Funded by the Constellation Gold Network Distributors
The human body generates hundreds of billions of new blood cells every day to replace old and dying cells. These new cells come from stems cells that live in the bone marrow. Sometimes the genetic material inside one of the stem cells is altered in a way that changes its behavior. The altered stem cells produce too many blood cells and slowly take over the bone marrow. In the clinic, we diagnose this as a type of blood cancer (called myeloproliferative neoplasm or MPN). Intriguingly, the same genetic alteration in different patients can result in very different forms of the disease. The disease outcome is just as unpredictable. Some patients show no symptoms for decades whereas others rapidly deteriorate. To understand this disease, for each patient, we would like to know where and when the disease originated and how the cancer cells expanded over decades. To answer these questions, we have developed technologies that allow us to measure molecular profiles of individual cells. To reconstruct the history of the disease, we will use the genomes of individual cancer cells in the same way that the evolutionary history of species is reconstructed from their present–day genomes. Our preliminary work has shown that cancer first occurs decades before diagnosis. Finally, to test therapies, we will engineer mice in which individual cells record their lineage histories in their own DNA. Together, our measurement will provide the most comprehensive molecular history of how cancers originate and progress in individual patients.
Funded by the Constellation Gold Network Distributors
Pancreatic cancer is one of the deadliest cancer types in the world. Most pancreatic cancer patients already developadvanced disease and are not suitable for surgery. A very small number of patients can live longer than ten years after surgery and are referred to as long-term survivors. Recently, unique bacteria were found in tumors from long-term survivors but not patients with shorter survival.In addition, long-term survivors tend to have higher numbers of T cells in their tumors – a cell type that is central to the immune system. Therefore, T cells might induce more powerful immune responses against cancer in long-term survivors through these unique bacteria.More precisely, we think that T cells in long-term survivors might “see” antigens from the bacteria and at the same time similar antigens from cancer cells. Our study is designed tounderstand the T cell responses unique to long-term survivors through T cell specificity inferences with our computer algorithms. The specificity inference will furtherguideour effortin finding these antigens that are “seen” by T cells in long-term survivors. Identifying these antigens from both cancer cells and the unique bacteria in long-term survivors will help usinventnew and better treatments for pancreatic cancer patients.
Cancer is a major cause of death worldwide. Immunotherapy is one of the most promising new ways to treat advanced stages of cancer. It works by “taking the breaks” off the immune system to let immune cells kill cancer cells better. Immunotherapy has revolutionized the treatment of cancers like melanoma, lung cancer and bladder cancer. Still, many patients do not respond to treatment. It is hard to know early who will respond and who won’t. We are developing and testing a method to predict response to immunotherapy early. We are doing this through a simple blood test thatmeasures signal from immune cells deep inside a patient’s tumor. We are testing our method in melanoma patients. If successful, our method will revolutionize the ability to predict cancer response to immunotherapy. This will give doctors vital information early and improve patient survival.
Kidney cancer is among the ten most common forms of human cancer. Whilemanageable in early stages, advanced kidney cancer remains incurable. Therefore, new drugsto treat this diseaseareurgentlyrequired.
Kidneycancers emerge when normal kidney cells acquire changes in their genetic program.DNA, our primary genetic source-code, is like a thread that is compactly wrapped into a complex spool called “chromatin”. This wrapping protectsDNA from environmental adversityand also allows precise control to switch genes on/off, when desired. Importantly, many of the kidney cancer-causing genetic changespromote improper “chromatin”spooling, which possibly drives cancer growth by switching onthe function ofkeytumor-promoting (onco)genes.Identifying and shutting off these misfiring oncogenes could thus block tumor growth, and be a means of therapy.
Our laboratory has begun comprehensively probing this idea.Using cutting-edge technology,we first identified numerous genesthat were associated with improper “chromatin” spooling andthuswere erroneously switched on in cancerous kidney cells. Among these genes, our follow-up studies shortlisted ten candidate oncogenes that promotedtumor growth in mouse models.Many of these gene products rewire the cancer cell’s metabolism. Here, we address which of these metabolic functions are indispensable for kidney cancer and how these changes fuel cancer growth. Cancer cells are perpetually hungry for nutrients to support their uncontrollable growth; therefore, starving kidney cancer cells of essential nutrientscan be exploited fortherapy.Together, our studies lay the foundations to establish such metabolic genes as clinically useful targets to treat kidney cancer.
Funded through the Stuart Scott Memorial Cancer Research Fund by John and Michele Truchard in honor of Jo Ann Truchard
Colorectal cancer is the second most common cause of cancer-related death in the United States. New research shows that colorectal cancer cases are increasing in younger age groups. We know that obesity is a major risk factor for colorectal cancer rates among younger adults, but we still don’t understand exactly how it works. Our research goal is to answer this important question. Obesity is mostly caused by unhealthy eating habits, including eating a diet rich in “bad fats”. First, we want to understand how healthy cells are damaged by “bad fats”. This is important because damages cells can produce harmful substances that cause cancer. “Bad fats” may also produce substances that feed harmful bacteria living in our intestines. These bacteria produce toxins that cause cancer. We will try to understand how the bad bacteria use this “food” to grow in the gut of obese individuals. This will help us show that “bad fats” cause cancer both by damaging cells and by feeding cancer-causing bacteria. If successful, our work will show how the dietary habits that lead to obesity can also cause colorectal cancer by damaging cells and feeding the growth of harmful bacteria. These findings will help us find new treatments for patients suffering from cancers caused by obesity.
Funded by 2020 Kay Yow Cancer Fund Final Four Research Award
Since the mid-1960s, New Orleans has had a majority AfricanAmerican (AA) population, many of whom are poor and uninsured. This, along with a lack of communication, misunderstanding of clinical research and limited funding for education and outreach, has led to a lack of access to clinical cancer research trialsamong this demographic.
The goal of this program is to assist in the enrollment of cancer patients and those at risk for cancer into clinical research trials, with particular emphasis on outreach, recruitment and enrollment of minority patients.
Pivotal to this effort is a patient navigator with extensive training in cultural competence who will be assigned specifically to clinical research. In addition to assisting enrollment in trials at our clinical sites, the Navigator will also use Tulane’s established relationships with community organizations, community leaders, area physicians and affiliate sites to help educate minorities about clinical research.
The Navigator will identify and approach prospective study patients;build a relationship with them, their caregivers and family members;and guide them through the enrollment processwhile serving as an essential link between the patient and the study team.
Funded in partnership with WWE in honor of Connor’s Cure
Hepatoblastoma (HB) is the most common cancer of the liver in children. Although usually very curable, some HBs have less than 20% survival. About 80% of these have changes in a protein known as b-catenin. Many also show abnormal regulation of another protein called YAP. Together, these are the most common changes in HB. Mice develop HB if a mutant form of b-catenin, termed D(90) and a mutant form of YAP known as YAPS127Aare expressed together in the liver although neither one alone causes tumors. 5-10% of HBs also contain mutations in a third protein, NFE2L2, that normally prevents certain types of DNA damage. In initialstudies, NFE2L2 mutants sped up tumor growth in response toD(90)+YAPS127A. Unexpectedly, NFE2L2 mutants caused tumors when present in livers with eitherD(90) or YAPS127A. Thus, any two combinations of thesemutations cause cancer. This research will ask exactly how each pair of mutant proteins alters tumor growth. It will also identify the small number of common changes that underlie these tumors. This has previously been impossible because the differences between normal livers and tumors is so large. Identifying the genes shared by different mutant combinations should make this easier. Our proposal is innovative because it will find the most important changes that cause HB. It is translationally important because knowing these changed genes may uncover new ways to treat HB and other pediatric and adult cancers.
Funded in partnership with Miami Dolphins Foundation
It is estimated that 1 in 8 women will be diagnosed with breast cancer in the US. During the last decades, breast cancer survival rates have greatly improved, mainly due to factors such as earlier detection and a better understanding of the disease. There are at least five different type of breast cancer. In this proposal, we will investigate one of the breast cancer subtypes, called estrogen receptor positive (ER+) breast cancer. ER+ breast cancer needs the estrogen to grow.Estrogen is a hormone that is important for sexual and reproductive development, mainly in women. ER+ breast canceraccounts for 70% of breast cancers and is typically treated with drugs designed to slow or stop the growth of cancer that uses estrogen to develop. Although thistype of therapy has been shown to reduce the risk of relapse and death from breast cancer,one third of patients develop resistance. This resultsin the spreading of cancer cells to other organs, known as metastasis. Thus, there is a critical need for identifying new treatments for patients who develop resistance to current therapies. The focus of this proposal is to understand the mechanisms of resistance to therapy and to overcome resistance by using a novel therapeutic approach. This is the next step towards our overarching goal, which is the identification of new therapeutic opportunities for the treatment of patients with aggressive breast cancer.
Funded in partnership with the Kansas City Chiefs Football Club
The immune system can destroy cancer cells. This is being taken advantage of in cancer therapy, withscientists trying to find ways to activate the immune system to better kill cancer cells. One therapy involves theinfusion of immune cells named natural killer (NK) cells. This therapy works well for some types of cancers.However, there has been limited success with this therapy against most tumors. The ultimate goal of our research is to increase the ability of this therapy to work against more cancers. One method proposed formaking NK cells better at killing cancer cells is treating the cells with activating signals that are termed IL-12, IL-15, and IL-18. We show that this makes the NK cells express proteins that affects the ability of the cells to killcancer cells.This leads us to think that IL-12,15, and18 treatmentalters NK cells in a way that can be good for the treatment of some, but bad for other, types of cancer.This is of highconcern because IL-12,15,18 treatment is proposed as a way to enhance NK cell treatment of cancers and isbeing tested in patients. Therefore, it is critical we determine how IL-12,15,18-treated NK cells affect the growth of different types of cancer. Here we propose to determine how IL-12,15,18-treatment, and the proteins this treatment induces on NK cells, alters the ability of NK cells to kill cancer in mouse models.
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.
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