We are testing a new system for linking grants to scientists.
The funding information displayed below comes from the
NIH Research Portfolio Online Reporting Tools and the
NSF Award Database.
The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
You can help! If you notice any innacuracies, please
sign in and mark grants as correct or incorrect matches.
Sign in to see low-probability grants and correct any errors in linkage between grants and researchers.
High-probability grants
According to our matching algorithm, Katherine M. Aird is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2015 — 2019 |
Aird, Katherine Marie |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Nucleotide Metabolism in Senescence and Platinum Resistance of Ovarian Cancer
? DESCRIPTION (provided by applicant): The goals of this Pathway to Independence Career Development Proposal are to request support for training to develop expertise in experimental models of ovarian cancer while addressing a fundamental gap in knowledge that could have a significant impact on the treatment of ovarian cancer patients. K99/R00 support during this transitional phase of my career will be integral to my successful development as an independent investigator at a top-tier research institute or university. The training plan outlined herein will take advantage of the extensive resources available at The Wistar Institute and neighboring University of Pennsylvania, as well as key senior personnel with track records of scientific excellence to serve as mentors, co-mentors, and collaborators. The scientific portion of this proposal focuses on experimentally and mechanistically determining the role of nucleotide metabolism in the early events in ovarian cancer tumorigenesis and whether this pathway can be targeted alone or in combination with platinum-based therapeutics to suppress chemoresistant cancer stem cells and obtain a sustained therapeutic response. The proposed studies are based on my previous findings that the rate-limiting protein in nucleotide synthesis, ribonucleotide reductase M2 (RRM2), is downregulated during oncogene-induced senescence, and an increase in nucleotides can overcome this tumor suppressive growth arrest. Additionally, RRM2 expression is highly increased in human EOC specimens and correlates with worse overall survival. I have published that knockdown or inhibition of RRM2 can decrease EOC cell growth via induction of senescence. My preliminary data show that knockdown of RRM2 can decrease aldehyde dehydrogenase 1 (ALDH1) activity, which is a marker of putative ovarian cancer stem cells (CSCs). Therefore, in line with these data I will explore two overarching scientific aims: 1) to determine whether nucleotide metabolism is increased in the early events in EOC tumorigenesis using a disease-relevant KRAS/MYC model; and 2) elucidate whether inhibition of nucleotide metabolism is synergistic with platinum treatment through a suppression of CSCs. The completion of the scientific aims of this proposal will develop my research skills in experimental models of EOC while also developing the rationale for clinical trials to obtain a sustained therapeutic response to platinum.
|
0.909 |
2021 |
Aird, Katherine Marie Snyder, Nathaniel W. (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Metabolic and Epigenetic Reprogramming in Cyclin E High Ovarian Cancer @ University of Pittsburgh At Pittsburgh
Project Summary/Abstract The ultimate goal of this mPI proposal is to address a fundamental gap in knowledge on the role of acetyl-CoA metabolic reprogramming in regulating cyclin E-high ovarian cancer DNA damage response, transformation, and response to therapy. The results from these studies could have a significant impact on the treatment of the ~20% of high grade serous ovarian cancer (HGSOC) patients with high cyclin E expression, which are resistant to emerging PARP inhibitor therapies due to proficiency in homologous recombination (HR)-mediated DNA repair. This research plan focuses on assessing the experimentally and mechanistically determining the spaciotemporal metabolic reprogramming of acetyl-CoA on histone hyperacetylation and enhancement of HR-mediated DNA repair and whether this pathway can be targeted in cyclin E-high HGSOC patients in combination with emerging PARP inhibitor therapies to obtain a synthetic lethality and sustained therapeutic response. The proposed studies are based on our preliminary findings that glucose-derived acetyl-CoA is upregulated in cyclin E-high cells, acetyl-CoA is spatially regulated in the cytoplasm and nucleus, and cyclin E-high cells display hyperacetylation of histones known to be involved in HR repair. In line with these data, we will explore two overarching scientific aims: 1) quantitatively dissect acetyl-CoA metabolic reprogramming in cyclin E-high HGSOC and its contribution to HR-mediated DNA repair; and 2) to determine whether acetyl-CoA mediated epigenetic changes contributes to ovarian tumorigenesis and therapeutic response. The completion of the scientific aims of this proposal will not only provide new mechanistic insights into the interplay between the acetyl-CoA-mediated metabolic-epigenetic axis during ovarian tumorigenesis, but will also establish targeting this axis as a strategy to improve therapeutic outcome for HGSOC patients with high cyclin E. The proposed research is of high impact because the mechanistic underpinning of these pathways has the potential to transform the management of HGSOC patients with high cyclin E. As PARP inhibitors are being developed for many cancer types, studies will have far-reaching implications for identifying novel strategies to inhibit HR-mediated DNA repair and develop future cancer therapeutics strategies for a wide range of patients.
|
0.97 |