational relevance in the areas of antithrombotic therapy, biomarker development, and transfusion therapy.

NIMH - National Institute of Mental Health

Abstract Despite the effectiveness of antiretroviral therapies (ART) in reducing systemic HIV viral loads, central nervous system (CNS) dysfunction remains prevalent in 30-50% of people living with HIV (PWH). ART does not eliminate viral reservoirs in the CNS, leading to chronic neuroimmune dysfunction and conditions like HIV-associated neurocognitive disorder (HAND). Current preclinical research has primarily focused on models that simulate acute HIV infection, but there is a pressing need for models that accurately reflect CNS dysfunction in the context of chronic ART-suppressed infections. Recent advancements in immunodeficient mouse models with humanized immune systems have shown promise, allowing for natural HIV infection and crossing of the blood-brain barrier. These models have provided insights into HIV infection in the CNS and the role of human microglia cells. However, significant gaps remain, particularly in developing models that incorporate multiple human CNS cell types and accurately represent chronic infection dynamics. This proposal aims to develop preclinical NeuroHIV models that better mimic CNS-immune interactions in general and in particular during ART suppression. Specifically, our goal is to develop the next generation NeuroHIV model composed of autologous peripheral human immune cells, relevant human glial cell types, and an intact blood-brain barrier all in the context of ART-mediated HIV suppression.

NCI - National Cancer Institute

The parathyroid hormone (PTH) receptor type 1 (PTH1R) is a G-protein coupled receptor (GPCR) and the only cell surface receptor for the PTH-related protein (PTHrP), which causes the “vicious” cycle of prostate cancer (PCa) bone metastases. Clinical trials to block PTHrP using neutralizing antibodies only showed palliative effects in cancer patients. We have identified a series of small molecules (referred to as Pitt molecules) that act as negative allosteric modulators of PTH1R signaling. We hypothesize that Pitt molecules have the potential to prevent PTH1R overactivity induced by PTHrP hypersecretion encountered in prostate cancer cells. As allosteric molecules, Pitt molecules have the key advantage over orthosteric antagonists to restore normal receptor activity when PTHrP is hypersecreted. Furthermore, PTH1R is recently identified as a target for enzalutamide resistance in PCa bone metastases. The goal of this project is to identify selective Pitt molecules targeting PTHrP- induced PTH1R overactivity as potential lead candidates for the development of drugs treating bone osteolysis induced by prostate cancer metastases. Specific Aim 1 will identify the most effective Pitt molecules for inhibition of PTH1R hyperactivation by PTHrP. We will use state-of- the-art optical analysis of receptor signaling in live cells expressing recombinant and native PTH1R. We will evaluate the toxicity and biostability of the Pitt molecules using assays in cell culture. Specific Aim 2 will determine the efficacy of selected Pitt molecules in prostate cancer metastases. We found that the selective deletion of PTH1R in mesenchymal lineage cells of a mouse model significantly inhibits prostate cancer metastases. We have successfully established cell culture and mouse models to longitudinally monitor prostate cancer tumor growth and metastases. We will use these models to test the efficacy of selected Pitt molecules, as a single agent or in combination with current clinical therapies such as enzalutamide, in inhibiting prostate cancer metastases. The significance of this research program lies in its premise to lay the groundwork for a future translational research program that will examine the development and therapeutic utility of Pitt molecules for treating prostate cancer bone metastases and overcoming enzalutamide resistance.

U.S. National Science Foundation

The main goal of the S-STEM program is to enable academically talented, low-income students to pursue successful careers in promising STEM fields. Ultimately, the S-STEM program seeks to increase the number of academically promising low-income students who graduate with an S-STEM eligible degree and contribute to the American innovation economy with their STEM knowledge. Recognizing that financial aid alone cannot increase retention and graduation in STEM, the program provides awards to institutions of higher education (IHEs) not only to fund scholarships, but also to adapt, implement, and study evidence-based curricular and co-curricular[a] activities that have been shown to be effective in supporting recruitment, retention, transfer (if appropriate), student success, academic/career pathways, and graduation in STEM. To be eligible, scholars must be domestic low-income students with academic ability, talent, or potential and demonstrated unmet financial need who are enrolled in an associate, baccalaureate, or graduate degree program in an S-STEM eligible discipline. Proposers must provide an analysis that articulates the characteristics and academic needs of the population of students they are trying to serve. NSF is particularly interested in supporting the attainment of degrees in fields identified as critical needs for the Nation. It is up to the proposer to make a compelling case that such a field serves a critical need in the United States. [a] an activity at a school or college pursued in addition to the normal course of study. S-STEM Eligible Degree Programs Associate of Arts, Associate of Science, Associate of Engineering, and Associate of Applied Science Bachelor of Arts, Bachelor of Science, Bachelor of Engineering and Bachelor of Applied Science Master of Arts, Master of Science, and Master of Engineering Doctoral (Ph.D. or other comparable doctoral degree) S-STEM Eligible Disciplines Disciplinary fields in which research is funded by NSF, including technology fields associated with the S-STEM-eligible disciplines (e.g., biotechnology, chemical technology, engineering technology, information technology, etc.). The following degrees and disciplines areexcluded: Clinical degree programs, including medical degrees, nursing, veterinary medicine, pharmacy, physical therapy, and others not funded by NSF, are ineligible degrees. Programs for STEM teacher certification or licensure currently covered by the Robert Noyce Teacher Scholarship program (NOYCE) are ineligible for S-STEM funding. Business school programs that lead to Bachelor of Arts or Science in Business Administration degrees (BABA/BSBA/BBA) are not eligible for S-STEM funding. Masters and Doctoral degrees in Business Administration are also excluded. Proposers are strongly encouraged to contact Program Officers before submitting a proposal if they have questions concerning degree or disciplinary eligibility. The S-STEM program particularly encourages proposals from 2-year institutions, predominately undergraduate institutions, and urban, suburban, and rural public institutions.

Government of Nunavut

Supports Inuit and other artists in Nunavut for traditional and contemporary art creation, cultural preservation, and community arts programming.

NWT Arts Council

Grants for artists and cultural organizations in the Northwest Territories to support creation, production, and preservation of arts and culture.

New York City Department of Cultural Affairs

The Cultural Development Fund (CDF) provides operating support to New York City nonprofit arts and cultural organizations through a competitive grant process.

NZ Lottery Grants Board

150M+ NZD/yr for community, health research, environment, arts, and heritage projects in New Zealand.

Oakland Digital Art and Literacy Cnt

"Inspire Oakland 2015" a 12-class, 6-week graphic arts program, aimed at developing artistic creativity while empowering the lives of 30 underserved Laney Community College graphic design students ages 18 to 55.

City of Oakland

Award winning Oakland-based documentary filmmaker Jake Schoneker will develop a semester-long media-arts class for 40 10th-grade students at MetWest High School in collaboration with KDOL-TV and Media Enterprise Alliance (MEA).

NIGMS - National Institute of General Medical Sciences

Project Summary/Abstract The Center for Structural Biology, located in the Life Sciences Institute, is a comprehensive structural biology resource for researchers at University of Michigan (U-M) whose mission is to provide access to state-of-the-art facilities as well as expertise and training on all aspects of protein production and characterization through structure determination and analysis. We are requesting funds to purchase an Octet-RH16 system employing bio-layer interferometry (BLI) technology to calculate the rate of association (ka), rate of dissociation (kd) and affinity constants (KD) for biomolecular interactions in real-time. To run a successful drug development program, of which U-M is a leader having contributed to the most FDA approved drugs of any University in the US (Patridge et al., Drug Discovery Today 20, 1182-1187, 2015), access to technology that measures the kinetics of biomolecular interactions of drug-like molecules and biologics to their targets to prove target engagement and rank order the compounds/biologics is essential to the optimization of leads for clinical trials. This system will replace our current failing Octet-Red system, which is a high-demand instrument and whose end of service life was July 2019. Currently there are no other BLI instruments on campus available to our center users. Our current users are developing therapeutics to treat or prevent a broad range of diseases. They are developing new vaccines, new antibiotics, new therapies to combat neurodevelopmental disorders such as autism, new therapeutics against blood cancers such as myeloproliferative neoplasm and acute myeloid leukemia, new therapeutics against castration-resistant prostate cancer, and systemic and ocular toxoplasmosis in vulnerable populations. They are also engineering biosynthetic pathways to develop new drugs or improve existing ones. The new Octet-RH16 will double the number of samples that we can measure in parallel (16) and increase the number of samples we can measure in a single experiment by 8-fold, thus increasing our throughput by 700%. In addition, the required sample volumes will decrease by 5-fold. The new regeneration and re-racking standard feature will be cost saving as it allows the reuse of biosensors. This increase in productivity and reliability along with the decrease in operating cost will open new avenues of research for the U-M research community. It will provide an opportunity to directly screen targets against small drug-like chemical libraries housed at the U-M Center for Chemical Genomics, for example the Prestwick Library, where 95% of the compounds are drugs approved by the FDA-, EMA-, or other agencies.

THE LEMON AD STAND

Editorial and Design and Graphic and Fine Art Services

C-STRATEGIES INC

Editorial and Design and Graphic and Fine Art Services

NEIGER DESIGN INC

Editorial and Design and Graphic and Fine Art Services

SI! ADVERTISING

Editorial and Design and Graphic and Fine Art Services

RISE STRATEGY GROUP LLC

Editorial and Design and Graphic and Fine Art Services

M HARRIS & CO

Editorial and Design and Graphic and Fine Art Services

MUSE COMMUNITY DESIGN LLC

Editorial and Design and Graphic and Fine Art Services

WSP USA INC

Editorial and Design and Graphic and Fine Art Services

MUSE COMMUNITY DESIGN LLC

Editorial and Design and Graphic and Fine Art Services

BLACKBERG GROUP LLC

Editorial and Design and Graphic and Fine Art Services

MORREALE COMMUNICATIONS

Editorial and Design and Graphic and Fine Art Services

Ohio Arts Council

Ohio Arts Council provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across OH.

Ohio Arts Council

Ohio Arts Council General Operating Support (GOS) grants provide multi-year operating support to established Ohio arts organizations, enabling strategic planning, programmatic stability, and sustained community engagement.