Identifying New Treatment Combinations in Lung Cancer
Read moreType: V Scholar
Designed to identify, retain and further the careers of talented young investigators. Provides funds directly to scientists developing their own independent laboratory research projects. These grants enable talented young scientists to establish their laboratories and gain a competitive edge necessary to earn additional funding from other sources. The V Scholars determine how to best use the funds in their research projects. The grants are $200,000, two-year commitments.
David Glenn DeNardo, Ph.D.
Geraldine J. Guasch, Ph.D.
Keith Syson Chan, Ph.D.
Funded by the Jimmy V Celebrity Golf Classic
Volunteer Award In honor of
Dave Gibson and Felicia Davis
Rafael Bejar, M.D., Ph.D.
Summer Gibbs, Ph.D.
Robert Doebele, M.D., Ph.D.
Funded in Memory of Calvin Bradham
with support from Crown Imports
Mazhar Adli, Ph.D.
Aberrant chromatin regulation is a hallmark of multiple developmental diseases including cancer. Various chromatin marks such as DNA methylation and histone modifications, known as “epigenetic marks”, are implicated in the dynamic regulation of chromatin structure and lineage specific gene expression. Epigenetic regulators are recurrently mutated in cancer. The reversible nature of epigenetic marks holds great therapeutic promise. Therefore much effort is devoted to developing small molecule epigenetic inhibitors however such approaches are targeting the entire genome, causing multiple unintended side effects. I am proposing to develop tools that enable locus-specific manipulation of chromatin structure and function. Bu using such locus specific epigenetic engineering tools, I aim to alter aberrantly regulated local epigenetic modifications at specifically targeted genomic region.
Andrew A. Lane, M.D., Ph.D.
Several common cancers occur more frequently in males than in females, but we do not understand why this is the case. It can’t be simply explained by differences in environmental exposures, like cigarette smoking. Males have two different “sex chromosomes,” called X and Y. Females have two copies of the X chromosome, but no Y. Having XY (males) or XX (females) determines why males and females are different – they look different, make different hormones, and have different roles in passing genes to their children. We think that the X and Y chromosome differences may also influence cancer risk, and explain why some cancers happen more frequently in men.
I am a hematologist/oncologist, and I take care of patients with blood cancers such as leukemia and lymphoma. We were studying blood cancers in the laboratory by sequencing cancer DNA from patients. We found something very surprising: there was a group of patients with mutations in their DNA in a gene that “lives” on the X chromosome, and 100% of those patients were men. We looked in the medical literature and found a few other examples of genes on chromosome X that were mutated in cancers that occur more often in men than women.
In this study, we will look at data from thousands of patients with many types of cancer to see if there is evidence for gene mutations on the X and Y chromosomes that explain some of the difference in cancer incidence between men and women. These findings may be relevant in the many cancers that are more frequent in men, including leukemia, myelodysplastic syndrome, kidney cancer, and bladder cancer. In addition, we will study these genes in the laboratory by deleting one copy in male cells, and one or two copies in female cells. Together, these studies will determine how differences in mutations and number of copies of genes on the X chromosome contribute to cancer. More broadly, we hope that by identifying and characterizing this new kind of cancer gene, we might also discover suggest new ways to prevent and/or treat these types of cancer.
