Liling Wan, PhD

Acute myeloid leukemia is the deadliest blood cancer. The mainstay chemotherapeutic treatments have met with limited success, and most patients will die from their disease. Thus, New treatments are desperately needed. To address this need, we have identified a cellular pathway leukemia cells rely on to live. In this project, we have developed an inhibitor that blocks this pathway and found that it kills leukemia grown in mice. We would like to understand why some leukemia cells rely on this pathway to survive and what determines the response to the inhibitor. If successful, our work will provide preclinical evidence for a new pathway as a target for acute myeloid leukemia and offer needed knowledge and chemical tools to guide future clinical studies. We are hopeful that our findings could lead to improvements in the lives of AML patients.  

Cihangir Duy, PhD, MS

Acute myeloid leukemia (AML) is an aggressive blood cancer that can recur after standard therapy. Although chemotherapy kills fast-growing AML cells, it often fails to destroy all cancer cells. As a result, the patient may appear to respond to therapy, but eventually the cancer returns. We found that the surviving cancer cells can overcome therapy by entering a senescence-like dormancy, allowing them to endure chemotherapy and resume cancerous activity after therapy has ended. The cancer cells become more aggressive than before treatment and showed changes in their epigenetic marks including DNA methylation. In this project, we will examine the mechanisms controlling the DNA methylation changes and their role in AML dormancy. Overall, this project will advance our understanding on the relevance of DNA methylation in cancer therapy and will define new therapeutic targets. Our long-term goal is to apply this information to develop new therapies to improve the survival of AML patients. 

Tullia Carmela Bruno, PhD

Funded in partnership with the Cancer Research Institute through the V Foundation’s Virginia Vine event and Wine Celebration Fund-A-Need

Our immune systems are internal barometers for the primary response to foreign invaders like viruses and bacteria within our body. Despite cancer arising from irregular growth of our own cells, the immune system can effectively kill cancer cells just as it identifies and kills infected cells. However, cancer can also effectively hide from the immune response (known as immune evasion), specifically because it grows from our normal cells becoming mutated or unchecked. Thus, preventing immune evasion and augmenting the immune response are now the focus of new and promising treatments. The immune cells found in cancer can be classified by function, helpers, killers, and suppressors.  Helpers educate the killers. Killers directly attack and eliminate the tumor cells. Suppressors hinder the immune response and promote cancer growth. Most immune-based therapies target the killers, however, there are many other components of the microenvironment in which cancer grows. In addition to the helpers and suppressors, the “soil” in which these cells thrive is important. We aim to understand how the “soil” (known as mesenchymal stem cells, MSCs) influences two key immune components in ovarian cancer patients, helper educational centers known as tertiary lymphoid structures (TLS) and suppressive T cells known as T regulatory cells (Tregs). Understanding this interplay is paramount to generating new and effective therapies for ovarian cancer patients, which is especially important in ovarian cancer because patients have not garnered the same therapeutic benefit with immune-based therapies as other solid tumors. In fact, only ~10% of ovarian cancer patients receive a survival benefit with immune-based therapies. Why is this? What is unique about ovarian cancer than allows it to effectively hide from the immune system? 

In ovarian cancer, the balance of the immune response is often tipped to enhance the suppressors, thus killers cannot effectively target and kill the tumor cells. We aim to determine how to increase the “soil” (MSCs) that promotes helper TLS and prevents suppressive Tregs utilizing novel therapies. “Soil” cells which start in the bone marrow (BM-MSCs) can initiate the building of helper TLS. Thus, these BM-MSCs work with the immune system to increase anti-cancer immunity. “Soil” cells that develop within the ovarian cancer environment (CA-MSCs) can help enhance ovarian cancer growth by amplifying the suppressive function of Tregs. Thus, these local CA-MSCs work against the immune system to decrease anti-cancer immunity. 

Altering the immune balance by targeting both the immune cells and the MSCs offers powerful new combinatorial treatment approaches. Our goal is to understand the specific factors within the ovarian cancer environment which impact this immune balance and to develop treatments to shift this balance to kill ovarian cancer. Specifically, we will study the steps necessary for BM-MSCs to support TLS formation and immune activation. We will also identify how local CA-MSCs recruit Tregs to decrease the immune response. We will specifically test if blocking the interaction between CA-MSCs and Tregs will shift the balance of immunity towards killing cancer. 

This work can be quickly moved into clinical trials as the blocking drug we are testing (neuropilin-1; NRP1) is already in early clinical development and our team includes an ovarian cancer clinician and translational immunologist with experience writing, conducting and analyzing clinical trials. The vision of the Clinic and Laboratory Integration Program (CLIP) is to improve the effectiveness of cancer immunotherapies. This grant will meet this vision by developing a therapy that targets MSCs and the immune system for a synergistic effect on improved patient outcomes. 

Avery Posey, Jr., PhD

FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND WITH SUPPORT FROM BRISTOL MYERS SQUIBB

Immune cell-based therapies represent the latest pillar of cancer therapy. Chimeric antigen receptor (CAR)-T cells have demonstrated significant anti-tumor activity against B cell leukemia and lymphoma and similar efficacies against multiple myeloma. CAR-NK cells are a newer addition to the cellular immunotherapy field but have already shown impressive results in the treatment of lymphoma. In this project, we will evaluate the activity of CAR-T and CAR-NK cell therapies targeting BCMA and TnMUC1 as single agents and combination strategies for the treatment of multiple myeloma. In addition, we will develop methods to enhance the efficacy and persistence of NK-cell based therapies through strategies to overcome immunosuppression. Successful completion of this project would generate novel and enhanced therapeutic strategies to treat multiple myeloma with immune cell-based therapies.   

Kristen Whitaker, MD

Funded by Hooters of America, LLC

Clinical trials test new treatments for patients. Clinical trials also help doctors learn what type of treatments work best for what patients. It is important for patients to participate in clinical trials so that we can continue to develop new treatments and improve the care of cancer patients. Very few adult patients with cancer join clinical trials. Black patients participate in trials less than white patients. We have learned several of the reasons that black patients are less likely to join clinical trials. Using what we have previously learned we will create an educational brochure designed specifically for black patients with breast cancer to see if it helps address some of the unique concerns black women have about joining clinical trials.

 

Edward Prochownik, M.D., Ph.D.

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 initial studies, 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 these mutations 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. 

Zachary Schug, Ph.D.

Funded by Hooters of America, LLC

The Schug laboratory is interested in understanding the way a cancer feeds itself in order to support its growth. The amounts and types of foods that cancers consume can be very different from the ones that our bodies normally use. For this reason, we believe that these differences can be used as new targeted treatment options for cancer patients. We have identified a specific food that is uniquely used by cancers to fuel their growth. Our goal is to create drugs that can block cancer’s ability to feed on this food. In addition, we are exploring the idea of combining this drug with other available treatments to improve patient survival. This research is important because it looks to block behaviors that are unique to cancer and therefore spares the body from harmful side effects. Furthermore, our results suggest that this food source is used by nearly all types of cancer. Because of this, we believe that our research is likely to make a major impact on the lives of many different cancer patients.

Sarah Tasian, M.D.

Funded by the Constellation Gold Network Distributors in honor of the Dick Vitale Pediatric Cancer Research Fund

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a common cancer in children and adults that does not respond well to regular chemotherapy medicines and often comes back. We found in earlier studies that Ph-like ALL has ‘miswired’ signaling networks inside its cells. These networks seem to be very sensitive to targeted medicines called kinase inhibitors. We are now testing one of these inhibitor medicines with chemotherapy in children with Ph-like ALL in a clinical trial, but we do not yet know if adding this new medication will be better than regular chemotherapy by itself. We will study leukemia cells from patients treated on this clinical trial to try to answer this question. We will also use specialized mouse models made from the children’s leukemia cells to understand what other miswired networks happen in Ph-like ALL and could be attacked by new medicines. These laboratory studies will help us to learn if using several inhibitor medicines together could be even better than current chemotherapy.  If this is the case, then we will then hope to test this new treatment idea in children with Ph-like ALL in future clinical trials.

Nicola Mason, DVM, Ph.D. & Don Siegel, M.D., Ph.D.

Funded by the Wine Celebration Fund-A-Need

Approximately 80,000 Americans will be diagnosed with bladder cancer in 2019 and 18,000 will die from their disease this year. Recent studies show that bladder cancer cells often carry a high number of genetic mutations which correlate with anti-tumor immune responses. New drugs known as immune checkpoint inhibitors (ICI), have produce dramatic clinical responses in up to 25% of bladder cancer patients, by enhancing anti-tumor immune responses that help control the tumor. However, despite intense efforts, biomarkers that predict response to ICI remain elusive. Furthermore, the mechanisms responsible for resistance to ICI are unknown. Predicting which patients respond to ICI would enable responders to be streamlined to receive ICIs, and resistant patients to receive alternative or combination therapies to improve their outcome. Pet dogs also develop bladder cancer that shares similar clinical, biological and genetic features with human bladder cancer. Despite standard of care treatment, most dogs will die of their disease within one year of diagnosis. Here we will investigate the genetic mutational burden in canine bladder cancer and determine whether it also correlates with tumor immune profiles. We will develop a canine ICI that can be used therapeutically in dogs with bladder cancer and we will determine whether effective ICI therapy is associated with enhanced anti-tumor immune responses and which factors or combination of factors predict ICI response. This work aims to establish the dog as a valuable model for human bladder cancer, provide a novel treatment for these dogs and guide biomarker discovery for humans.

Lori Goldstein, M.D.

Funded by Hooters of America, LLC

Hormone therapy medicine helps lower the chance of breast cancer growing or coming back. African American breast cancer survivors say they lack information about hormone therapy. Women also say that side effects are a main reason for stopping hormone therapy. We are doing a study that will test a text message program for these women. Women who join the study will be randomly assigned to one of two groups. One group will get text messages and the other will not. The text messages have information to help women deal with side effects. We think the women getting texts will have fewer side effects and greater belief they can manage hormone therapy. We also think they will understand why hormone therapy is important. We think this will help women worry less about hormone therapy and continue taking it. With the V-Foundation funding, our main goal is to increase the number of women who join the study. We will use our current partnership with community members and social media to recruit more women. This is the first study to test a text message program for African American women on hormone therapy. It is also one of the first to use a community partnership and social media to recruit women.

Mailing List Mailing List
Close Mailing List