My research interest is cancer genetics with an emphasis on clinically relevant questions that will improve our understanding of the cancer genetics of clinical phenotype and simultaneously improve patient care in oncology. I have extensive bench research experience in the fields of genome sequencing technology development, human genetic analysis through human genome sequencing and molecular assay development. My research benefits from the various innovations in genomic and genetic technologies that my group has developed.
Funded in partnership with the Morris Animal Foundation and the Wine Celebration Fund-A-Need
In 2012, Morris Animal Foundation launched its Golden Retriever Lifetime Study primarily to explore the risk factors related to cancer in golden retrievers. The Study has been following 3,044 dogs throughout their lives, collecting wide-ranging data on each animal each year, including environmental exposures, behavior, medical diagnoses, medications, diet and more. Golden retrievers were selected for this study because they are diagnosed with cancer at a much higher rate than most other breeds of dogs, and some of the most common cancers in golden retrievers are closely related to common human cancers.
This grant relates to genomics of our enrolled Study dogs. We will first test DNA samples from all of the dogs. We will be looking for small variations in hundreds of thousands of places along the DNA strands. Some variations may imply that a dog has a greater risk of a certain cancer type or one of the other diseases we are documenting. Similar studies are done for humans, but the advantage in dogs is that such information might ultimately be used in breeding programs to reduce the occurrence of cancer in the first place.
A second aspect of the grant will focus on biopsy specimens. We receive biopsy specimens from many of the cancers diagnosed in our Study dogs. We will be conducting a very detailed analysis of DNA, called sequencing, in these cancer tissues. Cancers occur due to changes in the DNA, called mutations. This study will allow us to determine which mutations are occurring in certain cancers that have similarity with those occurring in human patients. These include lymphoma (a cancer of white blood cells), osteosarcoma (bone cancer), and hemangiosarcoma (cancer of blood vessels). This information may lead to further studies on how to prevent and treat these cancers in both dogs and humans.
Funded in partnership with the Morris Animal Foundation and the Wine Celebration Fund-A-Need
In 2012, Morris Animal Foundation launched the Golden Retriever Lifetime Study primarily to explore the risk factors related to cancer in golden retrievers. The Study has been following 3,044 dogs throughout their lives, collecting wide-ranging data on each animal each year, including environmental exposures, behavior, medical diagnoses, medications, diet and more. Golden retrievers were selected for this study because they are diagnosed with cancer at a much higher rate than most other breeds of dogs, and some of the most common cancers in golden retrievers are closely related to common human cancers.
The data being collected by the Golden Retriever Lifetime Study is freely available for academic research via the Morris Animal Foundation Data Commons. The goal of the current project is to augment the Data Commons with high-resolution genotype data on each of the dogs and, eventually, complete DNA sequence data on all of the dogs diagnosed with cancer, along with a suitable number of other dogs as controls. As the genotyping and sequencing is completed, Morris Animal Foundation will perform preliminary data validation and analysis, and then incorporate the data into the Data Commons, where it will be available to everyone with an account. This will enable researchers from institutions around the world to participate with us in the effort better understand canine cancer as well as inform human cancer research.
Morris Animal Foundation Data Commons accounts can be requested by anyone involved in academic research by completing the registration form on the Data Commons website.
All cancer patients should have the opportunity to get very good care through research studies. Research studies are important to make cancer treatments and survival from cancer better but very few people of color are treated on cancer research studies called clinical trials. One way to solve this problem is to use specially trained staff to help cancer patients better understand clinical trials. These staff are called patient navigators. In this project, we will use patient navigators to teach and support patients asked to be in a cancer research study. These navigators will work as a team to make sure that all African Americans who receive care at the Cancer Center are considered for a clinical trial. In order for the patient navigator to know which patients may be fit to participate in research, we will use information from the medical record to create a list of patients that could be asked about their interest to get treatment with a clinical trial. The patient navigator will use this list to contact patients and will teach patients about clinical trials and connect patients to finance counselors, social workers and other helpful community services as needed. To understand if the project is a success, we will compare the total number of patients, by race, treated on a cancer research study before and after the project.
Funded in partnership with The Leukemia & Lymphoma Society’s PedAL Initiative and the Wine Celebration Fund-A-Need
Acute myeloid leukemia is a cancer of bone marrow cells. It can be difficult to treat, particularly in young patients. The disease can differ from one patient to another, depending on the kinds of mutations that are found in the cancer cell. Different mutations may respond to different treatments.
Dogs also develop acute leukemia. In this species the outcomes are dismal, with most dogs being euthanized within days of the diagnosis because of poor quality of life. Currently available chemotherapy is ineffective in this species.
In this project we will sequence DNA and RNA from 100 cases of naturally occurring acute leukemias in pet dogs. Our goal is to find mutations and gene expression patterns shared between dogs and people. Once these shared features are identified, new treatments can be devised which can be tested first in dogs, and if successful, translated to humans. This approach offers a chance at better therapies in both species.
Clinical trials offer a path to cure for cancer patients by testing methods to prevent, find or treat many types of illness. Yet, patient access to clinical trials varies; rural areas have limited health care services. Duke University has a wealth of clinical trials for patients with cancer. The goal of this effort is to increase the clinical trials available from Duke to the community. The clinical trials will focus on specific ethnic groups in specific locations. Two types of clinical trials will be the focus: Uncommon cancers– such as blood-based cancers, or cancers that have different effects on specific races – such as prostate.
Duke doctors with special knowledge in Prostate Cancer and blood cancers will go to specific clinics. The Duke doctors will talk with doctors and nurses in the community about patient cases. We will test to see if rural clinics can use central storage for test results from tumors. Central storage will let us match test results from tumors to available clinical trials.
Our team wants to include patients in our effort to improve knowledge about clinical trials. We want to help make them aware that clinical trials are available. A committee that includes patients will help guide the creation of educational tools for patients.
Prostate cancer afflicts one in seven men and is their second leading cause of death, justifying development of more effective therapies. Prostate cancer depends on testosterone binding to and activating the androgen receptor (AR), which in turn promotes the growth of prostate cancer. Current therapies for prostate cancer are aimed at reducing AR activity, either by blocking the production of testosterone or through agents which compete with testosterone for binding to the AR. Our approach is depleting cancer cells of the AR protein by promoting its degradation. We will accomplish this by manipulating the pathways (either genetically or with drugs) which control protein degradation. Our preliminary data show that we can promote degradation of the AR in cells in test tubes. In this proposal we will test if we can promote AR degradation in mouse models of prostate cancer.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Only half of children with neuroblastoma that is found to be “high-risk” (HR-NB) live after getting the best known treatments. To change this, we need to know what makes HR-NB grow, and find new targets to attack. The New Approaches to Neuroblastoma Therapy (NANT) (www.nant.org) is a team of doctors working with patients and/or in labs to find new treatment ideas and test them in children whose tumor didn’t go away after getting the best known treatments. If NANT’s new treatments are safe and make some tumors get smaller, they are then tested in more children to see if the new treatment is better than the best-known treatments. A little blood, bone marrow, and tumor are also taken from patients on NANT treatments to study in labs to see why our new idea did or didn’t work, and how we can make them better. There are 18 NANT hospitals in the United States, Canada, Australia, and Europe. NANT is the only group working only on new/better HR-NB treatments. This grant will support NANT doctors, labs, and the people who work in the NANT office to quickly take new ideas from labs and turn them into treatments being given to children with HR-NB. It also helps us to store patient samples so they can be used to keep finding new and better ideas. Our goal is to find safe treatments that will help more children with HR-NB to live.
Funded in partnership with Cannonball Kids cancer Foundation, in memory of Tyler Trent
Glioblastoma (GBM) is the most aggressive and devastating brain tumor, and it currently has no known cure. Less than 20% of young adults diagnosed with GBM survive more than 24 months. GBM can resist treatment in many ways. These include expressing an enzyme called CD73 and changing the expression of proteins on its surface. Natural killer cells are able to fight and kill GBM, however this ability is often blocked around growing GBM cells. In order to rescue the activity of these cells, we are developing new immunotherapies by genetically modifying natural killer cells to shut down ways that GBM uses to grow. We are also combining these cells with drugs that can help them travel deeper into tumors. This immunotherapy is an entirely new way to treat GBM and has significant promise, for patients, over traditional treatments.
Funded in partnership with the Goldberg Family Foundation
We need better tools to screen for and diagnose cancer earlier and at a curable stage in individuals that carry inherited mutations such as BRCA1/2 and other cancer susceptibility genes that put them at highrisk for breast, ovarian, prostate, pancreatic and other cancers. We propose to use powerful new approachesfor “next-generation” DNA sequencing from standard blood samples to identify circulating tumor DNA mutations as a very sensitive markerof early cancers in high-risk individuals. These “liquid biopsies” may prove to be a far easier and more sensitive way to screen for cancer than our current imaging based approachesusing mammograms, MRI’s, etc. To this end, we have been collecting blood samples from our genetically high-risk patients with and without cancer, and before and after prophylactic or cancer surgeries, for liquid-biopsy analyses using technology developed at Stanford.
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